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Doğukan FM, Karatay H, Yüzkan S, Burhan Ş, Erkan B, Yılmaz-Özgüven B. Clinicopathologic Correlates of PIT1 and SF1-Multilineage Pituitary Neuroendocrine Tumors and the Diagnostic Utility of NKX2.2 Immunohistochemistry in Pituitary Pathology. Arch Pathol Lab Med 2025; 149:83-89. [PMID: 38649148 DOI: 10.5858/arpa.2023-0543-oa] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/22/2023] [Indexed: 04/25/2024]
Abstract
CONTEXT.— PIT1 and SF1-multilineage pituitary neuroendocrine tumors (PitNETs) have been defined since the classification of adenohypophysial tumors based on the PIT1, SF1, and TPIT transcription factors. OBJECTIVE.— To describe the clinicopathologic features of PIT1 and SF1-multilineage PitNETs and to contribute to the pituitary pathology practice by questioning the expression of NKX2.2 in PitNETs. DESIGN.— We reviewed 345 PitNETs and described the clinicopathologic features of 8 PIT1 and SF1-multilineage tumors. NKX2.2 positivity and staining pattern were compared to those of 45 PitNETs from the control group. RESULTS.— PIT1 and SF1-multilineage PitNET patients had a mean age of 41.13 (range, 14-58 years) and a mean tumor diameter of 14.0 mm (range, 8-20 mm). The most common clinical presentation was acromegaly (6 of 8), and postoperative remission was achieved in all patients. On histomorphologic examination, a pseudopapillary pattern was seen in 5 of the tumors, either focally or diffusely. In addition to PIT1 and SF1, there was a diffuse staining with growth hormone and a predominantly perinuclear staining with cytokeratin 18. With NKX2.2, all multilineage tumors were positive, of which 5 were diffuse and 3 were focal. In the control group, 8 tumors (8 of 45) were positive, of which only 1 was diffuse and 7 were focal. CONCLUSIONS.— In conclusion, NKX2.2 is a transcription factor that can be used as an additional tool in pituitary pathology, and PIT1 and SF1-multilineage PitNETs are specific tumors that usually present with acromegaly, show signs of a nonaggressive clinical course, have a pseudopapillary histomorphology, and express NKX2.2.
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Affiliation(s)
- Fatih Mert Doğukan
- From the Department of Pathology, Başakşehir Çam ve Sakura City Hospital, University of Health Sciences, Istanbul, Turkey (Doğukan, Karatay, Yılmaz-Özgüven)
| | - Hüseyin Karatay
- From the Department of Pathology, Başakşehir Çam ve Sakura City Hospital, University of Health Sciences, Istanbul, Turkey (Doğukan, Karatay, Yılmaz-Özgüven)
| | - Sabahattin Yüzkan
- From the Department of Radiology, Başakşehir Çam ve Sakura City Hospital, University of Health Sciences, Istanbul, Turkey (Yüzkan)
| | - Şebnem Burhan
- Endocrinology, Başakşehir Çam ve Sakura City Hospital, University of Health Sciences, Istanbul, Turkey (Burhan)
| | - Buruç Erkan
- From the Department of Neurosurgery,Başakşehir Çam ve Sakura City Hospital, University of Health Sciences, Istanbul, Turkey (Erkan)
| | - Banu Yılmaz-Özgüven
- From the Department of Pathology, Başakşehir Çam ve Sakura City Hospital, University of Health Sciences, Istanbul, Turkey (Doğukan, Karatay, Yılmaz-Özgüven)
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Zhang L, Yan S, Xie SK, Wei YT, Liu HP, Li Y, Wu HB, Wang HL, Xu PF. Typical morphological characteristics of the immunohistochemical subtypes of pituitary microadenomas: a dual center study. Endocr Connect 2024; 13:e240378. [PMID: 39348234 PMCID: PMC11623279 DOI: 10.1530/ec-24-0378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 09/30/2024] [Indexed: 10/02/2024]
Abstract
Purpose This study aimed to investigate the relationship between magnetic resonance image (MRI) features and the immunohistochemical subtypes of pituitary microadenomas (PMAs) characterized by location and growth pattern. Materials and methods A double-center, retrospective review of MRI characteristics was conducted in 57 PMA cases recorded from February 2014 to September 2023, identified based on the 2017 World Health Organization classification of pituitary gland tumors. The geometric center of the tumor was defined, and the possibility of PMA vertical or lateral growth patterns was evaluated according to the ratio of maximum diameter between the X and Y axes. Results Among the PMAs, somatotroph adenomas (STAs) significantly frequented the lateral-anteroinferior portion of the pituitary gland (P = 0.036). Lactotroph adenomas (LTAs) showed a significant locational preference for the lateral-posteroinferior portion (P = 0.037), and gonadotroph adenomas (GTAs) were predominantly located in the central-anteroinferior portion (P = 0.022). Furthermore, PMAs in the suprasellar portion exhibited vertical extension with statistical significance (P = 0.0). Conclusion In our cohort, micro-STAs were predominantly located in the lateral-anteroinferior portion of the pituitary gland, micro-LTAs in the lateral-posteroinferior portion, and micro-GTAs in the central-anteroinferior portion. The growth pattern of PMAs was highly correlated with their vertical position instead of their immunohistochemical subtypes. Therefore, MRI shows potential in differentiating partial PMA subgroups, especially cases within the silent groups.
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Affiliation(s)
- Li Zhang
- Department of Neurology, Nanyang Central Hospital, Nanyang, Henan, China
| | - Shuai Yan
- Department of Neurological Function Examination, Affiliated Hospital of Hebei University, Hebei University, Baoding, China
| | - Shen-ke Xie
- Department of Neurosurgery, Nanyang Central Hospital, Nanyang, Henan, China
| | - Yi-tong Wei
- Department of Neurosurgery, Nanyang Central Hospital, Nanyang, Henan, China
| | - Hua-peng Liu
- Department of Endocrinology, Nanyang Central Hospital, Nanyang, Henan, China
| | - Yin Li
- Department of Pathology, Nanyang Central Hospital, Nanyang, Henan, China
| | - Hai-bo Wu
- Department of Neurology, Nanyang Central Hospital, Nanyang, Henan, China
| | - Hai-liang Wang
- Department of Neurosurgery, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Peng-fei Xu
- Department of Neurosurgery, Nanyang Central Hospital, Nanyang, Henan, China
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Durmuş ET, Kefeli M, Mete O, Çalışkan S, Aslan K, Onar MA, Çolak R, Durmuş B, Cokluk C, Atmaca A. Granulation Patterns of Functional Corticotroph Tumors Correlate with Tumor Size, Proliferative Activity, T2 Intensity-to-White Matter Ratio, and Postsurgical Early Biochemical Remission. Endocr Pathol 2024; 35:185-193. [PMID: 39046680 PMCID: PMC11387444 DOI: 10.1007/s12022-024-09819-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/15/2024] [Indexed: 07/25/2024]
Abstract
Unlike somatotroph tumors, the data on correlates of tumor granulation patterns in functional TPIT lineage pituitary neuroendocrine tumors (corticotroph tumors) have been less uniformly documented in most clinical series. This study evaluated characteristics of 41 well-characterized functional corticotroph tumors consisting of 28 densely granulated corticotroph tumors (DGCTs) and 13 sparsely granulated corticotroph tumors (SGCTs) with respect to preoperative clinical and radiological findings, tumor proliferative activity (including mitotic count and Ki-67 labeling index), and postoperative early biochemical remission rates. The median (interquartile range (IQR)) tumor size was significantly larger in the SGCT group [16.00 (16.00) mm in SGCT vs 8.5 (9.75) mm in DGCT, p = 0.049]. T2-weighted signal intensity and T2 intensity (quantitative) did not yield statistical significance based on tumor granulation; however, the T2 intensity-to-white matter ratio was significantly higher in SGCTs (p = 0.049). The median (IQR) Ki-67 labeling index was 2.00% (IQR 1.00%) in the DGCT group and 4.00% (IQR 7.00%) in the SGCT group (p = 0.043). The mitotic count per 2 mm2 was higher in the SGCT group (p = 0.001). In the multivariate analysis, the sparse granulation pattern (SGCT) remained an independent predictor of a lower probability of early biochemical remission irrespective of the tumor size and proliferative activity (p = 0.012). The current study further supports the impact of tumor granulation pattern as a biologic variable and warrants the detailed histological subtyping of functional corticotroph tumors as indicated in the WHO classification of pituitary neuroendocrine tumors. More importantly, the assessment of the quantitative T2 intensity-to-white matter ratio may serve as a preoperative radiological harbinger of SGCTs.
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Affiliation(s)
- Elif Tutku Durmuş
- Department of Endocrinology and Metabolism, Faculty of Medicine, Ondokuz Mayis University, 55200, Atakum Samsun, Turkey.
| | - Mehmet Kefeli
- Department of Pathology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Ozgur Mete
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
- Department of Pathology, University Health Network, 200 Elizabeth Street, 11 Floor, Toronto, ON, M5G 2C4, Canada
- Endocrine Oncology Site Group, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Sultan Çalışkan
- Department of Pathology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Kerim Aslan
- Department of Radiology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Mustafa Arda Onar
- Department of Radiology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Ramis Çolak
- Department of Endocrinology and Metabolism, Faculty of Medicine, Ondokuz Mayis University, 55200, Atakum Samsun, Turkey
| | - Buğra Durmuş
- Department of Endocrinology and Metabolism, Faculty of Medicine, Ondokuz Mayis University, 55200, Atakum Samsun, Turkey
| | - Cengiz Cokluk
- Department of Neurosurgery, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Ayşegül Atmaca
- Department of Endocrinology and Metabolism, Faculty of Medicine, Ondokuz Mayis University, 55200, Atakum Samsun, Turkey
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Ancil S, Gupta K, S S, Das L, Ahuja CK, Chhabra R, Dhandapani S, Dutta P. Clinico-radio-pathological predictors of outcomes in patients with acromegaly undergoing endoscopic transsphenoidal surgery. Surg Neurol Int 2024; 15:268. [PMID: 39246769 PMCID: PMC11380812 DOI: 10.25259/sni_1001_2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 07/07/2024] [Indexed: 09/10/2024] Open
Abstract
Background Acromegaly is a rare chronic endocrine disorder with variable biochemical remission rates from 40% to 85%. Hence, understanding the factors predicting biochemical cures helps in planning targeted and personalized treatment. We aimed to study the various clinico-radio-pathological predictors of outcomes in patients with pituitary neuroendocrine tumor (PitNET) who underwent transsphenoidal surgery (TSS) at 3 months follow-up. Methods Our cohort included 61 consecutive patients with acromegaly treated at an institute in northwest India between January 2019 and June 2021. The outcomes of TSS were assessed at the end of 3 months postoperatively as defined by Endocrine Society Guidelines 2014. Results The mean age at diagnosis was 38 ± 12 years, with the majority being females (67.2%). The median tumor volume was 2376 mm3 with high insulin-like growth factor-1 levels (3.12 ± 1.76 times the upper reference limit). Forty-two patients (68.8%) had radiological evidence of cavernous sinus invasion. Overall, the biochemical remission rate at 3 months was 34.4%. Unlike preoperative Knosp grading, T2-hypointensity was not predictive of biochemical remission. The granularity of PitNET, as well as immunohistochemical (IHC) markers such as Ki-67 index somatostatin receptor subtype (SSTR2/5) and low-molecular-weight cytokeratin (CAM5.2) expression, failed to show any significant correlation with remission. Conclusion Overall, bulky tumors, higher hormone burden, and advanced Knosp grades translated to lower rates of biochemical remission in the present study cohort. Contrary to earlier studies, conventional IHC markers such as Ki-67, SSTR2/5, and CAM5.2 were not useful for predicting biochemical remission at 3 months.
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Affiliation(s)
- Sanish Ancil
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Kirti Gupta
- Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Subin S
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Liza Das
- Department of Endocrinology and Telemedicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Chirag Kamal Ahuja
- Department of Radiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Rajesh Chhabra
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sivashanmugam Dhandapani
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pinaki Dutta
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Kiseljak-Vassiliades K, Lipe K, Turin CG, Fishbein L, Costello JC, Kerr JM, Holmstoen TB, Youssef AS, Lillehei KO, Kleinschmidt-DeMasters BK, Wierman ME. E-cadherin expression and gene expression profiles in corticotroph pituitary neuroendocrine tumor subtypes. J Neuropathol Exp Neurol 2024; 83:586-595. [PMID: 38777808 DOI: 10.1093/jnen/nlae034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2024] Open
Abstract
Corticotroph adenomas/pituitary neuroendocrine tumors (PitNETs) are associated with significant morbidity and mortality. Predictors of tumor behavior have not shown high prognostic accuracy. For somatotroph adenomas/PitNETs, E-cadherin expression correlates strongly with prognosis. E-cadherin expression has not been investigated in other PitNETs. A retrospective chart review of adults with corticotroph adenomas/PitNETs was conducted to assess correlation between E-cadherin expression and tumor characteristics. In addition, gene expression microarray was performed in subset of tumors (n = 16). Seventy-seven patients were identified; 71% were female, with median age of cohort 45.2 years. Seventy-five percent had macroadenomas, of which 22% were hormonally active. Ninety-five percent of microadenomas were hormonally active. Adrenocorticotropic hormone granulation pattern by IHC identified 63% as densely granulated (DG) and 34% as sparsely granulated (SG). All microadenomas were DG (p < .001); 50% of macroadenomas were DG associated with increased tumor invasion compared to SG. E-cadherin IHC was positive in 80%, diminished in 17%, and absent in 20% and did not correlate with corticotroph PitNETs subtype, size, or prognosis. In contrast to the distinct transcriptomes of corticotroph PitNETs and normal pituitaries, a comparison of clinically active and silent corticotroph PitNETs demonstrated similar molecular signatures indicating their common origin, but with unique differences related to their secretory status.
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Affiliation(s)
- Katja Kiseljak-Vassiliades
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Section of Endocrinology, Department of Medicine, Research Service at Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA
| | - Kristin Lipe
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Surgery, Good Samaritan Regional Medical Center, Corvallis, Oregon, USA
| | - Christie G Turin
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Lauren Fishbein
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Section of Endocrinology, Department of Medicine, Research Service at Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA
- Department of Biomedical Informatics, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - James C Costello
- Department of Pharmacology, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- University of Colorado Cancer Center, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Janice M Kerr
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Tessa B Holmstoen
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - A Samy Youssef
- Department of Neurosurgery, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Kevin O Lillehei
- Department of Neurosurgery, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Bette K Kleinschmidt-DeMasters
- Department of Neurosurgery, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Pathology, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Neurology, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Margaret E Wierman
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Section of Endocrinology, Department of Medicine, Research Service at Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA
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Hladik M, Nasi-Kordhishti I, Dörner L, Kandilaris K, Schittenhelm J, Bender B, Honegger J, Behling F. Comparative analysis of intraoperative and imaging features of invasive growth in pituitary adenomas. Eur J Endocrinol 2024; 190:489-500. [PMID: 38798200 DOI: 10.1093/ejendo/lvae059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 03/04/2024] [Accepted: 05/24/2024] [Indexed: 05/29/2024]
Abstract
BACKGROUND Most pituitary adenomas (PAs), also termed pituitary neuroendocrine tumors, are benign in nature and can be treated effectively by surgical resection, medical treatment, and in special cases by radiotherapy. However, invasive growth can be an important feature of a more aggressive behavior and adverse prognosis. The extension of PAs into the cavernous sinus can be categorized according to the Knosp criteria on magnetic resonance imaging (MRI). Comparative analyses of MRI features and intraoperative findings of invasive growth regarding different clinical factors are still scarce. MATERIALS AND METHODS We performed a retrospective single-center analysis of 764 PAs that were surgically treated between October 2004 and April 2018. Invasive growth was assessed according to the surgical reports and preoperative MRI (Knosp criteria). Clinical data, such as patient age at diagnosis and gender, histopathological adenoma type, and extent of resection, were collected. RESULTS Invasive features on MRI were seen in 24.4% (Knosp grades 3A-4, 186/764) of the cases. Intraoperatively, invasion was present in 42.4% (324/764). Complete resection was achieved in 80.0% of adenomas and subtotal resection, in 20.1%. By multivariate analysis, invasion according to intraoperative findings was associated with the sparsely granulated corticotroph (SGCA, P = .0026) and sparsely granulated somatotroph (SGSA, P = .0103) adenoma type as well as age (P = .0287). Radiographic invasion according to Knosp grades 3A-4 correlated with age (P = .0098), SGCAs (P = .0005), SGSAs (P = .0351), and gonadotroph adenomas (P = .0478). Both criteria of invasion correlated with subtotal resection (P = .0001, respectively). CONCLUSIONS Both intraoperative and radiographic signs of invasive growth are high-risk lesions for incomplete extent of resection and occur more frequently in older patients. A particularly high prevalence of invasion can be found in the SGCA and SGSA types. Cavernous sinus invasion is also more common in gonadotroph adenomas. Usage of the Knosp classification is a valuable preoperative estimation tool.
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Affiliation(s)
- Mirko Hladik
- Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
- Department of Neurosurgery and Neurotechnology, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
- Department of Orthopedic, Trauma and Spine Surgery, Thun Hospital, 3600 Thun, Switzerland
| | - Isabella Nasi-Kordhishti
- Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
- Department of Neurosurgery and Neurotechnology, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
| | - Lorenz Dörner
- Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
- Department of Neurosurgery and Neurotechnology, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
| | - Kosmas Kandilaris
- Faculty of Medicine, Medical Center, Institute for Surgical Pathology, Albert Ludwig University of Freiburg, 79098 Freiburg, Germany
| | - Jens Schittenhelm
- Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
- Department of Neuropathology, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
| | - Benjamin Bender
- Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
- Department of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
| | - Jürgen Honegger
- Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
- Department of Neurosurgery and Neurotechnology, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
| | - Felix Behling
- Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
- Department of Neurosurgery and Neurotechnology, University Hospital Tübingen, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
- Hertie Institute for Clinical Brain Research, 72076 Tübingen, Germany
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Guaraldi F, Ambrosi F, Ricci C, Di Sciascio L, Asioli S. Histopathology of growth hormone-secreting pituitary tumors: State of the art and new perspectives. Best Pract Res Clin Endocrinol Metab 2024; 38:101894. [PMID: 38614953 DOI: 10.1016/j.beem.2024.101894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/15/2024]
Abstract
Somatotroph (GH) adenomas/PitNETs typically arise from adenohypophysis and are biochemically active, leading to acromegaly and gigantism. More rarely, they present with ectopic origin and do not present overt biochemical or clinical features (silent variants). Histopathological examination should consider the clinical and radiological background, and include multiple steps assessing tumor morphology, pituitary transcription factors (PTFs), hormone secretion, proliferation markers, granulation, and somatostatin receptors (STRs), aimed at depicting as better as possible tumor origin (in case of non-functioning and/or metastatic tumor), and clinical behavior, including response to treatment. GH-secreting tumors are part of the Pit-1 family tumors and can secrete GH only (pure somatotrophs) or co-secrete prolactin (mixed tumors; in this case, various histological subtypes have been identified). Each subtype presents unique radiological, biochemical, and clinical characteristic. Therefore, the integration of biochemical, clinical, radiological, and histopathological elements is fundamental for proper diagnosis and management of pituitary adenomas/PitNETs, to be performed in referral Centers. In more recent times, the importance of genetic and epigenetic evaluation in the characterization of pituitary tumors (i.e., early identification of aggressive variants) has been outlined by some large studies, with the intention of improving targeted treatments.
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Affiliation(s)
- Federica Guaraldi
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
| | - Francesca Ambrosi
- Pathology Unit, Maggiore Hospital-AUSL Bologna, Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
| | - Costantino Ricci
- Pathology Unit, Maggiore Hospital-AUSL Bologna, Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
| | - Luisa Di Sciascio
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
| | - Sofia Asioli
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
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Calandrelli R, Mattogno PP, Chiloiro S, Gessi M, D’Apolito G, Tartaglione T, Giampietro A, Bianchi A, Doglietto F, Lauretti L, Gaudino S. Trouillas's Grading and Post-Surgical Tumor Residue Assessment in Pituitary Adenomas: The Importance of the Multidisciplinary Approach. Diagnostics (Basel) 2024; 14:274. [PMID: 38337790 PMCID: PMC10855691 DOI: 10.3390/diagnostics14030274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/18/2024] [Accepted: 01/23/2024] [Indexed: 02/12/2024] Open
Abstract
BACKGROUND We aim to assess the role of a multidisciplinary approach in pituitary adenomas (PitNETs) classification, evaluate criteria concordance, and compare intraoperative assessments with post-operative MRIs for tumor remnants. METHODS Clinical, radiological, histological, and intra- and post-operative data of the treated PitNETs were extracted from prospectively created records. PitNETs were graded according to Trouillas, and the evaluation of the tumor remnants was recorded. RESULTS Of 362 PitNETs, 306 underwent surgery, with Trouillas grading assigned to 296. Eight-nine radiologically non-invasive PitNETs progressed to grades 1b (27), 2a (42), or 2b (20) due to proliferative or surgical invasiveness criteria. Twenty-six radiologically invasive tumors were graded 2b due to proliferative criteria. Surgical resection details and post-surgical MRI findings revealed that residual tumors were more common in grades 2a and 2b. During surgery, small tumor remnants were documented in 14 patients which were not visible on post-surgical MRI. Post-surgical MRIs identified remnants in 19 PitNETs not seen during surgery, located in lateral recesses of the sella (4), retrosellar (2), or suprasellar regions (7), along the medial wall of the cavernous sinus (6). CONCLUSIONS The Pituitary Board allows for the correct grading of PitNETs to be obtained and an accurate identification of high-risk patients who should undergo closer surveillance due to tumor remnants.
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Affiliation(s)
- Rosalinda Calandrelli
- Radiology and Neuroradiology Unit, Department of Imaging, Radiation Therapy and Hematology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Largo A. Gemelli, 8, 00168 Roma, Italy; (G.D.); (T.T.); (S.G.)
| | - Pier Paolo Mattogno
- Neurosurgery Unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Largo A. Gemelli, 8, 00168 Roma, Italy; (P.P.M.); (F.D.); (L.L.)
| | - Sabrina Chiloiro
- Department of Endocrinology, Pituitary Unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Largo A. Gemelli, 8, 00168 Roma, Italy; (S.C.); (A.G.); (A.B.)
| | - Marco Gessi
- Department of Woman and Child Health Sciences and Public Health, Anatomic Pathology Unit, Fondazione Policlinico Universitario A. Gemelli—IRCCS, Largo A. Gemelli, 8, 00168 Roma, Italy;
| | - Gabriella D’Apolito
- Radiology and Neuroradiology Unit, Department of Imaging, Radiation Therapy and Hematology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Largo A. Gemelli, 8, 00168 Roma, Italy; (G.D.); (T.T.); (S.G.)
| | - Tommaso Tartaglione
- Radiology and Neuroradiology Unit, Department of Imaging, Radiation Therapy and Hematology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Largo A. Gemelli, 8, 00168 Roma, Italy; (G.D.); (T.T.); (S.G.)
| | - Antonella Giampietro
- Department of Endocrinology, Pituitary Unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Largo A. Gemelli, 8, 00168 Roma, Italy; (S.C.); (A.G.); (A.B.)
| | - Antonio Bianchi
- Department of Endocrinology, Pituitary Unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Largo A. Gemelli, 8, 00168 Roma, Italy; (S.C.); (A.G.); (A.B.)
| | - Francesco Doglietto
- Neurosurgery Unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Largo A. Gemelli, 8, 00168 Roma, Italy; (P.P.M.); (F.D.); (L.L.)
| | - Liverana Lauretti
- Neurosurgery Unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Largo A. Gemelli, 8, 00168 Roma, Italy; (P.P.M.); (F.D.); (L.L.)
| | - Simona Gaudino
- Radiology and Neuroradiology Unit, Department of Imaging, Radiation Therapy and Hematology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Largo A. Gemelli, 8, 00168 Roma, Italy; (G.D.); (T.T.); (S.G.)
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9
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Tomasik A, Stelmachowska-Banaś M, Maksymowicz M, Czajka-Oraniec I, Raczkiewicz D, Zieliński G, Kunicki J, Zgliczyński W. Pathologic Characteristics of Somatotroph Pituitary Tumors-An Observational Single-Center Study. Biomedicines 2023; 11:3315. [PMID: 38137536 PMCID: PMC10741635 DOI: 10.3390/biomedicines11123315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 11/26/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023] Open
Abstract
The pathologic evaluation of a tumor tissue is an essential part of an acromegaly patient's assessment. This study aimed to analyze the pathologic characteristics of pituitary tumors in patients with acromegaly. The demographic data, in addition to the hormonal, imaging, and pathologic results of 120 patients with acromegaly after pituitary surgery, were extracted from the Polish Acromegaly Registry. We compared sparsely and densely granulated tumors, GH(+), mixed GH(+)/PRL(+) and plurihormonal tumors, α-subunit-positive and α-subunit-negative tumors, and tumors of various Ki-67 indices in terms of the abovementioned features. Sparsely granulated tumors were more frequent in women than in men (p = 0.001) and in younger patients (p = 0.011), and they were larger (p < 0.001) compared to densely granulated tumors. Tumors with positive α-subunit were smaller (p = 0.013), showed extrasellar extension less often (p = 0.039), and were more often densely granulated (p < 0.001) compared to α-subunit-negative tumors. Patients with a higher Ki-67 index were younger (p < 0.001) and more often diagnosed with genetic syndromes (p = 0.02); they had higher GH concentrations (p = 0.007), larger tumors (p = 0.006), and cavernous sinus invasions more frequently (p = 0.022). Conclusions: The pathologic characteristics of somatotroph pituitary tumors are associated with patient's age, sex, hormonal results, tumor size, and the degree of extrasellar expansion.
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Affiliation(s)
- Agnieszka Tomasik
- Department of Endocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | | | - Maria Maksymowicz
- Department of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Izabella Czajka-Oraniec
- Department of Endocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | - Dorota Raczkiewicz
- Department of Medical Statistics, School of Public Health, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | - Grzegorz Zieliński
- Department of Neurosurgery, Military Institute of Medicine, 04-141 Warsaw, Poland
| | - Jacek Kunicki
- Department of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Wojciech Zgliczyński
- Department of Endocrinology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
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10
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Calandrelli R, Pilato F, D'Apolito G, Schiavetto S, Gessi M, D'Alessandris QG, Lauretti L, Gaudino S. MRI and Trouillas' grading system of pituitary tumors: the usefulness of T2 signal intensity volumetric values. Neuroradiology 2023; 65:1567-1578. [PMID: 37233819 DOI: 10.1007/s00234-023-03162-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 05/07/2023] [Indexed: 05/27/2023]
Abstract
PURPOSE To classify pituitary macroadenomas according to the Trouillas' grading system; to compare this grading system with T2 values of volumetric signal intensity to determine T2 values able to predict the final grade. METHODS A total of 106 patients with macroadenomas were grouped according to the grading system score combining proliferation and invasiveness criteria of Trouillas' classification. Normalized volumetric signal intensity values were extracted from coronal T2-weighted images (nT2mean, nT2Max, nT2min) and were compared with the final grading score system. RESULTS Thirty-three patients were in grade 1a (non-invasive, non-proliferative tumors), 17 patients in grade 1b (non-invasive, proliferative tumors), 36 patients in grade 2a (invasive, non-proliferative tumors), and 20 patients in grade 2b (invasive, proliferative tumors). No patient was in grade 3 (metastatic tumors). nT2Max and nT2min were the best quantitative values to discriminate invasive from non-invasive grades; in invasive grades, nT2Max intensity values were higher, and nT2min intensity values were lower than in non-invasive grades. Receiver operating characteristic analysis of nT2 values showed that nT2min values had a better diagnostic performance than nT2Max values because they allowed differentiating with a moderate accuracy invasive tumors (2a or 2b grades) from both non-invasive proliferative tumors (1b) and non-invasive-non proliferative tumors (1a) (2a vs 1b: AUCnT2min = 0.78, 2b vs 1b: AUCnT2min = 0.72, 2a vs 1a: AUCnT2min = 0.72, 2b vs 1a AUCnT2min = 0.69). CONCLUSION Volumetric nT2Max and nT2min values of MRI might be practical and non-invasive markers for assessing tumor invasiveness although nT2 min signal intensity values have more effects in discriminating tumor's invasive behavior.
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Affiliation(s)
- Rosalinda Calandrelli
- Radiology and Neuroradiology Unit, Department of Imaging, Radiation Therapy and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy.
| | - Fabio Pilato
- Research Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 21, 00128, Rome, Italy
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italia
| | - Gabriella D'Apolito
- Radiology and Neuroradiology Unit, Department of Imaging, Radiation Therapy and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Stefano Schiavetto
- Radiology and Neuroradiology Unit, Department of Imaging, Radiation Therapy and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Marco Gessi
- Neuropathology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
| | - Quintino Giorgio D'Alessandris
- Department of Neurosurgery, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Liverana Lauretti
- Department of Neurosurgery, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Simona Gaudino
- Radiology and Neuroradiology Unit, Department of Imaging, Radiation Therapy and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
- Catholic University of the Sacred Heart, Institute of Radiology, L.go A. Gemelli, Rome, Italy
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11
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Rahimian N, Sheida A, Rajabi M, Heidari MM, Tobeiha M, Esfahani PV, Ahmadi Asouri S, Hamblin MR, Mohamadzadeh O, Motamedzadeh A, Khaksary Mahabady M. Non-coding RNAs and exosomal non-coding RNAs in pituitary adenoma. Pathol Res Pract 2023; 248:154649. [PMID: 37453360 DOI: 10.1016/j.prp.2023.154649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 06/25/2023] [Accepted: 06/25/2023] [Indexed: 07/18/2023]
Abstract
Pituitary adenoma (PA) is the third most common primary intracranial tumor in terms of overall disease incidence. Although they are benign tumors, they can have a variety of clinical symptoms, but are mostly asymptomatic, which often leads to diagnosis at an advanced stage when surgical intervention is ineffective. Earlier identification of PA could reduce morbidity and allow better clinical management of the affected patients. Non-coding RNAs (ncRNAs) do not generally code for proteins, but can modulate biological processes at the post-transcriptional level through a variety of molecular mechanisms. An increased number of ncRNA expression profiles have been found in PAs. Therefore, understanding the expression patterns of different ncRNAs could be a promising method for developing non-invasive biomarkers. This review summarizes the expression patterns of dysregulated ncRNAs (microRNAs, long non-coding RNAs, and circular RNAs) involved in PA, which could one day serve as innovative biomarkers or therapeutic targets for the treatment of this neoplasia. We also discuss the potential molecular pathways by which the dysregulated ncRNAs could cause PA and affect its progression.
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Affiliation(s)
- Neda Rahimian
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran; Department of Internal Medicine, School of Medicine, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Sheida
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran; School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammadreza Rajabi
- Department of Pathology, Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Mahdi Heidari
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Department of Pediatric, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Tobeiha
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran; School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Pegah Veradi Esfahani
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran; School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Sahar Ahmadi Asouri
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Omid Mohamadzadeh
- Department of Neurological Surgery, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
| | - Alireza Motamedzadeh
- Department of Internal Medicine, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
| | - Mahmood Khaksary Mahabady
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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12
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An Overview of Pituitary Neuroendocrine Tumors (PitNET) and Algorithmic Approach to Diagnosis. Adv Anat Pathol 2023; 30:79-83. [PMID: 36069849 DOI: 10.1097/pap.0000000000000367] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The diagnostic algorithm and nomenclature of pituitary neuroendocrine tumors have evolved over the past decade, beginning with simpler categorical schemes focused on histomorphologic features and moving to a more sophisticated lineage-specific categorization. This contemporary overview highlights a multimodal approach to pituitary neuroendocrine tumors with a focus on changes in nomenclature, classification, and subclassification; including, brief comments on treatment, and new guidelines for genetic screening, particularly for young patients with such neoplasms.
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13
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Durmuş ET, Atmaca A, Kefeli M, Çalışkan S, Mete O, Aslan K, Fidan M, Çolak R, Durmuş B. Age, GH/IGF-1 levels, tumor volume, T2 hypointensity, and tumor subtype rather than proliferation and invasion are all reliable predictors of biochemical response to somatostatin analogue therapy in patients with acromegaly: A clinicopathological study. Growth Horm IGF Res 2022; 67:101502. [PMID: 36115256 DOI: 10.1016/j.ghir.2022.101502] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 09/02/2022] [Accepted: 09/04/2022] [Indexed: 11/24/2022]
Abstract
PURPOSE To determine whether biochemical responses to long-acting forms of first-generation somatostatin analogue (SSA) therapy in patients with acromegaly could be predicted from baseline and postoperative hormone concentrations, and tumor radiological and histopathological characteristics. METHODS A total of 68 patients with acromegaly for whom postoperative SSA therapy was started were categorized according to their responses to treatment (SSA-responders vs. non-responders). The patients were compared based on their demographic characteristics, hormone levels, magnetic resonance imaging (MRI), and histopathological findings. Receiver-operating-characteristic (ROC) curves were constructed using the predictive factors that were significant in the univariate analysis to determinate the optimal cut-off values. RESULTS The SSA-responders were significantly older (p = 0.041). Lower GH at diagnosis (p = 0.036), the postoperative 1st-week GH level (p = 0.027), baseline GH, insulin-like growth factor-1 (IGF-1) and IGF-1% upper limit of normal (ULN) (p = 0.001, p = 0.006, p = 0.023, respectively) were associated with biochemical response. T2-hypointensity and lower tumor volume were more common in the SSA-responders (p = 0.018, p = 0.03, respectively). Compared to sparsely granulated somatotroph tumors, densely granulated somatotroph tumors and other PitNETs causing GH excess including mammosomatotroph and mixed somatotroph and lactotroph tumors were more likely to respond to SSA therapy (p = 0.026, p = 0.03, respectively). The cut-off values generated by ROC curve analysis were GH at diagnosis of ≤8.8 ng/mL, GH at baseline of ≤2.69 ng/mL, IGF-1 at baseline ≤461.5 ng/mL, IGF-1% ULN at baseline ≤180.4%, and tumor volume of ≤1.11 cm3 (all p < 0.05). There were no differences between the groups in terms of tumor invasiveness, proliferative activity (mitotic count per 2 mm2 and Ki-67 labeling index) and quantitative analyses of T2-weighted MRI. CONCLUSION This study underscores that advanced age, low baseline GH and IGF-1 at diagnosis, low tumor volume, densely granulated tumor subtype, and T2 hypointensity may help predict biochemical response to SSA therapy in cases of acromegaly. These variables should be assessed with utmost attention for all patients prior to SSA treatment. In cases of possible resistance to SSA therapy, therapeutic activity should be monitored more closely and other therapies should be administered immediately in the event of poor response.
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Affiliation(s)
- Elif Tutku Durmuş
- Ondokuz Mayis University, Faculty of Medicine, Department of Endocrinology and Metabolism, Samsun, Turkey.
| | - Ayşegül Atmaca
- Ondokuz Mayis University, Faculty of Medicine, Department of Endocrinology and Metabolism, Samsun, Turkey
| | - Mehmet Kefeli
- Ondokuz Mayis University, Faculty of Medicine, Department of Pathology, Samsun, Turkey
| | - Sultan Çalışkan
- Ondokuz Mayis University, Faculty of Medicine, Department of Pathology, Samsun, Turkey
| | - Ozgur Mete
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology, University Health Network, 200 Elizabeth Street, 11th Floor, Toronto, ON M5G 2C4, Canada; Endocrine Oncology Site Group, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Kerim Aslan
- Ondokuz Mayis University, Faculty of Medicine, Department of Radiology, Samsun, Turkey
| | - Murat Fidan
- Ondokuz Mayis University, Faculty of Medicine, Department of Radiology, Samsun, Turkey
| | - Ramis Çolak
- Ondokuz Mayis University, Faculty of Medicine, Department of Endocrinology and Metabolism, Samsun, Turkey
| | - Buğra Durmuş
- Ondokuz Mayis University, Faculty of Medicine, Department of Endocrinology and Metabolism, Samsun, Turkey
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14
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Gruppetta M. A current perspective of pituitary adenoma MRI characteristics: a review. Expert Rev Endocrinol Metab 2022; 17:499-511. [PMID: 36373167 DOI: 10.1080/17446651.2022.2144230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 11/02/2022] [Indexed: 11/06/2022]
Abstract
INTRODUCTION MR imaging is an essential and fundamental tool in the diagnosis, management, and follow-up of patients with pituitary adenomas (PAs). Recent advances have continued to enhance the usefulness of this imaging modality. AREAS COVERED This article focuses on signal intensity patterns of PAs and associated clinical characteristics, vertical extension patterns, and cavernous sinus invasion with a special focus on the clinical implications that arise. A search using Medline and Google Scholar was conducted using different combinations of relevant keywords, giving preference to recent publications. EXPERT OPINION A higher proportion of GH-secreting PAs are hypointense on T2 weighted images compared to other tumor subtypes. Hypointense tumors are generally smaller compared to hyperintense ones, and among the GH-secreting subgroup, a better response to somatostatin analogue treatment was noted together with an association for a densely granulated pattern. Nonfunctional PAs show a predilection to extend upwards while GH-secreting PAs and prolactinomas show a predominantly inferior extension growth pattern. Further studies to better understand the mechanisms responsible for this behavior are anticipated. Further development, refining and validation of predictive scoring systems for tumor behavior might be useful adjuncts in the management of patients with PAs.
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Affiliation(s)
- Mark Gruppetta
- Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Mater Dei Hospital, Msida, Malta
- Department of Medicine, Neuroendocrine Clinic, Mater Dei Hospital, Msida, Malta
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15
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Portovedo S, Neto LV, Soares P, Carvalho DPD, Takiya CM, Miranda-Alves L. Aggressive nonfunctioning pituitary neuroendocrine tumors. Brain Tumor Pathol 2022; 39:183-199. [PMID: 35725837 DOI: 10.1007/s10014-022-00441-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Accepted: 05/31/2022] [Indexed: 11/29/2022]
Abstract
Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) are tumors that are not associated with clinical evidence of hormonal hypersecretion. According to the World Health Organization (WHO), there are some subtypes of PitNETs that exhibit more aggressive behavior than others. Among the types of potentially aggressive PitNETs, three are nonfunctional: silent sparsely granulated somatotropinomas, silent corticotropinomas, and poorly differentiated PIT-1 lineage tumors. Several biological markers have been investigated in NF-PitNETs. However, there is no single biomarker able to independently predict aggressive behavior in NF-PitNETs. Thus, a more complex and multidisciplinary proposal of a comprehensive definition of aggressive NF-PitNETs is necessary. Here, we suggest a combined and more complete criterion for the NF-PitNETs classification. We propose that aggressiveness is due to a multifactorial combination, and we emphasize the need to include new emerging markers that are involved in the aggressiveness of NF-PitNETs and the need to identify.
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Affiliation(s)
- Sérgio Portovedo
- Laboratório de Endocrinologia Experimental-LEEx, Centro de Ciências da Saúde, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco F - Sala F1-015 - Ilha do Fundão, Rio de Janeiro, RJ, 21941-912, Brazil.,Programa de Pós-Graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Leonardo Vieira Neto
- Programa de Pós-Graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.,Serviço de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Paula Soares
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal.,Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal.,Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (FMUP), Porto, Portugal
| | - Denise Pires de Carvalho
- Programa de Pós-Graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.,Laboratório de Fisiologia Endócrina Doris Rosenthal, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Christina Maeda Takiya
- Laboratório de Imunopatologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Leandro Miranda-Alves
- Laboratório de Endocrinologia Experimental-LEEx, Centro de Ciências da Saúde, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco F - Sala F1-015 - Ilha do Fundão, Rio de Janeiro, RJ, 21941-912, Brazil. .,Programa de Pós-Graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. .,Programa de Pós-Graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. .,Programa de Pós-Graduação em Ciências Morfológicas, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
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16
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Kontogeorgos G, Thodou E, Osamura RY, Lloyd RV. High-risk pituitary adenomas and strategies for predicting response to treatment. Hormones (Athens) 2022; 21:1-14. [PMID: 35061210 DOI: 10.1007/s42000-021-00333-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 10/18/2021] [Indexed: 12/30/2022]
Abstract
High-risk pituitary adenomas are aggressive. They show clinical and imaging features similar to those of carcinomas, including infiltration of the surrounding brain structures, but lack cerebrospinal or systemic metastases. In addition, they display distinct behavior, including tendency for fast growth and frequent recurrences, which are difficult to control. The term "high-risk" adenoma was first introduced in the 4th edition of the World Health Organization Classification of Endocrine Tumors in 2017. Five defined adenoma types belong to this category, including sparsely granulated somatotroph, lactotroph in men, Crooke cell, silent corticotroph, and plurihormonal PIT-1 positive adenomas. The morphological and immunohistochemical characteristics of high-risk adenomas are herein described in detail. In addition, the clinical features and the treatment options are presented. This review focuses on predictive markers assessed by immunohistochemistry, which help clinicians to design the appropriate treatment strategies for high-risk adenomas. Somatostatin receptor status predicts effectiveness of postsurgical treatment with somatostatin analogs, and MGMT expression predicts response to treatment with temozolomide. This comprehensive review presents the clinical and pathological features of high-risk pituitary adenomas, underlines the contribution of immunohistochemistry, and emphasizes the leading role of pathology in the design of optimal clinical management.
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Affiliation(s)
- George Kontogeorgos
- Division of Endocrinology, First Propaedeutic Department of Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens, Athens, Greece.
- Department of Pathology and Pituitary Tumor Reference Center, G. Gennimatas General Hospital of Athens, Athens, Greece.
| | - Eleni Thodou
- Department of Pathology, University of Thessaly, Larissa, Greece
| | - Robert Y Osamura
- Department of Pathology, Nippon Koukan Hospital, Kawasaki, Kanagawa, Japan
| | - Ricardo V Lloyd
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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17
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Mihajlović M, Manojlović-Gačić E. Neuroendocrine tumors of the pituitary gland: Modern diagnostic approach. MEDICINSKI PODMLADAK 2022. [DOI: 10.5937/mp73-37336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/19/2023] Open
Abstract
Pituitary neuroendocrine tumors (PitNET) are neuroendocrine tumors originating from adenohypophyseal cells. Although benign, PitNETs sometimes exhibit aggressive biological behavior that was the inspiration for the change of old and traditional name "pituitary adenomas". Current standard in PitNET diagnostics, according to WHO criteria, is immunohistochemistry, with application of antibodies to adenohypophysis hormones and transcription factors TPIT (T-box family member TBX19), PIT1 (pituitary transcription factor 1) and SF-1 (steroidogenic factor-1) according to which, the line of differentiation is assessed. In the PIT1 line of differentiation there are somatotroph, lactotroph and thyrotroph tumors. Somatotroph tumors are from PIT1 lineage that produce growth hormone (GH). The WHO defines the following subtypes of somatotroph tumors: densely granulated and sparsely granulated somatotroph tumor. Lactotroph tumors are the most common neuroendocrine tumors of the pituitary gland. The transcription factors PIT1 and the estrogen receptor a (ERa) play a key role in their genesis. There are two subtypes of lactotroph tumors, densely and sparsely granulated that are differentiated by the type of prolactine (PRL) staining pattern. Thyrotroph tumors expess both PIT1 and GATA binding protein 3 (GATA3), and can show variable positivity for thyroid-stimulating hormone (TSH). Beside these three main tumor types of PIT1 lineage, there are mixed lactotroph and somatotroph tumors, mamosomatotroph tumor, acifophilic "stem cell" tumor, mature and immature plurihormonal tumor. Corticotroph tumors express transcription factor TPIT, and produce adrenocorticotrophic hormone (ACTH). They can be densely granulated and sparsely granulated. Rare subtype of corticotroph tumors, that can show aggressive biological behavior, is Crooke cell tumor. Gonadotroph tumors are of SF1 lineage of differentiation, and they produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Null-cell tumors show no distinct cell lineage, and do not express any of the transcription factors. With the use of transcription factors, these tumors are diagnosed through elimination, and their number tented to decrease.
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18
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Lapshina AM, Pigarova EA, Abrosimov AY. [Algorithm for morphological diagnosis of neoplasms in the chiasmal-sellar region]. Arkh Patol 2021; 83:60-70. [PMID: 34859988 DOI: 10.17116/patol20218306160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
In the Turkish saddle area, there is a wide variety of pathological processes, the vast majority of which present as tumors of various origins (up to 90%). For a clear morphological verification of the diagnosis, it is proposed to use a diagnostic algorithm that includes the stages of differential diagnosis of normal adenohypophysis and neurohypophysis with tumors in the anterior and posterior lobes of the pituitary gland, non-pituitary origin neoplasms, as well as with non-tumor pathological processes (inflammation, cystic masses, and hyperplasia). For morphological diagnosis, histochemical and immunohistochemical methods are recommended using various staining techniques (silver impregnation, periodic acid Schiff reaction) of tissue specimens and antibody panels (pituitary hormones, low-molecular cytokeratins, pituitary transcription factors, neuroendocrine markers, etc.).
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Affiliation(s)
- A M Lapshina
- National Medical Research Center for Endocrinology of the Ministry of Health of Russia, Moscow, Russia
| | - E A Pigarova
- National Medical Research Center for Endocrinology of the Ministry of Health of Russia, Moscow, Russia
| | - A Yu Abrosimov
- National Medical Research Center for Endocrinology of the Ministry of Health of Russia, Moscow, Russia
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19
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Chanson P, Wolf P. Clinically non-functioning pituitary adenomas. Presse Med 2021; 50:104086. [PMID: 34718111 DOI: 10.1016/j.lpm.2021.104086] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Accepted: 10/20/2021] [Indexed: 12/30/2022] Open
Abstract
Clinically non functioning pituitary adenomas (NFPAs) include all pituitary adenomas that are not hormonally active. They are not associated with clinical syndromes such as amenorrhea-galactorrhea (prolactinomas), acromegaly, Cushing's disease or hyperthyroidism (TSH-secreting adenomas) and are therefore usually diagnosed by signs and symptoms related to a mass effect (headache, visual impairment, sometimes pituitary apoplexy), but also incidentally. Biochemical work up often documents several pituitary insufficiencies. In histopathology, the majority of NFPAs are gonadotroph. In the absence of an established medical therapy, surgery is the mainstay of treatment, unless contraindicated or in particular situations (e.g. small incidentalomas, distance from optic pathways). Resection, generally via a trans-sphenoidal approach (with the help of an endoscope), should be performed by a neurosurgeon with extensive experience in pituitary surgery, in order to maximize the chances of complete resection and to minimize complications. If a tumor remnant persists, watchful waiting is preferred to routine radiotherapy, as long as the tumor residue does not grow and is distant from the optic pathways. NFPA can sometimes recur even after complete resection, but predicting the individual risk of tumor remnant progression is difficult. Postoperative irradiation is only considered in case of residual tumor growth or relapse, due to its potential side effects.
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Affiliation(s)
- Philippe Chanson
- Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, 94275 Le Kremlin-Bicêtre, France.
| | - Peter Wolf
- Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, 94275 Le Kremlin-Bicêtre, France; Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, 1090 Vienna, Austria
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20
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Shih RY, Schroeder JW, Koeller KK. Primary Tumors of the Pituitary Gland: Radiologic-Pathologic Correlation. Radiographics 2021; 41:2029-2046. [PMID: 34597177 DOI: 10.1148/rg.2021200203] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Primary tumors of the pituitary gland are the second most common histologic category of primary central nervous system tumors across all age groups and are the most common in adolescents to young adults, despite originating from a diminutive endocrine gland that is often described as "about the size of a pea." The vast majority of these represent primary tumors of the adenohypophysis, specifically pituitary adenomas, which can be either functional or silent with regard to hormone hypersecretion. According to the fourth edition of the World Health Organization classification of endocrine tumors, published in 2017, cellular lineage and immunohistochemical stains for pituitary hormones and/or transcription factors help with making the correct pathologic diagnosis. From a radiologic standpoint, microadenomas pose challenges for accurate detection and avoiding false-negative or false-positive results, while macroadenomas pose challenges from local mass effect on surrounding structures. Pituitary carcinoma and pituitary blastoma also arise from the adenohypophysis and are characterized by metastatic disease and infantile presentation, respectively. While primary tumors of the adenohypophysis are common, a second category comprising primary tumors of the Rathke pouch (ie, craniopharyngioma) are uncommon, and a third category comprising primary tumors of the neurohypophysis (eg, pituicytoma) are rare. The authors review all three categories of pituitary tumors, with emphasis on radiologic-pathologic correlation, including the typical neuroimaging, histologic, and molecular features that may point toward a specific diagnosis. Work of the U.S. Government published under an exclusive license with the RSNA.
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Affiliation(s)
- Robert Y Shih
- From the Department of Radiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814 (R.Y.S.); Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Md (J.W.S.); and Department of Radiology, Mayo Clinic, Rochester, Minn (K.K.K.)
| | - Jason W Schroeder
- From the Department of Radiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814 (R.Y.S.); Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Md (J.W.S.); and Department of Radiology, Mayo Clinic, Rochester, Minn (K.K.K.)
| | - Kelly K Koeller
- From the Department of Radiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814 (R.Y.S.); Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Md (J.W.S.); and Department of Radiology, Mayo Clinic, Rochester, Minn (K.K.K.)
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21
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Kobalka PJ, Huntoon K, Becker AP. Neuropathology of Pituitary Adenomas and Sellar Lesions. Neurosurgery 2021; 88:900-918. [PMID: 33476394 DOI: 10.1093/neuros/nyaa548] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 10/22/2020] [Indexed: 12/12/2022] Open
Abstract
The pituitary gland is the site of numerous neoplastic and inflammatory processes. The overwhelmingly most frequent tumors arise from cells of the anterior lobe, the pituitary neuroendocrine tumors (PitNETs). Immunohistochemistry assay staining for pituitary hormones is the core tool for classifying PitNETs, resulting in the diagnosis of somatotroph PitNETs, lactotroph PitNETs, and so on. For cases showing no hormonal expression, the updated WHO classification system now considers the assessment of several transcription factors: PIT-1 (pituitary-specific POU-class homeodomain transcription factor); T-PIT (T-box family member TBX19); and SF-1 (steroidogenic factor regulating gonadotroph cell differentiation) before rendering a diagnosis of null cell adenoma. Other tumors and disease processes of this site often mimic PitNETs radiographically and sometimes even clinically (ie, compression of the optic chiasm). These potpourri of processes include germ cell neoplasms (especially germinomas), tumors that originate from Rathke's pouch (craniopharyngiomas, Rathke's cleft cyst), tumors that originate from the posterior lobe of the pituitary (pituicytoma, spindle cell oncocytoma, granular cell tumor), and tumors that originate from the meninges (especially meningiomas). In addition to neoplasms, several described inflammatory and related conditions exist that need to be distinguished from PitNETs. These include lymphocytic hypophysitis and Langerhans cell histiocytosis, a neoplastic disorder of histiocytes. In this review, we aim to briefly describe the main pituitary and sellar lesions, with emphasis on the most common tumors, the PitNETs.
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Affiliation(s)
- Peter J Kobalka
- Department of Pathology and Laboratory Medicine, The Ohio State University Medical Center, Columbus, Ohio
| | - Kristin Huntoon
- Department of Neurosurgery, The Ohio State University Medical Center, Columbus, Ohio
| | - Aline P Becker
- Department of Radiation Oncology, The Ohio State University Medical Center, Columbus, Ohio
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22
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Tamanini JVG, Dal Fabbro M, de Freitas LLL, Vassallo J, de Souza Queiroz L, Rogerio F. Digital analysis of hormonal immunostaining in pituitary adenomas classified according to WHO 2017 criteria and correlation with preoperative laboratory findings. Neurosurg Focus 2021; 48:E12. [PMID: 32480373 DOI: 10.3171/2020.3.focus2039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/03/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVE The authors sought to evaluate clinical and laboratory data from pituitary adenoma (PA) patients with functioning PA (associated with acromegaly [n = 10] or Cushing disease [n = 10]) or nonfunctioning PA (NFPA; n = 10) that were classified according to 2017 WHO criteria (based on the expression of the transcription factors pituitary-specific positive transcription factor 1 [Pit-1], a transcription factor member of the T-box family [Tpit], and steroidogenic factor 1 [SF-1]) and to assess the immunostaining results for growth hormone (GH) and adrenocorticotropic hormone (ACTH) in the corresponding tumors. METHODS Clinical and laboratory data were collected retrospectively. The percentage of tumoral cells positive for Pit-1, Tpit, or SF-1 was assessed and ImageJ software was used to evaluate immunopositivity in PAs with 2 different antibodies against GH (primary antibody 1 [AbGH-1] and primary antibody 2 [AbGH-2]) and 2 different antibodies against ACTH (primary antibody 1 [AbACTH-1] and primary antibody 2 [AbACTH-2]). RESULTS Cells with positive Pit-1 staining were more frequently observed in lesions from patients with acromegaly (acromegaly group) than in lesions from patients with Cushing disease (Cushing group; p < 0.001) and those from patients with NFPA (NFPA group; p < 0.001). The percentage of Tpit-positive cells was higher in the Cushing group than in the acromegaly (p < 0.001) and NFPA (p < 0.001) groups. No difference was detected regarding SF-1 frequency among all groups (p = 0.855). In acromegalic individuals, GH immunostaining levels varied depending on the antibody employed, and only one of the antibodies (AbGH-2) yielded higher values in comparison with the values for NFPA patients (p < 0.001). For all of the antibodies employed, no significant correlations were detected between GH tissue expression and the laboratory data (serum GH vs AbGH-1, p = 0.933; serum GH vs AbGH-2, p = 0.853; serum insulin-like growth factor-1 [IGF-1] vs AbGH-1, p = 0.407; serum IGF-1 vs AbGH-2, p = 0.881). In the Cushing group data, both antibodies showed similar ACTH tissue expression, which was higher than that obtained in the NFPA group (p < 0.001). There were no significant associations between ACTH immunohistochemical findings and ACTH serum levels (serum ACTH vs AbACTH-1, p = 0.651; serum ACTH vs AbACTH-2, p = 0.987). However, ACTH immunostaining evaluated with AbACTH-1 showed a significant correlation with 24-hour urinary cortisol (24-hour cortisol vs AbACTH-1, p = 0.047; 24-hour cortisol vs AbACTH-2, p = 0.071). CONCLUSIONS Immunostaining for Pit-1 and Tpit accurately identified lesions associated with acromegaly and Cushing disease, respectively. Conversely, SF-1 did not differentiate NFPA from lesions of the other two groups. Regarding hormonal tissue detection, results of the current investigation indicate that different antibodies may lead not only to divergent immunohistochemical results but also to lack of correlation with laboratory findings. Finally, PA classification based on transcription factor expression (Pit-1, Tpit, and SF-1), as proposed by the 2017 WHO classification of pituitary tumors, may avoid the limitations of PA classification based solely on digital immunohistochemical detection of hormones.
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Affiliation(s)
| | - Mateus Dal Fabbro
- 2Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
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23
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Liu X, Dai C, Feng M, Li M, Chen G, Wang R. Diagnosis and treatment of refractory pituitary adenomas: a narrative review. Gland Surg 2021; 10:1499-1507. [PMID: 33968701 DOI: 10.21037/gs-20-873] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Although aggressive pituitary adenomas (PAs) have been proposed and widely discussed for more than a decade, there is no general agreement regarding their definition, diagnosis or management. As one of the largest pituitary centers in China, we have diagnosed and treated more than fifty cases of aggressive PA and 3 pituitary carcinomas in the past 5 years and proposed a new term, i.e., refractory PAs, to define these adenomas. The definitions of aggressive and refractory PAs overlap with each other, though there are some differences between them. We interpret the definition for refractory PA in this review, emphasizing that more attention and early identification of these adenomas are needed. Although temozolomide (TMZ) has been used to treat pituitary carcinomas and refractory PA since 2006, which has significantly improved the prognosis of these patients, treatment of refractory PA is a tremendous challenge for endocrinologists and neurosurgeons. Overall, refractory PA is defined as PA with a Ki-67 labeling index ≥3%, a faster growth rate than that of normal PA, infiltration of surrounding tissues, recurrence or regrowth in the early postoperative period, and continued growth and/or secretion of excessive hormones despite attempts to control it. These criteria for refractory PA are stricter than for aggressive PA. The diagnosis and treatment of refractory PA requires the collaboration of a multidisciplinary team to achieve the best results.
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Affiliation(s)
- Xiaohai Liu
- Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, China.,Chinese Pituitary Specialists Congress, Beijing, China
| | - Congxin Dai
- Chinese Pituitary Specialists Congress, Beijing, China.,Department of Neurosurgery, Tongren Hospital Capital Medical University, Beijing, China
| | - Ming Feng
- Chinese Pituitary Specialists Congress, Beijing, China.,Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mingchu Li
- Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, China.,Chinese Pituitary Specialists Congress, Beijing, China
| | - Ge Chen
- Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, China.,Chinese Pituitary Specialists Congress, Beijing, China
| | - Renzhi Wang
- Chinese Pituitary Specialists Congress, Beijing, China.,Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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24
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Saeger W, Koch A. Clinical Implications of the New WHO Classification 2017 for Pituitary Tumors. Exp Clin Endocrinol Diabetes 2021; 129:146-156. [PMID: 33690870 DOI: 10.1055/a-1310-7900] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
According to the WHO classification 2017 of Pituitary Tumors adenomas are classified not only by structure and immunostaining for pituitary hormones but also by expression of the pituitary transcription factors Pit-1, T-pit and SF-1. By these factors, three cell lineages can be identified: Pit-1 for the GH-, Prolactin- and TSH-cell lineage, T-pit for the ACTH-cell lineage, and SF-1 for the gonadotrophic cell lineage. By this principle, all GH and/or Prolactin producing and all TSH producing adenomas must be positive for Pit-1, all corticotrophic adenomas for T-pit, and all gonadotrophic for SF-1. In adenomas without expression of pituitary hormones immunostainings for the transcription factors have to be examined. If these are also negative the criteria for an endocrine inactive null cell adenoma are fulfilled. If one transcription factor is positive the corresponding cell lineage indicates a potential hormonal activity of the adenoma. So Pit-1 expressing hormone-negative adenomas can account for acromegaly, hyperprolactinemia, or TSH hyperfunction. T-pit positive hormone negative adenomas can induce Cushing's disease, and SF-1 positive hormone negative tumors indicate gonadotrophic adenomas. Instead of the deleted atypical adenoma of the WHO classification of 2004 now (WHO classification 2017) criteria exist for the identification of aggressive adenomas with a conceivably worse prognosis. Some adenoma subtypes are described as aggressive "per se" without necessity of increased morphological signs of proliferation. All other adenoma subtypes must also be designated as aggressive if they show signs of increased proliferation (mitoses, Ki-67 index>3-5%, clinically rapid tumor growth) and invasion. By these criteria about one third of pituitary adenoma belong to the group of aggressive adenomas with potentially worse prognosis. The very rare pituitary carcinoma (0.1 % of pituitary tumors) is defined only by metastases. Many of them develop after several recurrences of Prolactin or ACTH secreting adenomas. The correlation of clinical findings and histological classification of pituitary adenomas is very important since every discrepancy has to be discussed between clinicians and pathologists. Based on data of the German Registry of Pituitary Tumors a table for examinations of correlations is shown in this review.
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Affiliation(s)
- Wolfgang Saeger
- Institute of Pathology and Neuropathology of the University of Hamburg, UKE, Hamburg, Germany
| | - Arend Koch
- Institute of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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25
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Micko A, Rötzer T, Hoftberger R, Vila G, Oberndorfer J, Frischer JM, Knosp E, Wolfsberger S. Expression of additional transcription factors is of prognostic value for aggressive behavior of pituitary adenomas. J Neurosurg 2021; 134:1139-1146. [PMID: 32302984 DOI: 10.3171/2020.2.jns2018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 02/10/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVE According to the latest WHO classification of tumors of endocrine organs in 2017, plurihormonal adenomas are subclassified by their transcription factor (TF) expression. In the group of plurihormonal adenomas with unusual immunohistochemical combinations (PAWUC), the authors identified a large fraction of adenomas expressing TFs for gonadotroph adenoma (TFGA) cells in addition to other TFs. The aim of this study was to compare clinicopathological parameters of PAWUC with TFGA expression to gonadotroph adenomas that only express TFGA. METHODS This retrospective single-center series comprises 73 patients with TFGA-positive pituitary adenomas (SF1, GATA3, estrogen receptor α): 22 PAWUC with TFGA (TFGA-plus group) and 51 with TFGA expression only (TFGA-only group). Patient characteristics, outcome parameters, rate of invasiveness (assessed by direct endoscopic inspection), and MIB1 and MGMT status were compared between groups. RESULTS Patients in the TFGA-plus group were significantly younger than patients in the TFGA-only group (age 46 vs 56 years, respectively; p = 0.007). In the TFGA-only group, pituitary adenomas were significantly larger (diameter 25 vs 18.3 mm, p = 0.002). Intraoperatively, signs of invasiveness were significantly more common in the TFGA-plus group than in the TFGA-only group (50% vs 16%, p = 0.002). Gross-total resection was significantly lower in the nonfunctioning TFGA-plus group than in the TFGA-only group (44% vs 86%, p = 0.004). MIB1 and MGMT status showed no significant difference between groups. CONCLUSIONS These data suggest a more aggressive behavior of TFGA-positive adenomas if an additional TF is expressed within the tumor cells. Shorter radiographic surveillance and earlier consideration for retreatment should be recommended in these adenoma types.
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Affiliation(s)
| | | | | | - Greisa Vila
- 3Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Austria
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26
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Rak B, Maksymowicz M, Pękul M, Zieliński G. Clinical, Biological, Radiological Pathological and Immediate Post-Operative Remission of Sparsely and Densely Granulated Corticotroph Pituitary Tumors: A Retrospective Study of a Cohort of 277 Patients With Cushing's Disease. Front Endocrinol (Lausanne) 2021; 12:672178. [PMID: 34135861 PMCID: PMC8202403 DOI: 10.3389/fendo.2021.672178] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 04/30/2021] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Cushing's disease is the most common cause of endogenous hypercortisolemia due to a corticotroph pituitary tumor. Up-to-date there is no reliable biomarker of invasiveness among corticotroph tumors, while it is well established in the literature that sparsely granulated somatotroph tumors are characterized by poorer prognosis. The aim of the study was to correlate multiple data including clinical, biochemical, radiological, and pathological findings (including granulation pattern) as well as immediate post-operative remission status among patients operated on due to corticotroph tumors. METHODS We enrolled all patients consecutively operated on for planned transsphenoidal neurosurgery due to corticotroph PitNETs in years 2010-2018. We excluded from analysis silent corticotroph tumors, plurihormonal PitNETs, and the Crooke's cell adenomas. RESULTS We recorded 348 hormonally active corticotroph PitNETs. The results of the analysis showed the female predominance 79.88% (n = 278), with the mean age of Cushing's disease occurrence 43.27 years of age. The mean time from the first signs and symptoms to the operation was 2 years. The women were diagnosed earlier (20-40 years of age vs. 50-60 years of age among men). We performed a detailed analysis of 277 cases classified by granularity pattern as DG or SG corticotroph PitNETs. Densely granulated tumors (DG) occurred four times more frequently than sparsely granulated (SG) (n = 225 vs. n = 52), at similar age (mean 42.94; median 40 vs. mean 45.46; median 45.5; p = 0.3896), but were characterized by lower Knosp's scale grades (p = 0.0147*), smaller preoperative tumors' volumes measured at MRI, and more commonly exhibited lower Ki-67 labeling index (<3%) (p = 0.0168*). What is more, DG adenomas more frequently achieved an immediate remission status (measured as postoperative cortisol concentration <2 µg/dl; p = 0.0180*), and the mean postoperative cortisol concentration in DG group was lower than in SG group (mean 5.375 µg/dl vs. 10.47 µg/dl; median 2.49 µg/dl vs. 6.52 µg/dl; p = 0.0028**). CONCLUSIONS Our study indicates that DG corticotroph adenomas occurred at younger age, more commonly were microadenomas as compared to SG tumors, less frequently had invasive features in comparison to SG corticotroph adenomas (p = 0.0019**), and more commonly achieved an immediate postsurgical hormonal remission (p = 0.0180*). We highlight the need for an accurate differentiation of DG and SG subtypes in the pathomorphological diagnosis of corticotropic tumors, especially in invasive PitNETs.
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Affiliation(s)
- Beata Rak
- Department of Internal Diseases and Endocrinology, Public Central Teaching Hospital, Medical University of Warsaw, and the Laboratory of Experimental Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Maria Maksymowicz
- Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Monika Pękul
- Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Grzegorz Zieliński
- Department of Neurosurgery, Military Institute of Medicine, Warsaw, Poland
- *Correspondence: Grzegorz Zieliński,
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Yamamoto M, Nakao T, Ogawa W, Fukuoka H. Aggressive Cushing's Disease: Molecular Pathology and Its Therapeutic Approach. Front Endocrinol (Lausanne) 2021; 12:650791. [PMID: 34220707 PMCID: PMC8242934 DOI: 10.3389/fendo.2021.650791] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 05/26/2021] [Indexed: 12/13/2022] Open
Abstract
Cushing's disease is a syndromic pathological condition caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (ACTHomas) mediated by hypercortisolemia. It may have a severe clinical course, including infection, psychiatric disorders, hypercoagulability, and metabolic abnormalities, despite the generally small, nonaggressive nature of the tumors. Up to 20% of ACTHomas show aggressive behavior, which is related to poor surgical outcomes, postsurgical recurrence, serious clinical course, and high mortality. Although several gene variants have been identified in both germline and somatic changes in Cushing's disease, the pathophysiology of aggressive ACTHomas is poorly understood. In this review, we focused on the aggressiveness of ACTHomas, its pathology, the current status of medical therapy, and future prospects. Crooke's cell adenoma (CCA), Nelson syndrome, and corticotroph pituitary carcinoma are representative refractory pituitary tumors that secrete superphysiological ACTH. Although clinically asymptomatic, silent corticotroph adenoma is an aggressive ACTH-producing pituitary adenoma. In this review, we summarize the current understanding of the pathophysiology of aggressive ACTHomas, including these tumors, from a molecular point of view based on genetic, pathological, and experimental evidence. The treatment of aggressive ACTHomas is clinically challenging and usually resistant to standard treatment, including surgery, radiotherapy, and established medical therapy (e.g., pasireotide and cabergoline). Temozolomide is the most prescribed pharmaceutical treatment for these tumors. Reports have shown that several treatments for patients with refractory ACTHomas include chemotherapy, such as cyclohexyl-chloroethyl-nitrosourea combined with 5-fluorouracil, or targeted therapies against several molecules including vascular endothelial growth factor receptor, cytotoxic T lymphocyte antigen 4, programmed cell death protein 1 (PD-1), and ligand for PD-1. Genetic and experimental evidence indicates that some possible therapeutic candidates are expected, such as epidermal growth factor receptor tyrosine kinase inhibitor, cyclin-dependent kinase inhibitor, and BRAF inhibitor. The development of novel treatment options for aggressive ACTHomas is an emerging task.
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Affiliation(s)
- Masaaki Yamamoto
- Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan
| | | | - Wataru Ogawa
- Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hidenori Fukuoka
- Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan
- *Correspondence: Hidenori Fukuoka,
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28
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Akirov A, Larouche V, Shimon I, Asa SL, Mete O, Sawka AM, Gentili F, Ezzat S. Significance of Crooke's Hyaline Change in Nontumorous Corticotrophs of Patients With Cushing Disease. Front Endocrinol (Lausanne) 2021; 12:620005. [PMID: 33815279 PMCID: PMC8013723 DOI: 10.3389/fendo.2021.620005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 03/01/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Glucocorticoid excess in Cushing disease (CD) leads to negative feedback suppression, resulting in Crooke's hyaline change (CC) of nontumorous pituitary corticotrophs. We aimed to determine the predictive value of CC of nontumorous corticotrophs in CD. METHODS The retrospective chart review study included patients with clinical, biochemical, radiologic and outcome data and evaluable histopathology specimens from pituitary surgery for CD. The main outcome was remission of CD, defined by clinical features, biochemical testing, and corticosteroid dependency. RESULTS Of 144 CD patients, 60 (50 women, mean age 43.6±14) had clinical follow-up, biochemical data and histopathology specimens that included evaluable nontumorous adenohypophysis. Specimens from 50 patients (83.3%) demonstrated CC in nontumorous corticotrophs, and 10 (16.7%) had no CC (including 3 with corticotroph hyperplasia). One patient with CC was lost to follow-up and one without CC had equivocal outcome results. During a mean (SD) follow-up period of 74.9 months (61.0), recurrent or persistent disease was documented in 18 patients (31.0%), while 40 (69.0%) were in remission. In patients with CC, the remission rate was 73.5% (95% CI, 59.7%-83.7%) (36/49), whereas it was 44.4% (95% CI, 18.9%-73.3%) (4/9) in patients with no CC. The combination of serum cortisol >138 nmol/L within a week of surgery coupled with absence of nontumorous CC greatly improved the prediction of recurrent or persistent disease. CONCLUSIONS CC of nontumorous corticotrophs was observed in 83% of patients with CD, and most patients with CC experienced remission. Absence of CC in nontumorous corticotrophs may serve as a predictor of reduced remission in patients with CD.
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Affiliation(s)
- Amit Akirov
- Department of Endocrine Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
- Institute of Endocrinology, Beilinson Hospital, Petach Tikva, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- *Correspondence: Amit Akirov,
| | - Vincent Larouche
- Department of Endocrine Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
- Division of Endocrinology and Metabolism, Jewish General Hospital, McGill University, Montreal, QC, Canada
| | - Ilan Shimon
- Institute of Endocrinology, Beilinson Hospital, Petach Tikva, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Sylvia L. Asa
- Department of Pathology, University Hospitals, Cleveland, Case Western Reserve University, Cleveland, OH, United States
| | - Ozgur Mete
- Department of Pathology, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Anna M. Sawka
- Division of Endocrinology, University Health Network and University of Toronto, Toronto, ON, Canada
| | - Fred Gentili
- Division of Neurosurgery, Toronto Western Hospital, University Health Network and Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Shereen Ezzat
- Department of Endocrine Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
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Varlamov EV, Wood MD, Netto JP, Thiessen J, Kim J, Lim DST, Yedinak CG, Banskota S, Cetas JS, Fleseriu M. Cystic appearance on magnetic resonance imaging in bihormonal growth hormone and prolactin tumors in acromegaly. Pituitary 2020; 23:672-680. [PMID: 32870441 DOI: 10.1007/s11102-020-01075-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
PURPOSE To investigate demographic, imaging and laboratory characteristics, and treatment outcomes of acromegaly patients who have bihormonal (BA) growth hormone (GH) and prolactin (PRL) immunoreactive adenomas compared to patients who have densely granulated GH adenomas (DGA) and sparsely granulated GH adenomas (SGA). METHODS Retrospective review of single-center surgically treated acromegaly patients; pathology was analyzed by a single neuropathologist using 2017 WHO criteria. Preoperative magnetic resonance imaging was assessed to evaluate tumor size, cystic component, invasion and T2 signal intensity. RESULTS Seventy-seven patients; 19 BA (9 mammosomatotroph and 10 mixed GH and PRL adenomas) were compared with 30 DGA, and 28 SGA. Patients with BA were older than SGA (49.6 vs 38.5 years, p = 0.035), had a higher IGF-1 index (3.3 vs 2.3, p = 0.040) and tumors were less frequently invasive (15.8% vs 57.1%, p = 0.005). BA more frequently had a cystic component on MRI than both SGA and DGA (52.6% vs 14.3%, and 22%, p = 0.005 and 0.033, respectively). When all histological types were combined, biochemical remission postoperatively was more common in non-cystic than cystic tumors (50% vs 22.5%, p = 0.042). Somatostatin receptor ligand response rate was 66.7%, 90.9% and 37.5% in BA, DGA and SGA patients, respectively (p = 0.053). CONCLUSION Imaging characteristics are an increasingly important adenoma behavior determinant. An adenoma cystic component may suggest that a GH adenoma is a BA. Cystic tumors exhibited lower rates of surgical remission in this series; therefore, optimized individual patient treatment is needed, as patients could be candidates for primary medical treatment.
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Affiliation(s)
- Elena V Varlamov
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
- Pituitary Center, Oregon Health & Science University, Mail Code CH8N, 3303 South Bond Ave, Portland, OR, 97239, USA
| | - Matthew D Wood
- Department of Pathology, Oregon Health & Science University, Portland, OR, USA
- Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
| | - Joao Prola Netto
- Department of Radiology, Oregon Health & Science University, Portland, OR, USA
| | - Jaclyn Thiessen
- Department of Radiology, Oregon Health & Science University, Portland, OR, USA
| | - Jung Kim
- Pituitary Center, Oregon Health & Science University, Mail Code CH8N, 3303 South Bond Ave, Portland, OR, 97239, USA
| | - Dawn Shao Ting Lim
- Pituitary Center, Oregon Health & Science University, Mail Code CH8N, 3303 South Bond Ave, Portland, OR, 97239, USA
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Christine G Yedinak
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
- Pituitary Center, Oregon Health & Science University, Mail Code CH8N, 3303 South Bond Ave, Portland, OR, 97239, USA
| | - Swechya Banskota
- Pituitary Center, Oregon Health & Science University, Mail Code CH8N, 3303 South Bond Ave, Portland, OR, 97239, USA
| | - Justin S Cetas
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
- Pituitary Center, Oregon Health & Science University, Mail Code CH8N, 3303 South Bond Ave, Portland, OR, 97239, USA
| | - Maria Fleseriu
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
- Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA.
- Pituitary Center, Oregon Health & Science University, Mail Code CH8N, 3303 South Bond Ave, Portland, OR, 97239, USA.
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Blackmon MM, Gilbert AR, Floyd J, Hafeez S, Seifi A. Lost to Follow-Up: Complications of an Invasive Giant Prolactinoma. Cureus 2020; 12:e9763. [PMID: 32944476 PMCID: PMC7489779 DOI: 10.7759/cureus.9763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Invasive giant prolactinomas are a rare type of prolactin-secreting tumors. Most lactotroph adenomas, including giant prolactinomas, consist of the sparsely granulated subtype and respond well to medical therapy with dopamine agonists. Proptosis due to intra-orbital tumor extension and ischemic infarction are two rare complications associated with these tumors. We report a case of a 51-year-old woman with a 30-year history of a macroprolactinoma who was lost to follow-up and returned with severe proptosis, a 10-cm invasive sellar mass on imaging, and markedly elevated serum prolactin levels, consistent with invasive giant prolactinoma. She was initially managed with dopamine agonists followed by palliative debulking of the tumor, which microscopically demonstrated a highly proliferative neoplasm predominantly consisting of sparsely granulated lactotroph adenoma with a minor component of the rare and aggressive acidophil stem cell adenoma subtype. Postoperatively, she developed a large left middle cerebral artery infarct and ultimately died. This case is notable in that it demonstrates the aggressive nature of invasive giant prolactinomas when not treated and highlights two rare findings in patients with this tumor: orbital invasion and ischemic infarct.
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Affiliation(s)
- Melodie M Blackmon
- Department of Emergency Medicine, University of Texas Health Science Center at San Antonio, San Antonio, USA
| | - Andrea R Gilbert
- Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, USA
| | - John Floyd
- Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, USA
| | - Shaheryar Hafeez
- Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, USA
| | - Ali Seifi
- Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, USA
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Orman G, Sungur G, Culha C. Assessment of inner retina layers thickness values in eyes with pituitary tumours before visual field defects occur. Eye (Lond) 2020; 35:1159-1164. [PMID: 32555546 DOI: 10.1038/s41433-020-1032-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 05/10/2020] [Accepted: 06/09/2020] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND The purpose of this study was to evaluate macula, retinal nerve layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) and macular nerve fibre layer (mNFL) thickness in patients with pituitary tumours who has normal visual field (VF). METHODS Thirty-five eyes of 35 patients with pituitary tumours with normal VF and 41 eyes of 41-healthy subjects were underwent a complete ophthalmic examination. The spectral domain- optical coherence tomography (OCT) was used to measure macular and optic disc parameters. Layer-by-layer segmentation was done automatically by using the new software. Data analyses were performed by using SPSS for Windows, version 22.0. RESULTS Average of total macula thickness inner temporal (p: 0.006), outer temporal (p < 0.001), inner nasal (p: 0.03), outer nasal (<0.001) were significantly lower in pituitary tumour group than normal group. Average of RNFL (p:0.009), temporal (p: 0.001), superiotemporal (p:0.004) and inferiotemporal (p: 0.01) were significantly lower in pituitary tumour group than normal group. Average of central GCL (p: 0.01) and central NFL (p: 0.03) were significantly lower in pituitary tumour group than normal group. There was no statistically significant difference between the two groups in IPL averages. CONCLUSIONS Pituitary tumour patients with normal VF had reduced nasal and temporal section of the total macula, temporal RNFL, central mGCL and mNFL thicknesses, reflecting the corresponding to the anatomical substrate of the underlying pathology of chiasmal compression. This indicates that the presence of retinal thinning may be a sign of early detection of anterior visual pathway injury before VF loss becomes apparent.
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Affiliation(s)
- Gozde Orman
- Ankara Training and Researching Hospital, Department of Ophthalmology, Ankara, Turkey.
| | - Gulten Sungur
- Ankara Training and Researching Hospital, Department of Ophthalmology, Ankara, Turkey
| | - Cavit Culha
- Ankara Training and Researching Hospital, Department of Endocrinology, Ankara, Turkey
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Zhou Y, Fu X, Zheng Z, Ren Y, Zheng Z, Zhang B, Yuan M, Duan J, Li M, Hong T, Lu G, Zhou D. Identification of gene co-expression modules and hub genes associated with the invasiveness of pituitary adenoma. Endocrine 2020; 68:377-389. [PMID: 32342269 DOI: 10.1007/s12020-020-02316-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 04/13/2020] [Indexed: 10/24/2022]
Abstract
In pituitary adenoma (PA), invasiveness is the main cause of recurrence and poor prognosis. Thus, identifying specific biomarkers for diagnosis and effective treatment of invasive PAs is of great clinical significance. In this study, from the Gene Expression Omnibus database, we obtained and combined several microarrays of PA by the "sva" R package. Weighted gene co-expression network analysis was performed to construct a scale-free topology model and analyze the relationships between the modules and clinical traits. Our analysis results indicated that three key modules (dark turquoise, saddle brown, and steel blue) were associated with the invasiveness of PA. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology analysis were performed for the functional annotation of the key modules. In addition, the hub genes in the three modules were identified and screened by differential expression analysis between normal samples and PA samples. Three upregulated differentially expressed genes (DGAT2, PIGZ, and DHRS2) were identified. The Fisher's exact test and receiver operating characteristic curve were used to validate the capability of these genes to distinguish invasive traits, and transcription factor interaction networks were used to further explore the underlying mechanisms of the three genes. Moreover, a lower expression level of DGAT2 in invasive PA tissue than in noninvasive PA tissue was validated by quantitative reverse transcription-polymerase chain reaction. In general, this study contributes to potential molecular biomarkers of invasive PAs and provides a broader perspective for diagnosis and new therapeutic targets for the invasive PAs.
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Affiliation(s)
- Yuancheng Zhou
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
- The First Clinical Medical College of Nanchang University, Nanchang, Jiangxi, PR China
| | - Xiaorui Fu
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
- Medical Department, Queen Mary College , Nanchang University, Nanchang, Jiangxi, China
| | - Zhicheng Zheng
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
- The Fourth Clinical Medical College of Nanchang University, Nanchang, Jiangxi, PR China
| | - Yu Ren
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
- The First Clinical Medical College of Nanchang University, Nanchang, Jiangxi, PR China
| | - Zijian Zheng
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
- The First Clinical Medical College of Nanchang University, Nanchang, Jiangxi, PR China
| | - Bohan Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
- The First Clinical Medical College of Nanchang University, Nanchang, Jiangxi, PR China
| | - Min Yuan
- Shanggao County People's Hospital, Yichun, Jiangxi, PR China
| | - Jian Duan
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
| | - Meihua Li
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
| | - Tao Hong
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China
| | - Guohui Lu
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
| | - Dongwei Zhou
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
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Bal E, Kulaç İ, Ayhan S, Söylemezoğlu F, Berker M. The Past, Present, and Future Statuses of Formerly Classified "Atypical Pituitary Adenomas": A Clinicopathological Assessment of 101 Cases in a Cohort of More than 1,000 Pure Endoscopically Treated Patients in Single Center. J Neurol Surg B Skull Base 2020; 82:e94-e100. [PMID: 34306922 DOI: 10.1055/s-0040-1702219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 01/10/2020] [Indexed: 10/24/2022] Open
Abstract
Objective This study was aimed to assess the clinical aggressiveness of pituitary neoplasms that were previously defined as atypical adenomas. Methods A total of 1,042 pituitary adenomas were included in the study and 101 of them were diagnosed as atypical adenoma. Demographic characteristics, radiological evaluations, and clinical information were obtained from a computer-based patient database. Cases were categorized as atypical or typical using the criteria listed in 2004 Classification of Tumors of Endocrine Organs. Results The cure and reoperation rates did not show any statistically significant difference between the typical and atypical adenomas. However, a higher K i -67 labeling index was found to be associated with a higher rate of reoperation ( p = 0.008) in atypical adenomas. Of note, cavernous sinus invasion or parasellar extension was found to be associated with lower cure rates in patients with atypical pituitary adenomas ( p < 0.001 and p = 0.001, respectively). Conclusion Although atypical pituitary adenomas are known to be more invasive, this study demonstrated that the reoperation and cure rates are the same for typical and atypical adenomas. Our findings advocate for omitting the use of atypical adenoma terminology based solely on pathological evaluation. As stated in the 4th edition of the World Health Organization (WHO) classification, accurate tumor subtyping, evaluation of proliferation by means of mitotic count and K i -67 labeling index, and radiological and intraoperative assessments of tumor invasion should be taken into consideration in the management of such neoplasms.
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Affiliation(s)
- Ercan Bal
- Department of Neurosurgery, Ankara Yıldırım Beyazıt University School of Medicine, Ankara, Turkey
| | - İbrahim Kulaç
- Department of Pathology, Koç University Hospital, İstanbul, Turkey
| | - Selim Ayhan
- Departments of Neurosurgery and Electroneurophsiology, Vocational School of Health Sciences, Acibadem Mehmet Ali Aydınlar University, İstanbul, Turkey
| | - Figen Söylemezoğlu
- Department of Pathology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Mustafa Berker
- Department of Neurosurgery, Hacettepe University School of Medicine, Ankara, Turkey
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Peng A, Dai H, Duan H, Chen Y, Huang J, Zhou L, Chen L. A machine learning model to precisely immunohistochemically classify pituitary adenoma subtypes with radiomics based on preoperative magnetic resonance imaging. Eur J Radiol 2020; 125:108892. [PMID: 32087466 DOI: 10.1016/j.ejrad.2020.108892] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 01/15/2020] [Accepted: 02/10/2020] [Indexed: 02/08/2023]
Abstract
PURPOSE The type of pituitary adenoma (PA) cannot be clearly recognized with preoperative magnetic resonance imaging (MRI) but can be classified with immunohistochemical staining after surgery. In this study, a model to precisely immunohistochemically classify the PA subtypes by radiomic features based on preoperative MR images was developed. METHODS Two hundred thirty-five pathologically diagnosed PAs, including t-box pituitary transcription factor (Tpit) family tumors (n = 55), pituitary transcription factor 1 (Pit-1) family tumors (n = 110), and steroidogenic factor 1 (SF-1) family tumors (n = 70), were retrospectively studied. T1-weighted, T2-weighted and contrast-enhanced T1-weighted images were obtained from all patients. Through imaging acquisition, feature extraction and radiomic data processing, 18 radiomic features were used to train support vector machine (SVM), k-nearest neighbors (KNN) and Naïve Bayes (NBs) models. Ten-fold cross-validation was applied to evaluate the performance of these models. RESULTS The SVM model showed high performance (balanced accuracy 0.89, AUC 0.9549) whereas the KNN (balanced accuracy 0.83, AUC 0.9266) and NBs (balanced accuracy 0.80, AUC 0.9324) models displayed low performance based on the T2-weighted images. The performance of the T2-weighted images was better than that of the other two MR sequences. Additionally, significant sensitivity (P = 0.031) and specificity (P = 0.012) differences were observed when classifying the PA subtypes by T2-weighted images. CONCLUSIONS The SVM model was superior to the KNN and NBs models and can potentially precisely immunohistochemically classify PA subtypes with an MR-based radiomic analysis. The developed model exhibited good performance using T2-weighted images and might offer potential guidance to neurosurgeons in clinical decision-making before surgery.
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Affiliation(s)
- AiJun Peng
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
| | - HuMing Dai
- College of Computer Science, Sichuan University, Chengdu, 610065, Sichuan Province, China.
| | - HaiHan Duan
- College of Computer Science, Sichuan University, Chengdu, 610065, Sichuan Province, China.
| | - YaXing Chen
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
| | - JianHan Huang
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
| | - LiangXue Zhou
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
| | - LiangYin Chen
- College of Computer Science, Sichuan University, Chengdu, 610065, Sichuan Province, China; The Institute for Industrial Internet Research, Sichuan University, Chengdu, Sichuan Province, China.
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Nishioka H, Yamada S. Cushing's Disease. J Clin Med 2019; 8:jcm8111951. [PMID: 31726770 PMCID: PMC6912360 DOI: 10.3390/jcm8111951] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Revised: 11/04/2019] [Accepted: 11/06/2019] [Indexed: 12/11/2022] Open
Abstract
In patients with Cushing's disease (CD), prompt diagnosis and treatment are essential for favorable long-term outcomes, although this remains a challenging task. The differential diagnosis of CD is still difficult in some patients, even with an organized stepwise diagnostic approach. Moreover, despite the use of high-resolution magnetic resonance imaging (MRI) combined with advanced fine sequences, some tumors remain invisible. Surgery, using various surgical approaches for safe maximum tumor removal, still remains the first-line treatment for most patients with CD. Persistent or recurrent CD after unsuccessful surgery requires further treatment, including repeat surgery, medical therapy, radiotherapy, or sometimes, bilateral adrenalectomy. These treatments have their own advantages and disadvantages. However, the most important thing is that this complex disease should be managed by a multidisciplinary team with collaborating experts. In addition, a personalized and individual-based approach is paramount to achieve high success rates while minimizing the occurrence of adverse events and improving the patients' quality of life. Finally, the recent new insights into the pathophysiology of CD at the molecular level are highly anticipated to lead to the introduction of more accurate diagnostic tests and efficacious therapies for this devastating disease in the near future.
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Affiliation(s)
- Hiroshi Nishioka
- Department of Hypothalamic and Pituitary surgery, Toranomon Hospital, Tokyo 1058470, Japan;
- Okinaka Memorial Institute for Medical Research, Tokyo 1058470, Japan
| | - Shozo Yamada
- Hypothalamic and Pituitary Center, Moriyama Neurological Center Hospital, Tokyo 1340081, Japan
- Okinaka Memorial Institute for Medical Research, Tokyo 1058470, Japan
- Correspondence: ; Tel.: +81-336-751-211
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Triviño V, Fidalgo O, Juane A, Pombo J, Cordido F. Gonadotrophin-releasing hormone agonist-induced pituitary adenoma apoplexy and casual finding of a parathyroid carcinoma: A case report and review of literature. World J Clin Cases 2019; 7:3259-3265. [PMID: 31667176 PMCID: PMC6819301 DOI: 10.12998/wjcc.v7.i20.3259] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 09/24/2019] [Accepted: 10/05/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Pituitary apoplexy represents one of the most serious, life threatening endocrine emergencies that requires immediate management. Gonadotropin-releasing hormone agonist (GnRHa) can induce pituitary apoplexy in those patients who have insidious pituitary adenoma coincidentally. CASE SUMMARY A 46-year-old woman, with a history of hypertension and menorrhagia was transferred to our hospital from a secondary care hospital after complaints of headache and vomiting, with loss of consciousness 5 min after an injection of GnRHa. The drug was prescribed by her gynecologist due to the presence of uterine myomas. The clinical neurological examination revealed right cranial nerve III palsy, ptosis and movement limitation of the right eye. Our first clinical consideration was a pituitary apoplexy. Blood hormonal analysis revealed mild hyperprolactinemia and high follicle stimulating hormone level; PTH and calcium was high with glomerular filtration rate mildly to moderately decrease. A computed tomography scan, revealed an enlarged pituitary gland (3.5 cm) impinging upon the optic chiasm with bone involvement of the sella. Following contrast media administration, the lesion showed homogeneous enhancement with high-density focus that suggests hemorrhagic infarction of the tumor. Transsphenoidal endoscopic surgery was perfomed and adenomatous tissue was removed. Immunohistochemistry was positive for luteinizing hormone (LH) and follicular-stimulating hormone (FSH). A solid hypoechoic nodule (14 mm x 13 mm x 16 mm) was found in the caudal portion of the right thyroid lobe after a parathyroid ultrasound. A genetic test of Multiple Endocrine Neoplasia type 1 (MEN1) was negative. A right lower parathyroidectomy was performed and the pathologic study showed the presence of an encapsulated parathyroid carcinoma of 1.5 cm. A MEN type 4 genetic test was performed result was negative. CONCLUSION This case demonstrates an uncommon complication of GnRH agonist therapy in the setting of a pituitary macroadenoma and the casual finding of parathyroid carcinoma. It also highlights the importance of suspecting the presence of a multiple endocrine neoplasia syndrome and to carry out relevant genetic studies.
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Affiliation(s)
- Vanessa Triviño
- Department of Endocrinology, Complejo Hospitalario Universitario A Coruña, A Coruña 15006, Spain
| | - Olga Fidalgo
- Department of Endocrinology, Complejo Hospitalario Universitario A Coruña, A Coruña 15006, Spain
| | - Antía Juane
- Department of Endocrinology, Complejo Hospitalario Universitario A Coruña, A Coruña 15006, Spain
| | - Jorge Pombo
- Department of pathological anatomy, Complejo Hospitalario Universitario A Coruña, A Coruña 15006, Spain
| | - Fernando Cordido
- Department of Endocrinology, Complejo Hospitalario Universitario A Coruña, A Coruña 15006, Spain
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Almeida JP, Stephens CC, Eschbacher JM, Felicella MM, Yuen KCJ, White WL, Mooney MA, Bernat AL, Mete O, Zadeh G, Gentili F, Little AS. Clinical, pathologic, and imaging characteristics of pituitary null cell adenomas as defined according to the 2017 World Health Organization criteria: a case series from two pituitary centers. Pituitary 2019; 22:514-519. [PMID: 31401793 DOI: 10.1007/s11102-019-00981-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE The 2017 World Health Organization classification of pituitary tumors redefined pituitary null cell adenomas (NCAs) by restricting this diagnostic category to pituitary tumors that are negative for pituitary transcription factors and adenohypophyseal hormones. The clinical behavior of this redefined entity has not been widely studied, and this is a major shortcoming of the classification. This study evaluated the imaging and clinical features of NCAs from two pituitary centers and compared them with those of gonadotroph adenomas (GAs). METHODS Imaging, pathologic, and clinical characteristics of NCAs and GAs were retrospectively reviewed. Tumor immunohistochemistry was performed to confirm absence of adenohypophyseal hormones and pituitary transcription factor expression. RESULTS Thirty-one NCAs were compared with 38 GAs. NCAs were more likely to invade the cavernous sinus (15/31 [48%] vs. 5/38 [13%], P = .003) and had a higher proliferative index (i.e., MIB-1 > 3%, 11/31 [35%] vs. 5/38 [13%], P = .04). Gross total resection was less likely in the NCA group (19/31 [61%] vs. 33/38 [87], P = .02). Progression-free survival was worse in the NCA cohort (5-year progression-free survival, 0.70 vs. 1.00; P = .011, by log-rank test). CONCLUSIONS Compared with GAs, NCAs are more invasive at the time of presentation and have a more aggressive clinical course. This study provides evidence that NCAs represent a distinct clinicopathologic entity with behavior that differs adversely from that of GAs. This may inform clinical decision-making, including frequency of postoperative tumor surveillance and timing of adjunctive treatments.
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Affiliation(s)
- Joao Paulo Almeida
- Division of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Corbin C Stephens
- Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA
| | | | | | - Kevin C J Yuen
- Department of Neuroendocrinology, Barrow Neurological Institute, Phoenix, AZ, USA
| | - William L White
- Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA
| | - Michael A Mooney
- Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA
| | - Anne Laure Bernat
- Division of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Ozgur Mete
- Laboratory Medicine Program, Department of Pathology, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Gelareh Zadeh
- Division of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Fred Gentili
- Division of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Andrew S Little
- Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA.
- c/o Neuroscience Publications, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 W. Thomas Rd, Phoenix, AZ, 85013, USA.
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Aydin S, Comunoglu N, Ahmedov ML, Korkmaz OP, Oz B, Kadioglu P, Gazioglu N, Tanriover N. Clinicopathologic Characteristics and Surgical Treatment of Plurihormonal Pituitary Adenomas. World Neurosurg 2019; 130:e765-e774. [DOI: 10.1016/j.wneu.2019.06.217] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 06/27/2019] [Accepted: 06/28/2019] [Indexed: 02/06/2023]
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Sen A, Das C, Mukhopadhyay M, Mukhopadhyay S, Deb S, Mukhopadhyay B. Cytohistological correlation in pituitary tumor and immunological assessment with the help of Ki-67. J Postgrad Med 2019; 63:96-99. [PMID: 27779153 PMCID: PMC5414435 DOI: 10.4103/0022-3859.192797] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Background: Tumors of the pituitary gland and sellar region represent approximately 10–15% of all brain tumors. Pituitary adenoma (PA), the most common pathology of the pituitary gland, can be effectively subclassified only with the help of immunohistochemistry (IHC). This is important and needed for individual patient management. Aims and Objectives: The objective of the study was to analyze the importance of intraoperative imprint smear cytology and correlating with final histopathological diagnosis. Furthermore, to classify the different types of PA with the help of IHC, prolactin (PRL), adrenocorticotropic hormone (ACTH), and growth hormone (GH) and to predict the benign, atypical, or malignant nature of the tumor with the help of prognostic marker Ki-67. Materials and Methods: A prospective study was done in 34 cases. The patients whose pituitary gland samples are referred from the endocrine and the neurosurgery department to the pathology department for histopathological examinations were selected. We have studied the clinical features, radiology and touch imprint cytology, histopathology, and IHC with the help of PRL, ACTH, GH, and Ki-67 of PA over 2 years. Results: In our study, we had 32 cases of PA of 34 cases over a span of 2 years. We have seen that there is a correlation between cytological and histological diagnosis of the subtypes of PA in 62% cases, and the Kappa statistics show a moderate extent of agreement (Kappa - 0.320, 95% confidence interval = 0.031–0.609). Ki-67 when compared to the radiological grading showed a high degree of comparability (Chi-square test: P < 0.001). All cases with invasion had a higher Ki-67. On using the Fisher's exact test, we found that the Ki-67 expression with GH-producing adenomas and ACTH-producing adenomas was comparable (P = 1.000) while in PRL-producing adenomas too this was not significant (P = 0.269). Conclusion: PA can be effectively classified with the help of IHC. Intraoperative cytology is important in diagnosing PA, but histopathology remains the gold standard in diagnosing and differentiating PA from other pathologies of the pituitary gland. The radiological grading together with immunological classification and the prognostic markers of Ki-67 is important in deciding the benign or atypical nature of the adenomas thus helping in better patient management.
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Affiliation(s)
- A Sen
- Department of Pathology, The Institute of Post-Graduate Medical Education and Research, Kolkata, West Bengal, India
| | - C Das
- Department of Pathology, The Institute of Post-Graduate Medical Education and Research, Kolkata, West Bengal, India
| | - M Mukhopadhyay
- Department of Pathology, The Institute of Post-Graduate Medical Education and Research, Kolkata, West Bengal, India
| | - S Mukhopadhyay
- Department of Endocrinology, The Institute of Post-Graduate Medical Education and Research, Kolkata, West Bengal, India
| | - S Deb
- Department of Neurosurgery, Bangur Institute of Neurology, Kolkata, West Bengal, India
| | - B Mukhopadhyay
- Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
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Drummond J, Roncaroli F, Grossman AB, Korbonits M. Clinical and Pathological Aspects of Silent Pituitary Adenomas. J Clin Endocrinol Metab 2019; 104:2473-2489. [PMID: 30020466 PMCID: PMC6517166 DOI: 10.1210/jc.2018-00688] [Citation(s) in RCA: 117] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 07/12/2018] [Indexed: 12/22/2022]
Abstract
CONTEXT Silent pituitary adenomas are anterior pituitary tumors with hormone synthesis but without signs or symptoms of hormone hypersecretion. They have been increasingly recognized and represent challenging diagnostic issues. EVIDENCE ACQUISITION A comprehensive literature search was performed using MEDLINE and EMBASE databases from January 2000 to March 2018 with the following key words: (i) pituitary adenoma/tumor and nonfunctioning; or (ii) pituitary adenoma/tumor and silent. All titles and abstracts of the retrieved articles were reviewed, and recent advances in the field of silent pituitary adenomas were summarized. EVIDENCE SYNTHESIS The clinical and biochemical picture of pituitary adenomas reflects a continuum between functional and silent adenomas. Although some adenomas are truly silent, others will show some evidence of biochemical hypersecretion or could have subtle clinical signs and, therefore, can be referred to as clinically silent or "whispering" adenomas. Silent tumors seem to be more aggressive than their secreting counterparts, with a greater recurrence rate. Transcription factors for pituitary cell lineages have been introduced into the 2017 World Health Organization guidelines: steroidogenic factor 1 staining for gonadotroph lineage; PIT1 (pituitary-specific positive transcription factor 1) for growth hormone, prolactin, and TSH lineage, and TPIT for the corticotroph lineage. Prospective studies applying these criteria will establish the value of the new classification. CONCLUSIONS A concise review of the clinical and pathological aspects of silent pituitary adenomas was conducted in view of the new World Health Organization classification of pituitary adenomas. New classifications, novel prognostics markers, and emerging imaging and therapeutic approaches need to be evaluated to better serve this unique group of patients.
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MESH Headings
- Biomarkers, Tumor/blood
- Chemotherapy, Adjuvant/methods
- Humans
- Magnetic Resonance Angiography
- Neoplasm Recurrence, Local/epidemiology
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/prevention & control
- Pituitary Gland, Anterior/diagnostic imaging
- Pituitary Gland, Anterior/pathology
- Pituitary Gland, Anterior/surgery
- Pituitary Hormones, Anterior/blood
- Pituitary Hormones, Anterior/metabolism
- Pituitary Neoplasms/blood
- Pituitary Neoplasms/diagnosis
- Pituitary Neoplasms/pathology
- Pituitary Neoplasms/therapy
- Prognosis
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Affiliation(s)
- Juliana Drummond
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Federico Roncaroli
- Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Ashley B Grossman
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Márta Korbonits
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Correspondenceand Reprint Requests: Márta Korbonits, MD, PhD, Department of Endocrinology, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, United Kingdom. E-mail:
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Mete O, Alshaikh OM, Cintosun A, Ezzat S, Asa SL. Synchronous Multiple Pituitary Neuroendocrine Tumors of Different Cell Lineages. Endocr Pathol 2018; 29:332-338. [PMID: 30215160 DOI: 10.1007/s12022-018-9545-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
We report clinicopathological features of a large series of synchronous multiple pituitary neuroendocrine tumors (PitNETs) of different cell lineages. Retrospective review of pathology records from 2001 to 2016 identified 13 synchronous multiple PitNETs from 1055 PitNETs classified using pituitary cell-lineage transcription factors, adenohypohyseal hormones, and other biomarkers. Clinical, radiological, and histopathological features of these tumors were reviewed. The series included seven females and six males. Mean age at diagnosis was 55.23 years (range 36-73). Imaging was unavailable for four patients; among the other nine, mean tumor size was 2.23 cm (range 0.9-3.9). Five patients had acromegaly, four had Cushing disease, and four had clinically non-functional tumors. Twelve had double PitNETs; one had a triple PitNET. The most common tumor type was corticotroph (n = 8; six densely and one sparsely granulated and one Crooke cell; three densely and one sparsely granulated were clinically silent), gonadotroph tumors (n = 8), and somatotroph tumors (n = 5; four sparsely granulated and one densely granulated somatotroph) were followed by lactotroph tumors (n = 4; all sparsely granulated), poorly differentiated Pit-1 lineage tumor (n = 1), and unusual plurihormonal tumor (n = 1). A 54-year-old man with Cushing disease had MEN1-driven Crooke cell and gonadotroph tumors. The triple pitNET consisted of a multilineage plurihormonal tumor associated with a gonadotroph and a sparsely granulated lactotroph tumor. The Ki67 (available from 10 specimens) ranged from 1 to 5% in individual tumors. Radiological and biochemical follow-up was available for 10 and 11 patients, respectively. Radiological tumor persistence/recurrence was identified in three patients with double PitNETs consisting of sparsely granulated lactotroph and gonadotroph tumors (n = 1), sparsely granulated somatotroph and silent corticotroph tumors (n = 1), and gonadotroph and silent corticotroph tumors (n = 1) with cavernous sinus invasion. Biochemical persistence was noted in four patients with double PitNETs consisting of sparsely granulated somatotroph and silent corticotroph tumors (n = 2), gonadotroph and Crooke cell tumors (n = 1), and densely granulated somatotroph and silent corticotroph tumors (n = 1). Multiple PitNETs represent about 1% of PitNETs and usually have hormone excess due to at least one tumor component. Clinical manifestations may be due to the minor component, especially in patients with Cushing disease. Invasive growth and aggressive histological subtypes predicted disease persistence/recurrence. This series also highlights the importance of routine application of pituitary cell lineage transcription factors along with hormones to distinguish and subtype multiple synchronous PitNETs.
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Affiliation(s)
- Ozgur Mete
- Department of Pathology, Princess Margaret Cancer Program, University Health Network, University of Toronto, 200 Elizabeth Street, 11th Floor, Toronto, ON, M5G 2M9, Canada.
| | - Omalkhaire M Alshaikh
- Department of Medicine, Princess Margaret Cancer Program, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Amber Cintosun
- Department of Pathology, Princess Margaret Cancer Program, University Health Network, University of Toronto, 200 Elizabeth Street, 11th Floor, Toronto, ON, M5G 2M9, Canada
| | - Shereen Ezzat
- Department of Medicine, Princess Margaret Cancer Program, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Sylvia L Asa
- Department of Pathology, Princess Margaret Cancer Program, University Health Network, University of Toronto, 200 Elizabeth Street, 11th Floor, Toronto, ON, M5G 2M9, Canada.
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Øystese KAB, Berg JP, Normann KR, Zucknick M, Casar-Borota O, Bollerslev J. The role of E and N-cadherin in the postoperative course of gonadotroph pituitary tumours. Endocrine 2018; 62:351-360. [PMID: 30051197 DOI: 10.1007/s12020-018-1679-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Accepted: 07/05/2018] [Indexed: 01/04/2023]
Abstract
PURPOSE Gonadotroph tumours are the most abundant of the clinically silent pituitary tumours. There is a lack of reliable prognostic markers predicting their clinical course. Our aim was to determine the level of E-cadherin and N-cadherin in a cohort of clinically silent gonadotroph pituitary tumours, and compare them to the rate of reintervention. METHODS Tumour tissue from primary surgery was retrospectively investigated and compared with clinical data. Immunohistochemical (N = 105) and real time-qPCR (N = 85) analyses for the levels of N-cadherin and the extra- and intracellular domains of E-cadherin were performed. The immunoreactive scores (IRS) and mRNA relative quantity were compared to the rate of reintervention. RESULTS The tumours presented a high IRS for N-cadherin (Median 12 (IQR 12-12)) and almost no immunoreactivity for the extracellular domain of E-cadherin (Median 0 (IQR 0-0)). The membranous staining for the intracellular domain of E-cadherin varied (Median 6 (IQR 4-6). Reduced membranous expression of the intracellular domain of E-cadherin was associated with nuclear presence of the same domain. Nuclear staining for the intracellular domain of E-cadherin was associated with a lower rate of reintervention (p = 0.01). CONCLUSION We found that silent gonadotroph tumours presented high IRS for N-cadherin and low IRS for the extracellular domain of E-cadherin. A substantial proportion of the tumours presented nuclear staining for the intracellular domain of E-cadherin, accompanied by a reduced membranous expression of the intracellular domain of E-cadherin. Absence of nuclear staining for the intracellular domain of E-cadherin served as an independent predictor of reintervention.
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Affiliation(s)
- Kristin Astrid Berland Øystese
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, P.b.4950 Nydalen, 0424, Oslo, Norway.
- Faculty of Medicine, University of Oslo, Oslo, Norway.
- Research Institute for Internal Medicine (IMF), OUS Rikshospitalet, Postboks 4950 Nydalen, 0424, Oslo, Norway.
| | - Jens Petter Berg
- Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Medical Biochemistry, Oslo University Hospital, 0424, Oslo, Norway
| | - Kjersti Ringvoll Normann
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, P.b.4950 Nydalen, 0424, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
- Research Institute for Internal Medicine (IMF), OUS Rikshospitalet, Postboks 4950 Nydalen, 0424, Oslo, Norway
| | - Manuela Zucknick
- Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Olivera Casar-Borota
- Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden
- Department of Clinical Pathology and Cytology, Uppsala University Hospital, Rudbeck Laboratory, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden
- Department of Pathology, Oslo University Hospital, Sognsvannsveien 20, 0372, Oslo, Norway
| | - Jens Bollerslev
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, P.b.4950 Nydalen, 0424, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
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Beltrame S, Rasmussen J, Plou P, Altszul M, Yampolsky C, Ajler P. [Optical coherence tomography as a predictor of visual recovery in patients with pituitary macroadenomas]. Surg Neurol Int 2018; 9:S57-S65. [PMID: 30186669 PMCID: PMC6108170 DOI: 10.4103/sni.sni_463_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 12/05/2017] [Indexed: 11/04/2022] Open
Abstract
Background With pituitary macroadenomas, there is a high incidence of visual loss from optic pathway compression. Surgical removal of the tumor usually prevents progression and allows visual recovery. Our objective was to evaluate if optical coherence tomography (OCT) predicts visual outcomes after surgical decompression. Methods Patients with pituitary macroadenomas were prospectively recruited between February 2015 and November 2016. We evaluated preoperative and postoperative visual acuity, automated perimetry, and OCT. We compared the results 6-12 weeks and 6-9 months after surgical removal of the tumor. Dependent and independent continuous variables were analyzed by Student's t-test, linear regression analysis, and Pearson's correlation coefficients, considering P < 0.05 as statistically significant. Results Visual acuity and visual field defects were much worse in patients with a thin preoperative retinal nerve fiber layer (RNFL). Both patients with normal RNFL thickness and patients with thin RNFL experienced significant improvement in postoperative visual perimetry 6-12 weeks after surgery. OCT values correlated inversely with pre- and postoperative visual fields, which means that, if the nerve was thicker, the visual field was better. Patients with a normal OCT had greater recovery because their preoperative perimetry values were better. The correlation between OCT values and visual field improvement was weak, suggesting that patients' visual fields improved after decompressive surgery independent of the nerve's thickness. Conclusion The computerized visual field continues to be the gold standard in the evaluation of patients with pituitary macroadenomas with optic pathway compression. Our results suggest that OCT might not be an accurate predictor of visual outcomes.
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Affiliation(s)
- Sofía Beltrame
- Servicio de Neurocirugía, Hospital Italiano de Buenos Aires, Buenos Aires
| | - Jorge Rasmussen
- Servicio de Neurocirugía, Hospital Italiano de Buenos Aires, Buenos Aires
| | - Pedro Plou
- Servicio de Neurocirugía, Hospital Italiano de Buenos Aires, Buenos Aires
| | - Moira Altszul
- Servicio de Oftalmología, Hospital Italiano de Buenos Aires, Buenos Aires
| | - Claudio Yampolsky
- Servicio de Neurocirugía, Hospital Italiano de Buenos Aires, Buenos Aires
| | - Pablo Ajler
- Servicio de Neurocirugía, Hospital Italiano de Buenos Aires, Buenos Aires
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Zahr R, Fleseriu M. Updates in Diagnosis and Treatment of Acromegaly. EUROPEAN ENDOCRINOLOGY 2018; 14:57-61. [PMID: 30349595 PMCID: PMC6182922 DOI: 10.17925/ee.2018.14.2.57] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 05/03/2018] [Indexed: 12/13/2022]
Abstract
Acromegaly is a rare disease, caused largely by a growth hormone (GH) pituitary adenoma. Incidence is higher than previously thought. Due to increased morbidity and mortality, if not appropriately treated, early diagnosis efforts are essential. Screening is recommended for all patients with clinical features of GH excess. There is increased knowledge that classical diagnostic criteria no longer apply to all, and some patients can have GH excess with normal GH response to glucose. Treatment is multifactorial and personalised therapy is advised.
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Affiliation(s)
- Roula Zahr
- Department of Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition
| | - Maria Fleseriu
- Department of Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition
- Department of Neurological Surgery
- Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, US
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Lapshina AM, Khandaeva PM, Belaya ZE, Rozhinskaya LY, Melnichenko GA. [Role of microRNA in oncogenesis of pituitary tumors and their practical significance]. TERAPEVT ARKH 2018. [PMID: 28635944 DOI: 10.17116/terarkh2016888115-120] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Microribonucleic acids (miRNAs) are a class of noncoding RNAs that regulate posttranscriptional gene expression. These molecules are regulators of cell proliferation, metabolism, apoptosis, and differentiation. MiRNAs are not degraded by RNAases and their concentrations can be measured in different body fluids, including serum. The expression of miRNAs varies in intact tissues and tumors, including pituitary adenomas. Pituitary tumors are encountered in 22.5% of the population and, in a number of cases, may be asymptomatic, but in case of invasion or/and hormone overproduction, their clinical presentation is severe with multiple symptoms leading to disability and even death. The mechanisms for the development and progression of pituitary tumors and the markers for remission and recurrence have not been adequately investigated. This literature review discusses the biological significance of miRNAs in pituitary tumors and the potential value of circulating miRNAs as biomarkers.
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Affiliation(s)
- A M Lapshina
- Endocrine Research Center, Ministry of Health of Russia, Moscow, Russia
| | - P M Khandaeva
- Endocrine Research Center, Ministry of Health of Russia, Moscow, Russia
| | - Zh E Belaya
- Endocrine Research Center, Ministry of Health of Russia, Moscow, Russia
| | - L Ya Rozhinskaya
- Endocrine Research Center, Ministry of Health of Russia, Moscow, Russia
| | - G A Melnichenko
- Endocrine Research Center, Ministry of Health of Russia, Moscow, Russia
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Lin P, Liu X, Wang S, Li X, Song Y, Li L, Cai S, Wang X, Chen J. Diagnosing pituitary adenoma in unstained sections based on multiphoton microscopy. Pituitary 2018; 21:362-370. [PMID: 29594837 DOI: 10.1007/s11102-018-0882-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE If we can find a new method that can achieve rapid diagnosis of adenoma during operation, it will help surgeon shorten the operation time and enhance the treatment efficacy. This study discusses the feasibility of multiphoton microscopy (MPM) in diagnosing pituitary adenoma. METHOD MPM, based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) is performed for the diagnosis of pituitary adenoma in unstained sections. RESULTS Our results show that MPM can reveal the variation of reticulin fiber by SHG signals of collagen, combined with the measurement of area of acinus, thickness of collagen fiber and collagen percentage. MPM can further reflect the change of meshwork in normal pituitary and hyperplasia quantitatively. And the characteristics of typical growth patterns of pituitary adenoma are demonstrated by the overlay of SHG and TPEF images. What's more, we can identify the boundary of normal pituitary, hyperplasia and adenoma from MPM images. And the experiment also results verify the feasibility of this method in frozen sections. CONCLUSION These results indicated that MPM can make a diagnosis of pituitary adenoma by the morphological changes without routine pathological processing including hematoxylin-eosin (H&E) staining and other special staining. Therefore, this technique is expected to help diagnosis of pituitary adenoma during operation.
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Affiliation(s)
- Peihua Lin
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, 350007, People's Republic of China
| | - Xueyong Liu
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People's Republic of China
| | - Shu Wang
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, 350007, People's Republic of China
| | - Xiaoling Li
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People's Republic of China
| | - Yankun Song
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People's Republic of China
| | - Lianhuang Li
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, 350007, People's Republic of China
| | - Shanshan Cai
- Department of Pathology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People's Republic of China
| | - Xingfu Wang
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People's Republic of China.
| | - Jianxin Chen
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, 350007, People's Republic of China.
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Dogansen SC, Yalin GY, Tanrikulu S, Tekin S, Nizam N, Bilgic B, Sencer S, Yarman S. Clinicopathological significance of baseline T2-weighted signal intensity in functional pituitary adenomas. Pituitary 2018; 21:347-354. [PMID: 29460202 DOI: 10.1007/s11102-018-0877-3] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
PURPOSE To assess baseline T2-weighted signal intensity (T2-WSI) of functional pituitary adenomas (FPA), and to investigate the relationship of baseline T2-WSI with clinical features, histopathological granulation patterns, and response to treatment in patients with acromegaly, prolactinoma and Cushing's disease (CD). METHODS Somatotroph adenomas (n = 87), prolactinomas (n = 78) and corticotroph adenomas (n = 29) were included in the study. Baseline T2-WSI findings (grouped as hypo-, iso- and hyperintense) were compared with hormone levels, tumor diameter, granulation patterns and response to treatment. RESULTS Somatotroph adenomas were mostly hypointense (53%), prolactinomas were dominantly hyperintense (55%), and corticotroph adenomas were generally hyperintense (45%). Hyperintense somatotroph adenomas were larger in size with sparsely granulated pattern and tumor shrinkage rate was lower after somatostatin analogues (SSA) (p = 0.007, p = 0.035, p = 0.029, respectively). T2 hypointensity was related with higher baseline IGF-1% ULN (upper limit of normal) levels and a better response to SSA treatment (p = 0.02, p = 0.045, respectively). In female prolactinomas, hyperintensity was correlated with a smaller adenoma diameter (p = 0.001). Hypointense female prolactinomas were related to younger age at diagnosis, higher baseline PRL levels and dopamine agonist (DA) resistance (p = 0.009, p = 0.022, p < 0.001, respectively). Hyperintense corticotroph adenomas were related to larger adenoma size and sparsely granulated pattern (p = 0.04, p = 0.017, respectively). There was no significant difference in the recurrence with T2WSI in CD. CONCLUSION Baseline hypointense somatotroph adenomas show a better response to SSA, whereas hypointensity was related to DA resistance in female prolactinomas.
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Affiliation(s)
- Sema Ciftci Dogansen
- Division of Endocrinology and Metabolism, Capa, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, 34090, Istanbul, Turkey.
| | - Gulsah Yenidunya Yalin
- Division of Endocrinology and Metabolism, Capa, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, 34090, Istanbul, Turkey
| | - Seher Tanrikulu
- Division of Endocrinology and Metabolism, Capa, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, 34090, Istanbul, Turkey
| | - Sakin Tekin
- Division of Endocrinology and Metabolism, Capa, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, 34090, Istanbul, Turkey
| | - Nihan Nizam
- Division of Endocrinology and Metabolism, Capa, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, 34090, Istanbul, Turkey
| | - Bilge Bilgic
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Serra Sencer
- Department of Neuroradiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Sema Yarman
- Division of Endocrinology and Metabolism, Capa, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, 34090, Istanbul, Turkey
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Polledo L, Grinwis GCM, Graham P, Dunning M, Baiker K. Pathological Findings in the Pituitary Glands of Dogs and Cats. Vet Pathol 2018; 55:880-888. [DOI: 10.1177/0300985818784162] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
With the exception of classic functional adenomas in dogs and horses, pituitary lesions are infrequently described in the veterinary literature. Approximately 10% of pituitary glands from asymptomatic humans contain abnormalities, but the equivalent proportion in small animals is unknown. Pituitary glands from 136 dogs and 65 cats collected during routine necropsies were examined to determine the prevalence of pituitary lesions and their histopathological diagnosis. Lesions were characterized in sections stained with hematoxylin and eosin, periodic acid-Schiff (PAS), Gordon and Sweet’s and reticulin stains, and immunohistochemistry for adrenocorticotropic hormone (ACTH), growth hormone, melanocyte stimulating hormone–α, and prolactin. Pituitary abnormalities were identified in 36 of 136 (26.4%) dogs and 10 of 65 (15.3%) cats. Cystic changes were the most common lesion, occurring in 18 (13.2%) dogs and 8 (12.3%) cats. Pituitary neoplasia was detected in 14.1% (12/85) of middle-aged and old dogs; 1 (1.5%) cat had pituitary nodular hyperplasia. PAS and reticulin stains helped differentiate ACTH-immunoreactive adenomas from hyperplastic nodules: adenomas contained PAS-positive intracytoplasmic granules and loss of the normal reticulin network. One dog had a pituitary carcinoma with infiltration into the thalamus. Other pituitary abnormalities included secondary metastases (2 dogs) and hypophysitis (4 dogs, 1 cat). In most cases, the lesion appeared to be subclinical and could be considered incidental, whereas clinical manifestations were apparent in only 4 dogs (2.9%) and none of the cats with pituitary lesions. Pituitary abnormalities are common in dogs and cats, and their clinical relevance requires further investigation.
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Affiliation(s)
- Laura Polledo
- School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
| | - Guy C. M. Grinwis
- Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht, the Netherlands
| | - Peter Graham
- School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
| | - Mark Dunning
- School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
| | - Kerstin Baiker
- School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
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Mete O, Cintosun A, Pressman I, Asa SL. Epidemiology and biomarker profile of pituitary adenohypophysial tumors. Mod Pathol 2018; 31:900-909. [PMID: 29434339 DOI: 10.1038/s41379-018-0016-8] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 12/11/2017] [Accepted: 12/17/2017] [Indexed: 12/23/2022]
Abstract
Recent studies have reported the prevalence of pituitary tumors to be ~1/1000 population. Many are prolactin-producing tumors that are managed medically, however, the epidemiology of surgically resected pituitary adenohypophysial neuroendocrine tumors has not been reported in a large series with detailed characterization. We reviewed 1055 adenohypophysial tumors from 1169 transsphenoidal resections from the pathology files of University Health Network, Toronto, 2001-2016. Tumors were characterized by immunohistochemical localization of transcription factors (Pit-1, ERα, SF-1, Tpit), hormones (adrenocorticotropin, growth hormone, prolactin, β-thyrotropin, β-folliculotropin, β-luteotropin, α-subunit), and other biomarkers (keratins, Ki67, p27, FGFR4). Electron microscopy was used only for unusual lesions. In this cohort, 51.3% of patients were female; the average age was 51 years. Gonadotroph tumors represented 42.5%. Pit-1-lineage-tumors represented 29.9%; these were subclassified as growth-hormone-predominant (somatotroph/mammosomatotroph/mixed; 53%), prolactin-predominant (lactotroph/acidophil-stem-cell; 28%), thyrotrophs (2%), plurihormonal (14%), and not-otherwise-specified (3%). Corticotroph tumors represented 17.1%. Only 4.5% were null cell tumors and 0.5% were unusual plurihormonal tumors. In 5.5% the tumor was not characterized for technical reasons (sample size, fixation, necrosis or other artifact). All corticotroph and plurihormonal tumors were positive for keratins; others tumors showed variable negativity with highest rates in gonadotroph (37.1%) and null cell tumors (28.2%). Tumors with a Ki67 ≥ 3% comprised 60% of this cohort. Global loss of p27 was most frequent in corticotroph neoplasms, specifically those associated with elevated glucocorticoid levels. Corticotroph and lactotroph tumors were more common among females; gonadotroph tumors were more common among males. Younger patients had mainly corticotroph and Pit-1-lineage neoplasms, whereas older patients harbored mainly gonadotroph tumors. This represents one of the largest surgical series of morphologically characterized pituitary tumors reported to date and the first to include the routine use of transcription factors for tumor classification. The data provide the basis for clinicopathologic correlations that are helpful for prognostic and predictive patient management.
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Affiliation(s)
- Ozgur Mete
- Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, ON, M5G 2M9, Canada.,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5G 2M9, Canada
| | - Amber Cintosun
- Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, ON, M5G 2M9, Canada.,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5G 2M9, Canada
| | - Irwin Pressman
- School of Mathematics and Statistics, Carlton University, Ottawa, ON, Canada
| | - Sylvia L Asa
- Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, ON, M5G 2M9, Canada. .,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5G 2M9, Canada.
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New WHO classification of pituitary adenomas (4th edition): assessment of pituitary transcription factors and the prognostic histological factors. Brain Tumor Pathol 2018; 35:57-61. [PMID: 29318396 DOI: 10.1007/s10014-017-0307-7] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 12/26/2017] [Indexed: 12/20/2022]
Abstract
WHO classification of pituitary adenomas was revised in 2017. The two major and significant changes are discussed. (1) The new classification focuses on adenohypophysial-cell lineage for the designation of adenomas, and thus, assessment of pituitary transcription factors is recommended. Its appropriate use has a complementary role in obtaining an accurate diagnosis, particularly in hormone-negative adenomas. Subclassification of nonfunctioning adenomas was revised accordingly and, consequently, null cell adenomas became quite rare. (2) "Atypical adenoma", a previous category, was eliminated due to the poor reproducibility and predictive value. Assessment of tumor proliferation marker and other clinical parameters such as invasion are recommended to predict aggressiveness. "High-risk adenomas" are those with rapid growth, radiological invasion, and a high Ki-67 proliferation index, whereas some special adenoma subtypes commonly show aggressive behavior.
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