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Liu Y, Peng J, Zhao Y, Wang W. Emerging pathological diagnostic strategies for solid pseudopapillary neoplasm of the pancreas: insights from omics and innovative techniques. J Pathol Clin Res 2025; 11:e70029. [PMID: 40312910 PMCID: PMC12046068 DOI: 10.1002/2056-4538.70029] [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] [Received: 12/11/2024] [Revised: 02/21/2025] [Accepted: 03/31/2025] [Indexed: 05/03/2025]
Abstract
Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare, low-grade malignant tumor, representing 0.9-2.7% of all exocrine pancreatic tumors. SPN patients generally have a favorable prognosis with a 5-year survival rate exceeding 95% following complete surgical resection. Accurate diagnosis is crucial to avoid unnecessary treatments. Currently, SPN diagnosis relies on imaging techniques such as CT and MRI, along with immunohistochemical analysis of biopsy and resection samples. The main challenge in diagnosis is the potential inability to accurately identify recurrent or metastatic SPN, as well as 'malignant' SPN, due to the lack of specific biomarkers. Advances in high-throughput omics technologies, including genomics, transcriptomics, proteomics and metabolomics, have opened new avenues for identifying novel biomarkers for SPN. Additional, liquid biopsy techniques have enabled more comprehensive analysis of biosamples such as pancreatic cyst fluid, offering promising prospects for preoperative diagnosis. This review highlights recent research on SPN diagnosis, focusing on immunohistochemical markers, tissue sampling methods and the potential of omics approaches. It also discusses the challenges and opportunities in improving diagnostic accuracy, particularly for high-grade and metastatic SPNs.
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Affiliation(s)
- Yuanhao Liu
- Department of PathologyPeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
| | - Junya Peng
- Institute of Clinical MedicinePeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
- State Key Laboratory of Complex, Severe, and Rare DiseasesPeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
| | - Yupei Zhao
- State Key Laboratory of Complex, Severe, and Rare DiseasesPeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
- Department of General SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
- Department of Basic Medical SciencesSchool of Medicine, Tsinghua UniversityBeijingPR China
- Peking University‐Tsinghua Center for Life SciencesBeijingPR China
| | - Wenze Wang
- Department of PathologyPeking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingPR China
- Molecular Pathology Research Center, Department of PathologyPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingPR China
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Xu YC, Fu DL, Yang F. Unraveling the enigma: A comprehensive review of solid pseudopapillary tumor of the pancreas. World J Gastrointest Oncol 2024; 16:614-629. [PMID: 38577449 PMCID: PMC10989376 DOI: 10.4251/wjgo.v16.i3.614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/28/2023] [Accepted: 01/16/2024] [Indexed: 03/12/2024] Open
Abstract
Solid pseudopapillary tumor of the pancreas (SPTP) is a rare neoplasm predominantly observed in young females. Pathologically, CTNNB1 mutations, β-catenin nuclear accumulation, and subsequent Wnt-signaling pathway activation are the leading molecular features. Accurate preoperative diagnosis often relies on imaging techniques and endoscopic biopsies. Surgical resection remains the mainstay treatment. Risk models, such as the Fudan Prognostic Index, show promise as predictive tools for assessing the prognosis of SPTP. Establishing three types of metachronous liver metastasis can be beneficial in tailoring individualized treatment and follow-up strategies. Despite advancements, challenges persist in understanding its etiology, establishing standardized treatments for unresectable or metastatic diseases, and developing a widely recognized grading system. This comprehensive review aims to elucidate the enigma by consolidating current knowledge on the epidemiology, clinical presentation, pathology, molecular characteristics, diagnostic methods, treatment options, and prognostic factors.
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Affiliation(s)
- Ye-Cheng Xu
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - De-Liang Fu
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Feng Yang
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai 200040, China
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Papadopoulos N, Hruban RH. Molecular Mechanisms of Cystic Neoplasia‐. THE PANCREAS 2023:630-637. [DOI: 10.1002/9781119876007.ch82] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Wang X, Zhu D, Bao W, Li M, Wang S, Shen R. Prognostic Enigma of Pancreatic Solid Pseudopapillary Neoplasm: A Single-Center Experience of 63 Patients. Front Surg 2021; 8:771587. [PMID: 34881287 PMCID: PMC8645639 DOI: 10.3389/fsurg.2021.771587] [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: 09/06/2021] [Accepted: 10/20/2021] [Indexed: 11/29/2022] Open
Abstract
Background: Studies investigating prognostic factors of solid pseudopapillary neoplasm (SPN) have been published with conflicting findings. Methods: Retrospective analysis of 63 consecutive cases of SPN in our institution from January 2010 to December 2019 was carried out. The clinicopathological features, treatment practices along with survival associations were collected and analyzed. Results: Fifteen patients (23.8%) were male, and 48 (76.2%) were female, with a median age of 34.0 ± 14.5 years. The larger tumor size was correlated with the more mixed components (p = 0.000) and the higher Ki-67 index (p = 0.042). No recurrence was found in the nine patients whose tumors fulfilled the WHO criteria for malignancy due to the presence of at least perineural invasion (6.4%), angiovascular invasion (2.3%), and/or adjacent organ invasion (6.4%). Microscopic infiltrative growth was detected in 9 (14.3%) tumors, which was correlated significantly with the WHO criteria (p = 0.002), capsule invasion (p = 0.005), and pancreatic parenchyma invasion (p = 0.001), but not with disease-free survival (p = 0.13). CD99 was found to be positively expressed in 88.9% (40/45) of tumors and more likely to have depressed Ki-67 index (p = 0.016). After a median follow-up of 58 months, only two patients (3.2%) had a recurrence after their first operation outside of our hospital. No patient died due to tumor progression. Conclusions: Although survival is favorable with aggressive surgery, it is actually difficult to assess the prognostic factors of resected SPNs. Future investigations into the role of clinicopathological evaluation will unveil the prognostic enigma of pancreatic SPN after resection.
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Affiliation(s)
- Xinbo Wang
- Research Institute of General Surgery, Jinling Hospital, Nanjing University Medical School, Nanjing, China
| | - Daojun Zhu
- Research Institute of General Surgery, Jinling Hospital, Nanjing University Medical School, Nanjing, China
| | - Wei Bao
- Department of Pathology, Jinling Hospital, Nanjing University Medical School, Nanjing, China
| | - Min Li
- Research Institute of General Surgery, Jinling Hospital, Nanjing University Medical School, Nanjing, China
| | - Sizhen Wang
- Research Institute of General Surgery, Jinling Hospital, Nanjing University Medical School, Nanjing, China
| | - Rongxi Shen
- Research Institute of General Surgery, Jinling Hospital, Nanjing University Medical School, Nanjing, China
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Shojaeepour S, Dabiri S, Dabiri B, Imani M, Fekri Soofi Abadi M, Hashemi F. Histopathological Findings of Testicular Tissue Following Cadmium Toxicity in Rats. IRANIAN JOURNAL OF PATHOLOGY 2021; 16:348-353. [PMID: 34567182 PMCID: PMC8463756 DOI: 10.30699/ijp.20201.130581.2443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 06/08/2021] [Indexed: 11/11/2022]
Abstract
Background & Objective: Reproductive toxicity of cadmium (Cd) as an environmental toxicant has been proved in animals and humans. Exposure to Cd impairs testes organs and can reduce male fertility. The present study was designed to investigate the spectrum of histopathological changes in testicular tissue focusing on Sertoli cells in rats following Cd intoxication. Methods: In the present experiment, acute testicular toxicity was induced by an intraperitoneal injection of 1.2 mg/kg CdCl2 to the animals in the test group, while the control group received normal saline. After 52 days, the animals were euthanized, and testicular tissue was stained by Hematoxylin and Eosin. In addition, immunohistochemical staining was performed on Sertoli cells for Wilms' Tumor, Melan-A, and CD99 to evaluate histopathological changes. Results: Cd caused significant alterations in seminiferous tubules with varying effects on the patterns of spermatozoa production. These histopathological changes were significantly higher in the Cd group, compared to the control group. Conclusion: The Cd-induced stepwise spectrum changes included sloughing, disorganization, hypospermatogenesis, spermatic cell arrest, germ cell hypoplasia, Sertoli cell-only pattern, fibro-hyalinized seminiferous tubules, and calcification. Sertoli cells accumulated and created multinucleated giant cells in the seminiferous tubules during the atrophic process, which could be dependent upon Sertoli cells viability and function.
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Affiliation(s)
- Saeedeh Shojaeepour
- Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Shahriar Dabiri
- Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Bahram Dabiri
- Department of Pathology, NYU Winthrop, Mineola NY, USA
| | - Masoud Imani
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
| | | | - Fatemeh Hashemi
- Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran
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Solid pseudo papillary tumor of the pancreas in a 7-year-old girl. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2021. [DOI: 10.1016/j.epsc.2021.101828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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La Rosa S, Bongiovanni M. Pancreatic Solid Pseudopapillary Neoplasm: Key Pathologic and Genetic Features. Arch Pathol Lab Med 2021; 144:829-837. [PMID: 31958381 DOI: 10.5858/arpa.2019-0473-ra] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2019] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor generally associated with a good prognosis. Solid pseudopapillary neoplasms show peculiar morphologic features, but sometimes the differential diagnosis with other pancreatic neoplasms (ie, pancreatic neuroendocrine tumors) can be a challenging task, especially in cytologic or biopsy specimens. In these cases immunohistochemistry is a useful tool, but the diagnostic utility of several proposed immunohistochemical markers is questionable. In recent years, despite several attempts to characterize the pathogenetic, molecular, and prognostic features of solid pseudopapillary neoplasms, they still remain unclear. OBJECTIVE.— To give the reader a comprehensive update on this entity. DATA SOURCES.— The PubMed database (US National Library of Medicine) was searched using the following string: pseudopapillary tumor [AND/OR] neoplasm [AND/OR] pancreas. All articles written in English were included. In addition, because a heterogeneous terminology has been used in the past to define solid pseudopapillary neoplasms, the reference lists of each paper selected in the PubMed database were also reviewed. CONCLUSIONS.— This review gives a comprehensive update on the pathologic, clinical, and molecular features of solid pseudopapillary neoplasms, particularly addressing issues and challenges related to diagnosis. In addition, we have tried to correlate the molecular alterations with the morphologic and clinical features.
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Affiliation(s)
- Stefano La Rosa
- From the Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland (Dr La Rosa); Synlab Swiss SA, Pathology, Lausanne, Switzerland (Dr Bongiovanni)
| | - Massimo Bongiovanni
- From the Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland (Dr La Rosa); Synlab Swiss SA, Pathology, Lausanne, Switzerland (Dr Bongiovanni)
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Chen H, Huang Y, Yang N, Yan W, Yang R, Zhang S, Yang P, Li N, Feng Z. Solid-Pseudopapillary Neoplasm of the Pancreas: A 63-Case Analysis of Clinicopathologic and Immunohistochemical Features and Risk Factors of Malignancy. Cancer Manag Res 2021; 13:3335-3343. [PMID: 33883945 PMCID: PMC8055352 DOI: 10.2147/cmar.s304981] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 03/26/2021] [Indexed: 01/17/2023] Open
Abstract
Purpose Solid-pseudopapillary neoplasm (SPN) of the pancreas, a rare tumor, has low malignant potential. However, some patients develop metastasis and recurrence after resection, with aggressive biological behaviors. This study aimed to explore the features and risk factors associated with the aggressive biological behaviors of SPNs. Patients and Methods We retrospectively analyzed the clinicopathological and long-term follow-up data of 63 patients diagnosed with SPN at the First Affiliated Hospital of Bengbu Medical College between January 2007 and February 2019. Results Sixty-three patients presented atypical clinical symptoms. The median tumor size was 7.0 cm (range, 2.4–17 cm), and imaging features were solid and cystic or solid tumors with uneven density. Frequent and diffuse nuclear LEF1 protein expression (94.2%) was observed with LEF1 having a higher sensitivity and specificity. Overall survival significantly correlated with tumor size, Ki-67 index, and lymph node metastasis (P < 0.05). Conclusion SPN is a rare low-grade malignancy with a specific pseudopapillary structure. LEF1 is an effective biomarker of SPNs. Although SPNs generally display indolent biological behavior, a large tumor size, high proliferation index, and lymph node metastasis may be risk factors for the aggressive behavior and poor prognosis of SPN.
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Affiliation(s)
- Hongchun Chen
- Department of Pathology, Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China.,Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China
| | - Yuchen Huang
- Department of Pathology, Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China.,Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China
| | - Ningning Yang
- Department of Pathology, Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China.,Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China
| | - Wentian Yan
- Department of Pathology, Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China.,Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China
| | - Ruxue Yang
- Department of Pathology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230000, People's Republic of China
| | - Shan Zhang
- Department of Pathology, Second People's Hospital of Hefei, Hefei, Anhui Province, 230000, People's Republic of China
| | - Panpan Yang
- Department of Pathology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230000, People's Republic of China
| | - Nan Li
- Department of Pathology, Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China.,Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China
| | - Zhenzhong Feng
- Department of Pathology, Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China.,Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China
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Ardengh JC, Lopes CV, Venco FE, Machado MA. Diagnosis of pancreatic solid pseudopapillary neoplasms using cell-blocks and immunohistochemical evaluation of endoscopic ultrasound-guided fine needle aspiration biopsy specimens. Cytopathology 2021; 32:50-56. [PMID: 32816310 DOI: 10.1111/cyt.12905] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 08/09/2020] [Accepted: 08/17/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Preoperative diagnostic imaging of pancreatic solid pseudopapillary neoplasms (SPNs) is challenging. A few studies have investigated the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the diagnosis of SPN. We investigated the diagnostic yield of cell-blocks and immunohistochemistry (IHC) for SPN using EUS-FNA specimens without cytological evaluation. PATIENTS AND METHODS We retrospectively analysed the histopathology records of patients with suspected SPN, who underwent EUS-FNA biopsy between January 1997 and January 2020. Diagnosis based on cell-blocks (haematoxylin-eosin staining with complementary IHC) was compared with the definitive surgical diagnosis. RESULTS This study included 25 patients (24 were women). Patients' mean age was 33.7 years (range 12-78 years). The most common symptom was abdominal pain. SPN was an incidental finding in 52% of the patients. The mean lesion size was 4.3 cm (range 1.2-11.4 cm), and the most common endosonographic features included solid-cystic (56%) or solid (40%) tumours. Final diagnoses included SPNs (n = 23) and non-functioning neuroendocrine tumours (n = 2). The overall accuracy of EUS-FNA was 80%. Tumour cells showed immunopositivity for β-catenin, CD10, CD99 and progesterone receptor (PR) in 93.7%, 87.5%, 83.3% and 66.6% of patients, respectively. No SPN showed immunopositivity for chromogranin A. CONCLUSIONS Intention-to-diagnose analysis showed that the diagnostic accuracy of EUS-FNA for SPNs using cell blocks and complementary IHC without cytological evaluation was fairly good. Evaluation of β-catenin, CD 10, CD99 and PR expression must be included in the IHC panel for diagnostic confirmation of SPNs using EUS-FNA biopsy specimens.
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Affiliation(s)
- José Celso Ardengh
- Division of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Endoscopy Unit, Hospital 9 de Julho, São Paulo, Brazil
| | - César Vivian Lopes
- Department of Gastroenterology and Digestive Endoscopy, Santa Casa Hospital, Porto Alegre, Brazil
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Din NU, Rahim S, Abdul-Ghafar J, Ahmed A, Ahmad Z. Clinicopathological and immunohistochemical study of 29 cases of solid-pseudopapillary neoplasms of the pancreas in patients under 20 years of age along with detailed review of literature. Diagn Pathol 2020; 15:139. [PMID: 33298094 PMCID: PMC7724627 DOI: 10.1186/s13000-020-01058-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 11/29/2020] [Indexed: 01/12/2023] Open
Abstract
Background Pancreatic Solid Pseudopapillary Neoplasms (SPNs) are rare low-grade malignant tumors with a marked preponderance for young females. Objective was to describe the morphology, differential diagnosis, and prognosis of SPNs in patients under 20 years of age and present a detailed review of literature. Methods A total of 29 cases in patients under 20 years of age reported as SPN during the period January 2014 to December 2019, were included in the study. These included 19 resection specimens, 4 incision biopsies and 6 cases received as blocks for second opinion. Hematoxylin and eosin (H&E) slides as well as immunohistochemistry (IHC) slides of all cases were retrieved and reviewed by the authors. TFE3 and Progesterone Receptor were performed retrospectively. Results Twenty-eight of the 29 patients were females. Ages of patients ranged from 12 to 19 years. Nineteen cases were resections. Tail was the commonest location. Mean tumor size was 9.5 cm. In 89.5% cases, tumor was confined to the pancreas. In 2 cases, distant metastasis was present. In 2 cases, extension beyond pancreas was seen. Solid and pseudopapillary areas were seen in all cases while other features were variable. Beta catenin and Cyclin D1 were positive in most cases while TFE3 was positive in 57% cases. Progesterone Receptor (PR) was positive in all 13 cases in which it was performed. Follow up was available in 14 patients. Follow up period ranged from 3 to 70 months. Twelve were alive and well without recurrence or metastasis while 2 were alive with recurrence and metastasis to liver and omentum respectively. Conclusions Although many studies on SPNs have been published, surgeons, oncologists and even pathologists in this part of the world are often not aware of these rare tumors leading to inaccuracies and delays in diagnosis. In addition, this paper focusses on the interesting observation that the majority of SPNs diagnosed in our department during study period occurred in patients under 20 years of age (29 versus 21 in patients over 20). However, clinico-epidemiological, morphologic and prognostic features were similar in both age groups. Possibility of SPNs should always be considered in case of pancreatic neoplasms occurring in patients under 20 years of age as well. We believe that this is a very interesting and helpful study for the clinicians as well as the pathologists.
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Affiliation(s)
- Nasir Ud Din
- Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Shabina Rahim
- Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Jamshid Abdul-Ghafar
- Department of Pathology and Clinical Laboratory, French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan.
| | - Arsalan Ahmed
- Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Zubair Ahmad
- Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan
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Signet ring cell-rich microcystic stromal tumor of the ovary: A poorly recognized variant. HUMAN PATHOLOGY: CASE REPORTS 2020. [DOI: 10.1016/j.ehpc.2020.200451] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Miller DL, Roy-Chowdhuri S, Illei P, James A, Hruban RH, Ali SZ. Primary pancreatic Ewing sarcoma: a cytomorphologic and histopathologic study of 13 cases. J Am Soc Cytopathol 2020; 9:502-512. [PMID: 32536453 DOI: 10.1016/j.jasc.2020.04.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 04/27/2020] [Accepted: 04/28/2020] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Ewing sarcoma (ES) is a small, round cell sarcoma that rarely occurs in solid organs, including the pancreas. A diagnostic overlap exists with other primary pancreatic neoplasms, especially for specimens from small biopsies and fine needle aspiration (FNA). To improve the diagnosis of this rare pancreatic tumor, we have reported a series of 13 cases of primary pancreatic ES and reviewed the cytopathologic, surgical pathology, clinical, and radiologic features of these neoplasms. MATERIALS AND METHODS We performed a retrospective case review of 13 patients with a diagnosis of pancreatic ES from 2 tertiary academic medical centers. A combination of cytology and histopathologic slides were reviewed, and the patient demographics, clinical information, somatic genetics, and radiologic findings were obtained from the electronic medical records. RESULTS Five FNA specimens from 5 patients and 8 surgical biopsy or resection specimens were identified and reviewed. The patients included 9 males and 4 females, with a median age of 27 years (range, 15-78 years). The cytology smears were highly cellular and showed a combination of complex tissue fragments and singly dispersed small round blue cells. The final diagnosis was ES for all 5 FNA specimens in accordance with the characteristic cytomorphology, diffuse and/or strong membranous immunolabeling for CD99, membranous β-catenin, and molecular confirmation of EWSR1 using fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction. CONCLUSIONS The cytologic diagnosis of ES is challenging, especially in unusual locations such as the pancreas. However, the correct cytologic diagnosis is important because these patients will require neoadjuvant therapy before surgery. Confirmatory molecular studies should be required to render the diagnosis of pancreatic ES.
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Affiliation(s)
- Daniel L Miller
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sinchita Roy-Chowdhuri
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Peter Illei
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Aaaron James
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ralph H Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Syed Z Ali
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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Chagas VL, Rosman FC, Carvalho MDGDC. Solid pseudopapillary neoplasia of the pancreas: a review. ACTA ACUST UNITED AC 2020; 66:87-94. [PMID: 32130387 DOI: 10.1590/1806-9282.66.1.87] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 09/01/2019] [Indexed: 01/20/2023]
Abstract
OBJECTIVES To review the literature and the diagnosis of conventional histopathological routine and immunohistochemistry of the cases diagnosed with Solid Pseudopapillary Neoplasm of the Pancreas (SPNP). METHODS The review of the literature was done using the Pubmed and solid Google-Scholar databases, through the historical, clinical aspects and diagnostic methods of SPNP. The review of SPNP cases diagnosed in the University Hospital Clementino Fraga Filho was carried out from 1977 to 2018. RESULTS Intratumoral phenotypic heterogeneity of SPNP was evidenced in the cases studied, taking into account macroscopic, microscopic, and immunohistochemical patterns. CONCLUSIONS The results show the importance of the examination of several fragments obtained from different regions of the neoplasia since not all of them present the same molecular alterations.
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Affiliation(s)
- Vera Lucia Chagas
- . Professora no Departamento de Patologias, Faculdade de Medicina do Hospital Clementino Fraga Filho da Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Fernando Colonna Rosman
- . Professor do Departamento de Patologias, Faculdade de Medicina do Hospital Clementino Fraga Filho da Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Maria da Gloria da Costa Carvalho
- . Pesquisadora no Departamento de Patologias, Faculdade de Medicina do Hospital Clementino Fraga Filho da Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
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SOX10 Dot-Like Paranuclear Positivity in Merkel Cell Carcinoma: Report of 2 Cases. Am J Dermatopathol 2019; 41:694-695. [DOI: 10.1097/dad.0000000000001230] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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15
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Heymann JJ, Siddiqui MT. Ancillary Techniques in Cytologic Specimens Obtained from Solid Lesions of the Pancreas: A Review. Acta Cytol 2019; 64:103-123. [PMID: 30970350 DOI: 10.1159/000497153] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 01/22/2019] [Indexed: 12/21/2022]
Abstract
Advanced methods of molecular characterization have elucidated the genetic, epigenetic, and proteomic alterations associated with the broad spectrum of pancreatic disease, particularly neoplasia. Next-generation sequencing, in particular, has revealed the genomic diversity among pancreatic ductal adenocarcinoma, neuroendocrine and acinar tumors, solid pseudopapillary neoplasm, and other pancreatico-biliary neoplasms. Differentiating these entities from one another by morphologic analysis alone may be challenging, especially when examining the small quantities of diagnostic material inherent to cytologic specimens. In order to enhance the sensitivity and specificity of pancreatic cytomorphology, multiple diagnostic, prognostic, and predictive ancillary tests have been and continue to be developed. Although a great number of such tests have been developed for evaluation of specimens collected from cystic lesions and strictures, ancillary techniques also play a significant role in the evaluation of cytologic specimens obtained from solid lesions of the pancreas. Furthermore, while some tests have been developed to differentiate diagnostic entities from one another, others have been developed to simply identify dysplasia and malignancy. Ancillary studies are particularly important in the subset of cases for which cytomorphologic analysis provides a result that is equivocal or insufficient to guide clinical management. Selection of appropriate ancillary testing modalities requires familiarity with both their methodology and the molecular basis of the pancreatic diseases for which testing is being performed.
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Affiliation(s)
- Jonas J Heymann
- Division of Cytopathology, Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital-Weill Cornell Medical College, New York, New York, USA,
| | - Momin T Siddiqui
- Division of Cytopathology, Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital-Weill Cornell Medical College, New York, New York, USA
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Chuah KL, Pang B, Lim D, Lee CK, Chau CYP. Combined hepatocellular carcinoma and high grade neuroendocrine carcinoma with EWSR1 gene rearrangement. Pathology 2018; 50:779-782. [DOI: 10.1016/j.pathol.2018.07.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 07/02/2018] [Accepted: 07/05/2018] [Indexed: 12/17/2022]
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Mei T, Zhang J, Wei L, Qi X, Ma Y, Liu X, Chen S, Li S, Wu J, Wang S. GLUT3 expression in cystic change induced by hypoxia in pituitary adenomas. Endocr Connect 2018; 7:1518-1527. [PMID: 30521480 PMCID: PMC6311462 DOI: 10.1530/ec-18-0444] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Accepted: 12/06/2018] [Indexed: 12/04/2022]
Abstract
Tumor cells require large amounts of energy to sustain growth. Through the mediated transport of glucose transporters, the uptake and utilization of glucose by tumor cells are significantly enhanced in the hypoxic microenvironment. Pituitary adenomas are benign tumors with high-energy metabolisms. We aimed to investigate the role of expression of glucose transporter 3 (GLUT3) and glucose transporter 1 (GLUT1) in pituitary adenomas, including effects on size, cystic change and hormone type. Pituitary adenomas from 203 patients were collected from January 2013 to April 2017, and immunohistochemical analysis was used to detect the expression of GLUT3 and GLUT1 in tumor specimens. GLUT3-positive expression in the cystic change group was higher than that in the non-cystic change group (P = 0.018). Proportions of GLUT3-positive staining of microadenomas, macroadenomas, and giant adenomas were 22.7 (5/22), 50.4 (66/131) and 54.0% (27/50), respectively (P = 0.022). In cases of prolactin adenoma, GLUT3-positive staining was predominant in cell membranes (P = 0.000006), while in cases of follicle-stimulating hormone or luteotropic hormone adenoma, we found mainly paranuclear dot-like GLUT3 staining (P = 0.025). In other hormonal adenomas, GLUT3 was only partially expressed, and the intensity of cell membrane or paranuclear punctate staining was weak. In contrast to GLUT3, GLUT1 expression was not associated with pituitary adenomas. Thus, our results indicate that the expression of GLUT3 in pituitary adenomas is closely related to cystic change and hormonal type. This study is the first to report a unique paranuclear dot-like GLUT3 staining pattern in pituitary adenomas.
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Affiliation(s)
- Tao Mei
- Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Jianhe Zhang
- Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China
| | - Liangfeng Wei
- Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China
| | - Xingfeng Qi
- Department of Pathology, Fuzhou General Hospital, Fuzhou, China
| | - Yiming Ma
- Department of Neurosurgery, Liuzhou General Hospital, Liuzhou, China
| | - Xianhua Liu
- Department of Pathology, Fuzhou General Hospital, Fuzhou, China
| | - Shaohua Chen
- Department of Pathology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Songyuan Li
- Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China
| | - Jianwu Wu
- Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China
| | - Shousen Wang
- Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China
- Correspondence should be addressed to S Wang:
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Kim EK, Jang M, Park M, Kim H. LEF1, TFE3, and AR are putative diagnostic markers of solid pseudopapillary neoplasms. Oncotarget 2017; 8:93404-93413. [PMID: 29212159 PMCID: PMC5706805 DOI: 10.18632/oncotarget.21854] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 09/23/2017] [Indexed: 12/11/2022] Open
Abstract
The diagnosis of solid pseudopapillary neoplasms (SPNs) is challenging because some SPNs share many similar morphological and immunohistochemical features with other pancreatic neoplasms. In this study, we investigated potential diagnostic markers of SPN. Based on the SPN-specific upregulated genes from a previous DNA microarray and proteome study, we selected six immunohistochemical markers [beta-catenin, androgen receptor (AR), lymphoid enhancer-binding factor 1 (LEF1), transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3), fused in sarcoma (FUS), and WNT inhibitory factor 1 (WIF-1)]. We also evaluated the Ki-67 proliferative index to investigate its associations with prognosis. To validate these markers, we studied 91 SPNs as well as 51 pancreatic ductal carcinomas (PDC) and 48 neuroendocrine tumors (NET) as controls. We found frequent and diffuse nuclear expressions of β-catenin (98.9%), AR (81.3%), LEF1 (93.4%), TFE3 (74.7%), FUS (84.6%), and cytoplasmic expression of WIF-1 (96.7%) in SPNs. In contrast, PDCs and NETs showed no expression. (P < 0.001). When beta-catenin, LEF1, and TFE3 staining were combined, the sensitivity and specificity were 100% and 91.9%, respectively. Four (4.4%) SPNs showed distant metastasis and these tumors were associated with a relatively high Ki-67 proliferative index (≥ 5%; P = 0.013). We identified LEF1, TFE3, and AR as putative diagnostic markers of SPN, auxiliary to β-catenin. Incorporated into an immunohistochemical panel, these markers could be beneficial to distinguish SPN from PDC and NET. In addition, we suggest that the Ki-67 proliferative index can be a predictive marker of metastasis in SPNs.
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Affiliation(s)
- Eun Kyung Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Mi Jang
- Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Minhee Park
- Departments of Pathology and Brain, Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hoguen Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Departments of Pathology and Brain, Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.,Healthcare Review and Assessment Committee, Health Insurance Review & Assessment Service, Seoul, Republic of Korea
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Hackeng WM, Hruban RH, Offerhaus GJA, Brosens LAA. Surgical and molecular pathology of pancreatic neoplasms. Diagn Pathol 2016; 11:47. [PMID: 27267993 PMCID: PMC4897815 DOI: 10.1186/s13000-016-0497-z] [Citation(s) in RCA: 86] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 05/28/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Histologic characteristics have proven to be very useful for classifying different types of tumors of the pancreas. As a result, the major tumor types in the pancreas have long been classified based on their microscopic appearance. MAIN BODY Recent advances in whole exome sequencing, gene expression profiling, and knowledge of tumorigenic pathways have deepened our understanding of the underlying biology of pancreatic neoplasia. These advances have not only confirmed the traditional histologic classification system, but also opened new doors to early diagnosis and targeted treatment. CONCLUSION This review discusses the histopathology, genetic and epigenetic alterations and potential treatment targets of the five major malignant pancreatic tumors - pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, acinar cell carcinoma and pancreatoblastoma.
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MESH Headings
- Biomarkers, Tumor/genetics
- Carcinoma, Acinar Cell/diagnosis
- Carcinoma, Acinar Cell/genetics
- Carcinoma, Acinar Cell/surgery
- Carcinoma, Pancreatic Ductal/diagnosis
- Carcinoma, Pancreatic Ductal/genetics
- Carcinoma, Pancreatic Ductal/surgery
- Eye Diseases, Hereditary/diagnosis
- Eye Diseases, Hereditary/genetics
- Eye Diseases, Hereditary/surgery
- Humans
- Neuroendocrine Tumors/diagnosis
- Neuroendocrine Tumors/genetics
- Neuroendocrine Tumors/surgery
- Optic Nerve Diseases/diagnosis
- Optic Nerve Diseases/genetics
- Optic Nerve Diseases/surgery
- Pancreas/pathology
- Pancreatic Neoplasms/diagnosis
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/surgery
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Affiliation(s)
- Wenzel M Hackeng
- Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Ralph H Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - G Johan A Offerhaus
- Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
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Chhadi TS, Deshpande AH, Chhadi SA, Kumbhalkar DT, Raut WK. A Solid Pseudopapillary Tumour of the Head of Pancreas: A Rare Case Report Diagnosed by Fine Needle Aspiration Cytology. J Clin Diagn Res 2016; 10:ED06-8. [PMID: 27504299 DOI: 10.7860/jcdr/2016/19456.7929] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 05/02/2016] [Indexed: 02/06/2023]
Abstract
Solid Pseudopapillary Tumour (SPPT) is a distinctive tumour of low malignant potential with a striking and unexplained predilection for adolescent girls and young women. Hence it is important to distinguish this rare tumour from other pancreatic tumours with similar cytomorphologic features because an accurate preoperative diagnosis is highly desirable since these patients can have long survival with adequate surgery. We report a case of the rare SPPT of the pancreas in a young girl who presented with nonspecific pain in the abdomen. Radiological investigations revealed a solid cystic mass in relation to the uncinate process of pancreas and third part of duodenum. The mass was diagnosed to be a solid pseudopapillary neoplasm of pancreas on ultrasound guided FNAC. Surgical removal of the pancreatic tumour and detailed histologic study confirmed the cytologic diagnosis. We present this case because, to date, there are few case reports on the cytological diagnosis of this tumour, about 60 cases, diagnosed by Fine-Needle Aspiration Cytology (FNAC) are reported in the literature. With widespread availability of high-quality imaging systems and a better understanding of its pathology, the number of cases reported in the literature has been steadily increasing in recent years. In our case, the cytological diagnosis was done even before the detailed imaging findings were available, the cytological features of this tumour are highly characteristic and it is possible to differentiate it from other pancreatic tumours with relative ease.
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Affiliation(s)
- Tulsi Shyam Chhadi
- Assistant Professor, Department of Pathology, Government Medical College , Nagpur, India
| | | | - Shyam Atmaram Chhadi
- Associate Professor, Department of Radiology, Government Medical College , Nagpur, India
| | - Dinkar T Kumbhalkar
- Professor, Department of Pathology, Government Medical College , Nagpur, India
| | - Waman K Raut
- Head of the Department, Department of Pathology, Government Medical College , Nagpur, India
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22
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Domínguez-Malagón HR, Michal M, Kazakov DV, Caro-Sánchez CH, Lino-Silva LS. Utility of CD99 Paranuclear Expression in the Differential Diagnosis of Merkel Cell Carcinoma. Int J Surg Pathol 2016; 24:293-296. [PMID: 26782152 DOI: 10.1177/1066896915623361] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
BACKGROUND Recent reviews have referred to the paranuclear dot-like staining pattern of CD99 in several neoplasms, including solid pseudopapillary tumors in the pancreas, colonic adenocarcinomas, and colonic adenomas as well as in Merkel cell carcinoma (MCC). The aim of this work was to explore the utility of CD99 paranuclear staining in the differential diagnosis of MCC. MATERIAL AND METHODS We explore paranuclear dot-like CD99 expression in several small, round blue cell neoplasms, including neuroendocrine neoplasms, Ewing sarcomas/primitive neuroectodermal tumors (EWS/PNET), melanomas, small cell lung carcinomas (SCC), lymphoblastic lymphoma/leukemia, and rhabdomyosarcomas, in comparison with 33 cases of MCC, to determine the specificity of the paranuclear dot-like CD99 expression in MCC. RESULTS Twenty MCC (60%) demonstrated focal expression of CD99 and of those, 14 (42.4%) showed the characteristic paranuclear dot-like expression. CD99 was also paranuclear positive in 4 of 11 (36%) SCC, in 3 of 7 (43%) EWS/PNET, in 1 of 6 (16%) lymphoblastic lymphoma/leukemia cases, in 3 of 3 (100%) rhabdomyosarcomas and all melanomas were negative for the CD99 reaction. CONCLUSION CD99 paranuclear dot-like expression was not exclusive of the MCC compared with several neoplasms included in its differential diagnosis. This expression is not a great diagnostic aid.
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Affiliation(s)
| | - Michal Michal
- Charles University Hospital Pilsen, Pilsen, Czech Republic
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Xie J, Zhu Y, Chen H, Shi M, Gu J, Zhang J, Shen B, Deng X, Zhan X, Peng C. The Immunohistochemical Evaluation of Solid Pseudopapillary Tumors of the Pancreas and Pancreatic Neuroendocrine Tumors Reveals ERO1Lβ as a New Biomarker. Medicine (Baltimore) 2016; 95:e2509. [PMID: 26765469 PMCID: PMC4718295 DOI: 10.1097/md.0000000000002509] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Solid pseudopapillary tumor of the pancreas (SPTP) is a class of low-grade malignant tumors that carry a favorable prognosis after surgery. Our group has reported that dysfunctions in the endoplasmic reticulum (ER) protein processing pathway may play a role in tumor development. However, alterations of this pathway in other pancreatic tumors had not been well investigated. In this study, we collected 35 SPTP and pancreatic neuroendocrine tumor (PNET) specimens and described the clinicopathological features of them. We performed immunohistochemistry (IHC) for 6 representative proteins (ERO1Lβ, TRAM1, GRP94, BIP, P4HB, and PDIA4) involved in the ER pathway in both SPTP and PNET specimens. We compared the IHC scoring results of tumors and matched normal pancreas tissues and demonstrated that these proteins were downregulated in SPTP specimens. Five of these proteins (TRAM1, GRP94, BIP, P4HB, and PDIA4) did not display significant changes between PNET and normal pancreas tissue. However, ERO1Lβ was upregulated in PNET tissues compared to the normal tissues, which could be used as a pathological biomarker in the future.
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Affiliation(s)
- Junjie Xie
- From the Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (JX, HC, JG, JZ, BS, XD, XZ, CP); Department of Surgery, The Second Affiliated Hospital of Zhejiang University, Hangzhou (YZ); and Research Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China (MS)
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Liu Z, Dong C, Wang C, Liu Q, Sun D, Wang L. Mixed acinar-endocrine carcinoma of pancreas: A case report and brief review of the literature. Onco Targets Ther 2015; 8:1633-42. [PMID: 26170699 PMCID: PMC4498721 DOI: 10.2147/ott.s87406] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Mixed acinar-endocrine carcinoma (MAEC) of the pancreas is a rare entity. We present a 65-year-old Chinese female who was admitted with jaundice and nagging epigastric pain with intermittent diarrhea for 1 month. She eventually underwent abdominal magnetic resonance imaging, which showed an 8×6 cm mass in the head of the pancreas and showed two abnormal lesions in the liver simultaneously. MAEC of the pancreas with synchronous hepatic metastasis was confirmed with immunohistochemistry after Whipple operation and hepatic partial resection of the lesions. Postoperative recovery of this patient was uneventful, and no evidence of recurrence or metastasis was observed after 12 months of follow-up. MAEC of pancreas is thought to be extremely rare and lack of typical clinical symptoms. The prognosis is poor overall, but early detection with complete resection may be beneficial to patients.
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Affiliation(s)
- Zhenzhen Liu
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People's Republic of China ; Dalian Medical University, Dalian, Liaoning Province, People's Republic of China
| | - Chengyong Dong
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People's Republic of China ; Dalian Medical University, Dalian, Liaoning Province, People's Republic of China
| | - Chengye Wang
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People's Republic of China ; Dalian Medical University, Dalian, Liaoning Province, People's Republic of China
| | - Qinlong Liu
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People's Republic of China
| | - Deguang Sun
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People's Republic of China
| | - Liming Wang
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People's Republic of China
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Bi R, Bai QM, Yang F, Wu LJ, Cheng YF, Shen XX, Cai X, Zhou XY, Yang WT. Microcystic stromal tumour of the ovary: frequent mutations of β-catenin (CTNNB1) in six cases. Histopathology 2015; 67:872-9. [PMID: 25913412 DOI: 10.1111/his.12722] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2015] [Accepted: 04/20/2015] [Indexed: 12/12/2022]
Abstract
AIMS To analyse the clinicopathological, immunohistochemical and β-catenin (CTNNB1) mutation characteristics of six cases of microcystic stromal tumour of the ovary (MCST). METHODS AND RESULTS Six Chinese patients with MCST who ranged in age from 29 to 69 years (mean 50 years) were included in the study. Five patients were detected with a pelvic mass during routine health examinations and one patient presented initially with opsomenorrhoea. All tumours involved the left ovary, with solid-cystic cut surface in five cases and cystic cut surface in one case. Microscopically, microcysts, solid nests and hyaline degenerated fibrous stroma were variably mixed. Immunohistochemically, the tumour cells in all cases were diffusely positive for CD10, vimentin and WT-1 and negative for α-inhibin and calretinin. β-catenin expression was observed in both the nucleus and the cytoplasm in five cases and only in the cytoplasm in one case. The results of CTNNB1 mutation analysis revealed four missense point mutations in four cases, which were c.97T>C, c.101G>A, c.110C>G and c.122C>T. CONCLUSIONS MCST shows a unique morphology with characteristic immunophenotype. β-catenin expression in the nucleus and β-catenin mutations were identified in the majority of cases, which suggests that the Wnt/β-catenin pathway may play a crucial role in the tumorigenesis of MCST.
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Affiliation(s)
- Rui Bi
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qian-Ming Bai
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Fei Yang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Li-Jing Wu
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yu-Fan Cheng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xu-Xia Shen
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xu Cai
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiao-Yan Zhou
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wen-Tao Yang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Lin F, Chen ZE, Wang HL. Utility of immunohistochemistry in the pancreatobiliary tract. Arch Pathol Lab Med 2015; 139:24-38. [PMID: 25549142 DOI: 10.5858/arpa.2014-0072-ra] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
CONTEXT Immunohistochemistry has become a useful ancillary study in the identification and classification of pancreatic neoplasms. The diagnostic accuracy has been significantly improved because of the continuous discoveries of tumor-associated biomarkers and the development of effective immunohistochemical panels. OBJECTIVES To identify and classify pancreatic neoplasms by immunohistochemistry. DATA SOURCES Literature review and authors' research data and personal practice experience were used. CONCLUSIONS To better guide therapeutic decisions and predict the prognostic outcome, it is crucial to make an accurate diagnosis of a pancreatic neoplasm. Application of appropriate immunohistochemical panels enables pathologists to differentiate pancreaticobiliary adenocarcinomas from reactive conditions and to identify rare types of pancreatic neoplasms. Knowing the utilities and pitfalls of each tumor-associated biomarker is essential to avoiding a potential diagnostic error because an absolutely cancer-specific biomarker does not exist. This article reviews frequently used tumor-associated biomarkers, provides lists of effective immunohistochemical panels, and recommends a diagnostic algorithm as a standard approach to pancreatic neoplasms.
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Affiliation(s)
- Fan Lin
- From the Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania (Drs Lin and Chen); and the Department of Pathology, University of California, Los Angeles (Dr Wang)
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Rishi A, Goggins M, Wood LD, Hruban RH. Pathological and molecular evaluation of pancreatic neoplasms. Semin Oncol 2014; 42:28-39. [PMID: 25726050 DOI: 10.1053/j.seminoncol.2014.12.004] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from the molecular and genetic perspectives.
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Affiliation(s)
- Arvind Rishi
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Michael Goggins
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Laura D Wood
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ralph H Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.
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Duodenum-preserving pancreatic head resection in solid pseudopapillary neoplasm-Report of a case. Int J Surg Case Rep 2014; 5:567-70. [PMID: 25105768 PMCID: PMC4201024 DOI: 10.1016/j.ijscr.2014.07.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Revised: 06/28/2014] [Accepted: 07/02/2014] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Solid pseudopapillary neoplasm (SPPN) was first characterized by Virginia Frantz in 1959. The duodenum-preserving pancreatic head resection (DPPHR) has been described as treatment for low-grade malignant tumors of the head of the pancreas including eight cases of SPPN. PRESENTATION OF CASE: A 16-year-old white female patient presented with abdominal pain and dyspepsia. Computed tomography scan of abdomen showed a 10 × 9 × 10 cm3 lesion on the pancreatic head. After radiological diagnosis of SPPN the patient was submitted to DPPHR. Resection was achieved with clear margins. Immunohistochemical study demonstrated positivity for progesterone receptor, β-catenin, cytoplasmic paranuclear dot-like CD99, negativity for chromogranin and S100 protein and Ki 67 index of 1%. DISCUSSION A large encapsulated pancreatic mass with well-defined borders that contains areas of calcifications and intratumoral hemorrhage on CT scan in a young female is virtually diagnostic of an SPPN. A particular dot-like intracytoplasmic expression of CD99 appears to be highly unique for SPPN CONCLUSION DPPHR should be considered in cases of SPPN in the pancreas head if there is no compromise with oncologic radicality.
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Zhu Y, Xu H, Chen H, Xie J, Shi M, Shen B, Deng X, Liu C, Zhan X, Peng C. Proteomic analysis of solid pseudopapillary tumor of the pancreas reveals dysfunction of the endoplasmic reticulum protein processing pathway. Mol Cell Proteomics 2014; 13:2593-603. [PMID: 24997997 DOI: 10.1074/mcp.m114.038786] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Solid pseudopapillary tumor of the pancreas (SPTP) is a low-grade malignant tumor with a favorable prognosis after surgery. Many previous studies have focused on clinical features or pathological biomarkers of the disease, but a better understanding of the molecular mechanisms underlying SPTP may help guide future therapeutic strategies. Here, we used isobaric tags for relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify differentially expressed proteins in SPTP specimens. A total of 1171 proteins with a threshold of a 1.5-fold change and a p value ≤ 0.05 between SPTP tissue and matched normal pancreas tissue were identified for bioinformatics analysis. Mass spectrometry results were then further confirmed by assessing six representative proteins (ACADL, EPHX2, MSI2, DKK4, JUP, and DAD1) in individual specimens with immunohistochemistry. Upon mapping of the differentially expressed proteins to the Kyoto Encyclopedia of Genes and Genomes pathways database, we found several new cell-adhesion molecules that could be used as pathologic biomarkers. Furthermore, we observed that many endoplasmic reticulum-associated proteins were altered, suggesting that endoplasmic reticulum stress may play an important role in SPTP tumorigenesis. Seven proteins (ERO1LB, TRIM1, GRP94, BIP, SEC61B, P4HB, and PDIA4) in this pathway were further validated by immunohistochemistry, and six of them (except SEC61B) coincided to the LC-MS/MS results. This first comprehensive analysis of the SPTP proteome confirms proteins that have been implicated in earlier reports and reveals novel candidates and pathways that could be investigated further for clinical applications.
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Affiliation(s)
- Yi Zhu
- From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Hong Xu
- §Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Hao Chen
- From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China;
| | - Junjie Xie
- §Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Minmin Shi
- From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Baiyong Shen
- From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Xiaxing Deng
- From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Chao Liu
- From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Xi Zhan
- From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Chenghong Peng
- From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China;
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Sanford Z, Israelsen S, Sehgal R, Cheung FH. Atypical growth on MRI in a case of Ewing's sarcoma despite lower SUV on PET. Skeletal Radiol 2014; 43:819-25. [PMID: 24352763 DOI: 10.1007/s00256-013-1779-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Revised: 10/23/2013] [Accepted: 11/06/2013] [Indexed: 02/02/2023]
Abstract
Ewing's sarcoma is a rare primary bone malignancy of small round blue cells. Treatment typically consists of neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy. The disease response to chemotherapy can be followed with fluorodeoxyglucose (FDG) positron emission tomography (PET), which measures the metabolic activity of the tumor, and by magnetic resonance imaging (MRI), which measures tumor size. We present a unique case in which the tumor grew in size following neoadjuvant chemotherapy but decreased in metabolic activity, making it difficult to judge efficacy of the chemotherapy. An atypical response to chemotherapy in this case caused tumor growth due to a fibrotic reaction while viable tumor cells were eradicated. This case highlights the ability of FDG-PET scan to identify the uncommon situation in which a tumor that increased in size may have had a favorable response to chemotherapy. This possibility should be considered in similar cases in which FDG-PET scan shows diminishing metabolic activity despite tumor growth.
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Affiliation(s)
- Zachary Sanford
- Joan C. Edwards School of Medicine (JCESOM), Marshall University, Huntington, WV, 25701, USA,
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Úrias U, Marie SKN, Uno M, da Silva R, Evagelinellis MM, Caballero OL, Stevenson BJ, Silva WA, Simpson AJ, Oba-Shinjo SM. CD99 is upregulated in placenta and astrocytomas with a differential subcellular distribution according to the malignancy stage. J Neurooncol 2014; 119:59-70. [PMID: 24797829 DOI: 10.1007/s11060-014-1462-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2013] [Accepted: 04/23/2014] [Indexed: 12/30/2022]
Abstract
In the present study, we searched for genes highly expressed in placenta and that could contribute to the establishment and maintenance of a malignant phenotype in different types of tumours, and in astrocytomas in particular. We employed a strategy based on the integration of in silico data from previously generated massively parallel signature sequencing and public serial analysis of gene expression databases. Among 12 selected genes, CD99 exhibited the highest relative mRNA expression in GBM compared to non-neoplastic brain tissues. In a larger cohort of astrocytic tumours, we further demonstrated increased CD99 expression in all malignant grades, with GBMs showing the highest values. These findings were confirmed at the protein level by Western blotting and immunohistochemistry. Additionally, we demonstrated the CD99 localisation profile in astrocytic tumours. Interestingly, CD99 expression was confined to the cytoplasm or membrane in more malignant astrocytomas, in contrast to non-neoplastic brain tissue or non-infiltrative pilocytic astrocytoma, which showed no obvious staining in these structures. Comparison of three GBM cell lines revealed higher CD99 expression at the membrane and higher migratory capacity in the A172 and U87MG lines, but lower CD99 expression and no migratory ability in the T98 line. Knocking down CD99 expression by siRNA decreased significantly the migration of both cell lines. These integrated CD99 gene and protein expression results suggest that CD99 expression in astrocytomas of different malignant grades might contribute to the infiltrative ability and support the importance of CD99 as a potential target to reduce infiltrative astrocytoma capacity in migration and invasion.
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Affiliation(s)
- Ursula Úrias
- Laboratory of Molecular and Cellular Biology, Department of Neurology, Faculdade de Medicina da, Universidade de São Paulo, São Paulo, SP, 01246-903, Brazil
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Bhatnagar R, Olson MT, Fishman EK, Hruban RH, Lennon AM, Ali SZ. Solid-pseudopapillary neoplasm of the pancreas: cytomorphologic findings and literature review. Acta Cytol 2014; 58:347-55. [PMID: 24969629 DOI: 10.1159/000363546] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Accepted: 05/08/2014] [Indexed: 01/17/2023]
Abstract
BACKGROUND Solid-pseudopapillary neoplasm (SPN) is a rare pancreatic malignancy with an excellent prognosis. It is most commonly diagnosed in young women. This article comprehensively reviews the clinical, pathological and radiological features of this neoplasm, as well as its clinical management. METHODS A literature review of SPN was performed of all articles published in the English language in PubMed prior to November 1, 2013. Cytomorphological features, histopathology, immunohistochemistry, patient general demographics, molecular studies, radiologic imaging and clinical management were reviewed. RESULTS SPN displays distinct cytomorphological features on fine-needle aspiration - thin, delicate, branching vessels in a 'Chinese character' pattern lined by one to several layers of loosely cohesive neoplastic cells. Nuclear features include indented or grooved nuclei with an evenly distributed chromatin pattern and small inconspicuous nucleoli. SPN is characteristically immunoreactive for CD10, β-catenin (in an abnormal nuclear pattern), CD99 in a perinuclear dot-like pattern, α1-antitrypsin, and progesterone receptor. Almost all SPNs harbor an activating point mutation in exon 3 of the β-catenin gene (CTNNB1). Clinicopathological features generally do not correlate with prognosis, and most patients experience excellent long-term survival. CONCLUSIONS SPN can mimic other neoplasms of the pancreas, which can lead to diagnostic challenges in a limited cytologic specimen. Distinct cytomorphological features can help distinguish SPNs from other pancreatic neoplasms. Complete surgical resection as well as resection of metastatic disease is preferred given a low rate of tumor recurrence and long periods of disease-free intervals.
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Affiliation(s)
- Ramneesh Bhatnagar
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Md., USA
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Ganeshan DM, Paulson E, Tamm EP, Taggart MW, Balachandran A, Bhosale P. Solid pseudo-papillary tumors of the pancreas: current update. ABDOMINAL IMAGING 2013; 38:1373-1382. [PMID: 23775388 DOI: 10.1007/s00261-013-0015-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Solid pseudo-papillary tumors are rare pancreatic tumors, which occur in females and are typically indolent neoplasms. However, atypical, aggressive variants can occur with locally advanced disease or metastases. They have characteristic imaging features, which vary according to size. This article provides a current update on the molecular biology, histopathology, clinico-radiological features, and management of these tumors.
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Affiliation(s)
- Dhakshina Moorthy Ganeshan
- Department of Diagnostic Imaging, Body Imaging section, Unit 1473, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030-4009, USA,
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Ghosh R, Mallik SR, Mathur SR, Iyer VK. CD 99 immunocytochemistry in solid pseudopapillary tumor of pancreas: A study on fine-needle aspiration cytology smears. J Cytol 2013; 30:151-5. [PMID: 24130404 PMCID: PMC3793349 DOI: 10.4103/0970-9371.117645] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Solid pseudopapillary tumor of pancreas (SPTP) is a rare pancreatic tumor of uncertain histogenesis usually affecting young women. Though these tumors have characteristic cytomorphology, it is sometimes difficult to differentiate them from neuroendocrine tumors of the pancreas. We reviewed cases of SPTP to delineate the diagnostic cytological features and also observed utility of CD 99 (MIC 2) immunostaining to aid in the diagnosis of this tumor. AIMS This study was designed to demonstrate the utility of CD 99 immunostaining along with cytological features for making a pre-operative diagnosis and delineating it from the neuroendocrine tumor of pancreas which is a close mimic. MATERIALS AND METHODS Cytomorphological features of 11 cases of solid pseudopapillary neoplasm diagnosed by pre-operative fine-needle aspiration cytology (FNAC) at our institute were reviewed. Immunocytochemistry for CD 99 was also performed on the smears. RESULTS All the cases had cellular smears with monomorphic cells lying singly, as loosely cohesive clusters as well as forming delicate pseudopapillae. Presence of intra and extra-cellular basement membrane material, background foamy macrophages and nuclear grooves were the other salient features. Immunocytochemistry for CD 99 could be performed on eight cases and demonstrated typical paranuclear dot-like positivity. CONCLUSIONS Pre-operative early diagnosis of SPTP can be made by FNAC which can further be aided by CD 99 immunocytochemistry.
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Affiliation(s)
- Ranajoy Ghosh
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
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36
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Luzar B, Calonje E. Paranuclear dot-like cytokeratin MNF116 positivity in cutaneous myoepithelioma. J Cutan Pathol 2013; 40:982-4. [PMID: 24102641 DOI: 10.1111/cup.12211] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2013] [Revised: 08/11/2013] [Accepted: 08/11/2013] [Indexed: 01/15/2023]
Affiliation(s)
- Boštjan Luzar
- Institute of Pathology, Medical Faculty University of Ljubljana, Ljubljana, Slovenia
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Solid pseudopapillary neoplasm of the pancreas in children: a 15-year experience and the identification of a unique immunohistochemical marker. J Pediatr Surg 2013; 48:2054-60. [PMID: 24094957 DOI: 10.1016/j.jpedsurg.2013.02.068] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2012] [Revised: 01/20/2013] [Accepted: 02/27/2013] [Indexed: 12/16/2022]
Abstract
PURPOSE To review our 15-year experience in the management of children with solid pseudopapillary neoplasm (SPPN) of the pancreas at a single pediatric institution, to delineate a unique immunohistochemical marker for SPPN, and to analyze cumulative data on this rare entity in the literature. METHODS We did a retrospective analysis of the demographic data, clinical presentation, immunohistochemical characteristics, surgical approach, and long-term outcomes of all patients diagnosed with SPPN between 1997 and 2012. RESULTS There were 6 patients in the series, 5 females and 1 male. Median age at presentation and at surgery was 15 years (11-18 years). Abdominal pain was the presenting symptom in 5 cases and jaundice in 1 case. Two patients had a pancreatic head tumor and underwent a pylorus-preserving pancreaticoduodenectomy. Two patients had the tumor in the pancreatic tail and underwent a distal pancreatectomy with splenectomy. Two patients had the tumor in the pancreatic body and underwent a distal pancreatectomy with splenectomy in one case and with preservation of the spleen in the other. All tumors were completely resected with pathologic margins free of disease. The median maximum diameter was 6.8 cm (3 to 15 cm). On immunohistochemistry the tumors exhibited different combinations of non-specific markers like chromogranin, vimentin and neuron-specific enolase, but all tumors showed the highly SPPN-specific paranuclear dot-like immunoreactivity pattern for CD99 in the solid as well as in the pseudopapillary areas. No patient had metastasis at presentation. Median follow-up was 6.5 years (6 months to 15 years). There were no recurrences, no long-term metastasis, and all patients are disease-free. CONCLUSION Our series supports the concept that complete resection is necessary to achieve the best possible long-term results. Additionally, we demonstrate that SPPN exhibits a very unique immunostaining pattern for CD99 that is present in all cases.
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Zhao P, deBrito P, Ozdemirli M, Sidawy MK. Solid-pseudopapillary neoplasm of the pancreas: Awareness of unusual clinical presentations and morphology of the clear cell variant can prevent diagnostic errors. Diagn Cytopathol 2013; 41:889-95. [DOI: 10.1002/dc.22989] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2012] [Accepted: 02/14/2013] [Indexed: 01/27/2023]
Affiliation(s)
- Po Zhao
- Department of Pathology; Georgetown University Hospital; Washington; District of Columbia
| | - Pedro deBrito
- Department of Pathology; Georgetown University Hospital; Washington; District of Columbia
| | - Metin Ozdemirli
- Department of Pathology; Georgetown University Hospital; Washington; District of Columbia
| | - Mary K. Sidawy
- Department of Pathology; Georgetown University Hospital; Washington; District of Columbia
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Huang SH, Wu SY, Chang KC. Paranuclear dot-like immunostaining of CD99 in rhabdomyosarcoma. Histopathology 2013; 62:814-6. [DOI: 10.1111/his.12063] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Shih-Hsuan Huang
- Department of Pathology; Kuang-Tien General Hospital; Taichung; Taiwan
| | - Shang-Yin Wu
- Department of Internal Medicine; National Cheng Kung University and Hospital; Tainan; Taiwan
| | - Kung-Chao Chang
- Department of Pathology; National Cheng Kung University and Hospital; Tainan; Taiwan
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40
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Samad A, Shah AA, Stelow EB, Alsharif M, Cameron SEH, Pambuccian SE. Cercariform cells: another cytologic feature distinguishing solid pseudopapillary neoplasms from pancreatic endocrine neoplasms and acinar cell carcinomas in endoscopic ultrasound-guided fine-needle aspirates. Cancer Cytopathol 2012; 121:298-310. [PMID: 23765692 DOI: 10.1002/cncy.21259] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2012] [Revised: 09/27/2012] [Accepted: 10/08/2012] [Indexed: 01/17/2023]
Abstract
BACKGROUND Solid pseudopapillary neoplasm (SPPN) is a rare tumor of unknown origin that occurs predominantly in the body or tail of the pancreas in young women. The authors recently identified cercariform (Greek: tailed) cells, similar to those described in urothelial carcinomas, as a consistent cytologic feature in ultrasound-guided fine-needle aspiration (EUS-FNA) samples from SPPNs. The objective of the current multi-institutional study was to define the value of these cells in the differential diagnosis of SPPN with other neoplasms characterized cytologically by the presence of monotonous, uniform cells in pancreatic aspirates: pancreatic neuroendocrine tumors (Pan-NETs) and acinar cell carcinomas (ACCs). METHODS The files of 4 academic hospitals were searched for SPPNs, Pan-NETs, and ACCs that were diagnosed by EUS-FNA. The slides were reviewed, and several cytologic features were recorded semiquantitatively to identify discriminating features between SPPNs, Pan-NETs, and ACCs. RESULTS From the analysis of 18 SPPNs, 4 ACCs, and 20 Pan-NETs, the following cytologic features were identified as common to all 3 neoplasms: single cells and rosettes/acinar cell groups, round-to-plasmacytoid cells, pale-to-granular cytoplasm, fine vacuoles, and binucleated cells. Papillary structures, cercariform cells, large cytoplasmic vacuoles, reniform nuclei, hyaline globules/magenta-colored material, and degenerative features (cholesterol crystals, calcifications, foam cells, or giant cells) were significantly more common in SPPNs. Prominent nuclear grooves were encountered in only 4 of 18 SPPNs. CONCLUSIONS The current results indicated that the presence of cercariform cells is another useful clue for the cytologic diagnosis of SPPN in challenging cases.
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Affiliation(s)
- Arbaz Samad
- Department of Laboratory Medicine and Pathology, University of Minnesota, University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota, USA
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Tamborini E, Rossi S, Tarantino E, Mauro V, Dei Tos AP, Pilotti S. Platelet-derived growth factor receptor alpha expression improves the diagnostic assessment of gastrointestinal stromal tumours. Histopathology 2012. [PMID: 23190090 DOI: 10.1111/j.1365-2559.2012.04345.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Rajagopalan A, Browning D, Salama S. CD99 expression in Merkel cell carcinoma: a case series with an unusual paranuclear dot-like staining pattern. J Cutan Pathol 2012; 40:19-24. [DOI: 10.1111/cup.12049] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2012] [Revised: 08/30/2012] [Accepted: 10/05/2012] [Indexed: 11/29/2022]
Affiliation(s)
- Ashwyn Rajagopalan
- Department of Pathology and Molecular Medicine; McMaster University; Hamilton; ON; Canada
| | - Debra Browning
- Department of Pathology; St. Joseph's Healthcare; Hamilton; ON; Canada
| | - Samih Salama
- Department of Pathology; St. Joseph's Healthcare; Hamilton; ON; Canada
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Kennedy SA, McEllistrem B, Kinsella A, Fan Y, Boyce S, Murphy K, McCarthy JF, Wood AE, Watson RWG. EuroSCORE and neutrophil adhesion molecules predict outcome post-cardiac surgery. Eur J Clin Invest 2012; 42:881-90. [PMID: 22448714 DOI: 10.1111/j.1365-2362.2012.02666.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND This study tested the hypothesis that surgical stress and the host response to this trauma trigger an inflammatory cascade in which the neutrophil plays a central role. We hypothesised that pre-operative neutrophil migratory responses will correlate with post-operative clinical outcome in our shock model of open-heart surgery patients. We also tested the hypothesis that surface expression of adhesion molecules involved in the migratory process - CD11b, CD47 and CD99 - could be used to predict outcome. We believe that combining neutrophil migratory response, CD11b, CD47 and CD99 with the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) will strengthen the power of the EuroSCORE not only in predicting post-operative mortality but also other clinical endpoints. MATERIALS AND METHODS Neutrophils were isolated pre-operatively from n = 31 patients undergoing open-heart surgery and allowed to migrate across endothelial monolayers in response to N-formyl-methionine-leucine-phenylalanine (fMLP). Isolated neutrophils were also assessed for surface expression of CD11b, CD47 and CD99 in response to fMLP by flow cytometry. Post-operative clinical parameters collected included days 1-5 white cell count and creatinine levels as well as intensive care unit (ICU) and post-operative hospital stay. RESULTS Pre-operative surface expression of CD99 and CD47 correlates with post-operative creatinine levels (P < 0·05), a measurement of renal injury. We also show that while the logistic EuroSCORE alone can be used as a predictor of ICU stay, when combined with pre-operative CD99 surface expression, it improves its AUC value (0·794). CONCLUSION Immunological markers, specifically the ability of the neutrophil to migrate, combined with the logistic EuroSCORE lead to improved sensitivity and specificity to predict patient outcome.
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Affiliation(s)
- Susan A Kennedy
- UCD School of Medicine and Medical Sciences, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
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Abstract
Cancer cells silence autosomal tumor suppressor genes by Knudson's two-hit mechanism in which loss-of-function mutations and then loss of heterozygosity occur at the tumor suppressor gene loci. However, the identification of X-linked tumor suppressor genes has challenged the traditional theory of 'two-hit inactivation' in tumor suppressor genes, introducing the novel concept that a single genetic hit can cause loss of tumor suppressor function. The mechanism through which these genes are silenced in human cancer is unclear, but elucidating the details will greatly enhance our understanding of the pathogenesis of human cancer. Here, we review the identification of X-linked tumor suppressor genes and discuss the potential mechanisms of their inactivation. In addition, we also discuss how the identification of X-linked tumor suppressor genes can potentially lead to new approaches in cancer therapy.
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Affiliation(s)
- Runhua Liu
- Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA
- Department of Genetics, School of Medicine, University of Alabama at Birmingham and Comprehensive Cancer Center, Birmingham, AL, USA
| | - Mandy Kain
- Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA
| | - Lizhong Wang
- Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA
- Department of Genetics, School of Medicine, University of Alabama at Birmingham and Comprehensive Cancer Center, Birmingham, AL, USA
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Navarro S, Ferrer J, Bombí JA, López-Boado MA, Ayuso JR, Ginés A, Fernández-Esparrach G, Vaquero E, Cuatrecasas M, Fernández-Cruz L. [Pseudopapillary solid tumor of the pancreas: report of 6 cases]. Med Clin (Barc) 2012; 138:114-8. [PMID: 22036462 DOI: 10.1016/j.medcli.2011.09.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2011] [Accepted: 09/06/2011] [Indexed: 10/15/2022]
Abstract
BACKGROUND AND OBJECTIVES Solid pseudopapillary neoplasms (SPNs) are rare tumours of the exocrine pancreas. Although they can develop metastasis, the prognosis is good. The aim of this study was to describe the characteristics of these tumours attended in our hospital. PATIENTS AND METHOD All cases of SPN in the database of the Pathology Department between 1991 and 2010 were included. Age, sex, symptoms, type of surgery, pathologic and immunohistochemical characteristics, and clinical evolution were analyzed. RESULTS Six cases were identified; all of them were women with a median age of 27.5 years. One patient presented haemoperitoneum, 2 abdominal pain and 3 were diagnosed incidentally. The most frequent localization was the pancreatic tail (n=4) and the median size was 7.7 cm. Four tumours were benign and 2 carcinomas. One of them had liver and lymph node metastases. Ki-67 proliferation index was low (1-3%). After a median follow-up of 33.5 months, all patients were alive and without evidence of relapse. CONCLUSION SPNs occur in young women. In most cases surgical resection is curative. A low mitotic index confers a good prognosis and a long survival.
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Affiliation(s)
- Salvador Navarro
- Servicio de Gastroenterología, Hospital Clínic, Universidad de Barcelona, IDIBAPS, CIBERehd, Barcelona, España.
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Paranuclear dot-like immunostaining for CD99: presence in colonic adenomas and adenocarcinomas. Am J Surg Pathol 2011; 35:1749-50. [PMID: 21997696 DOI: 10.1097/pas.0b013e31822bb546] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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