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1
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Wang H, Peng X, Li L, Yang Y. A retrospective study of imaging characteristics of mucinous tubular and spindle cell carcinoma in the kidney. Front Oncol 2025; 15:1515569. [PMID: 40182031 PMCID: PMC11965112 DOI: 10.3389/fonc.2025.1515569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 03/03/2025] [Indexed: 04/05/2025] Open
Abstract
Purpose To strengthen the recognition of mucinous tubular and spindle cell carcinomas of the kidney (MTSCC) by analyzing ultrasound and computed tomography findings. Materials and methods This study retrospectively enrolled eleven patients with pathologically confirmed mucinous tubular and spindle cell carcinomas from 2007 to 2022. The clinical, imaging, pathological features, and prognosis of all included patients were analyzed. All imaging features were evaluated in consensus by two genitourinary radiologists. Results All patients (48 ± 17 years, male to female, 3:8) presented with a solitary renal tumor with a mean diameter of 6.3 cm. Most of the lesions were located in the renal cortex. In ultrasonography, all 11 patients underwent conventional ultrasound and color Doppler flow imaging, and only three underwent contrast-enhanced ultrasound. In computed tomography (CT) examination, 8 of the 11 patients underwent plain CT and contrast-enhanced CT, and 1 patient underwent plain CT only. Grayscale ultrasound image demonstrated that most of the lesions were homogeneously hypoechoic with clear boundaries and regular shapes. Color Doppler flow imaging showed spotty blood flow in some cases. Contrast-enhanced ultrasound showed heterogeneous mild enhancement, and the contrast agent showed 'slow in and simultaneous/fast out' pattern. Plain CT showed equal or low density. CECT scanning showed slight heterogeneous enhancement in 6 patients, mild homogeneous enhancement in 2 patients. All lesions showed no hemorrhage, cystic degeneration or necrosis. Contrast-enhanced CT and contrast-enhanced ultrasound showed typical low-vascular tumors. Conclusion MTSCC are more common in middle-aged with a significant female preponderance. CT and ultrasound showed hypovascular tumors. Preoperative imaging diagnosis is difficult. It is necessary to distinguish from other hypovascular renal tumors.multimodal imaging may be helpful for preoperative diagnosis.
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Affiliation(s)
- Hong Wang
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaoyan Peng
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu, China
| | - Lutong Li
- West China Clinical Medical College of Sichuan University, West China Hospital of Sichuan University, Chengdu, China
| | - Yujia Yang
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu, China
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2
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Makker S, Shah NJ, Carlo MI, Kuo F, Hakimi AA, Chen YB, Iyer G, Kotecha RR. Immune Checkpoint Blockade Response in Mucinous Tubular and Spindle Cell Carcinoma. Curr Oncol 2025; 32:94. [PMID: 39996894 PMCID: PMC11854795 DOI: 10.3390/curroncol32020094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/30/2025] [Accepted: 02/05/2025] [Indexed: 02/26/2025] Open
Abstract
Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare kidney tumor which is usually characterized by indolent disease physiology. While several high-grade and sarcomatoid MTSCC tumors have been reported, the clinical experience with contemporary immune checkpoint blockade (ICB) combination therapies extrapolated from treatment paradigms of conventional renal cell carcinoma (RCC) remains limited. Here, we report two patients with metastatic MTSCC treated with first-line ipilimumab plus nivolumab therapy who both achieved great clinical benefit. We subsequently performed immune deconvolution analysis on previously identified MTSCC-like kidney tumors from The Cancer Genome Atlas (TCGA) and discovered significantly higher PD-L1 transcriptomic expression compared to similar papillary RCC tumors, providing additional biomarker data supporting the observed ICB response. These data implicate ICB therapy as an effective treatment for patients with metastatic MTSCC.
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Affiliation(s)
| | - Neil J. Shah
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (G.I.)
| | - Maria I. Carlo
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (G.I.)
| | - Fengshen Kuo
- Immunogenomics & Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - A. Ari Hakimi
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Ying-Bei Chen
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Gopa Iyer
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (G.I.)
| | - Ritesh R. Kotecha
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (G.I.)
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3
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Adeniran AJ, Shuch B, Humphrey PA. Sarcomatoid and Rhabdoid Renal Cell Carcinoma: Clinical, Pathologic, and Molecular Genetic Features. Am J Surg Pathol 2024; 48:e65-e88. [PMID: 38736105 DOI: 10.1097/pas.0000000000002233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2024]
Abstract
Renal cell carcinoma (RCC) with sarcomatoid and rhabdoid morphologies has an aggressive biological behavior and a typically poor prognosis. The current 2022 WHO classification of renal tumors does not include them as distinct histologic entities but rather as transformational changes that may arise in a background of various distinct histologic types of RCC. The sarcomatoid component shows malignant spindle cells that may grow as intersecting fascicles, which is reminiscent of pleomorphic undifferentiated sarcoma. The rhabdoid cells are epithelioid cells with eccentrically located vesicular nuclei with prominent nucleoli and large intracytoplasmic eosinophilic inclusions. Studies have shown that RCCs with sarcomatoid and rhabdoid differentiation have distinctive molecular features. Sarcomatoid RCC harbors shared genomic alterations in carcinomatous and rhabdoid components, but also enrichment of specific genomic alterations in the sarcomatoid element, suggesting molecular pathways for development of sarcomatoid growth from a common clonal ancestor. Rhabdoid differentiation also arises through clonal evolution although less is known of specific genomic alterations in rhabdoid cells. Historically, treatment has lacked efficacy, although recently immunotherapy with PD-1/PD-L1/CTLA-4 inhibitors has produced significant clinical responses. Reporting of sarcomatoid and rhabdoid features in renal cell carcinoma is required by the College of American Pathologists and the International Collaboration on Cancer Reporting. This manuscript reviews the clinical, pathologic, and molecular features of sarcomatoid RCC and rhabdoid RCC with emphasis on the morphologic features of these tumors, significance of diagnostic recognition, the molecular mechanisms of tumorigenesis and differentiation along sarcomatoid and rhabdoid lines, and advances in treatment, particularly immunotherapy.
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Affiliation(s)
| | - Brian Shuch
- Department of Urology, University of California Los Angeles, Los Angeles, CA
| | - Peter A Humphrey
- Department of Pathology, Yale University School of Medicine, New Haven, CT
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Ling C, Tan R, Li J, Feng J. Mucinous tubular and spindle cell carcinoma of the kidney: a report of seven cases. BMC Cancer 2023; 23:815. [PMID: 37649003 PMCID: PMC10470144 DOI: 10.1186/s12885-023-11252-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 08/03/2023] [Indexed: 09/01/2023] Open
Abstract
OBJECTIVE To further analyse the imaging features and tumour outcomes of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney. MATERIALS AND METHODS The current study retrospectively reviewed the clinical information of seven patients diagnosed with MTSCC at our institution from January 2011 to March 2023. RESULTS The median age at diagnosis was 52 years (range, 32-66 years) and the majority of patients were female (71.4%). On conventional abdominal ultrasound, the majority of the tumours (5/7) were heterogeneous hypoechoic or slightly hypoechoic. Colour Doppler flow imaging showed blood flow within the tumour in 2 cases and peripheral blood flow signal in 1 case. On non-enhanced CT, all tumours had a spherical or ovoid shape, with an expansile growth mode, and had clear or unclear boundaries with the surrounding renal parenchyma. The tumours were either partially exophytic (n = 4) or parenchymal (n = 3), while no cases of completely exophytic tumour was observed (n = 0). On contrast-enhanced CT, the majority of tumours (5/7) showed a heterogenous pattern of enhancement and the mean tumour diameter was 6.7 ± 4.4 cm (range, 2.1-16.8 cm). All patients underwent partial or radical nephrectomy for pT1a (42.9%), pT1b (28.5%), pT2 (14.3%) or pT3b (14.3%) stage. Among these, 1 patient (14.3%) had a level I tumour thrombus at diagnosis and died of disease 24.5 months later. The remaining patients had no recurrence or metastasis. CONCLUSION MTSCC is not universally indolent, which tends to occur in female patients of a broad range of ages. MTSCC is a hypovascular renal tumour, which is different from clear cell renal cell carcinoma (RCC); however, it is difficult to distinguish MTSCC from other hypovascular RCC subtypes because of the overlap of their imaging characteristics.
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Affiliation(s)
- Chunxiang Ling
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jingwu Road 324, Jinan, 250021, Shandong Provincial, China
| | - Ru Tan
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jingwu Road 324, Jinan, 250021, Shandong Provincial, China
| | - Jiamei Li
- Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jingwu Road 324, Jinan, 250021, Shandong Provincial, China
| | - Jizhen Feng
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jingwu Road 324, Jinan, 250021, Shandong Provincial, China.
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5
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Kang H, Xu W, Chang S, Yuan J, Bai X, Zhang J, Guo H, Ye H, Wang H. Mucinous tubular and spindle cell carcinomas of the kidney (MTSCC-Ks): CT and MR imaging characteristics. Jpn J Radiol 2022; 40:1175-1185. [PMID: 35644814 DOI: 10.1007/s11604-022-01294-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 05/07/2022] [Indexed: 10/18/2022]
Abstract
PURPOSE To strengthen the recognition of mucinous tubular and spindle cell carcinomas of the kidney (MTSCC-Ks) by analyzing CT and MR imaging findings of MTSCC-Ks. MATERIALS AND METHODS This study retrospectively enrolled ten patients with pathologically confirmed MTSCC-Ks from 2007 to 2020. The main observed imaging characteristics included growth pattern, signal characteristics on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), hemorrhage, necrosis, cystic degeneration, lipid component, pseudocapsule and the enhancement pattern. Apparent diffusion coefficient (ADC) value of MTSCC-Ks and normal renal cortex were measured, respectively. All imaging features were evaluated in consensus by two genitourinary radiologists. RESULTS All patients (53.1 ± 6.5 years, male to female, 3:7) presented with a solitary renal tumor with the mean diameter of 3.5 ± 0.4 cm. All lesions showed iso- or slight hypoattenuation on non-contrast CT with no hemorrhage but cystic degeneration (10%) and necrosis (10%). On T2WI, all lesions showed predominantly slight hypointensity with focal hyperintensity. The ADC value of MTSCC-Ks was 0.845 ± 0.017 × 10-3 mm2/s, and ADCtumor-to-ADCrenal cortex value was 0.376 ± 0.084. Pseudocapsules existed in all MTSCC-Ks on MRI. There were seven lesions showed heterogeneous enhancement, while three lesions showed homogeneous enhancement. Among them, six MTSCC-Ks showed slight multiple patchy enhancement (60%) in the corticomedullary phase, while the remaining MTSCC-Ks showed homogeneously slight enhancement (30%) or slightly stratified enhancement (10%). All MTSCC-Ks exhibited slow and progressive enhancement in the late phases. CONCLUSION Iso- or slight hypoattenuation on CT, slight hypointensity with focal hyperintensity on T2WI, marked diffusion restriction on DWI and ADC map, slight multiple patchy enhancement in the corticomedullary phase, and slow and progressive enhancement in the late phases are the imaging features of MTSCC-Ks, which may facilitate the diagnosis of MTSCC-Ks.
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Affiliation(s)
- Huanhuan Kang
- Medical School of Chinese PLA, Beijing, 100853, China.,Department of Radiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Wei Xu
- Department of Radiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Shuxiang Chang
- Department of Radiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Jing Yuan
- Department of Pathology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Xu Bai
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Jing Zhang
- Department of Radiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Huiping Guo
- Department of Radiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Huiyi Ye
- Department of Radiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Haiyi Wang
- Department of Radiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China.
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Paner GP, Chumbalkar V, Montironi R, Moch H, Amin MB. Updates in Grading of Renal Cell Carcinomas Beyond Clear Cell Renal Cell Carcinoma and Papillary Renal Cell Carcinoma. Adv Anat Pathol 2022; 29:117-130. [PMID: 35275846 DOI: 10.1097/pap.0000000000000341] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The World Health Organization (WHO) recommends grading of clear cell renal cell carcinoma (RCC) and papillary RCC using the WHO/International Society of Urological Pathology (ISUP) grade, which is primarily based on nuclear features. As the spectrum of RCC continues to evolve, with more recently described subtypes in the past decade, literature evidence on grading these subtypes is limited or not available for some tumor types. Herein, we outline a pragmatic approach to the topic of grading RCC, dividing the contemporarily described RCC subtypes into 7 categories based on the potential clinical applicability of grading as a useful prognostic parameter: (1) RCC subtypes that are reasonably validated and recommended for WHO/ISUP grading; (2) RCC subtypes where WHO/ISUP is not applicable; (3) RCC subtypes where WHO/ISUP grading is potentially clinically useful; (4) inherently aggressive RCC subtypes where histologic classification itself confers an aggressive biologic potential; (5) renal epithelial tumors where WHO/ISUP grading provides potentially misleading prognostic implication; (6) renal epithelial neoplasms where low WHO/ISUP grade features are a prerequisite for accurate histologic classification; and (7) renal epithelial neoplasms with no or limited data on grading or incomplete understanding of the biologic potential. Our aim in outlining this approach is 2-fold: (a) identify the gaps in understanding and application of grading in RCC subtypes so that researchers in the field may perform additional studies on the basis of which the important pathologic function of assignment of grade may be recommended to be performed as a meaningful exercise across a wider spectrum of RCC; and (b) to provide guidance in the interim to surgical pathologists in terms of providing clinically useful grading information in RCC based on currently available clinicopathologic information.
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Affiliation(s)
- Gladell P Paner
- Department of Pathology, University of Chicago
- Department of Surgery, Section of Urology, University of Chicago, Chicago, IL
| | | | - Rodolfo Montironi
- Molecular Medicine and Cell Therapy Foundation, Department of Clinical and Molecular Sciences, Polytechnic University of the Marche Region, Ancona, Italy
| | - Holger Moch
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
| | - Mahul B Amin
- Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN
- Department of Urology, USC Keck School of Medicine, Los Angeles, CA
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7
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Hasan N, Moatasim A. Mucinous tubular and spindle cell carcinoma with high-grade transformation: case report. SURGICAL AND EXPERIMENTAL PATHOLOGY 2022. [DOI: 10.1186/s42047-022-00105-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Mucinous tubular and spindle cell carcinoma (MTSCC) is a type of renal cell carcinoma (RCC) described as an entity with low-grade and low malignant potential. This report presents a high-grade transformation of MTSCC which is an uncommon finding in this subtype of RCC. Although most reported cases showed low malignant potential and good prognosis after surgical resection, a small subset of patients has been reported with aggressive phenotype and fatal outcome.
Case presentation
A case of a 23-year-old male is discussed with an incidental renal mass in the left kidney after a workup of bilateral flank pain. Morphologically, the tumor was composed of tubular structures lined by cuboidal cells mixed with spindle cells and sarcomatoid change was present in the tumor. Previously sarcomatoid change has been mostly reported along with conventional morphology in other common type of RCC with a worse prognosis.
Conclusions
The aim of this report is to draw the attention of pathologists and clinicians to the importance of high grade MTSCC owing to the unfavorable prognosis.
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8
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Xu H, Li W, Zhu C, Cheng N, Li X, Hao F, Zhu J, Huang L, Wang R, Wang L, Luo Z, Wang F. Proteomic profiling identifies novel diagnostic biomarkers and molecular subtypes for mucinous tubular and spindle cell carcinoma of the kidney. J Pathol 2022; 257:53-67. [PMID: 35043389 PMCID: PMC9311136 DOI: 10.1002/path.5869] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 01/08/2022] [Accepted: 01/12/2022] [Indexed: 11/30/2022]
Abstract
Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare renal epithelial neoplasm resembling type 1 papillary renal cell carcinoma (PRCC) morphologically and immunohistochemically. The accurate diagnosis of MTSCC remains a challenge. Here, by using proteomic profiling, we characterized MTSCC and PRCC to identify diagnostic biomarkers. We found that the MTSCC tumor proteome was significantly enriched in B‐cell‐mediated immunity when compared with the proteome of adjacent normal tissues of MTSCC or tumors of PRCC. Importantly, we identified MZB1, VCAN, and SOSTDC1 as diagnostic biomarkers to distinguish MTSCC from the solid variant of type 1 PRCC, with an AUC of 0.985 when combined. MZB1 was inversely correlated with tumor clinical stage and may play an anti‐tumor role by activating the complement system. Finally, unsupervised clustering revealed two molecular subtypes of MTSCC, displaying different morphology, expression signatures of oxidative phosphorylation, and aggravation. In summary, our analyses identified a three‐protein diagnostic panel and molecular subtypes for MTSCC. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Huiya Xu
- Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Wei Li
- Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Chongmei Zhu
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.,Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Na Cheng
- Department of Pathology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiaoxia Li
- Department of Pathology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Fengyun Hao
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Junfeng Zhu
- Department of Pathology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Liyun Huang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.,Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Ran Wang
- Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Liantang Wang
- Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zhenhua Luo
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Fen Wang
- Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
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Catalano F, Rebuzzi SE, Murianni V, Damassi A, Martelli V, Borea R, Rollandi GA, Fornarini G. Rare anti-VEGFR therapy-induced toxicity and long-term response to immunotherapy in a rare non-clear cell renal cell carcinoma patient. Anticancer Drugs 2022; 33:e724-e729. [PMID: 34261919 DOI: 10.1097/cad.0000000000001152] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Advanced non-clear cell renal cell carcinoma (nccRCC) has a poor prognosis and clinical data on the therapeutic options currently available, including immunotherapy, are generally limited highlighting an unmet clinical need. Moreover, the onset of rare adverse events raises the need of a better therapeutic management of limited treatment options. We report the clinical case of a 63-year-old man with the diagnosis of metastatic mucinous tubular and spindle cell carcinoma, a rare nccRCC, with sarcomatoid differentiation who developed two episodes of posterior reversible encephalopathy syndrome (PRES) to first-line sunitinib. It appeared after 5 months the start of the targeted therapy and reappeared at the reintroduction of the therapy. PRES is a rare and unusual adverse event to anti-vascular endothelial growth factor receptor (VEGFR) therapies, which is characterized by acute neurological disorders along with typical changes on neurological imaging, especially MRI. Moreover, this rare histotype of RCC experienced a long-term response to immunotherapy which is lasting more than 2 years. This clinical case is interesting for its rarity as a rare neurological adverse event developed twice in a rare type of RCC which also experienced an unusual long-term benefit to immunotherapy.
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Affiliation(s)
| | | | | | - Alessandra Damassi
- Academic Unit of Medical Oncology, IRCCS Ospedale Policlinico San Martino IST
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10
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Zhong M, Zhang Z, Qi W, Zhou Y, Lv G, Jiang X. OUP accepted manuscript. J Surg Case Rep 2022; 2022:rjac185. [PMID: 35495080 PMCID: PMC9048658 DOI: 10.1093/jscr/rjac185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 04/05/2022] [Indexed: 11/14/2022] Open
Abstract
Mucinous tubule and spindle cell carcinoma (MTSCC) of the kidney is a rare renal pleomorphic tumor considered as low-grade malignant, with occurring mainly in female. Few mucin-poor MTSCC cases have been reported so far. A typical MTSCC is composed of closely arranged tubules with pale mucus matrix and spindle cell components. Mucin-poor MTSCC is difficult to distinguish from other renal cell carcinomas due to small amount of mucus. We reported a case of mucin-poor MTSCC in a 37-year-old male with detailed imaging, histology, immunohistochemical and next-generation sequencing information, looking forward to providing an insight into mucin-poor MTSCC.
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Affiliation(s)
- Minglei Zhong
- Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China
| | - Zhaocun Zhang
- Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China
| | - Wenqiang Qi
- Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China
| | - Yongheng Zhou
- Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China
| | - Guangda Lv
- Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China
| | - Xianzhou Jiang
- Correspondence address. Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China. Tel: +86 18560083895; E-mail:
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11
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Agaimy A, Hartmann A, Trpkov K, Hes O. Undifferentiated and dedifferentiated urological carcinomas: lessons learned from the recent developments. Semin Diagn Pathol 2021; 38:152-162. [PMID: 34579992 DOI: 10.1053/j.semdp.2021.09.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 09/13/2021] [Indexed: 02/07/2023]
Abstract
Loss of the morphological and immunophenotypic characteristics of a neoplasm is a well-known phenomenon in surgical pathology and occurs across different tumor types in almost all organs. This process may be either partial, characterized by transition from well differentiated to undifferentiated tumor component (=dedifferentiated carcinomas) or complete (=undifferentiated carcinomas). Diagnosis of undifferentiated carcinoma is significantly influenced by the extent of sampling. Although the concept of undifferentiated and dedifferentiated carcinoma has been well established for other organs (e.g. endometrium), it still has not been fully defined for urological carcinomas. Accordingly, undifferentiated/ dedifferentiated genitourinary carcinomas are typically lumped into the spectrum of poorly differentiated, sarcomatoid, or unclassified (NOS) carcinomas. In the kidney, dedifferentiation occurs across all subtypes of renal cell carcinoma (RCC), but certain genetically defined RCC types (SDH-, FH- and PBRM1- deficient RCC) seem to have inherent tendency to dedifferentiate. Histologically, the undifferentiated component displays variable combination of four patterns: spindle cells, pleomorphic giant cells, rhabdoid cells, and undifferentiated monomorphic cells with/without prominent osteoclastic giant cells. Any of these may occasionally be associated with heterologous mesenchymal component/s. Their immunophenotype is often simple with expression of vimentin and variably pankeratin or EMA. Precise subtyping of undifferentiated (urothelial versus RCC and the exact underlying RCC subtype) is best done by thorough sampling supplemented as necessary by immunohistochemistry (e.g. FH, SDHB, ALK) and/ or molecular studies. This review discusses the morphological and molecular genetic spectrum and the recent develoments on the topic of dedifferentiated and undifferentiated genitourinary carcinomas.
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Affiliation(s)
- Abbas Agaimy
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital, Erlangen, Germany.
| | - Arndt Hartmann
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Kiril Trpkov
- Department of Pathology and Laboratory Medicine, Alberta Precision Labs and University of Calgary, Calgary, Alberta, Canada
| | - Ondrej Hes
- Department of Pathology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
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12
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Fuchizawa H, Kijima T, Takada‐Owada A, Nagashima Y, Okazaki A, Yokoyama M, Nishihara D, Ishida K, Kamai T. Metastatic mucinous tubular and spindle cell carcinoma of the kidney responding to nivolumab plus ipilimumab. IJU Case Rep 2021; 4:333-337. [PMID: 34497997 PMCID: PMC8413205 DOI: 10.1002/iju5.12342] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 06/12/2021] [Accepted: 06/16/2021] [Indexed: 11/20/2022] Open
Abstract
INTRODUCTION Mucinous tubular and spindle cell carcinoma is a rare subtype of renal cell carcinoma. Little is known regarding the efficacy of systemic therapy on its metastatic form because of its rarity. CASE PRESENTATION We present the case of a patient with metastatic mucinous tubular and spindle cell carcinoma who achieved durable complete remission of multiple osseous metastases after undergoing cytoreductive nephrectomy followed by combination immunotherapy (ipilimumab plus nivolumab). Immunohistochemical analyses of the primary tumor revealed the presence of the tumor-infiltrating immune cells, including activated CD8+ T cells and PD-L1 expression, suggesting an immunologically hot tumor. CONCLUSION Combination immunotherapy was a viable treatment option for this disease. Immunohistochemical analyses of the tumor-infiltrating immune cells predicted the efficacy of immune checkpoint inhibitors against rare renal cancers.
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Affiliation(s)
| | - Toshiki Kijima
- Department ofUrologyDokkyo Medical UniversityShimotsugaTochigiJapan
| | - Atsuko Takada‐Owada
- Department ofDiagnostic PathologyDokkyo Medical UniversityShimotsugaTochigiJapan
| | - Yoji Nagashima
- Department of Surgical PathologyTokyo Women’s Medical UniversityTokyoJapan
| | - Akihito Okazaki
- Department ofUrologyDokkyo Medical UniversityShimotsugaTochigiJapan
| | - Megumi Yokoyama
- Department ofUrologyDokkyo Medical UniversityShimotsugaTochigiJapan
| | | | - Kazuyuki Ishida
- Department ofDiagnostic PathologyDokkyo Medical UniversityShimotsugaTochigiJapan
| | - Takao Kamai
- Department ofUrologyDokkyo Medical UniversityShimotsugaTochigiJapan
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13
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Baniak N, Barletta JA, Hirsch MS. Key Renal Neoplasms With a Female Predominance. Adv Anat Pathol 2021; 28:228-250. [PMID: 34009777 DOI: 10.1097/pap.0000000000000301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Renal neoplasms largely favor male patients; however, there is a growing list of tumors that are more frequently diagnosed in females. These tumors include metanephric adenoma, mixed epithelial and stromal tumor, juxtaglomerular cell tumor, mucinous tubular and spindle cell carcinoma, Xp11.2 (TFE3) translocation-associated renal cell carcinoma, and tuberous sclerosis complex (somatic or germline) associated renal neoplasms. The latter category is a heterogenous group with entities still being delineated. Eosinophilic solid and cystic renal cell carcinoma is the best-described entity, whereas, eosinophilic vacuolated tumor is a proposed entity, and the remaining tumors are currently grouped together under the umbrella of tuberous sclerosis complex/mammalian target of rapamycin-related renal neoplasms. The entities described in this review are often diagnostic considerations when evaluating renal mass tissue on biopsy or resection. For example, Xp11.2 translocation renal cell carcinoma is in the differential when a tumor has clear cell cytology and papillary architecture and occurs in a young or middle-aged patient. In contrast, tuberous sclerosis complex-related neoplasms often enter the differential for tumors with eosinophilic cytology. This review provides an overview of the clinical, gross, microscopic, immunohistochemical, genetic, and molecular alterations in key renal neoplasms occurring more commonly in females; differential diagnoses are also discussed regardless of sex predilection.
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Affiliation(s)
- Nicholas Baniak
- Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Justine A Barletta
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Michelle S Hirsch
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
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14
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New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia. Mod Pathol 2021; 34:1392-1424. [PMID: 33664427 DOI: 10.1038/s41379-021-00779-w] [Citation(s) in RCA: 148] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 02/11/2021] [Accepted: 02/11/2021] [Indexed: 12/28/2022]
Abstract
The Genitourinary Pathology Society (GUPS) reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature. Key prognostic features for clear cell renal cell carcinoma (RCC) remain WHO/ISUP grade, AJCC/pTNM stage, coagulative necrosis, and rhabdoid and sarcomatoid differentiation. Accrual of subclonal genetic alterations in clear cell RCC including SETD2, PBRM1, BAP1, loss of chromosome 14q and 9p are associated with variable prognosis, patterns of metastasis, and vulnerability to therapies. Recent National Comprehensive Cancer Network (NCCN) guidelines increasingly adopt immunotherapeutic agents in advanced RCC, including RCC with rhabdoid and sarcomatoid changes. Papillary RCC subtyping is no longer recommended, as WHO/ISUP grade and tumor architecture better predict outcome. New papillary RCC variants/patterns include biphasic, solid, Warthin-like, and papillary renal neoplasm with reverse polarity. For tumors with 'borderline' features between oncocytoma and chromophobe RCC, a term "oncocytic renal neoplasm of low malignant potential, not further classified" is proposed. Clear cell papillary RCC may warrant reclassification as a tumor of low malignant potential. Tubulocystic RCC should only be diagnosed when morphologically pure. MiTF family translocation RCCs exhibit varied morphologic patterns and fusion partners. TFEB-amplified RCC occurs in older patients and is associated with more aggressive behavior. Acquired cystic disease (ACD) RCC-like cysts are likely precursors of ACD-RCC. The diagnosis of renal medullary carcinoma requires a negative SMARCB1 (INI-1) expression and sickle cell trait/disease. Mucinous tubular and spindle cell carcinoma (MTSCC) can be distinguished from papillary RCC with overlapping morphology by losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. MTSCC with adverse histologic features shows frequent CDKN2A/2B (9p) deletions. BRAF mutations unify the metanephric family of tumors. The term "fumarate hydratase deficient RCC" ("FH-deficient RCC") is preferred over "hereditary leiomyomatosis and RCC syndrome-associated RCC". A low threshold for FH, 2SC, and SDHB immunohistochemistry is recommended in difficult to classify RCCs, particularly those with eosinophilic morphology, occurring in younger patients. Current evidence does not support existence of a unique tumor subtype occurring after chemotherapy/radiation in early childhood.
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15
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Cimadamore A, Cheng L, Scarpelli M, Massari F, Mollica V, Santoni M, Lopez-Beltran A, Montironi R, Moch H. Towards a new WHO classification of renal cell tumor: what the clinician needs to know-a narrative review. Transl Androl Urol 2021; 10:1506-1520. [PMID: 33850785 PMCID: PMC8039604 DOI: 10.21037/tau-20-1150] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
In 1952, renal cell carcinomas had been divided into 2 categories—clear cell or granular cell—depending upon their cytoplasmic staining characteristics. In the following years, the inventory of renal epithelial tumors has expanded by the addition of tumors named by their architectural pattern (i.e., papillary RCC, tubulocystic RCC), anatomic location (i.e., collecting duct carcinoma, renal medullary carcinoma), associated diseases (i.e., acquired cystic disease-associated RCCs). With the extensive application of molecular diagnostic techniques, it becomes possible to detect genetic distinctions between various types of renal neoplasm and discover new entities, otherwise misdiagnosed or diagnosed as unclassified RCC. Some tumors such as ALK rearrangement-associated RCC, MiT family translocation renal carcinomas, SDH-deficient renal cancer or FH-deficient RCC, are defined by their molecular characteristics. The most recent World Health Organization (WHO) classification of renal neoplasms account for more than 50 entities and provisional entities. New entities might be included in the upcoming WHO classification. The aim of this review is to summarise and discuss the newly acquired data and evidence on the clinical, pathological, molecular features and on the prognosis of new RCC entities, which will hopefully increase the awareness and the acceptance of these entities among clinicians and improve prognostication for individual patients.
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Affiliation(s)
- Alessia Cimadamore
- Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Marina Scarpelli
- Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy
| | | | - Veronica Mollica
- Division of Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy
| | | | | | - Rodolfo Montironi
- Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy
| | - Holger Moch
- Department of Pathology and Molecular Pathology, University and University Hospital Zurich, CH-8091 Zurich, Switzerland
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16
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Yang C, Cimera RS, Aryeequaye R, Jayakumaran G, Sarungbam J, Al-Ahmadie HA, Gopalan A, Sirintrapun SJ, Fine SW, Tickoo SK, Epstein JI, Reuter VE, Zhang Y, Chen YB. Adverse histology, homozygous loss of CDKN2A/B, and complex genomic alterations in locally advanced/metastatic renal mucinous tubular and spindle cell carcinoma. Mod Pathol 2021; 34:445-456. [PMID: 32879414 PMCID: PMC7855055 DOI: 10.1038/s41379-020-00667-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 08/17/2020] [Accepted: 08/20/2020] [Indexed: 12/29/2022]
Abstract
Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma with characteristic histologic features and chromosomal alterations. Although typically indolent, a small subset of cases has been reported to exhibit aggressive clinical behavior. We retrospectively identified 33 patients with MTSCC, consisting of 10 cases of locally advanced/metastatic MTSCC (pT3 or N1 or M1) and 23 kidney-confined MTSCC (pT1/T2) without disease recurrence or progression. Utilizing a single-nucleotide polymorphism array and a targeted next-generation sequencing platform, we examined genome-wide molecular alterations in 24 cases, including 11 available samples from 8 patients with locally advanced/metastatic MTSCC. Ten patients with locally advanced/metastatic MTSCC were 8 females (80%) and 2 males (20%). At nephrectomy, 7 of these 10 cases (70%) were pT3 or pN1 while the remaining 3 (30%) were pT1/T2. Eight patients (80%) developed metastases and common sites included lymph node (4, 40%), bone (4, 40%), and retroperitoneum (3, 30%). Four patients died of disease (40%) during follow-up. Locally advanced/metastatic MTSCCs shared typical MTSCC genomic profiles with loss of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22, while some exhibited additional complex genomic alterations, most frequently a relative gain of 1q (7/8). Homozygous loss of CDKN2A/B was observed in 3 (38%) locally advanced/metastatic MTSCCs. Tumor necrosis, solid nested/sheet pattern, irregular trabecular/single-file infiltration in a desmoplastic stroma, lymphovascular space invasion, and increased mitotic activity were associated with locally advanced/metastatic MTSCCs (all p < 0.05). Our findings reveal that MTSCCs with aggressive clinical behavior have progressed through clonal evolution; CDKN2A/B deletion and additional complex genomic abnormalities may contribute to this process. Recognizing the morphologic presentation of high-grade MTSCC and evaluating adverse histologic features seen in these tumors can help establish a definitive diagnosis and stratify patients for treatment and prognostication.
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Affiliation(s)
- Chen Yang
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Robert S Cimera
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Ruth Aryeequaye
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Gowtham Jayakumaran
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Judy Sarungbam
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Hikmat A Al-Ahmadie
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Anuradha Gopalan
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - S Joseph Sirintrapun
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Samson W Fine
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Satish K Tickoo
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Jonathan I Epstein
- Departments of Pathology, Urology, and Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
| | - Victor E Reuter
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Yanming Zhang
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Ying-Bei Chen
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
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17
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Adamane SA, Menon S, Prakash G, Bakshi G, Joshi A, Popat P, Desai SB. Mucinous tubular and spindle cell carcinoma of the kidney: A case series with a brief review of the literature. Indian J Cancer 2020; 57:267-281. [PMID: 32675442 DOI: 10.4103/ijc.ijc_642_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Background Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare low grade renal tumour exhibiting characteristic morphological features. We share our experience and discuss briefly, a review of the current literature. Methods Electronic medical records were searched between January 2005 to January 2017. The histopathology and immunohistochemistry slides were retrieved and reviewed. Results Eleven cases of MTSCC were identified. Mean age at presentation was 53.9 (age range 41 to 71) years with a slight female preponderance (F: M=6:5). Clinical stage at presentation was: Stage I (4 cases), Stage II (3 cases), Stage III (1 case), and Stage IV (3 cases). The average tumour size was 7.5cm (range 3.5 to 17cm). Microscopically, characteristic biphasic tumour with tubular and spindle cell morphology with variable mucinous stroma was noted in all. The prominent immunohistochemical profile revealed positivity for CK7 (7/8, 87.5%), AMACR (6/8, 75%), AE1/3 (4/4, 100%), CD10 (3/10, 27.3%), and Vimentin (3/3, 100%). Seven patients (Stage I and II) had been treated with nephrectomy, whereas only a diagnostic biopsy was available in four patients who presented with locally advanced disease (n=1) or distant metastasis (n=3) at presentation. The mean follow-up was 37.8 months (range 8 to 96 months), available in 10 out of 11 patients, without recurrence in nine while one died 8 months after diagnosis. Conclusion MTSCC is an indolent renal cancer with characteristic morphology. However, presentation with locally advanced disease or distant metastasis may be seen in a subset of these patients. This warrants close follow-up in even localized tumors.
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Affiliation(s)
- Shraddha A Adamane
- Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Santosh Menon
- Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Gagan Prakash
- Department of Uro-oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Ganesh Bakshi
- Department of Uro-oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Amit Joshi
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Palak Popat
- Department of Radiology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Sangeeta B Desai
- Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
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18
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Gong P, Zhuang Q, Wang X, Xu R, Ding T, Yin S, He X. Mucinous tubular and spindle cell carcinoma of the kidney: Five case reports and review of the literature. Oncol Lett 2020; 20:337. [PMID: 33123248 PMCID: PMC7583836 DOI: 10.3892/ol.2020.12201] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 09/01/2020] [Indexed: 11/15/2022] Open
Abstract
Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare and polymorphic tumor, which has been previously considered to be a low-grade malignancy, predominantly occurring in women. To the best of our knowledge, MTSCC with bladder metastasis has never been reported. The current study presents five adult cases of MTSCC that included three male and two female patients. Among the male cases, two were of advanced stage, one with MTSCC and renal chromophobe cell carcinoma with bladder metastasis and the other with MTSCC with invasion of the renal vein. The other three cases with small masses were at an early stage. All five cases had a good prognosis and were without recurrence after several years of follow-up. A 70-year-old male with intermittent gross hematuria, intermittent renal colic, and groin radiation pain for a year (case 1), was incidentally detected to have a left renal density mass by total abdominal enhanced computed tomography scans. In the other four cases, renal masses were found by B-ultrasound. The patient in case 1 underwent a retroperitoneal laparoscopic radical nephroureterectomy with bladder cuff resection and transurethral resection of the bladder tumor, and received gemcitabine hydrochloride via intravesical instillation therapy plus cisplatin chemotherapy every 3 months. The patient in case 2 underwent an open left radical nephrectomy and renal pedicle lymph node dissection. The other three patients underwent a laparoscopic radical nephrectomy. All five patients had no recurrence or new metastasis in other organs after follow-up. In conclusion, the incidence of MTSCC in men and women is not as disparate as reported in previous publications. The characteristics of the images of the five adult cases in the present study showed a considerable consistency, with only minor differences. The malignancy and prognosis of MTSCC are still controversial, and thus inclusion and review of more cases is required to reach a definite final conclusion. Sunitinib and gemcitabine chemotherapy in combination with cisplatin may be effective for the therapy of MTSCC patients with metastasis, but a larger range of treatments needs to be identified.
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Affiliation(s)
- Pengfeng Gong
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003 P.R. China
| | - Qianfeng Zhuang
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003 P.R. China
| | - Xiaogang Wang
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003 P.R. China
| | - Renfang Xu
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003 P.R. China
| | - Tao Ding
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003 P.R. China
| | - Shuai Yin
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003 P.R. China
| | - Xiaozhou He
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003 P.R. China
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19
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Tretiakova MS. Renal Cell Tumors: Molecular Findings Reshaping Clinico-pathological Practice. Arch Med Res 2020; 51:799-816. [PMID: 32839003 DOI: 10.1016/j.arcmed.2020.08.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 08/11/2020] [Indexed: 02/07/2023]
Abstract
Over the past 20 years, the number of subtypes of renal epithelial cell neoplasia has grown. This growth has resulted from detailed histological and immunohistochemical characterization of these tumors and their correlation with clinical outcomes. Distinctive molecular phenotypes have validated the unique nature of many of these tumors. This growth of unique renal neoplasms has continued after the 2016 World Health Organization (WHO) Classification of Tumours. A consequence is that both the pathologists who diagnose the tumors and the clinicians who care for these patients are confronted with a bewildering array of renal cell carcinoma variants. Many of these variants have important clinical features, i.e. familial or syndromic associations, genomics alterations that can be targeted with systemic therapy, and benignancy of tumors previously classified as carcinomas. Our goal in the review is to provide a practical guide to help recognize these variants, based on small and distinct sets of histological features and limited numbers of immunohistochemical stains, supplemented, as necessary, with molecular features.
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Affiliation(s)
- Maria S Tretiakova
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
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20
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Williamson SR, Gill AJ, Argani P, Chen YB, Egevad L, Kristiansen G, Grignon DJ, Hes O. Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: III: Molecular Pathology of Kidney Cancer. Am J Surg Pathol 2020; 44:e47-e65. [PMID: 32251007 PMCID: PMC7289677 DOI: 10.1097/pas.0000000000001476] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Renal cell carcinoma (RCC) subtypes are increasingly being discerned via their molecular underpinnings. Frequently this can be correlated to histologic and immunohistochemical surrogates, such that only simple targeted molecular assays, or none at all, are needed for diagnostic confirmation. In clear cell RCC, VHL mutation and 3p loss are well known; however, other genes with emerging important roles include SETD2, BAP1, and PBRM1, among others. Papillary RCC type 2 is now known to include likely several different molecular entities, such as fumarate hydratase (FH) deficient RCC. In MIT family translocation RCC, an increasing number of gene fusions are now described. Some TFE3 fusion partners, such as NONO, GRIPAP1, RBMX, and RBM10 may show a deceptive fluorescence in situ hybridization result due to the proximity of the genes on the same chromosome. FH and succinate dehydrogenase deficient RCC have implications for patient counseling due to heritable syndromes and the aggressiveness of FH-deficient RCC. Immunohistochemistry is increasingly available and helpful for recognizing both. Emerging tumor types with strong evidence for distinct diagnostic entities include eosinophilic solid and cystic RCC and TFEB/VEGFA/6p21 amplified RCC. Other emerging entities that are less clearly understood include TCEB1 mutated RCC, RCC with ALK rearrangement, renal neoplasms with mutations of TSC2 or MTOR, and RCC with fibromuscular stroma. In metastatic RCC, the role of molecular studies is not entirely defined at present, although there may be an increasing role for genomic analysis related to specific therapy pathways, such as for tyrosine kinase or MTOR inhibitors.
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MESH Headings
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Renal Cell/diagnosis
- Carcinoma, Renal Cell/genetics
- Carcinoma, Renal Cell/metabolism
- Carcinoma, Renal Cell/pathology
- Humans
- Immunohistochemistry
- In Situ Hybridization, Fluorescence
- Kidney Neoplasms/diagnosis
- Kidney Neoplasms/genetics
- Kidney Neoplasms/metabolism
- Kidney Neoplasms/pathology
- Mutation
- Neoplasm Metastasis
- Neoplastic Syndromes, Hereditary/diagnosis
- Neoplastic Syndromes, Hereditary/genetics
- Neoplastic Syndromes, Hereditary/metabolism
- Neoplastic Syndromes, Hereditary/pathology
- Pathology, Clinical
- Pathology, Molecular
- Prognosis
- Societies, Medical
- Urology
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Affiliation(s)
- Sean R Williamson
- Department of Pathology and Laboratory Medicine and Henry Ford Cancer Institute, Henry Ford Health System
- Department of Pathology, Wayne State University School of Medicine, Detroit, MI
| | - Anthony J Gill
- NSW Health Pathology, Department of Anatomical Pathology
- Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards
- Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Pedram Argani
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ying-Bei Chen
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Lars Egevad
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
| | | | - David J Grignon
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN
| | - Ondrej Hes
- Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czechia
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21
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Miura K, Adachi Y, Shirahase T, Nagashima Y, Suemune K, Sakaida N, Nakano Y, Sakai Y, Shimizu S, Ikehara S. A case of high-grade mucinous tubular and spindle cell carcinoma. J Surg Case Rep 2020; 2020:rjaa014. [PMID: 32104563 PMCID: PMC7033487 DOI: 10.1093/jscr/rjaa014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 02/06/2020] [Indexed: 01/31/2023] Open
Abstract
Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal cell carcinoma that initially presents as low-grade renal cell carcinoma. However, cases of MTSCC with high-grade histology and poor prognosis have been reported. Here, we report a case of MTSCC with high-grade histological features and metastasis. A 77-year-old woman consulted a hospital following frequent and painful micturition. Computed tomography scan revealed a tumor of the left kidney. First, chemotherapy was performed, with no effects. Therefore, nephrectomy was subsequently performed. Histologically, the tumor showed the features of MTSCC with sarcomatoid component. Metastasis of the tumor into the lymph node was also observed. Although adjuvant chemotherapy was performed after nephrectomy, metastasis to the lungs and bone and local recurrence was observed. The patient is still alive 2 years after nephrectomy with metastasis and recurrence of the tumor. High-grade MTSCC shows a relatively poor prognosis, specifically MTSCC with metastasis upon nephrectomy.
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Affiliation(s)
- Koujin Miura
- Resident, Toyooka Hospital, Toyooka, Hyogo, Japan
| | - Yasushi Adachi
- Department of Diagnostic Pathology, Toyooka Hospital, Toyooka, Hyogo, Japan
| | | | - Yoji Nagashima
- Department of Surgical Pathology, Tokyo Women's Medical University Tokyo, Tokyo, Japan
| | | | - Noriko Sakaida
- Department of Pathology and Cytology Center, BML Group PCL Japan, Ibaraki, Osaka, Japan.,Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Yorika Nakano
- Department of Histopathology and Cytology, Japanese Red Cross Kyoto Daini Hospital, Kyoto City, Kyoto, Kyoto, Japan
| | - Yasuhiro Sakai
- Department of Diagnostic Pathology, Hyogo Cancer Center, Akashi, Hyogo, Japan
| | - Shigeki Shimizu
- Department of Pathology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Susumu Ikehara
- Department of Stem Cell Disorders, Kansai Medical University, Hirakata, Osaka, Japan
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22
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New and Emerging Subtypes of Renal Cell Carcinoma. KIDNEY CANCER 2020. [DOI: 10.1007/978-3-030-28333-9_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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23
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Major Subtypes of Renal Cell Carcinoma. KIDNEY CANCER 2020. [DOI: 10.1007/978-3-030-28333-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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24
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Alaghehbandan R, Perez Montiel D, Luis AS, Hes O. Molecular Genetics of Renal Cell Tumors: A Practical Diagnostic Approach. Cancers (Basel) 2019; 12:E85. [PMID: 31905821 PMCID: PMC7017183 DOI: 10.3390/cancers12010085] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Revised: 12/20/2019] [Accepted: 12/23/2019] [Indexed: 12/12/2022] Open
Abstract
Renal epithelial cell tumors are composed of a heterogeneous group of tumors with variable morphologic, immunohistochemical, and molecular features. A "histo-molecular" approach is now an integral part of defining renal tumors, aiming to be clinically and therapeutically pertinent. Most renal epithelial tumors including the new and emerging entities have distinct molecular and genetic features which can be detected using various methods. Most renal epithelial tumors can be diagnosed easily based on pure histologic findings with or without immunohistochemical examination. Furthermore, molecular-genetic testing can be utilized to assist in arriving at an accurate diagnosis. In this review, we presented the most current knowledge concerning molecular-genetic aspects of renal epithelial neoplasms, which potentially can be used in daily diagnostic practice.
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Affiliation(s)
- Reza Alaghehbandan
- Department of Pathology, Faculty of Medicine, University of British Columbia, Royal Columbian Hospital, Vancouver, BC V3E 0G9, Canada;
| | - Delia Perez Montiel
- Department of Pathology, Institute Nacional de Cancerologia, INCAN, Mexico DF 14080, Mexico;
| | - Ana Silvia Luis
- Department of Pathology, Centro Hospitalar de Vila Nova de Gaia-Espinho, Vila Nova de Gaia, Cancer Biology and Epigenetics Group (CBEG), IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), 4200-072 Porto, Portugal;
- Department of Microscopy, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4200-072 Porto, Portugal
| | - Ondrej Hes
- Department of Pathology, Charles University in Prague, Faculty of Medicine in Plzen, 304 60 Pilsen, Czech Republic
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25
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MacLennan GT, Cheng L. Five decades of urologic pathology: the accelerating expansion of knowledge in renal cell neoplasia. Hum Pathol 2019; 95:24-45. [PMID: 31655169 DOI: 10.1016/j.humpath.2019.09.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 09/06/2019] [Indexed: 02/07/2023]
Abstract
Those who are knowledgeable in cosmology inform us that the expansion of the universe is such that the velocity at which a distant galaxy is receding from the observer is continually increasing with time. We humbly paraphrase that as "The bigger the universe gets, the faster it gets bigger." This is an interesting analogy for the expansion of knowledge in the field of renal tumor pathology over the past 30 to 50 years. It is clear that a multitude of dedicated investigators have devoted incalculable amounts of time and effort to the pursuit of knowledge about renal epithelial neoplasms. As a consequence of the contributions of numerous investigators over many decades, the most recent World Health Organization classification of renal neoplasms includes about 50 well defined and distinctive renal tumors, as well as various miscellaneous and metastatic tumors. In addition, a number of emerging or provisional new entities are under active investigation and may be included in future classifications. In this review, we will focus on a number of these tumors, tracing as accurately as we can the origins of their discovery, relating relevant additions to the overall knowledge base surrounding them, and in some instances addressing changes in nomenclature.
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Affiliation(s)
- Gregory T MacLennan
- Department of Pathology and Laboratory Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH.
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
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26
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Ged Y, Chen YB, Knezevic A, Donoghue MTA, Carlo MI, Lee CH, Feldman DR, Patil S, Hakimi AA, Russo P, Voss MH, Motzer RJ. Mucinous Tubular and Spindle-Cell Carcinoma of the Kidney: Clinical Features, Genomic Profiles, and Treatment Outcomes. Clin Genitourin Cancer 2019; 17:268-274.e1. [PMID: 31151928 DOI: 10.1016/j.clgc.2019.04.006] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 03/13/2019] [Accepted: 04/09/2019] [Indexed: 11/17/2022]
Abstract
BACKGROUND Mucinous tubular and spindle-cell carcinoma (MTSCC) is a rare kidney cancer subtype with limited cases reported in the literature. We report on outcomes of 25 patients with this variant who were managed at our institution. MATERIALS AND METHODS The institution database was queried, and clinical data extracted for patients with MTSCC. Molecular features examined included next-generation sequencing with Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets and allele-specific copy number analysis using the Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) algorithm in a subset of patients. RESULTS All patients underwent primary tumor-directed therapy (nephrectomy = 23, cryoablation = 2). Metastases were diagnosed in 6 patients (24%), 3 (12%) of whom had de novo metastatic disease. Five of 6 patients with metastatic disease had high-grade histological features compared with 0 of 19 nonmetastatic patients (83% vs. 0%; P < .001, Fisher exact test). Three-year overall survival from diagnosis was 84.8% (95% confidence interval, 59.6-94.9) with a median follow-up time of 3.9 years (range, 1 month to 10.3 years). Three deaths occurred, all from metastatic disease. Four patients received systemic therapy with time to treatment failure ≤6 months across different agents with the exception of 1 patient with prolonged response with sunitinib treatment (30.6 months). The most frequent molecular alterations were neurofibromin 2 mutations (n = 2; 40%), germline alterations (n = 2; 40%) including checkpoint kinase 2 and BRCA2 DNA repair associated mutations, multiple chromosomal copy number losses, and mismatch repair deficiency in 1 patient. CONCLUSION MTSCC is characterized by localized tumors treated successfully with primary tumor-directed therapy. However, patients with high-grade histological features were more likely to develop metastatic disease with limited responses to standard therapies.
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Affiliation(s)
- Yasser Ged
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Ying-Bei Chen
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Andrea Knezevic
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Mark T A Donoghue
- Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Maria I Carlo
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Chung-Han Lee
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Darren R Feldman
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Sujata Patil
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - A Ari Hakimi
- Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Paul Russo
- Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Martin H Voss
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Robert J Motzer
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
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27
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Wang L, Zhang Y, Chen YB, Skala SL, Al-Ahmadie HA, Wang X, Cao X, Veeneman BA, Chen J, Cieślik M, Qiao Y, Su F, Vats P, Siddiqui J, Xiao H, Sadimin ET, Epstein JI, Zhou M, Sangoi AR, Trpkov K, Osunkoya AO, Giannico GA, McKenney JK, Argani P, Tickoo SK, Reuter VE, Chinnaiyan AM, Dhanasekaran SM, Mehra R. VSTM2A Overexpression Is a Sensitive and Specific Biomarker for Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of the Kidney. Am J Surg Pathol 2018; 42:1571-1584. [PMID: 30285995 PMCID: PMC7903805 DOI: 10.1097/pas.0000000000001150] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Our recent study revealed recurrent chromosomal losses and somatic mutations of genes in the Hippo pathway in mucinous tubular and spindle cell carcinoma (MTSCC). Here, we performed an integrative analysis of 907 renal cell carcinoma (RCC) samples (combined from The Cancer Genome Atlas and in-house studies) and the Knepper data set of microdissected rat nephrons. We identified VSTM2A and IRX5 as novel cancer-specific and lineage-specific biomarkers in MTSCC. We then assessed their expression by RNA in situ hybridization (ISH) in 113 tumors, including 33 MTSCC, 40 type 1 papillary RCC, 8 type 2 papillary RCC, 2 unclassified RCC, 15 clear cell RCC, and 15 chromophobe RCC. Sensitivity and specificity were calculated as the area under the receiver operating characteristics curve (AUC). All MTSCC tumors demonstrated moderate to high expression of VSTM2A (mean ISH score=255). VSTM2A gene expression assessed by RNA sequencing strongly correlated with VSTM2A ISH score (r(2)=0.81, P=0.00016). The majority of non-MTSCC tumors demonstrated negative or low expression of VSTM2A. IRX5, nominated as a lineage-specific biomarker, showed moderate to high expression in MTSCC tumors (mean ISH score=140). IRX5 gene expression assessed by RNA sequencing strongly correlated with IRX5 ISH score (r(2)=0.69, P=0.00291). VSTM2A (AUC: 99.2%) demonstrated better diagnostic efficacy than IRX5 (AUC: 87.5%), and may thus serve as a potential diagnostic marker to distinguish tumors with overlapping histology. Furthermore, our results suggest MTSCC displays an overlapping phenotypic expression pattern with the loop of Henle region of normal nephrons.
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MESH Headings
- Adenocarcinoma, Mucinous/genetics
- Adenocarcinoma, Mucinous/pathology
- Adult
- Aged
- Aged, 80 and over
- Animals
- Biomarkers, Tumor/genetics
- Canada
- Carcinoma, Papillary/genetics
- Carcinoma, Papillary/pathology
- Carcinoma, Renal Cell/genetics
- Carcinoma, Renal Cell/pathology
- Diagnosis, Differential
- Female
- Gene Expression Regulation, Neoplastic
- Homeodomain Proteins/genetics
- Humans
- In Situ Hybridization
- Kidney Neoplasms/genetics
- Kidney Neoplasms/pathology
- Loop of Henle/chemistry
- Male
- Membrane Proteins/genetics
- Middle Aged
- Neoplasm Grading
- Predictive Value of Tests
- Rats
- Reproducibility of Results
- Transcription Factors/genetics
- Tumor Burden
- United States
- Up-Regulation
- Young Adult
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Affiliation(s)
- Lisha Wang
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Yuping Zhang
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ying-Bei Chen
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Stephanie L. Skala
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Xiaoming Wang
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Xuhong Cao
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Brendan A. Veeneman
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Jin Chen
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Marcin Cieślik
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Yuanyuan Qiao
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Fengyun Su
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Pankaj Vats
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Javed Siddiqui
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Hong Xiao
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Evita T. Sadimin
- Department of Pathology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Jonathan I. Epstein
- Departments of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Ming Zhou
- Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Ankur R. Sangoi
- Department of Pathology, EI Camino Hospital, Mountain View, California, USA
| | - Kiril Trpkov
- Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Adeboye O. Osunkoya
- Departments of Pathology and Urology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Giovanna A. Giannico
- Departments of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Jesse K. McKenney
- Robert J Tomsich Pathology and Laboratory Medicine Institute, Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, USA
| | - Pedram Argani
- Departments of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Satish K. Tickoo
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Victor E. Reuter
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Arul M. Chinnaiyan
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA
- Department of Urology, University of Michigan, Ann Arbor, Michigan, USA
- Howard Hughes Medical Institute, Ann Arbor, Michigan, USA
| | - Saravana M. Dhanasekaran
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Rohit Mehra
- Michigan Center for Translational Pathology, Ann Arbor, Michigan, USA
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA
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28
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Ren Q, Wang L, Al-Ahmadie HA, Fine SW, Gopalan A, Sirintrapun SJ, Tickoo SK, Reuter VE, Chen YB. Distinct Genomic Copy Number Alterations Distinguish Mucinous Tubular and Spindle Cell Carcinoma of the Kidney From Papillary Renal Cell Carcinoma With Overlapping Histologic Features. Am J Surg Pathol 2018; 42:767-777. [PMID: 29462091 PMCID: PMC6685145 DOI: 10.1097/pas.0000000000001038] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare type of renal cell carcinoma that frequently exhibits histologic and immunophenotypic features overlapping with type 1 papillary renal cell carcinoma (PRCC). To clarify molecular attributes that can be used for this difficult differential diagnosis, we sought to delineate the genome-wide copy number alterations in tumors displaying classic histologic features of MTSCC in comparison to the solid variant of type 1 PRCC and indeterminate cases with overlapping histologic features. The study included 11 histologically typical MTSCC, 9 tumors with overlapping features between MTSCC and PRCC, and 6 cases of solid variant of type 1 PRCC. DNA samples extracted from macrodissected or microdissected tumor areas were analyzed for genome-wide copy number alterations using an SNP-array platform suitable for clinical archival material. All cases in the MTSCC group exhibited multiple chromosomal losses, most frequently involving chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22, while lacking trisomy 7 or 17. In contrast, cases with overlapping morphologic features of MTSCC and PRCC predominantly showed multiple chromosomal gains, most frequently involving chromosomes 7, 16, 17, and 20, similar to the chromosomal alteration pattern that was seen in the solid variant of type 1 PRCC cases. Morphologic comparison of these molecularly characterized tumors identified histologic features that help to distinguish MTSCC from PRCC, but immunohistochemical profiles of these tumors remained overlapping, including a marker for Hippo-Yes-associated protein signaling. Characteristic patterns of genome-wide copy number alterations strongly support MTSCC and PRCC as distinct entities despite their immunohistochemical and certain morphologic overlap, and help define histologic features useful for the classification of questionable cases.
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MESH Headings
- Adenocarcinoma, Mucinous/chemistry
- Adenocarcinoma, Mucinous/genetics
- Adenocarcinoma, Mucinous/pathology
- Adult
- Aged
- Biomarkers, Tumor/analysis
- Biomarkers, Tumor/genetics
- Carcinoma, Renal Cell/chemistry
- Carcinoma, Renal Cell/genetics
- Carcinoma, Renal Cell/pathology
- DNA Copy Number Variations
- Diagnosis, Differential
- Female
- Gene Dosage
- Gene Expression Profiling/methods
- Genetic Predisposition to Disease
- Humans
- Immunohistochemistry
- Kidney Neoplasms/chemistry
- Kidney Neoplasms/genetics
- Kidney Neoplasms/pathology
- Male
- Middle Aged
- Oligonucleotide Array Sequence Analysis
- Phenotype
- Polymorphism, Single Nucleotide
- Predictive Value of Tests
- Retrospective Studies
- Young Adult
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Affiliation(s)
- Qinghu Ren
- Department of Pathology, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
| | - Lu Wang
- Department of Pathology, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
| | - Hikmat A. Al-Ahmadie
- Department of Pathology, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
| | - Samson W. Fine
- Department of Pathology, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
| | - Anuradha Gopalan
- Department of Pathology, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
| | | | - Satish K. Tickoo
- Department of Pathology, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
| | - Victor E. Reuter
- Department of Pathology, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
| | - Ying-Bei Chen
- Department of Pathology, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
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29
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Sadimin ET, Chen YB, Wang L, Argani P, Epstein JI. Chromosomal abnormalities of high-grade mucinous tubular and spindle cell carcinoma of the kidney. Histopathology 2017; 71:719-724. [DOI: 10.1111/his.13298] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 06/23/2017] [Indexed: 11/28/2022]
Affiliation(s)
- Evita T Sadimin
- Department of Pathology; Rutgers Cancer Institute of New Jersey; New Brunswick NJ USA
| | - Ying-Bei Chen
- Department of Pathology; Memorial Sloan Kettering Cancer Center; New York NY USA
| | - Lu Wang
- Department of Pathology; Memorial Sloan Kettering Cancer Center; New York NY USA
| | - Pedram Argani
- Department of Pathology and Oncology; Johns Hopkins Medical Institutions; Baltimore MD USA
| | - Jonathan I Epstein
- Department of Pathology, Urology and Oncology; Johns Hopkins Medical Institutions; Baltimore MD USA
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30
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Uchida S, Suzuki K, Uno M, Nozaki F, Li CP, Abe E, Yamauchi T, Horiuchi S, Kamo M, Hattori K, Nagashima Y. Mucin-poor and aggressive mucinous tubular and spindle cell carcinoma of the kidney: Two case reports. Mol Clin Oncol 2017; 7:777-782. [PMID: 29075488 PMCID: PMC5649005 DOI: 10.3892/mco.2017.1400] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Accepted: 08/28/2017] [Indexed: 11/16/2022] Open
Abstract
Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare renal epithelial neoplasm. Although MTSCC is considered to be a low-grade and indolent neoplasm, aggressive cases have been recently reported. The present study discussed two additional cases of high-grade MTSCC causing multiple distant metastases with a fatal course. In case 1, a 71-year-old patient presented with hematuria and pyuria. Computed tomography (CT) scan of the right kidney revealed a mass lesion, for which partial nephrectomy was performed. However, a follow-up CT imaging revealed distant metastases in the liver, the paraaortic lymph nodes and the bone. Despite molecular targeted therapy and irradiation, the patient succumbed due to tumor progression. In case 2, a 64-year-old patient presented with an incidentally identified mass lesion in the right kidney. A laparoscopic nephrectomy was performed, and a follow-up CT imaging revealed metastases in the skin and lungs. The cytology of pleural effusion revealed pleuritis carcinomatosa. Histologically, both cases were diagnosed as mucin-poor MTSCC with high-grade transformation, which comprised uniform tumor cells primarily forming slender tubules. The tumors contained low- and high-grade regions. In addition, venous invasion and necrosis were observed. The tumor cells also demonstrated increased Ki-67 labeling indices and cellular tumor antigen p53 (p53) nuclear accumulation. High-grade transformation, large tumor size, necrosis, venous invasion, high Ki-67 labeling index and p53 nuclear accumulation are generally predictive findings for aggressive behavior of malignant tumors. In the current report, it was emphasized that MTSCC possesses a wide spectrum of clinicopathological features. Thus, careful postoperative investigation is required for MTSCC with high-grade elements due to its aggressive nature.
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Affiliation(s)
- Shiro Uchida
- Department of Diagnostic Pathology, St. Luke's International Hospital, Tokyo, Japan
| | - Koyu Suzuki
- Department of Diagnostic Pathology, St. Luke's International Hospital, Tokyo, Japan
| | - Mieko Uno
- Department of Diagnostic Pathology, St. Luke's International Hospital, Tokyo, Japan
| | - Fumi Nozaki
- Department of Diagnostic Pathology, St. Luke's International Hospital, Tokyo, Japan
| | - Chih-Ping Li
- Department of Pathology, Saitama Medical University, Saitama, Japan
| | - Eriko Abe
- Department of Diagnostic Pathology, St. Luke's International Hospital, Tokyo, Japan
| | - Teruo Yamauchi
- Department of Internal Medicine, Division of Medical Oncology, St. Luke's International Hospital, Tokyo, Japan
| | - Saya Horiuchi
- Department of Radiology, St. Luke's International Hospital, Tokyo, Japan
| | - Minobu Kamo
- Department of Radiology, St. Luke's International Hospital, Tokyo, Japan
| | - Kazunori Hattori
- Department of Urology, St. Luke's International Hospital, Tokyo, Japan
| | - Yoji Nagashima
- Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo, Japan
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31
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Ziouani O, Elalaoui A, Elbote H, Belhabib S, El Sayegh H, Iken A, Benslimane L, Zouaidia F, Nouini Y. [Mucinous tubular and spindle cell carcinoma: a rare renal tumor]. Pan Afr Med J 2017; 26:187. [PMID: 28674580 PMCID: PMC5483371 DOI: 10.11604/pamj.2017.26.187.10456] [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: 08/02/2016] [Accepted: 03/10/2017] [Indexed: 11/26/2022] Open
Abstract
Le carcinome tubulo-mucineux et fusiforme désigne une tumeur rare décrite dans la classification OMS 2004 comme une nouvelle entité. Elle est reconnue de comportement relativement indolent. Nous rapportons l'observation d'une femme âgée de 60 ans qui présentait des douleurs lombaires, et chez qui la tomodensitométrie a révélé la présence d'une masse rénale gauche mesurant 55 x 40 mm. La patiente a été traitée par néphrectomie partielle gauche dont l'examen macroscopique a montré la présence d'une tumeur bien limitée d'aspect charnu avec des remaniements hémorragiques et nécrotiques. L'étude histologique a confirmé le carcinome tubulo-mucineux et à cellules fusiformes de bas grade. L'immunohistochimie a révélé une positivité à la cytokératine (CK 7 et CK 19) et à l'antigène des membranes épithéliales (EMA), et une négativité au CD10. L'évolution était favorable avec un recul de 6 mois. Mucinous tubular and spindle cell carcinoma is a rare tumor defined in the 2004 WHO classification as a new entity. It is characterized by a relatively indolent behavior We report the case of a 60-year old woman presenting with lumbar pain. CT scan showed left renal mass measuring 55 x 40 mm. The patient underwent left partial nephrectomy. Macroscopic examination showed a well limited fleshy tumor with hemorrhagic or necrotic elements. Histological examination confirmed low grade mucinous tubular and spindle cell carcinoma. Immunohistochemistry revealed cytokeratin positive cells (CK 7 and CK 19), epithelial membrane antigen positive cells (EMA), and CD10-negativity cells. Patient's evolution was favorable, with a follow-up period of 6 months.
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Affiliation(s)
| | | | - Hicham Elbote
- Service d'Urologie A, Hôpital Ibn Sina, CHU Rabat, Maroc
| | - Salwa Belhabib
- Service d'Anatomie Pathologique, Hôpital Ibn Sina, CHU Rabat, Maroc
| | | | - Ali Iken
- Service d'Urologie A, Hôpital Ibn Sina, CHU Rabat, Maroc
| | | | - Fouad Zouaidia
- Service d'Anatomie Pathologique, Hôpital Ibn Sina, CHU Rabat, Maroc
| | - Yassine Nouini
- Service d'Urologie A, Hôpital Ibn Sina, CHU Rabat, Maroc
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32
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Abstract
The fourth edition of the World Health Organization (WHO) report was published in January 2016 and focused especially on the kidney tumors and several new concepts. Many steps forward in the subclassification have been taken. Several new entities have been added, as major progress on a genetic level has been made. Some already well-known entities have new prognosis in accordance with longer follow up and research, and some concepts of well-known groups have been refined.
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Affiliation(s)
- Eva Compérat
- Service d'anatomie et cytologie pathologique, Hôpital Tenon, UPMC Paris VI, Paris.
| | - Justine Varinot
- Service d'anatomie et cytologie pathologique, Hôpital Tenon, UPMC Paris VI, Paris
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33
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Mikami H, Endo Y, Yanagi M, Nemoto K, Hamasaki T, Kimura G, Suzuki Y, Kondo Y. [LAPAROSCOPIC LYMPHADENECTOMY FOR POSTOPERATIVE LYMPH-NODE METASTASIS OF RENAL MUCINOUS TUBULAR AND SPINDLE CELL CARCINOMA: A CASE REPORT]. Nihon Hinyokika Gakkai Zasshi 2017; 108:30-34. [PMID: 29367506 DOI: 10.5980/jpnjurol.108.30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
We describe renal mucinous tubular and spindle cell carcinoma (MTSCC) that metastasized to the lymph nodes seven years after radical nephrectomy. An 80-year-old man was admitted for treatment of a right renal tumor. A 6.5×6.0-cm tumor in the right kidney (cT1bN0M0) revealed by abdominal computed tomography was treated by laparoscopic radical nephrectomy. The pathological findings at that time suggested papillary renal cell carcinoma type 1. Imaging findings seven years later revealed enlarged pre-caval and right external iliac lymph nodes indicative of delayed metastasis, and these were treated by laparoscopic lymphadenectomy. The pathological findings and re-evaluation of the primary tumor suggested MTSCC. The patient remains free of metastasis at 24 months of follow-up. MTSCC has been a distinct entity in the World Health Organization classification of kidney tumors since 2004. Tumors consist of tubules and cords separated by pale mucinous material in some areas, whereas others have dense cellularity without significant mucin. They are usually of low malignant potential, and metastasis has rarely been reported. To our knowledge, this is the first report of MTSCC with retroperitoneal lymph node metastasis treated by lymphadenectomy.
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Affiliation(s)
- Hikaru Mikami
- The Department of Urology, Nippon Medical School Chiba Hokusou Hospital
| | - Yuki Endo
- The Department of Urology, Nippon Medical School
| | - Masato Yanagi
- The Department of Urology, Nippon Medical School Chiba Hokusou Hospital
| | - Kaoru Nemoto
- The Department of Urology, Nippon Medical School Chiba Hokusou Hospital
| | | | - Go Kimura
- The Department of Urology, Nippon Medical School
| | - Yasutomo Suzuki
- The Department of Urology, Nippon Medical School Chiba Hokusou Hospital
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34
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Hirsch MS, Signoretti S, Dal Cin P. Adult Renal Cell Carcinoma: A Review of Established Entities from Morphology to Molecular Genetics. Surg Pathol Clin 2016; 8:587-621. [PMID: 26612217 DOI: 10.1016/j.path.2015.09.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
According to the current World Health Organization (WHO), renal cell carcinomas (RCCs) that primarily affect adults are classified into 8 major subtypes. Additional emerging entities in renal neoplasia have also been recently recognized and these are discussed in further detail by Mehra et al (Emerging Entities in Renal Neoplasia, Surgical Pathology Clinics, 2015, Volume 8, Issue 4). In most cases, the diagnosis of a RCC subtype can be based on morphologic criteria, but in some circumstances the use of ancillary studies can aid in the diagnosis. This review discusses the morphologic, genetic, and molecular findings in RCCs previously recognized by the WHO, and provides clues to distinction from each other and some of the newer subtypes of RCC. As prognosis and therapeutic options vary for the different subtypes of RCC, accurate pathologic distinction is critical for patient care.
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Affiliation(s)
- Michelle S Hirsch
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
| | - Sabina Signoretti
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Paola Dal Cin
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
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Ananthakrishnan L, Kapur P, Leyendecker JR. The spectrum of renal cell carcinoma in adults. Abdom Radiol (NY) 2016; 41:1052-65. [PMID: 27108133 DOI: 10.1007/s00261-016-0737-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The spectrum of renal cell carcinoma (RCC) includes many neoplasms with distinct cytogenetics, biologic behaviors, and imaging appearances. The advent of molecular therapies targeting different tumor types, new insights into the relative roles of biopsy and surveillance for small incidental tumors, and a growing array of nephron-sparing interventions have altered management of RCC. Similarly, the role of the radiologist is changing, and it is becoming increasingly important for radiologists to familiarize themselves with the various types of RCC. This article introduces the reader to the common and uncommon recognized types of renal cell carcinoma and discusses how these neoplasms differ in imaging appearance and behavior.
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36
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The 2012 ISUP Vancouver and 2016 WHO classification of adult renal tumors: changes for common renal tumors. ACTA ACUST UNITED AC 2016. [DOI: 10.1016/j.mpdhp.2016.01.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Unusual Case of Coexisting Renal Malignancies: Mucinous Tubular and Spindle Cell Carcinoma Kidney With Sarcomatoid Dedifferentiation. J Kidney Cancer VHL 2016; 3:8-13. [PMID: 28326279 PMCID: PMC5347374 DOI: 10.15586/jkcvhl.2016.51] [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: 02/19/2016] [Accepted: 05/03/2016] [Indexed: 11/18/2022] Open
Abstract
Mucinous tubular and spindle cell carcinoma (MTSCC) is a recent entity introduced in the World Health Organization 2004 Classification. It is a tumour of low malignant potential. MTSCC is a subtype of renal cell carcinoma (RCC), which is characterized by a polymorphous histology, wherein the spindled epithelial cell is an inherent carcinomatous component. We report the case of a 57-year-old man presenting with loin pain and dragging sensation. Imaging revealed a large mass arising from the left kidney. Radical nephrectomy was performed, and histopathology revealed spindle cell elements of MTSCC with low-grade cytology, which occasionally blended with tubular structures in variable mucinous stroma admixed with spindle sarcomatoid cells with marked nuclear pleomorphism, associated with significant necrosis and mitoses of up to 5/10 high-power field. A final diagnosis of MTSCC along with high-grade areas consistent with sarcomatoid dedifferentiation was made. Sarcomatoid dedifferentiation has been well documented in various subtypes of RCC, and its presence signifies a worse prognosis in RCC.
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Zhao M, He XL, Teng XD. Mucinous tubular and spindle cell renal cell carcinoma: a review of clinicopathologic aspects. Diagn Pathol 2015; 10:168. [PMID: 26377921 PMCID: PMC4573286 DOI: 10.1186/s13000-015-0402-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2015] [Accepted: 08/28/2015] [Indexed: 02/03/2023] Open
Abstract
Mucinous tubular and spindle cell renal cell carcinoma is a rare, recently described variant of renal cell carcinoma characterized by an admixture of cuboidal cells in tubules and sheets of spindle cells, and variable amounts of mucinous stroma. It has been recognized as a distinct entity in the 2004 World Health Organization tumor classification. Since then, several dozen of these tumor have been reported with additional complementary morphologic characteristics, immunohistochemical profile, and molecular genetic features that have further clarified its clinicopathologic aspects. Although originally considered as a low grade renal cell carcinoma on the basis of its bland appearing nuclear features and indolent clinical course, mucinous tubular and spindle cell renal cell carcinoma has currently been proven to be a tumor that has a histological spectrum ranging from low to high grade that includes sarcomatoid differentiation. In this review, we present a detailed summary of the current knowledge regarding the clinicopathologic, immunohistochemical, molecular genetic, and prognostic characteristics, as well as differential diagnoses of mucinous tubular and spindle cell renal cell carcinoma.
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Affiliation(s)
- Ming Zhao
- Depatment of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
| | - Xiang-Lei He
- Depatment of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, China.
| | - Xiao-Dong Teng
- Department of Pathology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, 310003, China.
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Peckova K, Martinek P, Sperga M, Montiel DP, Daum O, Rotterova P, Kalusová K, Hora M, Pivovarcikova K, Rychly B, Vranic S, Davidson W, Vodicka J, Dubová M, Michal M, Hes O. Mucinous spindle and tubular renal cell carcinoma: analysis of chromosomal aberration pattern of low-grade, high-grade, and overlapping morphologic variant with papillary renal cell carcinoma. Ann Diagn Pathol 2015; 19:226-31. [PMID: 26009022 DOI: 10.1016/j.anndiagpath.2015.04.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Accepted: 04/30/2015] [Indexed: 11/27/2022]
Abstract
The chromosomal numerical aberration pattern in mucinous tubular and spindle renal cell carcinoma (MTSRCC) is referred to as variable with frequent gains and losses. The objectives of this study are to map the spectrum of chromosomal aberrations (extent and location) in a large cohort of the cases and relate these findings to the morphologic variants of MTSRCC. Fifty-four MTSRCCs with uniform morphologic pattern were selected (of 133 MTSRCCs available in our registry) and divided into 3 groups: classic low-grade MTSRCC (Fuhrman nucleolar International Society of Urological Pathology grade 2), high-grade MTSRCC (grade 3), and overlapping MTSRCC with papillary renal cell carcinoma (RCC) morphology. Array comparative genomic hybridization analysis was applied to 16 cases in which DNA was well preserved. Four analyzable classic low-grade MTSRCCs showed multiple losses affecting chromosomes 1, 4, 8, 9, 14, 15, and 22. No chromosomal gains were found. Four analyzable cases of MTSRCC showing overlapping morphology with PRCC displayed a more variable pattern including normal chromosomal status; losses of chromosomes 1, 6, 8, 9, 14, 15, and 22; and gains of 3, 7, 16, and 17. The group of 4 high-grade MTSRCCs exhibited a more uniform chromosomal aberration pattern with losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22 and without any gains detected. (1) MTSRCC, both low-grade and high-grade, shows chromosomal losses (including 1, 4, 6, 8, 9, 13, 14, 15, and 22) in all analyzable cases; this seems to be the most frequent chromosomal numerical aberration in this type of RCC. (2) Cases with overlapping morphologic features (MTSRCC and PRCC) showed a more variable pattern with multiple losses and gains, including gains of chromosomes 7 and 17 (2 cases). This result is in line with previously published morphologic and immunohistochemical studies that describe the broad morphologic spectrum of MTSRCC, with changes resembling papillary RCC. (3) The diagnosis of MTSRCC in tumors with overlapping morphology (MTSRCC and PRCC) showing gains of both chromosomes 7 and 17 remains questionable. Based on our findings, we recommend that such tumors should not be classified as MTSRCC but rather as PRCC.
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Affiliation(s)
- Kvetoslava Peckova
- Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic
| | - Petr Martinek
- Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic
| | - Maris Sperga
- Department of Pathology, East University Riga Riga, Latvia
| | - Delia Perez Montiel
- Department of Pathology, Instituto Nacional de Cancerologia, Mexico City, Mexico
| | - Ondrej Daum
- Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic
| | - Pavla Rotterova
- Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic
| | - Kristýna Kalusová
- Department of Urology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic
| | - Milan Hora
- Department of Urology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic
| | - Kristýna Pivovarcikova
- Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic
| | | | - Semir Vranic
- Department of Pathology, University Clinical Centre, Sarajevo, Bosnia and Hercegovina
| | - Whitney Davidson
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS
| | - Josef Vodicka
- Department of Surgery, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic
| | - Magdaléna Dubová
- Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic
| | - Michal Michal
- Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic
| | - Ondrej Hes
- Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic; Biomedical Centre, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czech Republic.
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Abstract
Papillary architecture is one of the most common morphological patterns in renal cell neoplasms. Many renal cell neoplasms can also exhibit, diffusely or focally, papillary growth pattern. This article reviews all the renal cell neoplasms with papillary or pseudopapillary architecture, with an emphasis on recently described new histological types. New insights into the "old" entities, including their immunohistochemical and genetic features, will also be discussed.
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Affiliation(s)
- Fang-Ming Deng
- Department of Pathology, New York University Langone Medical Center, New York, New York; Department of Urology, New York University Langone Medical Center, New York, New York
| | - Max X Kong
- Department of Pathology, New York University Langone Medical Center, New York, New York; Department of Urology, New York University Langone Medical Center, New York, New York
| | - Ming Zhou
- Department of Pathology, New York University Langone Medical Center, New York, New York; Department of Urology, New York University Langone Medical Center, New York, New York.
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41
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Kenney PA, Vikram R, Prasad SR, Tamboli P, Matin SF, Wood CG, Karam JA. Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney: a detailed study of radiological, pathological and clinical outcomes. BJU Int 2015; 116:85-92. [PMID: 25395040 DOI: 10.1111/bju.12992] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To characterise the clinical, radiological and histological features of mucinous tubular and spindle cell carcinoma (MTSCC), as well as oncological outcomes. PATIENTS AND METHODS This is a single institution retrospective analysis of all patients with MTSCC from 2002 to 2011. Patients were excluded if MTSCC could not be confirmed on pathology re-review (four patients). Clinical characteristics, pathology, imaging, and outcomes were reviewed for the 19 included patients. RESULTS The median (range) age at diagnosis was 59 (17-71) years with a female predominance (78.9%). On contrast-enhanced computed tomography, MTSCC enhanced less than the cortex during the corticomedullary phase. The mean (range) tumour attenuation was 36 (24-48), 67 (41-133), 89 (49-152), and 76 (52-106) Hounsfield units in the pre-contrast, corticomedullary, nephrographic and excretory phases, respectively. In all, 16 patients were treated with partial (five patients) or radical nephrectomy (11) for pT1 (62.5%), pT2 (31.3%), and pT3a disease (6.3%). One patient underwent active surveillance. Of three patients (13.0%) managed with energy ablation, there was one recurrence that was treated with salvage surgery. One patient (5.3%) had metastatic disease at diagnosis and died from disease 64.7 months later. A patient with a pT2bN0M0 MTSCC with sarcomatoid dedifferentiation developed bone metastases 9.5 months after diagnosis and was alive at 19.0 months. The remainder were free of recurrence or progression. CONCLUSION MTSCC is a rare renal cell carcinoma (RCC) variant. In this largest series to date, MTSCC presented at a broad range of ages and displayed a female predilection. Imaging and pathological features of MTSCC display some overlap with papillary RCC. MTSCC is associated with excellent outcomes overall, but is not universally indolent.
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Affiliation(s)
- Patrick A Kenney
- Department of Urology, Yale School of Medicine, New Haven, CT, USA
| | - Raghunandan Vikram
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Srinivasa R Prasad
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Pheroze Tamboli
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Surena F Matin
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Christopher G Wood
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jose A Karam
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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42
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Ozturk H. (18)F-fluorodeoxyglucose-positron-emission tomography/computed tomography staging of mucinous tubular and spindle cell carcinoma of the kidney. Indian J Nucl Med 2015; 30:68-71. [PMID: 25589812 PMCID: PMC4290072 DOI: 10.4103/0972-3919.147550] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) is an extremely rare carcinoma of the kidney, which develops by malignant differentiation of the collecting ducts or the loop of Henle. The tumor can occur at all ages, with 4 times higher prevalence in females than in males. A 62-year-old female patient presented with an asymptomatic mass lesion in the left kidney. The ultrasound revealed a hyperechogenic mass lesion measuring 4 cm in diameter and centrally located in the left kidney. Computed tomography (CT) revealed an isodense mass lesion measuring 4 cm in diameter and posterolaterally located in the left kidney. Magnetic resonance imaging revealed a renal mass of 4 cm in diameter with hypervascular contrast uptake. For primary staging, (18)F-fluorodeoxyglucose-positron-emission tomography ((18)FDG-PET)/CT revealed left renal cell carcinoma (RCC) with a maximum standard uptake value of 6.7. The patient underwent transperitoneal radical nephrectomy. The immunohistochemical examination revealed MTSCC-K. (18)FDG-PET/CT provides 81-89% sensitivity and 83-100% specificity in primary staging of the renal cancers, in diagnosing metastatic RCC, and monitoring the response to therapy. Its use in the staging of MTSCC of the kidney has not been previously described in the literature. This case highlights the usefulness of (18)FDG-PET/CT in the staging of this rare tumor.
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Affiliation(s)
- Hakan Ozturk
- Department of Urology, School of Medicine, Sifa University, Izmir, Turkey
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43
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Sircar K, Tamboli P. Pathologic Considerations. KIDNEY CANCER 2015. [DOI: 10.1007/978-3-319-17903-2_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Zhang Y, Yong X, Wu Q, Wang X, Zhang Q, Wu S, Yu D. Mucinous tubular and spindle cell carcinoma and solid variant papillary renal cell carcinoma: a clinicopathologic comparative analysis of four cases with similar molecular genetics datum. Diagn Pathol 2014; 9:194. [PMID: 25476569 PMCID: PMC4262063 DOI: 10.1186/s13000-014-0194-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2014] [Accepted: 10/07/2014] [Indexed: 11/30/2022] Open
Abstract
Mucinous tubular and spindle cell carcinoma (MTSC) was first recognized as a specific entity in the World Health Organization 2004 classification. The “classic” tumor presentation includes an extracellular blue-gray mucinous/myxoid matrix accompanying the typical tubular and spindle cell epithelial components. Tubules are lined by cuboidal to columnar cells with bland nuclei, central small to medium sized nucleoli, and few to no mitoses. By expanding the histologic spectrum, a number of studies highlighted the distinction between MTSC and solid variant of papillary renal cell carcinoma (sPRCC), although controversy still exists. Here, we evaluated two cases of MTSC and compared two cases of sPRCC by light microscopy, special staining, immunohistochemical staining and fluorescence in situ hybridization (FISH). We found that morphologic and immunophenotyping features showed more overlap between MTSC and sPRCC. In addition, gains of chromosomes 7 and 17 and loss of Y, which are characteristic of PRCC, were observed in two cases of sPRCC and one case of MTSC, suggesting that MTSC is similar to sPRCC or may be a subtype of PRCC. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_194
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Affiliation(s)
- Yanling Zhang
- Department of Pathology, the Frist Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, 233000, Bengbu, Anhui, PR China.
| | - Xiang Yong
- Department of Pathology, the Frist Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, 233000, Bengbu, Anhui, PR China.
| | - Qiong Wu
- Department of Pathology, the Frist Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, 233000, Bengbu, Anhui, PR China.
| | - Xiaoli Wang
- Department of Pathology, the Frist Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, 233000, Bengbu, Anhui, PR China.
| | - Qiong Zhang
- Department of Pathology, the Frist Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, 233000, Bengbu, Anhui, PR China.
| | - Shiwu Wu
- Department of Pathology, the Frist Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, 233000, Bengbu, Anhui, PR China.
| | - Donghong Yu
- Department of Pathology, the Frist Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, 233000, Bengbu, Anhui, PR China.
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45
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Renal Mucinous Tubular and Spindle Cell Carcinoma and 18F-Fluorodeoxyglucose-PET/CT Findings. Clin Genitourin Cancer 2014; 12:e161-6. [DOI: 10.1016/j.clgc.2014.03.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 03/14/2014] [Accepted: 03/24/2014] [Indexed: 11/18/2022]
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Sorrentino M, Bernardi S, Bruschi F, Scannavacca F, Brizzolari M, Hysko F, Cataldi P, Londero AP, Bertozzi S. Mucinous tubular and spindle cell carcinoma of the kidney: a rare case diagnosed in the early postpartum. Int J Surg Pathol 2014; 22:659-62. [PMID: 24619013 DOI: 10.1177/1066896914526775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
A 27-year-old women requesting assistance for an unspecified abdominal pain localized in the right flank that worsened after a recent delivery was discovered to have a solid mass in the upper pole of her right kidney. Radiological findings showed benign characteristics but without a clear diagnosis. Subsequently, a laparotomic nephron-sparing enucleation of a solid, encapsulated, brownish-white mass, localized in the cortical portion of the upper kidney pole, was performed. Pathological examination of the specimen showed a rare mucinous tubular and spindle cell carcinoma with an almost total mucinous component. To our knowledge, this is the first case of this disease discovered during pregnancy or puerperium. A multidisciplinary approach should be mandatory in order to correctly recognize and treat such a rare disease and to avoid administration of excessive adjuvant treatment to patients with a low-grade malignancy during pregnancy or puerperium.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Serena Bertozzi
- University of Udine, AOU "Santa Maria della Misericordia," Udine, Italy
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47
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Crumley SM, Divatia M, Truong L, Shen S, Ayala AG, Ro JY. Renal cell carcinoma: Evolving and emerging subtypes. World J Clin Cases 2013; 1:262-275. [PMID: 24364021 PMCID: PMC3868710 DOI: 10.12998/wjcc.v1.i9.262] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Accepted: 12/11/2013] [Indexed: 02/05/2023] Open
Abstract
Our knowledge of renal cell carcinoma (RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC.
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48
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Wu XR, Chen YH, Sha JJ, Zhao L, Huang JW, Bo JJ, Liu DM, Huang YR. Renal mucinous tubular and spindle cell carcinoma: a report of 8 cases and review of the literature. Diagn Pathol 2013; 8:206. [PMID: 24330589 PMCID: PMC3937160 DOI: 10.1186/1746-1596-8-206] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2013] [Accepted: 11/28/2013] [Indexed: 12/03/2022] Open
Abstract
Background Mucinous tubular and spindle cell carcinoma of kidney (MTSCC-K) is a rare variant of renal tumor. The current data show most of MTSCCs are of low malignant potential and rare cases metastatic to lymph nodes have been reported; however, the recorded computed tomography (CT) and follow up data are limited. Material and method In the present study, we retrospectively analyzed CT and clinicopathological data of eight patients with renal MTSCC-K. Results A total of eight cases, including six females and two males, were included in this analysis with a mean age of 48.4 (range 25 to 81) years. Mean tumor size was 4.2 (range 2.5 to 10.0) cm. Preoperative CT demonstrated that all tumors were slightly enhanced on both corticomedullary and nephrographic phase, which was different from many other renal cell carcinomas. Three of them were treated with open radical nephrectomy, three with laparoscopic radical nephrectomy and the other two with laparoscopic partial nephrectomy. No postoperative therapy was applied. Patients were followed up for 15 to 64 months and there was no evidence of recurrence and metastasis. Conclusions The MTSCC-K has special clinicopathological characteristics, low degree of malignancy and relative good prognosis. The diagnosis mainly depends on the histopathological examination and CT may help to differentiate with papillary renal cell carcinoma. Surgical treatment is recommended and additional therapies are not necessary. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8435581771088249.
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Affiliation(s)
| | | | | | | | | | | | - Dong-ming Liu
- Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China.
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49
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Yang OC, Maxwell PH, Pollard PJ. Renal cell carcinoma: translational aspects of metabolism and therapeutic consequences. Kidney Int 2013; 84:667-81. [DOI: 10.1038/ki.2013.245] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2013] [Revised: 03/12/2013] [Accepted: 03/14/2013] [Indexed: 02/08/2023]
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50
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Malignant tumors in patients with end stage renal failure undergoing renal replacement therapy. Contemp Oncol (Pozn) 2012; 16:382-7. [PMID: 23788914 PMCID: PMC3687441 DOI: 10.5114/wo.2012.31765] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2011] [Revised: 01/25/2012] [Accepted: 02/15/2012] [Indexed: 12/16/2022] Open
Abstract
In 1975 Matas and co-workers were the first in the world literature to show an increased risk of malignant tumor occurrence in the group of hemodialyzed patients and kidney transplant recipients. The report is an analysis of world literature from the last 35 years in reference to epidemiology as well as the profile of screening tests and diagnostic methods related to malignant tumors in the population with end stage renal disease, especially hemodialyzed patients.
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