Renal Cell Carcinoma: from a Pathologist's Perspective
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SMGr up Histologic Aspect of Renal Cell Carcinomas Solène-Florence Kammerer-Jacquet and Nathalie Rioux-Leclercq* Department*Corresponding of Pathology, author: Pontchaillou Hospital, France Nathalie Rioux-Leclercq, Department of Pathology, Pontchaillou Hospital, 2 rue Henri le Guilloux, 35300 Rennes Cedex 9, France, Tel: +33 2 99 28 42 79; Fax: +Published 33 2 99 28 Date: 42 84; Email: [email protected] July 18, 2016 ABSTRACT the ISUP (International Society of Urologic Pathology). The most recent recommendations were International guidelines for the classification of renal tumors in adults are provided from (RCC). In this established in 2012, and the 2016 WHO classification incorporated these guidelines but also clinical, pathological, and molecular characteristics of the renal cell carcinomas review, we focus on the macroscopic, histologic immunohistochemical and cytogenetic criteria (ccRCC) (P-RCC) (Ch-RCC), MiT family translocation RCC, that lead to the diagnosis of RCC. The main histologic subtypes of RCC include clear cell RCC collecting duct carcinoma, and medullary renal cell carcinoma. We also describe the other and rare , papillary RCC , chromophobe RCC entities of RCC recognized in the 2016 WHO classification: hereditary leiomyomatosis associated RCC, succinate dehydrogenase deficient RCC, mucinous tubular and spindle cell carcinoma, (AML). tubulocystic RCC, acquired cystic disease associated RCC, mixed epithelial and stromal tumor of Renalthe kidney, Cell Carcinoma clear cell | www.smgebooks.com papillary RCC, and epithelioid angiomyolipoma 1 Copyright Rioux-Leclercq N.This book chapter is open access distributed under the Creative Commons Attribu- tion 4.0 International License, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited. Keywords: ² Abbreviations:Renal Ch-RCC cell carcinoma; diagnosis; histology; WHO classificationccRCC ISUP: P-RCC: : Chromophobe renal cell carcinoma; : Clear cell renal cell RCC: WHO: World health organization carcinoma; International Society of Urologic Pathology; Papillary renal cell INTRODUCTIONcarcinoma; Renal cell carcinoma; The last WHO histologic classification of renal tumors was published in 2014. In the past decade, the ISUP members organized several consensus conferences to redefine renal tumor entities with a 2012 ISUP Vancouver classification published in 2013. The new WHO classification was just published in 2016 and included the ISUP recommendations [1,2,3]. In this review, we renal cell carcinomas (RCC) in adults. focus and describe the new entities and changes proposed by the 2016 WHO classification for MATERIALS AND METHODS A systematic review of the literature search was performed for relevant publications from the database Pubmed/MedLine, and focused on the following keywords: Carcinomas, Kidney, Renal Cell carcinomas, Classification, ISUP, WHO. We also use the diagnostic criteria for RCC published RESULTSin the 2016 WHO classification of the urinary system and male genital organs. (ccRCC), (P-RCC), (Ch-RCC), MiT family translocation RCC, collecting duct carcinoma, and The main histologic subtypes of RCC include clear cell RCC papillary RCC chromophobe RCC medullary renal cell carcinoma. All these subtypes represent almost 80% - 90% of RCC. Even if more than 20 subtypes of renal tumors have been defined, 5% of RCC remain unclassified RCC. Among the different prognostic markers published in the literature, only 5 were approved by the ISUP members to be reported in routine practice: - The histologic subtype: medullary RCC and collecting duct carcinoma are considered to have the worse prognosis of RCC with a highly aggressive behavior and a high risk of dissemination and metastases. Chromophobe RCC has a favorable prognosis compared to ccRCC and papillary RCC with a 5-year survival of 80% -100% [1]. - The ISUP nucleolar grading system: the ISUP system includes 4 nucleolar grades: grade1 (nucleoli are not present at x400 magnification), grade 2 (nucleoli visible at x400 magnification), grade 3 (nucleoli visible and prominent at x100 magnification), and grade 4 (nuclear and nucleolar pleomorphism with tumor giant cells). A sarcomatoid and/or a rhabdoid component are considered as a grade 4. The ISUP grading system is applied only for clear cell RCC and papillary RCC [4]. - Sarcomatoid and/or rhabdoid differentiation is associated with a less favorable behavior and Renal Cell Carcinoma | www.smgebooks.com 2 should be reported in the pathologic report. Copyright Rioux-Leclercq N.This book chapter is open access distributed under the Creative Commons Attribu- tion 4.0 International License, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited. - The presence of tumor necrosis and vessel invasion - The pTNM 2010 tumorTable staging1: [Table 1] [5]. T : Primary Tumour pTNM 2010 classification of renal carcinomas. Tx: T0 :primary tumour cannot be assessed T1 no evidence of primary tumour : Tumour ≤ 7 cm in greatest dimension limited to the kidney - T1a : Tumour ≤ 4 cm T2 - T1b : Tumour> 4 cm Tumour> 7 cm in greatest dimension limited to the kidney - T2a : > 7 cm but ≤ 10 cm T3 - T2b : > 10 cm Tumour extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond theGerota fascia - T3a :Tumour grossly extends into the renal vein or its segmental (muscle containing) branches, or tumour invades perirenal and/or renal sinus fat but not beyond the Gerota fascia - T3b :Tumour grossly extends into the vena cava below the diaphragm - T3c :Tumour grossly extends into the vena cava above the diaphragm or invades the wall of theT4 vena cava Tumourinvades beyond the Gerota fascia, including contiguous extension into the ipsilateralN : Regional adrenal lymph gland nodes Nx :Regional lymph nodescan not be assessed N0 :No regional lymph node metastasis N1M :Distant : Regional metastasis lymph nodes metastasis M0 :No distant metastasis M1 :Distant metastasis Renal Cell Carcinoma | www.smgebooks.com 3 Copyright Rioux-Leclercq N.This book chapter is open access distributed under the Creative Commons Attribu- tion 4.0 International License, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited. The main histologic subtypes of adult renal epithelial neoplasm are clear cell RCC (ccRCC), papillary RCC (P-RCC), Chromophobe RCC (Ch-RCC), MiT family translocation RCC, Collecting duct features of these tumours. carcinoma, and Medullary RCC. We review the macroscopic, histologic and immunohistochemical Clear Cell RCC (ccRCC) CcRCC are usually solitary and cortical carcinoma with a variable size. Macroscopically, the tumour is golden yellow with frequent haemorrhage, and possible necrosis [Figure 1]. Histologically, the architecteure can be alveolar, acinar or cystic. In low grade tumor, the tumor cells have a clear cytoplasm filled with lipids that becomes eosinophilic in higher nucleolar grade 3 or 4. These tumours are characterized by a well-developed vascular network [Figure 2]. Immunohistochemically, as all RCC, tumor cells are positive for PAX8 and can be also positive for CAIX and focally positive for CK7 [6]. In young adults under the age of 30 years, an autosomal dominant Von Hippel Lindau disease has to be ruled out. Figure 1: Macroscopic aspect of clear cell renal cell carcinoma. Renal Cell Carcinoma | www.smgebooks.com 4 Copyright Rioux-Leclercq N.This book chapter is open access distributed under the Creative Commons Attribu- tion 4.0 International License, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited. Figure 2: Papillary RCC (P-RCC) Histologic aspect of clear cell renal cell carcinoma. P-RCC is a heterogeneous disease including 2 types of renal cancers with indolent to aggressive behavior. Type 1 P-RCC has a better prognosis than P-RCC of type 2. Macroscopically, P-RCC has a friable consistency with a colour varying from grey to yellow; tan or dark [Figure 3]. Type 1P-RCC has small cubical cells with scanty pale cytoplasm arranged in a single layer, and is defined by multiple chromosomal gains including at least gain of chromosomes 7 and 17 [Figure 4]. Tumor cells in type 2 P-RCC are cylindrical, and have eosinophilic cytoplasm with atypical nuclei and nucleoli and nuclear pseudo stratification [Figure 5]. Type 2 P-RCC has a high degree of aneuploidy with multiple chromosomal losses especially loss of chromosome 9p [7]. P-RCC is characterized by a strong cytokeratin 7 and P504S immunoexpression [8]. Concerning papillary adenoma, in the 2016 WHO classification of renal tumours, the diagnosis is based on a tumour with a papillary architecture with a diameter < 15 mm [WHO 2016]. Renal Cell Carcinoma | www.smgebooks.com 5 Copyright Rioux-Leclercq N.This book chapter is open access distributed under the Creative Commons Attribu- tion 4.0 International License, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited. Figure 3: Macroscopic aspect of papillary renal cell carcinoma. Figure 4: Renal Cell Carcinoma | www.smgebooks.com Histologic aspect of type 1 papillary renal cell carcinoma. 6 Copyright Rioux-Leclercq