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Huang S, Zhang Y, Zhang W, Tian T, Dai H, Qi M, Su M, Zeng H, Huang R. Metabolic tumor parameters on 18F-FDG PET/CT can predict the expression of PD-L1 and prognosis in patients with fumarate hydratase-deficient renal cell carcinoma. Ann Nucl Med 2025:10.1007/s12149-025-02039-2. [PMID: 40088403 DOI: 10.1007/s12149-025-02039-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 03/04/2025] [Indexed: 03/17/2025]
Abstract
OBJECTIVE This study aimed to comprehensively evaluate the performance of fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and investigate the association between metabolic parameters, programmed cell death ligand 1 (PD-L1) expression, and prognosis in patients with fumarate hydratase-deficient renal cell carcinoma (FHRCC). METHODS Twenty-nine patients with FHRCC were prospectively enrolled from May 2020 to February 2023 for 18F-FDG PET/CT. The maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary/recurrent tumors were analyzed. The relationship between PET metabolic parameters, clinicopathological features and prognosis were evaluated. RESULTS Primary/recurrent and metastatic lesions showed FDG avidity, without metabolic differences between them. In our analysis, SUVmax of whole body (WB-SUVmax), SUVpeak of whole body (WB-SUVpeak), MTV of whole body (WB-MTV), and TLG of whole body (WB-TLG) were associated with the expression of PD-L1. The optimal cut-off values of WB-SUVmax, WB-SUVpeak, WB-MTV, and WB-TLG for predicting positive PD-L1 expression were 9.86 (AUC 0.814), 6.92 (AUC 0.848), 19.61 cm3 (AUC 0.803), and 58.39 g (AUC 0.841), respectively. Survival analysis further demonstrated that patients with WB-SUVpeak ≥ 8.92 had shorter time to progression than those with WB-SUVpeak < 8.92 (11.0 mo vs. 21.0 mo, P = 0.047). CONCLUSIONS 18F-FDG PET/CT is effective in detecting FHRCC lesions due to their hypermetabolic nature. PET metabolic parameters can serve as predictors of positive PD-L1 expression, with higher values observed in FHRCC patients with positive PD-L1 expression. Additionally, WB-SUVpeak is a significant predictor of prognosis in patients with FHRCC.
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Affiliation(s)
- Shuhui Huang
- Department of Nuclear Medicine, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People's Republic of China
| | - Yaowen Zhang
- Department of Urology, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People's Republic of China
| | - Wei Zhang
- Department of Nuclear Medicine, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People's Republic of China
| | - Tian Tian
- Department of Nuclear Medicine, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People's Republic of China
| | - Hongyuan Dai
- Department of Nuclear Medicine, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People's Republic of China
| | - Mengfang Qi
- Department of Nuclear Medicine, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People's Republic of China
| | - Minggang Su
- Department of Nuclear Medicine, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People's Republic of China
| | - Hao Zeng
- Department of Urology, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People's Republic of China.
| | - Rui Huang
- Department of Nuclear Medicine, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People's Republic of China.
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Mansour H, Tran-Dang MA, Walkden M, Boleti E, Barod R, Patki P, Mumtaz F, Tran MGB, Bex A, El Sheikh S. Renal mass biopsy - a practical and clinicopathologically relevant approach to diagnosis. Nat Rev Urol 2025; 22:8-25. [PMID: 38907039 DOI: 10.1038/s41585-024-00897-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/09/2024] [Indexed: 06/23/2024]
Abstract
Advancements in imaging modalities have increased the frequency of renal mass discovery. Imaging has typically been considered sufficient to guide management for a large proportion of these tumours, but renal mass biopsies (RMBs) have an increasing role in determining malignancy and can be a valuable tool for preventing unnecessary surgery in patients with benign tumours. A structured approach should be used to help to navigate the expanding repertoire of renal tumours, many of which are molecularly defined. In terms of tumour subtyping, the pathologist's strategy should focus on stratifying patients into clinically different prognostic groups according to our current knowledge of tumour behaviour, including benign, low-grade or indolent, intermediate malignant or highly aggressive. Crucial pathological features and morphological mimicry of tumours can alter the tumour's prognostic group. Thus, pathologists and urologists can use RMB to select patients with tumours at a reduced risk of progression, which can be safely managed with active surveillance within a tailored imaging schedule, versus tumours for which ablation or surgical intervention is indicated. RMB is also crucial in the oncological setting to distinguish between different high-grade tumours and guide tailored management strategies.
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Affiliation(s)
- Hussein Mansour
- Research Department of Pathology, UCL Cancer Institute, London, UK
| | - My-Anh Tran-Dang
- Specialist centre for kidney cancer, Royal Free London Hospital, London, UK
| | - Miles Walkden
- Specialist centre for kidney cancer, Royal Free London Hospital, London, UK
- UCL Division of Surgery and Interventional Science, Rowland Street, London, UK
| | - Ekaterini Boleti
- Specialist centre for kidney cancer, Royal Free London Hospital, London, UK
| | - Ravi Barod
- Specialist centre for kidney cancer, Royal Free London Hospital, London, UK
- UCL Division of Surgery and Interventional Science, Rowland Street, London, UK
| | - Prasad Patki
- Specialist centre for kidney cancer, Royal Free London Hospital, London, UK
- UCL Division of Surgery and Interventional Science, Rowland Street, London, UK
| | - Faiz Mumtaz
- Specialist centre for kidney cancer, Royal Free London Hospital, London, UK
- UCL Division of Surgery and Interventional Science, Rowland Street, London, UK
| | - Maxine G B Tran
- Specialist centre for kidney cancer, Royal Free London Hospital, London, UK
- UCL Division of Surgery and Interventional Science, Rowland Street, London, UK
| | - Axel Bex
- Specialist centre for kidney cancer, Royal Free London Hospital, London, UK
- UCL Division of Surgery and Interventional Science, Rowland Street, London, UK
| | - Soha El Sheikh
- Research Department of Pathology, UCL Cancer Institute, London, UK.
- Specialist centre for kidney cancer, Royal Free London Hospital, London, UK.
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Wang X. Clinical and molecular prognostic nomograms for patients with papillary renal cell carcinoma. Discov Oncol 2024; 15:780. [PMID: 39692801 DOI: 10.1007/s12672-024-01669-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/04/2024] [Indexed: 12/19/2024] Open
Abstract
OBJECTIVE To summarize the clinicopathological characteristics and prognostic factors of papillary renal cell carcinoma (pRCC) and to construct clinical and molecular prognostic nomograms using existing databases. METHODS Clinical prognostic models were developed using the Surveillance, Epidemiology, and End Results (SEER) database, while molecular prognostic models were constructed using The Cancer Genome Atlas (TCGA) database. Cox regression and LASSO regression were employed to identify clinicopathological features and molecular markers related to prognosis. The accuracy of the prognostic models was assessed using ROC curves, C-index, decision curve analysis (DCA) curves, and calibration plots. RESULTS In the 2004-2015 SEER cohort, Cox regression analysis revealed that age, grade, AJCC stage, N stage, M stage, and surgery were independent predictors of overall survival (OS) and cancer-specific survival (CSS) in pRCC patients. ROC curves, C-index, and DCA curves indicated that the prognostic nomogram based on clinical independent predictors had better predictive ability than TNM staging and SEER staging. Additionally, in the TCGA cohort, M stage, clinical stage, and the molecular markers IDO1 and PLK1 were identified as independent risk factors. The prognostic nomogram based on molecular independent risk factors effectively predicted the 3-year and 5-year OS and CSS for pRCC patients. CONCLUSIONS The clinical and molecular nomograms constructed in this study provide robust predictive tools for individualized prognosis in pRCC patients, offering better accuracy than traditional staging systems.
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Affiliation(s)
- Xuhui Wang
- Department of Urology, The Affiliated People's Hospital of Ningbo University, No.251, Baizhang East Road, Yinzhou District, Ningbo, 315040, China.
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Lu Y, Hu C, Jia J, Liu Y, Wen Y, Zhang H, Wang X, Li H, Shen G, Huang W. A rare case of FH-deficient renal cell carcinoma with signet ring cells features. Diagn Pathol 2024; 19:159. [PMID: 39695805 PMCID: PMC11654279 DOI: 10.1186/s13000-024-01583-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 11/28/2024] [Indexed: 12/20/2024] Open
Abstract
Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a clinically aggressive tumor with high rates of progression and mortality. A wide range of morphological variations has been observed in FH-deficient RCC, initially described as type 2 papillary RCC or unclassified RCC. Here, we report a case of FH-deficient RCC with rare signet ring cells features. The patient was diagnosed with FH-deficient renal cell carcinoma and suspected to have hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. After 4 months, pulmonary metastasis occurred in the patient. We herein describe the first case of FH-deficient renal tumor with signet ring cells features, which expands the morphological spectrum of this tumor. More importantly, this variant can be a diagnostic pitfall, we emphasize that pathologists should consider not only the diagnosis of metastatic signet ring cell carcinoma and ALK rearrangement renal cell carcinoma but also FH-deficient renal cell carcinoma.
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Affiliation(s)
- Yin Lu
- Shenzhen Hospital, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
- Departments of Pathology, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
| | - Chunfang Hu
- Shenzhen Hospital, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
- Departments of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jiedong Jia
- Shenzhen Hospital, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
- Departments of urology, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
| | - Ye Liu
- Shenzhen Hospital, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
- Departments of Pathology, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
| | - Yanlin Wen
- Shenzhen Hospital, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
- Departments of Pathology, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
| | - Huijuan Zhang
- Shenzhen Hospital, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
- Departments of Pathology, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
| | - Xiaoliang Wang
- Shenzhen Hospital, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
- Departments of Pathology, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
| | - Haitao Li
- Shenzhen Hospital, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
- Departments of urology, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
| | - Guihua Shen
- Shenzhen Hospital, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
- Departments of Pathology, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
| | - Wenting Huang
- Shenzhen Hospital, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
- Departments of Pathology, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China.
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Bellal S, Kammerer-Jacquet SF, Rioux-Leclercq N. [2022 WHO classification of renal cell carcinomas: Focus on papillary renal cell carcinoma]. Ann Pathol 2024; 44:314-322. [PMID: 38729793 DOI: 10.1016/j.annpat.2024.04.018] [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: 11/09/2022] [Revised: 03/10/2024] [Accepted: 04/16/2024] [Indexed: 05/12/2024]
Abstract
Renal cell carcinomas (RCC) represent a group of heterogeneous tumors whose classification has greatly evolved since 1981. The latest update in 2022 classifies all renal cell carcinomas into six categories according to their morphology or the detection of specific molecular alterations. Molecular disassembly of renal cell carcinomas with papillary features has enabled the identification of new entities characterized by a specific molecular alteration, such as Fumarate Hydratase (FH) deficient RCC, TFE3-rearranged RCC or TFEB-altered RCC. This new classification allows for a more accurate diagnosis but requires a thorough knowledge of the genomic alterations to search for with immunohistochemical or molecular biology techniques. According to the new WHO 2022 classification, papillary renal cell carcinoma (PRC) type 1 or type 2 classification is no longer recommended. A classification based on nucleolar ISUP grade must be preferred: low-grade PRC (ISUP 1-2) or high-grade PRC (ISUP 3-4). The other prognostic factors remain the same: the pTNM stage, lymphovascular invasion, and the presence or absence of dedifferentiated areas referring to sarcomatoid or rhabdoid features. Of note, the presence of necrosis is not currently recognized as a poor prognostic element for this type of carcinoma. The diagnosis of high-grade PRC is from now on a diagnosis of exclusion. It can only be sustained after having ruled out TFE3-rearranged RCC, TFEB-altered RCC, and FH-deficient RCC. For clinicians, the diagnosis of PRC implies suggesting an oncogenetic consultation to screen for an associated genetic tumor syndrome regardless of the patient's age.
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Affiliation(s)
- Sarah Bellal
- Département de pathologie cellulaire et tissulaire, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France
| | - Solène-Florence Kammerer-Jacquet
- Service d'anatomie et cytologie pathologiques, CHU de Rennes-Hôpital Pontchaillou, 2, rue Henri-Le-Guilloux, 35033 Rennes cedex 9, France
| | - Nathalie Rioux-Leclercq
- Service d'anatomie et cytologie pathologiques, CHU de Rennes-Hôpital Pontchaillou, 2, rue Henri-Le-Guilloux, 35033 Rennes cedex 9, France.
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Cao HH, Li H, Guo XH, Cao ZX, Zhang BH. Eosinophilic solid and cystic renal cell carcinoma with aggressive behavior: Two case reports. World J Clin Cases 2024; 12:5124-5130. [DOI: 10.12998/wjcc.v12.i22.5124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 05/29/2024] [Accepted: 06/17/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Eosinophilic solid and cystic (ESC) renal cell carcinoma (RCC), a unique and emerging subtype of RCC, has an indolent nature; in some rare instances, it may exhibit metastatic potential. Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices.
CASE SUMMARY Herein, we report two patients with ESC RCC. Patient 1 was a young woman with classical pathological characteristics. Patient 2 was a 52-year-old man with multifocal metastases, involving the pulmonary hilar and mediastinal lymph nodes, liver, brain, mesosternum, vertebra, rib, femur, and symphysis pubis. Awareness of ESC RCC, along with its characteristic architecture and immunophenotype, would contribute to making a definitive diagnosis, even on core biopsy samples.
CONCLUSION The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future.
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Affiliation(s)
- Hui-Hui Cao
- Department of Pathology, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, Guangdong Province, China
| | - Hong Li
- Department of Pathology, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, Guangdong Province, China
| | - Xiao-Hong Guo
- Department of Pathology, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, Guangdong Province, China
| | - Zhi-Xing Cao
- Department of Pathology, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, Guangdong Province, China
| | - Bo-Hui Zhang
- Department of Pathology, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, Guangdong Province, China
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Li S, Yan MQ, Wang ZY, Wang ZB, Kuang HX. Phytochemistry of Genus Buxus and Pharmacology of Cyclovirobuxine D. Chem Biodivers 2024; 21:e202400494. [PMID: 38744674 DOI: 10.1002/cbdv.202400494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 05/13/2024] [Accepted: 05/13/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND Genus Buxus plants, commonly known as "boxwood", are widely distributed in China. The stems, branches, and leaves of the plant are traditionally used for rheumatism, toothache, chest pain, abdominal gas, and other diseases. However, an overview of the genus Buxus remains to be provided. PURPOSE To provide a scientific basis for the appropriate use and further research the recent advancements in the traditional usage, phytochemistry, and, pharmacology of Buxus. STUDY DESIGN Chemical composition and pharmacological correlation studies through a literature review. METHODS Between 1970 and 2023, the available data concerning Buxus was compiled from online scientific sources, such as Sci-Finder, PubMed, CNKI, Google Scholar, and the Chinese Pharmacopoeia. Plant names were verified from "The Plant List" (http://www.theplantlist.org/). RESULTS To date, 266 structurally diverse chemicals have been extracted and identified from the genus Buxus. Alkaloids constitute one of its primary bioactive phytochemicals. A summary of the channels of action of Cyclovirobuxine D on the cytotoxicity of a variety of cancers has been provided. CONCLUSION Numerous findings from contemporary phytochemical and pharmacological studies support the traditional use, facilitating its application. Further research is necessary to address various shortcomings, including the identification of the active ingredients and quality control of the genus Buxus.
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Affiliation(s)
- Sen Li
- Key Laboratory of Basic and Application Research of Beiyao, (Ministry of Education), Heilongjiang University of Chinese Medicine, 150040, Harbin, China
| | - Meng-Qi Yan
- Key Laboratory of Basic and Application Research of Beiyao, (Ministry of Education), Heilongjiang University of Chinese Medicine, 150040, Harbin, China
| | - Zhen-Yue Wang
- Key Laboratory of Basic and Application Research of Beiyao, (Ministry of Education), Heilongjiang University of Chinese Medicine, 150040, Harbin, China
| | - Zhi-Bin Wang
- Key Laboratory of Basic and Application Research of Beiyao, (Ministry of Education), Heilongjiang University of Chinese Medicine, 150040, Harbin, China
| | - Hai-Xue Kuang
- Key Laboratory of Basic and Application Research of Beiyao, (Ministry of Education), Heilongjiang University of Chinese Medicine, 150040, Harbin, China
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Kamboj M, Gupta G, Pasricha S, Mehta A, Rawal S, Singh A, Sharma A, Durga G, Bansal D, Diwan H. Fumarate hydratase-deficient renal cell carcinoma: an oncology care institutional experience. APMIS 2024; 132:544-552. [PMID: 38775301 DOI: 10.1111/apm.13425] [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: 10/25/2023] [Accepted: 04/26/2024] [Indexed: 07/11/2024]
Abstract
Renal cell carcinoma (RCC) accounts for 2% of all cancer cases worldwide, and majority are sporadic. The latest World Health Organization (WHO) classification of renal cell tumors (fifth edition, 2022) has molecularly defined renal tumor entities, which includes fumarate hydratase (FH)-deficient RCC. FH-deficient RCC is an aggressive carcinoma caused by pathogenic alterations in FH gene, seen in 15% of patients with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) syndrome. These tumors occur more frequently at a younger age and present at an advanced stage, carrying a dismal prognosis. We report a series of 10 cases of FH-deficient RCC. The mean age was 49.8 years, and all cases presented in advanced stages (III and IV). Morphologically, the cases had varied architectural patterns with characteristic eosinophilic macronucleoli and perinucleolar halo. On immunohistochemistry (IHC), all showed diffuse nucleo-cytoplasmic expression of S-(2-succino)-cysteine (2-SC), with loss of FH in seven cases. FH-deficient RCCs are aggressive neoplasms and can be diagnosed using specific IHC markers (FH and 2-SC). These patients should undergo germline testing for FH gene mutation, genetic counseling, and surveillance of family members.
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Affiliation(s)
- Meenakshi Kamboj
- Department of Histopathology and Cytopathology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
| | - Gurudutt Gupta
- Department of Histopathology and Cytopathology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
| | - Sunil Pasricha
- Department of Histopathology and Cytopathology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
| | - Anurag Mehta
- Laboratory Services & Molecular Diagnostics, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
| | - Sudhir Rawal
- Department of GenitoUro-Oncology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
| | - Amitabh Singh
- Department of GenitoUro-Oncology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
| | - Anila Sharma
- Department of Histopathology and Cytopathology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
| | - Garima Durga
- Department of Histopathology and Cytopathology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
| | - Divya Bansal
- Department of Histopathology and Cytopathology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
| | - Himanshi Diwan
- Department of Histopathology and Cytopathology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
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Fu S, Chen D, Wang S, Wu M, Zhang Y, Hu T. Analysis of Imaging and Pathologic Features in Eosinophilic Solid and Cystic Renal Cell Carcinoma. Clin Genitourin Cancer 2024; 22:102124. [PMID: 38852436 DOI: 10.1016/j.clgc.2024.102124] [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: 11/23/2023] [Accepted: 05/19/2024] [Indexed: 06/11/2024]
Abstract
OBJECTIVE Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is rare and difficult to diagnose. Therefore, we aim to investigate the imaging and pathologic features of ESC-RCC. METHODS Fifteen cases of ESC-RCC with pathologically confirmed diagnoses were retrospectively collected: CT was performed in 15 cases and MRI in 9 cases. RESULTS In these patients (6 males and 9 females) (age: mean, 53.3 ± 14.7 years; range, 27-72 years), all tumors were unilateral, renal, and solitary with no clinical symptoms and were classified into-type 1: cystic-solid component, with equal cystic and solid components, was the most common (8/15, 53.3%); type 2: predominantly cystic with a small solid component (4/15, 26.7%); and type 3: predominantly solid (3/15, 20%). The solid component showed equal/slightly higher density on the CT-plain-scan, equal/slightly high signal on the T1-weighted image (T1WI), and low signal on the T2-weighted image (T2WI). Ten cases showed progressive enhancement, while 5 showed a fast-wash-in and fast-wash-out enhancement. One patient experienced hemorrhage, while the others showed no signs of hemorrhage, necrosis, fat, or calcification. Pathologically, the tumor showed cystic solidity, with eosinophilic cytoplasm and granular basophilic-colored spots with focal or diffuse expression of CK20. Ten patients had componential nephrectomy and 5 had radical nephrectomy. No recurrence or metastasis was noted in any case at the follow-up (8-49 months). CONCLUSION This study describes the imaging and pathologic features of a rare type of renal cancer and proposes 3 imaging types to enhance physicians' diagnosis of this disease and guide clinical diagnosis and treatment.
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Affiliation(s)
- Sunya Fu
- Department of Radiology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang Province, PR China
| | - Dawei Chen
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang Province, PR China
| | - Suying Wang
- Department of Pathology, Ningbo Clinical Pathology Diagnosis Center, Ningbo, Zhejiang Province, PR China
| | - Mingjie Wu
- Department of Radiology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang Province, PR China
| | - Yuqin Zhang
- Department of Radiology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang Province, PR China.
| | - Tiebo Hu
- Department of Radiology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang Province, PR China
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Zhang X, Li L, Wang L, Yu M, Zhang D. Composite eosinophilic solid and cystic renal cell carcinoma and clear cell renal cell carcinoma: a rare case report and literature review. BMC Urol 2024; 24:160. [PMID: 39080639 PMCID: PMC11287965 DOI: 10.1186/s12894-024-01542-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 07/11/2024] [Indexed: 08/03/2024] Open
Abstract
BACKGROUND Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel subtype of renal cell carcinoma characterized by its relatively low incidence and indolent behavior. We report a rare case of ESC-RCC concurrent with clear cell renal cell carcinoma (ccRCC) in a single kidney. CASE PRESENTATION A 48-year-old male, was found to have a mixed echogenic mass in the left kidney during a physical examination. He has no history of hematuria and flank pain. An abdominal CT scan revealed a 3.0 * 1.9 * 2.5 cm3 mass with unclearly bordered at the lower pole of the left kidney. Abdominal MRI showed two nodules of different sizes in the left kidney, suggesting the possibility of a tumor. The patient underwent a subtotal nephrectomy, and the postoperative pathological results indicated ESC-RCC combined with ccRCC. The patient recovered well without tumor recurrence during the 12-month follow-up. CONCLUSION We reported a case of renal composite tumors, comprising the rare ESC-RCC and the more common ccRCC. Imaging combined with postoperative pathological examination is crucial for the definitive diagnosis of these rare tumors.
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Affiliation(s)
- Xian Zhang
- Department of Radiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, 441000, China
| | - Lin Li
- Department of Cardiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, 441000, China
| | - Lisha Wang
- Department of Radiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, 441000, China
| | - Mengxing Yu
- Department of Pathology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, 441000, China
| | - Dongdong Zhang
- Department of Oncology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Jiefang Road No.15, Xiangyang, 441000, Hubei, China.
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Choiniere R, Al Qa'qa' S, Cheung CC, Finelli A, Prendeville S. Frequency and clinicopathologic features of renal low-grade oncocytic tumour and eosinophilic vacuolated tumour: reclassification of 605 eosinophilic tumours including patients managed with active surveillance. J Clin Pathol 2024:jcp-2024-209711. [PMID: 39033022 DOI: 10.1136/jcp-2024-209711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 07/06/2024] [Indexed: 07/23/2024]
Abstract
AIMS Low-grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT) are recently described emerging entities, which demonstrate distinct features but are not yet recognised as separate neoplasms in the fifth WHO classification. Published series to date have been largely multi-institutional and based on surgically resected tumours. This study aims to determine the frequency, clinicopathologic features and outcome of LOT and EVT in a single institutional series of oncocytic/eosinophilic renal neoplasms, including patients managed with active surveillance and non-surgical intervention. METHODS AND RESULTS Cases were identified from a consecutive institutional series of in-house renal tumours diagnosed on biopsy and/or nephrectomy (2003-2023). Tumours with a diagnosis or differential diagnosis of oncocytoma, chromophobe renal cell carcinoma or oncocytic neoplasm not otherwise specified (including LOT, EVT and tumours with overlapping hybrid features) were retrospectively reviewed and classified/reclassified.In total, 605 oncocytic/eosinophilic renal neoplasms were reviewed, among which 33 LOT (5.5%) and 5 EVT (0.8%) were identified. LOT were CK7+, CD117- and GATA3+ (94%). EVT were CD117+, CK7 focal+ (80%) and cathepsin K+ (80%). At the median follow-up of 34 months (range 2-253) and 56 months (range 8-90) for LOT and EVT, respectively, there was no evidence of recurrence following ablation/surgical resection, metastasis or death from disease for all patients, including the 22 managed with active surveillance (20 LOT and 2 EVT). CONCLUSIONS LOT and EVT comprised a minority of oncocytic renal neoplasms in this series. We report a large institutional series including patients managed non-surgically, with no adverse outcome, adding to the existing literature indicating a benign outcome.
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Affiliation(s)
- Roselyne Choiniere
- Division of Anatomic Pathology, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
- Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Shifaa' Al Qa'qa'
- Division of Anatomic Pathology, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
- Department of Pathology and Forensic Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan
| | - Carol C Cheung
- Division of Anatomic Pathology, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
- Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Antonio Finelli
- Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Susan Prendeville
- Division of Anatomic Pathology, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
- Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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12
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AlAkrash HS, Ghabbani HM, AlSaleh FA, Nassar RM, AlHumaidan AA, AlHasan AM, AlMosa AM, AlBluwi AA, Eltholoth HS, Ali NM, AlZahrani AY. Anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma: Rare subset case report. Urol Case Rep 2024; 55:102798. [PMID: 39104401 PMCID: PMC11298843 DOI: 10.1016/j.eucr.2024.102798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 07/09/2024] [Indexed: 08/07/2024] Open
Abstract
Anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC) is a rare subtype of renal cell carcinoma characterized by genetic rearrangements involving the ALK gene. Managing ALK-RCC is challenging due to its rarity and limited treatment options. Targeted therapies directed at the ALK gene have shown promise. ALK-RCC is a rare subtype of renal cell carcinoma with unique clinical and pathological features. ALK inhibitors may hold promise as a targeted therapy for ALK-RCC. Further research is needed to understand the behavior of ALK-RCC and develop effective treatment strategies.
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Affiliation(s)
- Hamad S. AlAkrash
- Urology Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Hisham M. Ghabbani
- Urology Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Faisal A. AlSaleh
- Urology Department, King Khaled University Hospital, Riyadh, Saudi Arabia
| | - Rashad M. Nassar
- Urology Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Almaha A. AlHumaidan
- College of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | | | - Abdullah M. AlMosa
- Urology Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | | | - Hossam S. Eltholoth
- Urology Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Nagoud M. Ali
- Histopathology Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Ahmed Y. AlZahrani
- Urology Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
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13
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Nova-Camacho LM, Sangoi AR. Clear Cell Renal Cell Carcinoma With Syncytial-Type Multinucleated Giant Tumor Cells: A Clinicopathologic Study of 14 Cases. Int J Surg Pathol 2024; 32:731-737. [PMID: 37525565 DOI: 10.1177/10668969231189798] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2023]
Abstract
The presence of syncytial-type multinucleated giant tumor cells with emperipolesis in clear cell renal cell carcinoma (RCC) is uncommon, with only 31 cumulative published cases to date. After a rereview of 125 clear cell RCC of World Health Organization/International Society of Urological Pathology grade 3 or 4, 14 clear cell RCCs with admixed syncytial-type giant cells (to our knowledge, the largest series to date) were found with a mean patient age of 67 years and with no sex difference (M = 7, F = 7). Mean tumor size was 7.3 cm. The syncytial-type giant cells comprised between 2% and 20% of the tumor and were present mainly around areas of necrosis. Five tumors were staged as pT1 or pT2, 8 as pT3, and 1 as pT4. Other findings included sarcomatoid differentiation (3/14), rhabdoid differentiation (4/14), and emperipolesis (12/14). Positive immunostains included keratin AE1/AE3 (13/13), carbonic anhydrase 9 and CD10 (12/14 each), vimentin (8/14), EMA (5/12), and alpha-methyacyl-CoA racemase (3/12). Keratin 7, keratin 20, human melanoma black 45, KIT, TFE3, cathepsin K, CD68, CD61, and beta human chorionic gonadotropin were negative. Six of 13 patients had recurrence or metastases during a mean follow-up time of 56 months. Four of 13 patients died of disease, 2 of 13 patients were alive with the disease, and 7 of 13 patients had no evidence of disease. Although the incidence of finding syncytial-type multinucleated giant tumor cells in clear cell RCC is low (approximately 1.2%), given that a subset of the patients showed poor outcomes while lacking other poor histologic parameters (eg, sarcomatoid or rhabdoid differentiation), it may be prudent to recognize and report this feature when encountered.
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Affiliation(s)
| | - Ankur R Sangoi
- Department of Pathology, Stanford University, Stanford, CA, USA
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14
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Chai JL, Siegmund SE, Hirsch MS, Silverman SG. Low-grade oncocytic tumor: a review of radiologic and clinical features. Abdom Radiol (NY) 2024; 49:1940-1948. [PMID: 38372764 DOI: 10.1007/s00261-023-04167-7] [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: 09/13/2023] [Revised: 12/09/2023] [Accepted: 12/16/2023] [Indexed: 02/20/2024]
Abstract
PURPOSE The 2022 World Health Organization classification of renal neoplasia expanded the spectrum of oncocytic neoplasms to encompass newly established and emerging entities; one of the latter is the low-grade oncocytic tumor (LOT). This study reports the radiologic appearance and clinical behavior of LOT. METHODS In this IRB-approved, HIPPA-compliant retrospective study, our institution's pathology database was searched for low-grade oncocytic tumors or neoplasms. Patient age, gender, and comorbidities were obtained from a review of electronic medical records, and imaging characteristics of the tumors were assessed through an imaging platform. RESULTS The pathology database search yielded 14 tumors in 14 patients. Four patients were excluded, as radiologic images were not available in three, and one did not fulfill diagnostic criteria after pathology re-review. The resulting cohort consisted of 10 tumors (median diameter 2.3 cm, range 0.7-5.1) in 10 patients (median age 68 years, range 53-91, six women). All tumors presented as a solitary, well-circumscribed, mass with solid components. All enhanced as much or almost as much as adjacent renal parenchyma; all but one enhanced heterogeneously. None had lymphadenopathy, venous invasion, or metastatic disease at presentation or at clinical follow-up (median, 22.2 months, range 3.4-71.6). Among five tumors undergoing active surveillance, mean increase in size was 0.4 cm/year at imaging follow-up (median 16.7 months, range 8.9-25.4). CONCLUSION LOT, a recently described pathologic entity in the kidney, can be considered in the differential diagnosis of an avidly and typically heterogeneously enhancing solid renal mass in an adult patient.
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Affiliation(s)
- Jessie L Chai
- Division of Abdominal Imaging and Intervention, Department of Radiology, Brigham and Women's Hospital, 75 Francis St, Boston, MA, 02115, USA.
| | | | - Michelle S Hirsch
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
| | - Stuart G Silverman
- Division of Abdominal Imaging and Intervention, Department of Radiology, Brigham and Women's Hospital, 75 Francis St, Boston, MA, 02115, USA
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15
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Siegmund SE, Al-Obaidy KI, Tsai HK, Idrees MT, Akgul M, Acosta AM, Hirsch MS. Concordance of MTOR Pathway Mutations and the Diagnosis of Renal Low-Grade Oncocytic Tumor (LOT). Int J Surg Pathol 2024; 32:316-330. [PMID: 37357748 DOI: 10.1177/10668969231178032] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/27/2023]
Abstract
The differential diagnosis for oncocytic renal tumors spans the spectrum from benign entities to more aggressive renal cell carcinomas (RCC). Recent work has characterized a provisional renal oncocytic neoplasm, namely the low-grade oncocytic tumor (LOT), which demonstrates overlapping morphologic features with oncocytoma and chromophobe RCC, but also has a unique immunoprofile (ie, diffusely positive for KRT7, negative for KIT) and a high rate (80% to 100%) of mTOR pathway gene alterations. Given the diagnostic overlap among oncocytic tumors, we looked for concordance between mTOR pathway mutations and LOT. Thirty low-grade renal oncocytic neoplasms underwent histologic review and immunohistochemistry for KRT7 and KIT. Tumors were classified as "determinate" (eg, LOT) for tumors with solid, nested or vaguely tubular growth and diffuse KRT7 staining and negative KIT, or "indeterminate" if the morphology and/or immunostains did not fully support a definitive LOT diagnosis. Next-generation sequencing was performed without any knowledge of the diagnoses, and identified mTOR pathway mutations in 80% (12/15) of the determinate tumors, compared with 7% (1/15) in the indeterminate group. One determinate tumor was reclassified as papillary RCC (MTOR mutation negative) and 6 indeterminate tumors were confirmed to be oncocytoma (N = 4), clear cell RCC or papillary RCC with reverse polarity, respectively. Overall, integration of morphology, immunohistochemistry, and molecular data enabled a final definitive diagnosis for 70% of tumors (21 of the total 30), with a high concordance (93%) for LOT specifically in the determinate group; the remaining 9 tumors (30%) were classified as renal oncocytic neoplasm, not otherwise specified.
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Affiliation(s)
- Stephanie E Siegmund
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Khaleel I Al-Obaidy
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Harrison K Tsai
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Center for Advanced Molecular Diagnostics, Brigham and Women's Hospital, Boston, MA, USA
| | - Muhammad T Idrees
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mahmut Akgul
- Department of Pathology, Albany Medical Center, Albany, NY, USA
| | - Andres M Acosta
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Michelle S Hirsch
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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16
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Nova-Camacho LM, Acosta AM, Akgul M, Panizo A, Galea LA, Val-Carreres A, Talavera JA, Guerrero-Setas D, Martin-Arruti M, Ruiz I, García-Martos M, Sangoi AR. Biphasic papillary (biphasic squamoid alveolar) renal cell carcinoma: a clinicopathologic and molecular study of 17 renal cell carcinomas including 10 papillary adenomas. Virchows Arch 2024; 484:441-449. [PMID: 38388964 DOI: 10.1007/s00428-024-03768-x] [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: 12/03/2023] [Revised: 01/12/2024] [Accepted: 02/07/2024] [Indexed: 02/24/2024]
Abstract
Biphasic papillary renal cell carcinoma (synonymous with biphasic squamoid alveolar renal cell carcinoma) is considered within the spectrum of papillary renal cell carcinoma (PRCC). With < 70 reported cases of biphasic PRCC, there is limited data on the pathologic spectrum and clinical course. Seventeen biphasic PRCC cases and 10 papillary adenomas with similar biphasic morphology were assessed. The mean age of the biphasic PRCC patients was 62 years (male to female ratio of 1.8:1), from 10 partial nephrectomies, 6 radical nephrectomies, and 1 biopsy. The mean tumor size was 3.6 cm (range 1.6-8 cm), with 24% showing multifocality. Fifteen out of 17 cases were limited to the kidney (one of which was staged as pT2a but had lung metastases at diagnosis) and 2/17 cases were staged as T3a. All tumors showed typical biphasic morphology with an extent of squamoid foci widely variable from 10 to 95%. Emperipolesis was identified in 88% of cases. All biphasic PRCC tested exhibited positivity for PAX8 (16/16), keratin 7 (17/17), EMA (15/15), AMACR (17/17), and vimentin (12/12) in both large and small cells; cyclin D1 was only expressed in the large cells (16/16). The 10 papillary adenomas showed a similar immunoprofile to biphasic PRCC. NGS testing performed on 13 biphasic PRCC revealed 4 (31%) harboring MET SNVs. In 1/5 (20%) papillary adenomas, a pathogenic MET SNV was identified. Biphasic PRCC is rare with a generally similar immunoprofile to "type 1" PRCC but with notable strong positivity for cyclin D1 in the large cell component. Although most of the biphasic PRCC cases were of small size, low stage, and with an indolent behavior, one patient had metastatic disease and one patient died of the disease.
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Affiliation(s)
- Luiz M Nova-Camacho
- Department of Pathology, Donostia University Hospital, San Sebastian, Spain.
- , Gainesville, USA.
| | - Andres M Acosta
- Department of Pathology, Indiana University, Indianapolis, IN, USA
| | - Mahmut Akgul
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA
| | - Angel Panizo
- Department of Pathology, University Hospital of Navarra, Pamplona, Spain
| | - Laurence A Galea
- Department of Anatomical Pathology, Sonic Healthcare, Melbourne PathologyVictoria, Australia
| | | | - Juan A Talavera
- Department of Internal Medicine, Diagnósticos da America DASA, Sao Paulo, Brazil
| | | | - Maialen Martin-Arruti
- Department of Pathology, Donostia University Hospital, San Sebastian, Spain
- Laboratory of Molecular Pathology and Therapeutic Targets, Donostia University Hospital, San Sebastian, Spain
| | - Irune Ruiz
- Department of Pathology, Donostia University Hospital, San Sebastian, Spain
- Laboratory of Molecular Pathology and Therapeutic Targets, Donostia University Hospital, San Sebastian, Spain
| | - María García-Martos
- Department of Pathology, Gregorio Marañon University Hospital, Madrid, Spain
| | - Ankur R Sangoi
- Department of Pathology, Stanford University, Stanford, CA, USA
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17
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Lerma LA, Pease G, Malleis J, Antic T, Hes O, Tretiakova M. Actual encounters of the kidney kind: Exploring 48 cases of renal collision tumors through the lens of literature. Hum Pathol 2024; 145:26-33. [PMID: 38340966 DOI: 10.1016/j.humpath.2024.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 02/02/2024] [Accepted: 02/06/2024] [Indexed: 02/12/2024]
Abstract
Multiple tumors of different lineages merging into a single mass, termed collision tumors, are considered a rare phenomenon in the kidney. Tumor components, or partners, may be malignant (including metastatic disease), borderline, or benign. We report the largest cohort to date of 48 cases. The cases were identified from the archives of three institutions in the last 16 years, including 43 (90%) with 2 tumor partners (dyad) and 5 (10%) with 3 partners (triad), totaling 101 individual neoplasms. The majority of cases involved immunohistochemical workup, and 5 underwent FISH or molecular studies. Forty (83%) cases featured a malignant entity, including all triads. Twenty dyads and two triads were composed entirely of malignant tumors. The most common malignant partner was clear cell renal cell carcinoma (RCC) (N = 19) followed by papillary RCC (N = 17). Nine (19%) cases featured borderline entities, including 5 multilocular cystic neoplasms of low malignant potential and 6 clear cell papillary renal cell tumors. Twenty one (44%) cases contained a benign partner, including 6 benign dyads. Papillary adenoma (N = 13) and oncocytoma (N = 8) were most common. Epithelial tumors were present in all 48 cases, and non-epithelial neoplasms in 9 cases (19%). Our cohort includes many novel combinations and collision partners with rare entities such as SDH-deficient RCC, TFE3-rearranged RCC, eosinophilic solid and cystic RCC, and acquired cystic disease associated RCC. A comprehensive literature review and analysis of collision tumor phenomenon in kidney placed these cases in context suggesting that collision tumors of the kidney are more common than previously recognized.
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Affiliation(s)
- L Angelica Lerma
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
| | - Garrison Pease
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
| | - James Malleis
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
| | - Tatjana Antic
- Department of Pathology, University of Chicago, Chicago, IL, USA
| | - Ondrej Hes
- Department of Pathology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - Maria Tretiakova
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
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18
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Shah RB, Mehra R. Renal Cell Carcinoma Associated With TSC/MTOR Genomic Alterations: An Update on its Expanding Spectrum and an Approach to Clinicopathologic Work-up. Adv Anat Pathol 2024; 31:105-117. [PMID: 37899532 DOI: 10.1097/pap.0000000000000419] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2023]
Abstract
Renal cell carcinoma (RCC) with tuberous sclerosis complex (TSC)/mammalian target of rapamycin (MTOR) pathway-related genomic alterations have been classically described in hereditary TSC syndrome setting involving germline mutations, whereby cells with a bi-allelic inactivation of genes originate tumors in a classic tumor-suppressor "two-hit" Knudson paradigm. Initial studies of TSC-associated RCC categorized tumors into 3 broad heterogeneous morphologic groups: RCC with smooth muscle stroma, chromophobe-like, and eosinophilic-macrocytic. Recently, a similar morphologic spectrum has been increasingly recognized in novel and emerging entities characterized by somatic mutations in the TSC1/2 and MTOR in patients who do not suffer from the TSC. Correct recognition of RCC with TSC / MTOR mutations is critical for accurate prognostication because such tumors with aggressive behavior have the potential to be tailored to mTOR inhibitors. Whether TSC/MTOR mutated renal epithelial neoplasms represent a distinct molecular class has been confounded by the fact that TSC1/2 , and the gene encoding the downstream protein MTOR, are mutated secondarily in ∼5% of the more common subtypes of RCC, including the commonest subtype of clear cell RCC. This review summarizes the expanding morphologic spectrum of renal tumors with TSC/mTOR pathway alterations, specifically for sporadically occurring tumors where these genomic alterations likely are primary pathologic events. Finally, a practical surgical pathology approach to handling these tumors, and a conceptual framework of renal epithelial tumors with TSC/MTOR mutations as a "family of tumors", is presented.
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Affiliation(s)
- Rajal B Shah
- Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX
| | - Rohit Mehra
- Department of Pathology and Michigan Center for Translational Pathology, University of Michigan School of Medicine, Ann Arbor, MI
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19
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Bai J, Li X, Wen Y, Lu Q, Chen R, Liu R, Shangguan T, Ye Y, Lin J, Cai W, Kang D, Chen J. The clinicopathologic and molecular features, and treatment outcome of fumarate hydratase-deficient renal cell carcinoma: a retrospective comparison with type 2 papillary renal cell carcinoma. Aging (Albany NY) 2024; 16:3631-3646. [PMID: 38376408 PMCID: PMC10929833 DOI: 10.18632/aging.205549] [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: 10/03/2023] [Accepted: 12/27/2023] [Indexed: 02/21/2024]
Abstract
BACKGROUND To compare clinicopathologic, molecular features, and treatment outcome between fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and type 2 papillary renal cell carcinoma (T2 pRCC). METHODS Data of T2 pRCC patients and FH-dRCC patients with additional next-generation sequencing information were retrospectively analyzed. The cancer-specific survival (CSS) and disease-free survival (DFS) were primary endpoint. RESULTS A combination of FH and 2-succino-cysteine (2-SC) increased the rate of negative predictive value of FH-dRCC. Compared with T2 pRCC cases, FH-dRCC cases displayed a greater prevalence in young patients, a higher frequency of radical nephrectomy. Seven FH-dRCC and two T2 pRCC cases received systemic therapy. The VEGF treatment was prescribed most frequently, with an objective response rate (ORR) of 22.2% and a disease control rate (DCR) of 30%. A combined therapy with VEGF and checkpoint inhibitor reported an ORR of 40% and a DCR of 100%. FH-dRCC cases showed a shortened CSS (P = 0.042) and DFS (P < 0.001). The genomic sequencing revealed 9 novel mutations. CONCLUSIONS Coupled with genetic detection, immunohistochemical biomarkers (FH and 2-SC) can distinguish the aggressive FH-dRCC from T2 pRCC. Future research is awaited to illuminate the association between the novel mutations and the clinical phenotypes of FH-dRCC in the disease progression.
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Affiliation(s)
- Junjie Bai
- Department of Urology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
- The Graduate School of Fujian Medical University, Fuzhou 350000, Fujian, P.R. China
| | - Xiaoyan Li
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
| | - Yahui Wen
- The Graduate School of Fujian Medical University, Fuzhou 350000, Fujian, P.R. China
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
| | - Qing Lu
- Department of Urology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
| | - Ru Chen
- Department of Urology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
| | - Rong Liu
- Department of Urology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
| | - Tong Shangguan
- Department of Urology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
- The Graduate School of Fujian Medical University, Fuzhou 350000, Fujian, P.R. China
| | - Yushi Ye
- Department of Urology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
- The Graduate School of Fujian Medical University, Fuzhou 350000, Fujian, P.R. China
| | - Jun Lin
- Department of Urology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
- The Graduate School of Fujian Medical University, Fuzhou 350000, Fujian, P.R. China
| | - Weizhong Cai
- Department of Urology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
| | - Deyong Kang
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
| | - Jianhui Chen
- Department of Urology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
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20
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Sun W, Yue J, Fan L. Clear cell renal cell carcinoma with syncytial giant cells: Not that rare. Pathol Res Pract 2024; 253:155043. [PMID: 38183816 DOI: 10.1016/j.prp.2023.155043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 11/30/2023] [Accepted: 12/16/2023] [Indexed: 01/08/2024]
Abstract
Syncytial giant cells (SGCs) are neoplastic giant cells of epithelial origin. The nuclear morphology of SGCs is uniform and similar to those of adjacent mononuclear tumor cells. Clear cell renal cell carcinoma (ccRCC) with SGCs is a rare microscopic morphology. In this study, the clinical and pathological data of 16 ccRCC cases with SGCs were retrospectively reviewed. The incidence of SGCs in pathological stages pT3 and above (12.1%, 8/66) was significantly higher than that in pT1 and pT2 (2.6%, 8/306) (P = 0.002). The incidence of SGCs in the WHO/ISUP nuclear grade 3 or 4 ccRCC (12.4%, 14/113) was significantly higher than that in grade 1 or 2 (0.8%, 2/259) (P < 0.001). Two forms of SGCs were observed, some exhibited nuclear pyknosis and degeneration. Of the 16 cases, eight cases were accompanied by necrosis and seven cases had lymphovascular invasion. Both SGCs and mononuclear tumor cells were positive for ccRCC markers (PAX8, CAIX, CD10 and Vimentin). None of the SGC nuclei were positive for Ki-67. Follow-up information was available on 14 patients, with a median follow-up time of 27.5 months. Ten patients were alive without disease, three were alive with metastatic disease, and one patient died 10 months after surgery. These findings indicated that SGCs are not rare, especially in ccRCC with high nuclear grade and pathological stage, and often co-exist with other adverse prognostic features. SGCs may be senescent tumor cells, the presence of SGCs should not be considered as Fuhrman and WHO/ISUP nuclear grading 4.
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Affiliation(s)
- Wenjia Sun
- Department of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430070, Hubei, China
| | - Junqiu Yue
- Department of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430070, Hubei, China
| | - Lifang Fan
- Department of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430070, Hubei, China.
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21
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Li J, Wilkerson ML, Deng FM, Liu H. The Application and Pitfalls of Immunohistochemical Markers in Challenging Diagnosis of Genitourinary Pathology. Arch Pathol Lab Med 2024; 148:13-32. [PMID: 37074862 DOI: 10.5858/arpa.2022-0493-ra] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2023] [Indexed: 04/20/2023]
Abstract
CONTEXT.— The morphologic features of different entities in genitourinary pathology overlap, presenting a diagnostic challenge, especially when diagnostic materials are limited. Immunohistochemical markers are valuable when morphologic features alone are insufficient for definitive diagnosis. The World Health Organization classification of urinary and male genital tumors has been updated for 2022. An updated review of immunohistochemical markers for newly classified genitourinary neoplasms and their differential diagnosis is needed. OBJECTIVE.— To review immunohistochemical markers used in the diagnosis of genitourinary lesions in the kidney, bladder, prostate, and testis. We particularly emphasized difficult differential diagnosis and pitfalls in immunohistochemistry application and interpretation. New markers and new entities in the 2022 World Health Organization classifications of genitourinary tumors are reviewed. Recommended staining panels for commonly encountered difficult differential diagnoses and potential pitfalls are discussed. DATA SOURCES.— Review of current literature and our own experience. CONCLUSIONS.— Immunohistochemistry is a valuable tool in the diagnosis of problematic lesions of the genitourinary tract. However, the immunostains must be carefully interpreted in the context of morphologic findings with a thorough knowledge of pitfalls and limitations.
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Affiliation(s)
- Jianhong Li
- From the Department of Pathology, Geisinger Medical Center, Danville, Pennsylvania (Li, Wilkerson, Liu)
| | - Myra L Wilkerson
- From the Department of Pathology, Geisinger Medical Center, Danville, Pennsylvania (Li, Wilkerson, Liu)
| | - Fang-Ming Deng
- the Department of Pathology, New York University Grossman School of Medicine, New York City (Deng)
| | - Haiyan Liu
- From the Department of Pathology, Geisinger Medical Center, Danville, Pennsylvania (Li, Wilkerson, Liu)
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22
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Alchoueiry M, Cornejo K, Henske EP. Kidney cancer: Links between hereditary syndromes and sporadic tumorigenesis. Semin Diagn Pathol 2024; 41:1-7. [PMID: 38008653 DOI: 10.1053/j.semdp.2023.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 11/06/2023] [Indexed: 11/28/2023]
Abstract
Multiple hereditary syndromes predispose to kidney cancer, including Von Hippel-Lindau syndrome, BAP1-Tumor Predisposition Syndrome, Hereditary Papillary Renal Cell Carcinoma, Tuberous Sclerosis Complex, Birt-Hogg-Dubé syndrome, Hereditary Paraganglioma-Pheochromocytoma Syndrome, Fumarate Hydratase Tumor Predisposition Syndrome, and Cowden syndrome. In some cases, mutations in the genes that cause hereditary kidney cancer are tightly linked to similar histologic features in sporadic RCC. For example, clear cell RCC occurs in the hereditary syndrome VHL, and sporadic ccRCC usually has inactivation of the VHL gene. In contrast, mutations in FLCN, the causative gene for Birt-Hogg-Dube syndrome, are rarely found in sporadic RCC. Here, we focus on the genes and pathways that link hereditary and sporadic RCC.
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Affiliation(s)
- Michel Alchoueiry
- Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Kristine Cornejo
- Pathology Department, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Elizabeth P Henske
- Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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23
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Kim B, Lee S, Moon KC. Papillary renal neoplasm with reverse polarity: a clinicopathologic study of 43 cases with a focus on the expression of KRAS signaling pathway downstream effectors. Hum Pathol 2023; 142:1-6. [PMID: 37797754 DOI: 10.1016/j.humpath.2023.09.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 09/25/2023] [Accepted: 09/28/2023] [Indexed: 10/07/2023]
Abstract
Papillary renal neoplasm with reverse polarity (PRNRP) is a renal tumor with frequent KRAS mutations. In this study, we aimed to report the clinical, histological, and immunohistochemical characteristics of PRNRP and the protein expression of various KRAS signaling pathway downstream effectors in PRNRP. PRNRP samples from patients who underwent surgical resection at Seoul National University Hospital over an 11-year period (January 2011 to December 2021) were analyzed. We identified 43 PRNRPs, defined as papillary renal tumors with a thin papillary architecture, eosinophilic finely granular cytoplasm, and apical nuclear position. Immunohistochemistry revealed typical characteristics of PRNRP, including exclusively positive GATA3 (43/43); highly positive L1CAM (43/43), PAX8 (43/43), and EMA (43/43); and low positive AMACR (4/43), RCC (1/43), and vimentin (1/43). KRAS signaling pathway effectors, such as p-ERK, RalA, and RalB, were highly expressed in PRNRP compared to papillary renal cell carcinoma (pRCC) with low or high nuclear grade (P < .001, all). Compared to pRCC with high nuclear grade, patients with PRNRP exhibited significantly longer progression-free survival (P < .001). PRNRP showed the best clinical outcome, with no disease progression in any of the cases. Our study analyzed the largest number of PRNRP cases and is the first to analyze the association between PRNRP and the KRAS downstream signaling pathway. PRNRP was found at a high frequency among all papillary renal tumors (43/207) and demonstrated a very good prognosis. PRNRP showed high GATA3, L1CAM, PAX8, and EMA protein expression as well as high p-ERK, RalA, and RalB protein expression.
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Affiliation(s)
- Bohyun Kim
- Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 03080, Republic of Korea
| | - Seokhyeon Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Kyung Chul Moon
- Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Pathology, Seoul National University Hospital, Seoul 03080, Republic of Korea; Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
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24
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Ricci C, Ambrosi F, Franceschini T, Giunchi F, Grillini A, Franchini E, Grillini M, Schiavina R, Massari F, Mollica V, Tateo V, Bianchi FM, Bianchi L, Droghetti M, Maloberti T, Tallini G, Colecchia M, Acosta AM, Lobo J, Trpkov K, Fiorentino M, de Biase D. Evaluation of an institutional series of low-grade oncocytic tumor (LOT) of the kidney and review of the mutational landscape of LOT. Virchows Arch 2023; 483:687-698. [PMID: 37845471 PMCID: PMC10673759 DOI: 10.1007/s00428-023-03673-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/24/2023] [Accepted: 09/29/2023] [Indexed: 10/18/2023]
Abstract
The 2022 WHO classification of urinary and male genital tumors introduced several novel kidney entities exhibiting eosinophilic/oncocytic features with specific mutational backgrounds. Thus, molecular techniques, such as next-generation sequencing (NGS), became more commonly used for their evaluation. We studied 12 low-grade oncocytic tumors (LOT) of the kidney (from 11 patients), identified in a cohort of 210 eosinophilic/oncocytic renal tumors, diagnosed in our institution between October 2019 and May 2023, which represented 5.7% (12/210) of all eosinophilic/oncocytic renal tumors during this period. We reviewed their clinicopathologic, histologic, and immunohistochemical features, as well as their mutational profiles. We also reviewed the literature on NGS-derived data of LOT, by selecting papers in which LOT diagnosis was rendered according to the criteria proposed initially. Median age was 65 years (mean: 63.5; range 43-79) and median tumor size was 2.0 cm (mean: 2.2; range: 0.9-3.1). All tumors were positive for PAX8, CK7, and GATA3, and negative or focally positive for CD117/KIT. We found the following gene mutations: MTOR ((6/11), 54.5%)), TSC1 ((2/11), 18.2%)), and 1 had both NOTCH1 and NOTCH4 ((1/11), 9.1%)). Wild-type status was found in 2/11 (18.2%) patients and one tumor was not analyzable. A review of 8 previous studies that included 79 LOTs revealed frequent mutations in the genes that regulate the mammalian target of rapamycin (mTOR) pathway: MTOR (32/79 (40.5%)), TSC1 (21/79 (26.6%)), and TSC2 (9/79 (11.4%)). Other mutated genes included PIK3CA, NF2, and PTEN, not typically known to affect the mTOR pathway, but potentially acting as upstream and downstream effectors. Our study shows that LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without "canonical" mutations.
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Affiliation(s)
- Costantino Ricci
- Pathology Unit, Maggiore Hospital-AUSL Bologna, Bologna, Italy.
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.
| | - Francesca Ambrosi
- Pathology Unit, Maggiore Hospital-AUSL Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | | | - Francesca Giunchi
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | | | | | - Marco Grillini
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Riccardo Schiavina
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
- Division of Urology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Francesco Massari
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Veronica Mollica
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Valentina Tateo
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | | | - Lorenzo Bianchi
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
- Division of Urology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Matteo Droghetti
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
- Division of Urology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Thais Maloberti
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
- Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Giovanni Tallini
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
- Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Maurizio Colecchia
- Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Andres Martin Acosta
- Department of Pathology, Indiana University School of Medicine, Indianapolis, USA
| | - João Lobo
- Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal
- Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (P.CCC), Research Center of IPO Porto (GEBC CI-IPOP)/RISE@CI-IPOP (Health Research Network), Porto, Portugal
- Department of Pathology and Molecular Immunology, ICBAS-School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Porto, Portugal
| | - Kiril Trpkov
- Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary and Alberta Precision Laboratories, Calgary, Canada
| | - Michelangelo Fiorentino
- Pathology Unit, Maggiore Hospital-AUSL Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
| | - Dario de Biase
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
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25
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Kapur P, Brugarolas J, Trpkov K. Recent Advances in Renal Tumors with TSC/mTOR Pathway Abnormalities in Patients with Tuberous Sclerosis Complex and in the Sporadic Setting. Cancers (Basel) 2023; 15:4043. [PMID: 37627070 PMCID: PMC10452688 DOI: 10.3390/cancers15164043] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 08/04/2023] [Accepted: 08/04/2023] [Indexed: 08/27/2023] Open
Abstract
A spectrum of renal tumors associated with frequent TSC/mTOR (tuberous sclerosis complex/mechanistic target of rapamycin) pathway gene alterations (in both the germline and sporadic settings) have recently been described. These include renal cell carcinoma with fibromyomatous stroma (RCC FMS), eosinophilic solid and cystic renal cell carcinoma (ESC RCC), eosinophilic vacuolated tumor (EVT), and low-grade oncocytic tumor (LOT). Most of these entities have characteristic morphologic and immunohistochemical features that enable their recognition without the need for molecular studies. In this report, we summarize recent advances and discuss their evolving complexity.
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Affiliation(s)
- Payal Kapur
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Kidney Cancer Program at Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - James Brugarolas
- Kidney Cancer Program at Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Hematology-Oncology Division of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Kiril Trpkov
- Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2L 2K5, Canada
- Alberta Precision Labs, Rockyview General Hospital, 7007 14 St., Calgary, AB T2V 1P9, Canada
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26
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Klontzas ME, Koltsakis E, Kalarakis G, Trpkov K, Papathomas T, Sun N, Walch A, Karantanas AH, Tzortzakakis A. A pilot radiometabolomics integration study for the characterization of renal oncocytic neoplasia. Sci Rep 2023; 13:12594. [PMID: 37537362 PMCID: PMC10400617 DOI: 10.1038/s41598-023-39809-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 07/31/2023] [Indexed: 08/05/2023] Open
Abstract
Differentiating benign renal oncocytic tumors and malignant renal cell carcinoma (RCC) on imaging and histopathology is a critical problem that presents an everyday clinical challenge. This manuscript aims to demonstrate a novel methodology integrating metabolomics with radiomics features (RF) to differentiate between benign oncocytic neoplasia and malignant renal tumors. For this purpose, thirty-three renal tumors (14 renal oncocytic tumors and 19 RCC) were prospectively collected and histopathologically characterised. Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) was used to extract metabolomics data, while RF were extracted from CT scans of the same tumors. Statistical integration was used to generate multilevel network communities of -omics features. Metabolites and RF critical for the differentiation between the two groups (delta centrality > 0.1) were used for pathway enrichment analysis and machine learning classifier (XGboost) development. Receiver operating characteristics (ROC) curves and areas under the curve (AUC) were used to assess classifier performance. Radiometabolomics analysis demonstrated differential network node configuration between benign and malignant renal tumors. Fourteen nodes (6 RF and 8 metabolites) were crucial in distinguishing between the two groups. The combined radiometabolomics model achieved an AUC of 86.4%, whereas metabolomics-only and radiomics-only classifiers achieved AUC of 72.7% and 68.2%, respectively. Analysis of significant metabolite nodes identified three distinct tumour clusters (malignant, benign, and mixed) and differentially enriched metabolic pathways. In conclusion, radiometabolomics integration has been presented as an approach to evaluate disease entities. In our case study, the method identified RF and metabolites important in differentiating between benign oncocytic neoplasia and malignant renal tumors, highlighting pathways differentially expressed between the two groups. Key metabolites and RF identified by radiometabolomics can be used to improve the identification and differentiation between renal neoplasms.
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Affiliation(s)
- Michail E Klontzas
- Department of Medical Imaging, University Hospital of Heraklion, Crete, Heraklion, Greece
- Computational BioMedicine Laboratory, Institute of Computer Science, Foundation for Research and Technology (FORTH), Crete, Heraklion, Greece
- Department of Radiology, School of Medicine, University of Crete, Voutes Campus, Heraklion, Greece
- Division of Radiology, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Emmanouil Koltsakis
- Department of Diagnostic Radiology, Karolinska University Hospital, Solna, Stockholm, Sweden
| | - Georgios Kalarakis
- Division of Radiology, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
- Department of Diagnostic Radiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden
- University of Crete, School of Medicine, 71500, Heraklion, Greece
| | - Kiril Trpkov
- Department of Pathology and Laboratory Medicine, Alberta Precision Labs, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Thomas Papathomas
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
- Department of Clinical Pathology, Vestre Viken Hospital Trust, Drammen, Norway
| | - Na Sun
- Research Unit Analytical Pathology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany
| | - Axel Walch
- Research Unit Analytical Pathology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany
| | - Apostolos H Karantanas
- Department of Medical Imaging, University Hospital of Heraklion, Crete, Heraklion, Greece
- Computational BioMedicine Laboratory, Institute of Computer Science, Foundation for Research and Technology (FORTH), Crete, Heraklion, Greece
- Department of Radiology, School of Medicine, University of Crete, Voutes Campus, Heraklion, Greece
| | - Antonios Tzortzakakis
- Division of Radiology, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
- Medical Radiation Physics and Nuclear Medicine, Section for Nuclear Medicine, Karolinska University Hospital, Huddinge, C2:74, 14 186, Stockholm, Sweden.
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27
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Siadat F, Mansoor M, Hes O, Trpkov K. Kidney Tumors: New and Emerging Kidney Tumor Entities. Clin Lab Med 2023; 43:275-298. [PMID: 37169446 DOI: 10.1016/j.cll.2023.03.003] [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: 05/13/2023]
Abstract
This review summarizes current knowledge on several novel and emerging renal entities, including eosinophilic solid and cystic renal cell carcinoma (RCC), RCC with fibromyomatous stroma, anaplastic lymphoma kinase-rearranged RCC, low-grade oncocytic renal tumor, eosinophilic vacuolated tumor, thyroidlike follicular RCC, and biphasic hyalinizing psammomatous RCC. Their clinical features, gross and microscopic morphology, immunohistochemistry, and molecular and genetic features are described. The diagnosis of most of them rests on recognizing their morphologic features using immunohistochemistry. Accurate diagnosis of these entitles will further reduce the category of "unclassifiable renal carcinomas/tumors" and will lead to better clinical management and improved patient prognostication.
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Affiliation(s)
- Farshid Siadat
- Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Rockyview General Hospital, 7007 14 Street, Calgary, Alberta T2V 1P9, Canada. https://twitter.com/FSiadat
| | - Mehdi Mansoor
- Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Rockyview General Hospital, 7007 14 Street, Calgary, Alberta T2V 1P9, Canada
| | - Ondrej Hes
- Department of Pathology, Charles University in Prague, Faculty of Medicine in Plzeň, University Hospital Plzen, Alej Svobody 80, 304 60 Pilsen, Czech Republic
| | - Kiril Trpkov
- Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Rockyview General Hospital, 7007 14 Street, Calgary, Alberta T2V 1P9, Canada.
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28
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Ventriglia J, Passarelli A, Pisano C, Cecere SC, Rossetti S, Feroce F, Forte M, Casartelli C, Tambaro R, Pignata S, Perversi F, Di Napoli M. The role of immunotherapy treatment in non-clear cell renal cell carcinoma: an analysis of the literature. Crit Rev Oncol Hematol 2023:104036. [PMID: 37263397 DOI: 10.1016/j.critrevonc.2023.104036] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 05/11/2023] [Accepted: 05/23/2023] [Indexed: 06/03/2023] Open
Abstract
Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group representing 15-30% of renal tumors. They are mostly excluded from immunotherapy trials due to their rarity and worse prognosis. This, alongside nccRCC misdiagnosis/misclassification, lack of immune-biomarker expression rate data, lack of homogeneous data reporting, the retrospective nature of many studies, small sample sizes, and the fact that high-grade evidence only stems from trials mostly addressing the clear cell subtype, result in poorly defined treatments. We thus reviewed available data from several clinical trials, retrospective studies, and meta-analyses on immunotherapy responses and their correlation with histological subtypes and prognostic biomarkers. The papillary and unclassified subtypes are the best candidate for immunotherapy, showing response rates up to ~35%. Chromophobe cancers, on the other end, have mostly null response rates. Cancers with sarcomatoid features respond very well to immunotherapy, regardless of their histology. Available data for translocation, medullary, collecting duct, and other nccRCCs are inconclusive. Regarding PD-L1, its expression correlates with better responses, but its prognostic value remains to be determined due to small sample sizes hindering direct statistical comparisons. It is necessary to involve a larger number of nccRCC patients and centers in clinical trials and report tumor response rates and PD-(L)1 and other markers' expression rates divided by nccRCC subtypes and not just for the whole cohorts. This will allow us to collect more robust data to best identify patients who can benefit from immunotherapy and ultimately define the standard of treatment. AVAILABILITY OF DATA AND MATERIAL: N/A.
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Affiliation(s)
- Jole Ventriglia
- Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80138 Naples, Italy.
| | - Anna Passarelli
- Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80138 Naples, Italy.
| | - Carmela Pisano
- Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80138 Naples, Italy.
| | - Sabrina Chiara Cecere
- Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80138 Naples, Italy.
| | - Sabrina Rossetti
- Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80138 Naples, Italy.
| | - Florinda Feroce
- Pathology Unit, Istituto Nazionale Tumori Fondazione G Pascale IRCCS, Naples, 80131, Italy.
| | - Miriam Forte
- Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, Napoli, Campania(,) Italy.
| | - Chiara Casartelli
- Medical oncology Unit, University Hospital of Parma, Parma 43126, Italy.
| | - Rosa Tambaro
- Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80138 Naples, Italy.
| | - Sandro Pignata
- Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80138 Naples, Italy.
| | | | - Marilena Di Napoli
- Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 80138 Naples, Italy.
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29
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Chen T, Peng Y, Lei T, Wu C, Wang H, Shi Y. Low-grade oncocytic tumour (LOT) of the kidney is characterised by GATA3 positivity, FOXI1 negativity and mTOR pathway mutations. Pathol Oncol Res 2023; 29:1610852. [PMID: 36816543 PMCID: PMC9928737 DOI: 10.3389/pore.2023.1610852] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 01/12/2023] [Indexed: 02/04/2023]
Abstract
Aims: We present a 5-case series of low-grade oncocytic tumour of the kidney to further discuss their clinicopathological characteristics. Methods and results: Five patients were included in this study. There were three females and two males aged 45-66 years, with a median age of 65 years. Four tumours were located in the right kidney, and one was located in the left kidney. Most of the tumour sections were yellow-brown in colour. Tumour sizes ranged from 2.5 to 4.5 cm, with a median size of 3 cm. Microscopically, the tumours were well-circumscribed but lacked a fibrous capsule; the tumours consisted of monomorphous oncocytic cells arranged mainly in solid and nested architectural patterns. The tumour cells had uniformly round to oval nuclei and often had perinuclear halos but lacked significant irregularities. Immunohistochemically, the tumour cells showed a diffuse and strong positivity for CK7 and were negative for CD117. The tumour cells were also positive for GATA3, E-cadherin, Pax-8, Succinate dehydrogenase B (SDHB) and Fumarate hydratase (FH), and negative for vimentin, Carbonic anhydrase 9 (CA9), CD10, P504s, CK20, TFE3, TFEB, HMB45, ALK and Forkhead box protein I1 (FOXI1). Next-generation sequencing identified genetic variations in these tumours, including MTOR gene mutations (4/5) and PIK3CA gene mutation (1/5). All patients were alive without disease progression at a median follow-up of 32 months (range 10-57 months). Conclusion: LOT is an emerging renal entity of indolent behaviour that has morphologic overlap with some renal tumours with eosinophilic cytoplasm, primarily with oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma. Familiarity with the distinctive morphological features, immunophenotype and molecular genetics of LOT helps avoid misdiagnosis.
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Affiliation(s)
- Tongbing Chen
- Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China
| | - Yan Peng
- Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China
| | - Ting Lei
- Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China
| | - Chao Wu
- Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China
| | - Hui Wang
- Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China
| | - Yongqiang Shi
- Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China
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30
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Eosinophilic solid and cystic renal cell carcinoma: a review of literature focused on radiological findings and differential diagnosis. ABDOMINAL RADIOLOGY (NEW YORK) 2023; 48:350-357. [PMID: 36222870 DOI: 10.1007/s00261-022-03694-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/25/2022] [Accepted: 09/26/2022] [Indexed: 01/21/2023]
Abstract
Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a rare type of renal cell carcinoma with inert biological behavior that has not yet been included in the 2016 World Health Organization (WHO) classification, and its imaging manifestations are unclear due to its rarity. Although there have only been a few cases, the CT and MRI findings of ESC-RCC are characterized by its cystic solid structure, according to the proportion of cystic and solid components observed on images, ESC-RCC can be categorized into three types. Especially the Type I, when the cystic-solid components are almost equal, the imaging findings are illustrated as "lotus root-like," which may be helpful in the differential diagnosis of ESC-RCC from other types of renal tumors. In fact, ESC-RCC has diverse radiological appearances, and the differentiation of clear cell renal cell carcinoma, renal oncocytoma, chromophobe renal cell carcinoma, and renal angiomyolipoma remains challenging. This review aims to discuss ESC-RCC with a focus on the radiological findings and differential diagnosis of ESC-RCC.
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Cabanillas G, Montoya-Cerrillo D, Kryvenko ON, Pal SK, Arias-Stella JA. "Collecting duct carcinoma of the kidney: diagnosis and implications for management". Urol Oncol 2022; 40:525-536. [PMID: 34116936 DOI: 10.1016/j.urolonc.2021.04.041] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 04/07/2021] [Accepted: 04/28/2021] [Indexed: 01/13/2023]
Abstract
Collecting duct carcinoma of the kidney is a rare and aggressive subtype of renal cell carcinoma (RCC) arising from the distal convoluted tubules. At the time of diagnosis, patients are more frequently symptomatic, with advanced locoregional stage, and have metastatic disease. The 2016 WHO Classification of Tumours of the Urinary System defined diagnostic criteria for this entity. However, the diagnostic features continue to evolve, with typical, but not entirely specific, histologic and immunophenotypic characteristics. In addition, the lack of consistent molecular alterations makes collecting duct carcinoma a diagnosis of exclusion, with historical cases being re-classified as fumarate hydratase deficient RCC, ALK rearranged RCC, renal medullary carcinoma or high-grade urothelial carcinoma. The rarity and poor prognosis of the tumor makes it difficult to reach consensus guidelines to guide therapy. In this manuscript we review the clinicopathologic features of collecting duct carcinoma including pathologic diagnostic criteria, molecular characteristics and differential diagnosis, and their possible implications for management.
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Affiliation(s)
- Gerardo Cabanillas
- Internal Medicine Department, Pacifica Hospital of the Valley, Serra Medical Group, Sun Valley, CA
| | | | - Oleksandr N Kryvenko
- Department of Pathology and Laboratory Medicine; Department of Urology; Sylvester Comprehensive Cancer Center, University of Miami / Jackson Memoria Hospital, Miami, FL
| | - Sumanta K Pal
- Department of Medical Oncology & Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA
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32
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Pathak NJ, Singh AG, Jain PS, Soni SM, Ganpule AP, Sabnis RB, Desai MR. Eosinophilic solid and cystic renal cell carcinoma: a single Indian tertiary center experience of three cases of a newly described entity. AFRICAN JOURNAL OF UROLOGY 2022. [DOI: 10.1186/s12301-022-00312-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Abstract
Background
Among adult malignant tumors, renal cell carcinoma accounts for 2–3% and has the worst prognosis among common urologic tumors. Recently, an eosinophilic, solid and cystic (ESC) renal cell carcinoma (RCC) histological subtype has been described and proposed as an entity separate than the 16 subtypes described in the 2016 WHO classification. The aim of the present study is to share our experience of three such cases of this newly described entity.
Methods
We retrospectively reviewed our cases of renal cell carcinoma and describe the presentation, diagnosis and management with follow-up details of ESC RCC.
Results
Our three patients presented at an advanced stage with flank pain or mass, and one patient had metastasis. All patients underwent radical nephrectomy, diagnosis proved by histopathological examination with immunohistochemistry (IHC), with abundant eosinophilic cytoplasm in all three cases. On IHC, CK 20 was positive in two cases and one patient with CK 20, CK 7 negative and PAX 8 positive.
Conclusions
ESC RCC is a newly described entity, with increasing incidence probably due to better diagnosis. Previously, 66 such cases are described, with female predominance, lower stage and indolent behavior. Only four cases with metastasis are described.
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Muacevic A, Adler JR, Ghoundale O, Azami MA. Renal Cell Carcinoma With Fibromyomatous Stroma: A New Case. Cureus 2022; 14:e32238. [PMID: 36620787 PMCID: PMC9815789 DOI: 10.7759/cureus.32238] [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] [Accepted: 12/05/2022] [Indexed: 12/12/2022] Open
Abstract
In the 2016 World Health Organization (WHO) classification of renal tumors, renal cell carcinoma with fibromyomatous stroma (RCC FMS) (formerly RCC with leiomyomatous or smooth muscle stroma) was classified as an emerging or provisional entity of renal cell carcinoma (RCC). We report a rare case of RCC FMS in a 62-year-old male patient with hypertension, type II diabetes mellitus, and early chronic kidney disease. He was referred to the Department of Urology for an incidental finding of a 2-cm-long left renal nodule on a routine abdominal ultrasound. A laparoscopic right partial nephrectomy was performed. Histopathology and immunohistochemistry studies confirm the diagnosis of RCC FMS. The purpose of this work is to review and discuss newly acquired data and evidence on the clinical, pathological, immunohistochemical, molecular, and prognostic aspects of this unusual entity in the hopes of assisting pathologists in accurate diagnosis.
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34
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Siadat F, Mansoor M, Hes O, Trpkov K. Kidney Tumors: New and Emerging Kidney Tumor Entities. Surg Pathol Clin 2022; 15:713-728. [PMID: 36344185 DOI: 10.1016/j.path.2022.07.006] [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: 05/18/2023]
Abstract
This review summarizes current knowledge on several novel and emerging renal entities, including eosinophilic solid and cystic renal cell carcinoma (RCC), RCC with fibromyomatous stroma, anaplastic lymphoma kinase-rearranged RCC, low-grade oncocytic renal tumor, eosinophilic vacuolated tumor, thyroidlike follicular RCC, and biphasic hyalinizing psammomatous RCC. Their clinical features, gross and microscopic morphology, immunohistochemistry, and molecular and genetic features are described. The diagnosis of most of them rests on recognizing their morphologic features using immunohistochemistry. Accurate diagnosis of these entitles will further reduce the category of "unclassifiable renal carcinomas/tumors" and will lead to better clinical management and improved patient prognostication.
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Affiliation(s)
- Farshid Siadat
- Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Rockyview General Hospital, 7007 14 Street, Calgary, Alberta T2V 1P9, Canada. https://twitter.com/FSiadat
| | - Mehdi Mansoor
- Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Rockyview General Hospital, 7007 14 Street, Calgary, Alberta T2V 1P9, Canada
| | - Ondrej Hes
- Department of Pathology, Charles University in Prague, Faculty of Medicine in Plzeň, University Hospital Plzen, Alej Svobody 80, 304 60 Pilsen, Czech Republic
| | - Kiril Trpkov
- Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Rockyview General Hospital, 7007 14 Street, Calgary, Alberta T2V 1P9, Canada.
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35
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Moch H, Amin MB, Berney DM, Compérat EM, Gill AJ, Hartmann A, Menon S, Raspollini MR, Rubin MA, Srigley JR, Hoon Tan P, Tickoo SK, Tsuzuki T, Turajlic S, Cree I, Netto GJ. The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol 2022; 82:458-468. [PMID: 35853783 DOI: 10.1016/j.eururo.2022.06.016] [Citation(s) in RCA: 330] [Impact Index Per Article: 110.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 06/21/2022] [Indexed: 02/07/2023]
Abstract
The fifth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "Blue Book"), published in 2022, contains significant revisions. This review summarises the most relevant changes for renal, penile, and testicular tumours. In keeping with other volumes in the fifth edition series, the WHO classification of urogenital tumours follows a hierarchical classification and lists tumours by site, category, family, and type. The section "essential and desirable diagnostic criteria" included in the WHO fifth edition represents morphologic diagnostic criteria, combined with immunohistochemistry and relevant molecular tests. The global introduction of massive parallel sequencing will result in a diagnostic shift from morphology to molecular analyses. Therefore, a molecular-driven renal tumour classification has been introduced, taking recent discoveries in renal tumour genomics into account. Such novel molecularly defined epithelial renal tumours include SMARCB1-deficient medullary renal cell carcinoma (RCC), TFEB-altered RCC, Alk-rearranged RCC, and ELOC-mutated RCC. Eosinophilic solid and cystic RCC is a novel morphologically defined RCC entity. The diverse morphologic patterns of penile squamous cell carcinomas are grouped as human papillomavirus (HPV) associated and HPV independent, and there is an attempt to simplify the morphologic classification. A new chapter with tumours of the scrotum has been introduced. The main nomenclature of testicular tumours is retained, including the use of the term "germ cell neoplasia in situ" (GCNIS) for the preneoplastic lesion of most germ cell tumours and division from those not derived from GCNIS. Nomenclature changes include replacement of the term "primitive neuroectodermal tumour" by "embryonic neuroectodermal tumour" to separate these tumours clearly from Ewing sarcoma. The term "carcinoid" has been changed to "neuroendocrine tumour", with most examples in the testis now classified as "prepubertal type testicular neuroendocrine tumour".
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Affiliation(s)
- Holger Moch
- Department of Pathology and Molecular Pathology, University Hospital Zuerich and University of Zuerich, Zuerich, Switzerland.
| | - Mahul B Amin
- Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN, USA; Department of Urology, USC Keck School of Medicine, Los Angeles, CA, USA
| | - Daniel M Berney
- Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Cellular Pathology, Barts Health NHS Trust, London, UK
| | - Eva M Compérat
- Department of Pathology, Medical University of Vienna, General Hospital of Vienna, Vienna, Austria
| | - Anthony J Gill
- Sydney Medical School, University of Sydney, Sydney, Australia; NSW Health Pathology, Department of Anatomical Pathology and Pathology Group Kolling Institute of Medical Research Royal North Shore Hospital St Leonards, Sydney, Australia
| | - Arndt Hartmann
- Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Santosh Menon
- Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Maria R Raspollini
- Histopathology and Molecular Diagnostics, University Hospital Careggi, Florence, Italy
| | - Mark A Rubin
- Department for BioMedical Research (DBMR), Bern Center for Precision Medicine (BCPM), University of Bern and Inselspital, Bern, Switzerland
| | - John R Srigley
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Puay Hoon Tan
- Division of Pathology, Singapore General Hospital, Singapore
| | - Satish K Tickoo
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Toyonori Tsuzuki
- Department of Surgical Pathology, Aichi Medical University Hospital, Nagakut, Japan
| | - Samra Turajlic
- The Francis Crick Institute and The Royal Marsden NHS Foundation Trust, London, UK
| | - Ian Cree
- International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France
| | - George J Netto
- Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
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36
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Amin MB, McKenney JK, Martignoni G, Campbell SC, Pal S, Tickoo SK. Low grade oncocytic tumors of the kidney: a clinically relevant approach for the workup and accurate diagnosis. Mod Pathol 2022; 35:1306-1316. [PMID: 35896615 DOI: 10.1038/s41379-022-01108-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 05/02/2022] [Accepted: 05/09/2022] [Indexed: 11/09/2022]
Abstract
Renal oncocytoma and chromophobe renal cell carcinoma were accepted as unique renal tumors in the late 1990s. Since their formal description, criteria for diagnosis have evolved and additional distinct tumor subtypes originally considered as one these two entities are now recognized. The last two decades have witnessed unprecedented interest in the spectrum of low grade oncocytic renal neoplasms in three specific areas: (1) histologic characterization of tumors with overlapping morphologic features between oncocytoma and chromophobe renal cell carcinoma; (2) description of potentially unique entities within this spectrum, such as eosinophilic vacuolated tumor and low-grade oncocytic tumor; and (3) better appreciation of the association between a subset of low grade oncocytic tumors and hereditary renal neoplasia. While this important work has been academically rewarding, the proposal of several histologic entities with overlapping morphologic and immunophenotypic features (which may require esoteric adjunctive immunohistochemical and/or molecular techniques for confirmation) has created frustration in the diagnostic pathology and urology community as information evolves regarding classification within this spectrum of renal neoplasia. Pathologists, including genitourinary subspecialists, are often uncertain as to the "best practice" diagnostic approach to such tumors. In this review, we present a practical clinically relevant algorithmic approach to classifying tumors within the low grade oncocytic family of renal neoplasia, including a proposal for compressing terminology for evolving categories where appropriate without sacrificing prognostic relevance.
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Affiliation(s)
- Mahul B Amin
- Department of Pathology and Laboratory Medicine, University of Tennessee Health Science, Memphis, TN, USA.
| | - Jesse K McKenney
- Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Guido Martignoni
- Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy.,Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Italy
| | - Steven C Campbell
- Department of Urology, and Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Sumanta Pal
- Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Satish K Tickoo
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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37
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Zhang J, Dong A, Wang Y. FDG PET/CT in Eosinophilic Solid and Cystic Renal Cell Carcinoma With Lung Metastases. Clin Nucl Med 2022; 47:921-922. [PMID: 35605053 DOI: 10.1097/rlu.0000000000004282] [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: 11/25/2022]
Abstract
ABSTRACT Eosinophilic solid and cystic renal cell carcinoma is a recently described emerging renal tumor. Usefulness of FDG PET/CT in the management of eosinophilic solid and cystic renal cell carcinoma has been rarely reported. We describe FDG PET/CT findings in a case of eosinophilic solid and cystic renal cell carcinoma with lung metastases. The primary renal tumor and its metastases showed intense FDG uptake with SUV max of 29.3 for the primary tumor and 21 for the lung metastases.
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Affiliation(s)
- Jun Zhang
- From the Department of Cardiothoracic Surgery, The Second Affiliated Hospital, Jiaxing University, Jiaxing
| | - Aisheng Dong
- Department of Nuclear Medicine, Changhai Hospital, Navy Medical University
| | - Yang Wang
- Department of Pathology, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
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38
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Lobo J, Ohashi R, Amin MB, Berney DM, Compérat EM, Cree IA, Gill AJ, Hartmann A, Menon S, Netto GJ, Raspollini MR, Rubin MA, Tan PH, Tickoo SK, Tsuzuki T, Turajlic S, Zhou M, Srigley JR, Moch H. WHO 2022 landscape of papillary and chromophobe renal cell carcinoma. Histopathology 2022; 81:426-438. [PMID: 35596618 DOI: 10.1111/his.14700] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/04/2022] [Accepted: 05/18/2022] [Indexed: 12/01/2022]
Abstract
The 5th edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems contains relevant revisions and introduces a group of molecularly defined renal tumour subtypes. Herein we present the World Health Organization (WHO) 2022 perspectives on papillary and chromophobe renal cell carcinoma with emphasis on their evolving classification, differential diagnosis, and emerging entities. The WHO 2022 classification eliminated the type 1/2 papillary renal cell carcinoma (pRCC) subcategorization, given the recognition of frequent mixed tumour phenotypes and the existence of entities with a different molecular background within the type 2 pRCC category. Additionally, emerging entities such as biphasic squamoid alveolar RCC, biphasic hyalinising psammomatous RCC, papillary renal neoplasm with reverse polarity, and Warthin-like pRCC are included as part of the pRCC spectrum, while additional morphological and molecular data are being gathered. In addition to oncocytomas and chromophobe renal cell carcinoma (chRCC), a category of 'other oncocytic tumours' with oncocytoma/chRCC-like features has been introduced, including emerging entities, most with TSC/mTOR pathway alterations (eosinophilic vacuolated tumour and so-called 'low-grade' oncocytic tumour), deserving additional research. Eosinophilic solid and cystic RCC was accepted as a new and independent tumour entity. Finally, a highly reproducible and clinically relevant universal grading system for chRCC is still missing and is another niche of ongoing investigation. This review discusses these developments and highlights emerging morphological and molecular data relevant for the classification of renal cell carcinoma.
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Affiliation(s)
- João Lobo
- Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (GEBC CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (P.CCC), Porto, Portugal
- Department of Pathology and Molecular Immunology, ICBAS-School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Porto, Portugal
| | - Riuko Ohashi
- Histopathology Core Facility, Niigata University Faculty of Medicine, Niigata, Japan
- Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Mahul B Amin
- Department of Pathology and Laboratory Medicine, University of Tennessee Health Sciences Center, Memphis, USA
- Department of Urology, University of Southern California, Los Angeles, CA, USA
| | - Daniel M Berney
- Centre for Molecular Oncology, Barts and the London School of Medicine and Dentistry, London, UK
| | - Eva M Compérat
- Department of Pathology, Hôpital Tenon, Sorbonne University, Paris, France
| | - Ian A Cree
- International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France
| | - Anthony J Gill
- Sydney Medical School, The University of Sydney, Sydney, Australia
- Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia
- NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, NSW Health Pathology, St Leonards, New South Wales, Australia
| | - Arndt Hartmann
- Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Santosh Menon
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - George J Netto
- Department of Pathology, University of Alabama, Birmingham, AL, USA
| | - Maria R Raspollini
- Histopathology and Molecular Diagnostics, Careggi University Hospital, Florence, Italy
| | - Mark A Rubin
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA
- Department for BioMedical Research, University of Bern, Bern, Switzerland
- Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, NY, USA
| | - Puay Hoon Tan
- Division of Pathology, Singapore General Hospital, Singapore
| | - Satish K Tickoo
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Toyonori Tsuzuki
- Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Japan
| | - Samra Turajlic
- Renal and Skin Units, The Royal Marsden Hospital NHS Foundation Trust, London, UK
- The Francis Crick Institute, London, UK
| | - Ming Zhou
- Department of Pathology, Tufts Medical Center, Boston, Massachusetts, USA
| | - John R Srigley
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Holger Moch
- Department of Pathology and Molecular Pathology, University and University Hospital Zurich, Zurich, Switzerland
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Matsui K, Uchida K, Kanai M, Asakawa K, Usui M, Murata T. A case of primary renal oncocytic tumor: Chromophobe renal cell carcinoma or oncocytoma? IJU Case Rep 2022; 6:18-21. [PMID: 36605678 PMCID: PMC9807339 DOI: 10.1002/iju5.12535] [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: 01/08/2022] [Accepted: 09/01/2022] [Indexed: 01/07/2023] Open
Abstract
Introduction "Other oncocytic renal tumors of the kidney" is a new category constituted by 2022 WHO classification and different in the point of morphology and immunohistochemistory from typical oncocytic/eosinophilic renal tumors including chromophobe renal cell carcinoma and oncocytoma. Case presentation The patient was an 84-year-old woman in whom a left renal tumor was incidentally discovered. She underwent left nephrectomy, and the pathological specimens showed a borderline eosinophilic renal tumor between chromophobe renal cell carcinoma and renal oncocytoma. After all recognized oncocytic tumors were excluded, we diagnosed the tumor as other oncocytic renal tumor of the kidney. Conclusion Other oncocytic renal tumor of the kidney is a provisional category. Therefore, further research and accumulation of similar cases are necessary.
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Affiliation(s)
- Kenta Matsui
- Department of Pathology and Laboratory MedicineJA Suzuka General hospitalSuzukaJapan,Department of PathologyMie University HospitalMieJapan
| | | | - Masahiro Kanai
- Department of UrologyJA Suzuka General hospitalSuzukaJapan
| | - Kana Asakawa
- Department of Pathology and Laboratory MedicineJA Suzuka General hospitalSuzukaJapan
| | - Miki Usui
- Department of Pathology and Laboratory MedicineJA Suzuka General hospitalSuzukaJapan,Department of PathologyMie University HospitalMieJapan
| | - Tetsuya Murata
- Department of Pathology and Laboratory MedicineJA Suzuka General hospitalSuzukaJapan
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40
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Yu Z, Ding J, Pang H, Fang H, He F, Xu C, Li X, Ren K. A triple-classification for differentiating renal oncocytoma from renal cell carcinoma subtypes and CK7 expression evaluation: a radiomics analysis. BMC Urol 2022; 22:147. [PMID: 36096829 PMCID: PMC9469588 DOI: 10.1186/s12894-022-01099-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 08/29/2022] [Indexed: 11/10/2022] Open
Abstract
Background To investigate the value of computed tomography (CT)-based radiomics model analysis in differentiating renal oncocytoma (RO) from renal cell carcinoma subtypes (chromophobe renal cell carcinoma, clear cell carcinoma) and predicting the expression of Cytokeratin 7 (CK7). Methods In this retrospective study, radiomics was applied for patients with RO, chRCC and ccRCC who underwent surgery between January 2013 and December 2019 comprised the training cohort, and the testing cohort was collected between January and October 2020. The corticomedullary (CMP) and nephrographic phases (NP) were manually segmented, and radiomics texture parameters were extracted. Support vector machine was generated from CMP and NP after feature selection. Shapley additive explanations were applied to interpret the radiomics features. A radiomics signature was built using the selected features from the two phases, and the radiomics nomogram was constructed by incorporating the radiomics features and clinical factors. Receiver operating characteristic curve was calculated to evaluate the above models in the two sets. Furthermore, Rad-score was used for correlation analysis with CK7. Results A total of 123 patients with RO, chRCC and ccRCC were analyzed in the training cohort and 57 patients in the testing cohort. Subsequently, 396 radiomics features were selected from each phase. The radiomics features combining two phases yielded the highest area under the curve values of 0.941 and 0.935 in the training and testing sets, respectively. The Pearson’s correlation coefficient was statistically significant between Rad-score and CK7. Conclusion We proposed a non-invasive and individualized CT-based radiomics nomogram to differentiation among RO, chRCC and ccRCC preoperatively and predict the immunohistochemical protein expression for accurate clinical diagnosis and treatment decision. Supplementary Information The online version contains supplementary material available at 10.1186/s12894-022-01099-0.
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Affiliation(s)
- Ziyang Yu
- School of Medicine, Xiamen University, Xiamen, Fujian Province, China
| | - Jie Ding
- Radiology, Xiang'an Hospital of Xiamen University, Xiamen, China
| | - Huize Pang
- Department of Radiology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Hongkun Fang
- School of Medicine, Xiamen University, Xiamen, Fujian Province, China
| | - Furong He
- School of Medicine, Xiamen University, Xiamen, Fujian Province, China
| | - Chenxi Xu
- School of Medicine, Xiamen University, Xiamen, Fujian Province, China
| | - Xuedan Li
- Department of Radiology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
| | - Ke Ren
- School of Medicine, Xiamen University, Xiamen, Fujian Province, China. .,Department of Radiology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China. .,Radiology, Xiang'an Hospital of Xiamen University, Xiamen, China.
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41
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Do we need an updated classification of oncocytic renal tumors? : Emergence of low-grade oncocytic tumor (LOT) and eosinophilic vacuolated tumor (EVT) as novel renal entities. Mod Pathol 2022; 35:1140-1150. [PMID: 35273336 DOI: 10.1038/s41379-022-01057-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 02/07/2022] [Accepted: 02/14/2022] [Indexed: 02/07/2023]
Abstract
The category of "oncocytic renal tumors'' includes well-recognized entities, such as renal oncocytoma (RO) and eosinophilic variant of chromophobe renal cell carcinoma (eo-ChRCC), as well as a group of "gray zone" oncocytic tumors, with overlapping features between RO and eo-ChRCC that create ongoing diagnostic and classification problems. These types of renal tumors were designated in the past as "hybrid oncocytoma-chromophobe tumors". In a recent update, the Genitourinary Pathology Society (GUPS) proposed the term "oncocytic renal neoplasm of low malignant potential, not further classified", for such solitary and sporadic, somewhat heterogeneous, but relatively indolent tumors, with equivocal RO/eo-ChRCC features. GUPS also proposed that the term "hybrid oncocytic tumor" be reserved for tumors found in a hereditary setting, typically arising as bilateral and multifocal ones (as in Birt-Hogg-Dubé syndrome). More recent developments in the "gray zone" of oncocytic renal tumors revealed that potentially distinct entities may have been "hidden" in this group. Recent studies distinguished two new entities: "Eosinophilic Vacuolated Tumor" (EVT) and "Low-grade Oncocytic Tumor" (LOT). The rapidly accumulated evidence on EVT and LOT has validated the initial findings and has expanded the knowledge on these entities. Both are uniformly benign and are typically found in a sporadic setting, but rarely can be found in patients with tuberous sclerosis complex. Both have readily distinguishable morphologic and immunohistochemical features that separate them from similar renal tumors, without a need for detailed molecular studies. These tumors very frequently harbor TSC/MTOR mutations that are however neither specific nor restricted to these two entities. In this review, we outline a proposal for a working framework on how to classify such low-grade oncocytic renal tumors. We believe that such framework will facilitate their handling in practice and will stimulate further discussions and studies to fully elucidate their spectrum.
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LOT and HOT ... or not. The proliferation of clinically insignificant and poorly characterised types of renal neoplasia. Pathology 2022; 54:842-847. [DOI: 10.1016/j.pathol.2022.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 09/09/2022] [Indexed: 11/22/2022]
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Mass Spectrometry Imaging Spatial Tissue Analysis toward Personalized Medicine. LIFE (BASEL, SWITZERLAND) 2022; 12:life12071037. [PMID: 35888125 PMCID: PMC9318569 DOI: 10.3390/life12071037] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/04/2022] [Accepted: 07/10/2022] [Indexed: 12/19/2022]
Abstract
Novel profiling methodologies are redefining the diagnostic capabilities and therapeutic approaches towards more precise and personalized healthcare. Complementary information can be obtained from different omic approaches in combination with the traditional macro- and microscopic analysis of the tissue, providing a more complete assessment of the disease. Mass spectrometry imaging, as a tissue typing approach, provides information on the molecular level directly measured from the tissue. Lipids, metabolites, glycans, and proteins can be used for better understanding imbalances in the DNA to RNA to protein translation, which leads to aberrant cellular behavior. Several studies have explored the capabilities of this technology to be applied to tumor subtyping, patient prognosis, and tissue profiling for intraoperative tissue evaluation. In the future, intercenter studies may provide the needed confirmation on the reproducibility, robustness, and applicability of the developed classification models for tissue characterization to assist in disease management.
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Abstract
PURPOSE OF THE REVIEW Papillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype and represents 15-20% of all RCC. Classification of pRCC is changing because novel tumour entities have been discovered in the last years. In this review, we summarise recent studies relevant for the understanding of the molecular complexity and the broader differential diagnosis of pRCC. RECENT FINDINGS It has been 25 years ago, that pRCC was morphologically subdivided into type 1 and type 2. Recently described tumour entities in the 2022 WHO classification challenged this concept and allow a new view on the molecular background in pRCC. Biphasic hyalinizing psammomatous RCC and papillary renal neoplasm with reversed polarity are emerging tumour entities derived from the new concept of molecularly defined RCC subtypes. Immune checkpoint inhibition and tyrosine kinase inhibitors have been introduced as the new backbone in the first-line treatment of advanced pRCCs. To identify novel targeted treatments for patients with pRCC it is crucial to investigate the specific molecular background of pRCC considering emerging pRCC subtypes. SUMMARY In the future, a deeper understanding of the correlation between molecular aberrations and new pRCC subtypes may improve the classification of pRCC patients and could reveal potential predictive biomarkers for each subgroup.
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Affiliation(s)
- Silvia Angori
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
| | - João Lobo
- Department of Pathology, Portuguese Oncology Institute of Porto (IPOP)
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr António Bernardino de Almeida
- Department of Pathology and Molecular Immunology, ICBAS–School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Porto, Portugal
| | - Holger Moch
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
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Zhang Y, Xu Y, Yu T, Chen J, Zhao M, Lin C. Biphasic squamoid alveolar renal cell carcinoma: description of a rare case and a literature analysis. Quant Imaging Med Surg 2022; 12:3987-3994. [PMID: 35782264 PMCID: PMC9246752 DOI: 10.21037/qims-21-1230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 04/12/2022] [Indexed: 09/03/2024]
Affiliation(s)
- Yang Zhang
- Cancer Center, Department of Radiology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Yuyun Xu
- Cancer Center, Department of Radiology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Taihen Yu
- Cancer Center, Department of Radiology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Junfa Chen
- Cancer Center, Department of Radiology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Ming Zhao
- Cancer Center, Department of Pathology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Chunmiao Lin
- Cancer Center, Department of Radiology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
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Parkhi M, Chatterjee D, Kumar A, Kumar S. Walking the thin line—Low-grade oncocytic tumor of kidney: An emerging entity. Med J Armed Forces India 2022; 78:355-359. [DOI: 10.1016/j.mjafi.2021.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 02/02/2021] [Indexed: 10/21/2022] Open
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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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Tomaszewski Z, Littler Y. Unclassified Oncocytic Renal Neoplasm with Rib and Liver Metastases: Metastatic Oncocytoma? Int J Surg Pathol 2022; 30:810-815. [PMID: 35274993 DOI: 10.1177/10668969221084265] [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: 11/15/2022]
Abstract
Renal tumors with oncocytic or chromophobe-like morphology can be a common source of diagnostic difficulty. In some series, they constitute the largest group of unclassified renal cell carcinomas, a term used for neoplasms that do not fit the current classification of renal tumors. We describe the histological, immunohistochemical, and molecular findings of an eosinophilic renal neoplasm which presented with rib and liver metastases, and provide a review of the literature. The possibility of a renal oncocytoma with metastases was initially considered but excluded on the basis of several morphological and immunohistochemical features. Additionally, the tumor did not correspond with other traditional or newly emerging categories of renal neoplasms. It was therefore regarded as an unclassified oncocytic renal neoplasm which demonstrated evidence of malignant potential due to the presence of multiple metastases.
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Affiliation(s)
- Zoe Tomaszewski
- Leicester Royal Infirmary, 4490University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Yvonne Littler
- Leicester Royal Infirmary, 4490University Hospitals of Leicester NHS Trust, Leicester, UK
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Oncocytic renal neoplasms with diffuse keratin 7 immunohistochemistry harbor frequent alterations in the mammalian target of rapamycin pathway. Mod Pathol 2022; 35:361-375. [PMID: 34802045 DOI: 10.1038/s41379-021-00969-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 10/21/2021] [Accepted: 10/25/2021] [Indexed: 11/08/2022]
Abstract
Low-grade oncocytic tumor (LOT) has been recently proposed as a unique renal tumor. However, we have encountered tumors with more oncocytoma-like morphology that show diffuse keratin 7 reactivity, which we sought to characterize molecularly. Eighteen tumors with a diffuse keratin 7 positive and KIT negative pattern were identified from 184 with predominantly oncocytoma-like histology. These tumors were subjected to detailed immunohistochemical evaluation and 14 were evaluated using the Illumina® HiSeq 4000 platform for 324 cancer-associated genes. Patients' ages ranged from 39 to 80 (median = 59.5 years) with a male to female ratio of 1.25:1. Morphology was predominantly oncocytoma-like with discrete nests, compared to the solid and edematous patterns described in LOT. Other than positive keratin 7 and negative KIT, the tumor cells were positive for PAX8, E-cadherin, AE1/AE3, Ber-EP4, AMACR, CD10, and MOC31, and were negative for other studied markers. FH and INI1 were normal. Eleven of 14 harbored genomic abnormalities, likely sporadic, primarily involving the MTOR pathway (73%). Overall, the alterations included MTOR activating mutation (n = 1), TSC1 inactivating mutation (n = 1), TSC2 mutation (p.X534 splice site, n = 1), STK11 (a negative regulator of the MTOR pathway) mutation (n = 1), both STK11 and TSC1 mutations (n = 1), biallelic loss of PTEN and TSC1 deletion (n = 1), and MET amplification and TSC1 inactivating mutation (n = 1). Amplification of FGFR3 was identified in one additional tumor. Other alterations included FOXP1 loss (n = 1), NF2 E427 homozygous loss (n = 1), and PI3KCA activating mutation (n = 1). At a median follow-up of 68 months (2-147 months) for 15 patients, all were alive without disease. Oncocytic renal tumors with diffuse keratin 7 labeling show frequent alterations in the TSC/MTOR pathway, despite more oncocytoma-like morphology than initially described in LOT, likely expanding the morphologic spectrum of the latter.
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Gopee-Ramanan P, Chin SS, Lim C, Shanbhogue KP, Schieda N, Krishna S. Renal Neoplasms in Young Adults. Radiographics 2022; 42:433-450. [PMID: 35230920 DOI: 10.1148/rg.210138] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Renal cell carcinoma (RCC) is usually diagnosed in older adults (the median age of diagnosis is 64 years). Although less common in patients younger than 45 years, RCCs in young adults differ in clinical manifestation, pathologic diagnosis, and prognosis. RCCs in young adults are typically smaller, are more organ confined, and manifest at lower stages of disease. The proportion of clear cell RCC is lower in young adults, while the prevalence of familial renal neoplastic syndromes is much higher, and genetic testing is routinely recommended. In such syndromic manifestations, benign-appearing renal cysts can harbor malignancy. Radiologists need to be familiar with the differences of RCCs in young adults and apply an altered approach to diagnosis, treatment, and surveillance. For sporadic renal neoplasms, biopsy and active surveillance are less often used in young adults than in older adults. RCCs in young adults are overall associated with better disease-specific survival after surgical treatment, and minimally invasive nephron-sparing treatment options are preferred. However, surveillance schedules, need for biopsy, decision for an initial period of active surveillance, type of surgery (enucleation or wide-margin partial nephrectomy), and utilization of ablative therapy depend on the presence and type of underlying familial renal neoplastic syndrome. In this pictorial review, syndromic, nonsyndromic, and newer RCC entities that are common in young adults are presented. Their associated unique epidemiology, characteristic imaging and pathologic traits, and key aspects of surveillance and management of renal neoplasms in young adults are discussed. The vital role of the informed radiologist in the multidisciplinary management of RCCs in young adults is highlighted. Online supplemental material is available for this article. ©RSNA, 2022.
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Affiliation(s)
- Prasaanthan Gopee-Ramanan
- From the Department of Medical Imaging, University Health Network, Sinai Health System, Women's College Hospital, University of Toronto, 200 Elizabeth St, Toronto, ON, Canada M5G 2C4 (P.G.R., S.S.C., S.K.); Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ont, Canada (C.L.); Department of Radiology, NYU Langone Medical Center, New York, NY (K.P.S.); and Department of Radiology, The Ottawa Hospital, University of Ottawa, Ottawa, Ont, Canada (N.S.)
| | - Sook Suzy Chin
- From the Department of Medical Imaging, University Health Network, Sinai Health System, Women's College Hospital, University of Toronto, 200 Elizabeth St, Toronto, ON, Canada M5G 2C4 (P.G.R., S.S.C., S.K.); Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ont, Canada (C.L.); Department of Radiology, NYU Langone Medical Center, New York, NY (K.P.S.); and Department of Radiology, The Ottawa Hospital, University of Ottawa, Ottawa, Ont, Canada (N.S.)
| | - Chris Lim
- From the Department of Medical Imaging, University Health Network, Sinai Health System, Women's College Hospital, University of Toronto, 200 Elizabeth St, Toronto, ON, Canada M5G 2C4 (P.G.R., S.S.C., S.K.); Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ont, Canada (C.L.); Department of Radiology, NYU Langone Medical Center, New York, NY (K.P.S.); and Department of Radiology, The Ottawa Hospital, University of Ottawa, Ottawa, Ont, Canada (N.S.)
| | - Krishna P Shanbhogue
- From the Department of Medical Imaging, University Health Network, Sinai Health System, Women's College Hospital, University of Toronto, 200 Elizabeth St, Toronto, ON, Canada M5G 2C4 (P.G.R., S.S.C., S.K.); Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ont, Canada (C.L.); Department of Radiology, NYU Langone Medical Center, New York, NY (K.P.S.); and Department of Radiology, The Ottawa Hospital, University of Ottawa, Ottawa, Ont, Canada (N.S.)
| | - Nicola Schieda
- From the Department of Medical Imaging, University Health Network, Sinai Health System, Women's College Hospital, University of Toronto, 200 Elizabeth St, Toronto, ON, Canada M5G 2C4 (P.G.R., S.S.C., S.K.); Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ont, Canada (C.L.); Department of Radiology, NYU Langone Medical Center, New York, NY (K.P.S.); and Department of Radiology, The Ottawa Hospital, University of Ottawa, Ottawa, Ont, Canada (N.S.)
| | - Satheesh Krishna
- From the Department of Medical Imaging, University Health Network, Sinai Health System, Women's College Hospital, University of Toronto, 200 Elizabeth St, Toronto, ON, Canada M5G 2C4 (P.G.R., S.S.C., S.K.); Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ont, Canada (C.L.); Department of Radiology, NYU Langone Medical Center, New York, NY (K.P.S.); and Department of Radiology, The Ottawa Hospital, University of Ottawa, Ottawa, Ont, Canada (N.S.)
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