Oncocytic renal neoplasms are a major source of diagnostic challenge in genitourinary pathology; however, they are typically nonaggressive in general, raising the question of whether distinguishing different subtypes, including emerging entities, is necessary. Emerging entities recently described include eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low-grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and papillary renal neoplasm with reverse polarity (PRNRP). A survey was shared among 65 urologic pathologists using SurveyMonkey.com (Survey Monkey, Santa Clara, CA, USA). De-identified and anonymized respondent data were analyzed. Sixty-three participants completed the survey and contributed to the study. Participants were from Asia (n = 21; 35%), North America (n = 31; 52%), Europe (n = 6; 10%), and Australia (n = 2; 3%). Half encounter oncocytic renal neoplasms that are difficult to classify monthly or more frequently. Most (70%) indicated that there is enough evidence to consider ESC RCC as a distinct entity now, whereas there was less certainty for LOT (27%), EVT (29%), and PRNRP (37%). However, when combining the responses for sufficient evidence currently and likely in the future, LOT and EVT yielded > 70% and > 60% for PRNRP. Most (60%) would not render an outright diagnosis of oncocytoma on needle core biopsy. There was a dichotomy in the routine use of immunohistochemistry (IHC) in the evaluation of oncocytoma (yes = 52%; no = 48%). The most utilized IHC markers included keratin 7 and 20, KIT, AMACR, PAX8, CA9, melan A, succinate dehydrogenase (SDH)B, and fumarate hydratase (FH). Genetic techniques used included TSC1/TSC2/MTOR (67%) or TFE3 (74%) genes and pathways; however, the majority reported using these very rarely. Only 40% have encountered low-grade oncocytic renal neoplasms that are deficient for FH. Increasing experience with the spectrum of oncocytic renal neoplasms will likely yield further insights into the most appropriate work-up, classification, and clinical management for these entities.
- Klíčová slova
- Emerging, Eosinophilic, Oncocytic, Renal neoplasms, Uropathologists,
- MeSH
- karcinom z renálních buněk * patologie diagnóza MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory ledvin * patologie diagnóza MeSH
- oxyfilní adenom * patologie diagnóza MeSH
- patologové * MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery MeSH
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.
- Klíčová slova
- Collision tumor, Kidney tumor, Renal cell carcinoma, Renal tumor,
- MeSH
- adenom * MeSH
- karcinom z renálních buněk * genetika patologie MeSH
- karcinom * MeSH
- ledviny patologie MeSH
- lidé MeSH
- nádory ledvin * genetika patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
AIMS: Renal cell carcinoma (RCC) with clear cells and psammoma-like calcifications would often raise suspicion for MITF family translocation RCC. However, we have rarely encountered tumours consistent with clear cell RCC that contain focal psammomatous calcifications. METHODS AND RESULTS: We identified clear cell RCCs with psammomatous calcifications from multiple institutions and performed immunohistochemistry and fluorescence and RNA in-situ hybridisation (FISH and RNA ISH). Twenty-one tumours were identified: 12 men, nine women, aged 45-83 years. Tumour size was 2.3-14.0 cm (median = 6.75 cm). Nucleolar grade was 3 (n = 14), 2 (n = 4) or 4 (n = 3). In addition to clear cell pattern, morphology included eosinophilic (n = 12), syncytial giant cell (n = 4), rhabdoid (n = 2), branched glandular (n = 1), early spindle cell (n = 1) and poorly differentiated components (n = 1). Labelling for CA9 was usually 80-100% of the tumour cells (n = 17 of 21), but was sometimes decreased in areas of eosinophilic cells (n = 4). All (19 of 19) were positive for CD10. Most (19 of 20) were positive for AMACR (variable staining = 20-100%). Staining was negative for keratin 7, although four showed rare positive cells (four of 20). Results were negative for cathepsin K (none of 19), melan A (none of 17), HMB45 (none of 17), TFE3 (none of 5), TRIM63 RNA ISH (none of 13), and TFE3 (none of 19) and TFEB rearrangements (none of 12). Seven of 19 (37%) showed chromosome 3p deletion. One (one of 19) showed trisomy 7 and 17 without papillary features. CONCLUSIONS: Psammomatous calcifications in RCC with a clear cell pattern suggests a diagnosis of MITF family translocation RCC; however, psammomatous calcifications can rarely be found in true clear cell RCC.
- Klíčová slova
- TFE3, TFEB, TRIM63, clear cell renal cell carcinoma, psammoma bodies,
- MeSH
- chromozomální aberace MeSH
- kalcinóza * MeSH
- karcinom z renálních buněk * patologie MeSH
- lidé MeSH
- nádorové biomarkery genetika MeSH
- nádory ledvin * patologie MeSH
- transkripční faktory BHLH-Zip genetika MeSH
- translokace genetická MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery MeSH
- transkripční faktory BHLH-Zip MeSH
Predicting the clinical behavior and trajectory of chromophobe renal cell carcinoma (ChRCC) by histologic features has so far proven to be challenging. It is known that ChRCC represents a heterogeneous group of neoplasms demonstrating variable, yet distinctive morphologic and genetic profiles. In this international multi-institutional study, we aimed to assess the impact of histologic diversity in ChRCC (classic/eosinophilic versus rare subtypes) on survival outcome. This is an international multi-institutional matched case-control study including 14 institutions, examining the impact of histologic subtypes of ChRCC on survival outcome. The study group (cases) included 89 rare subtypes of ChRCC. The control group consisted of 70 cases of ChRCC including classic and eosinophilic features, age- and tumor size-matched. Most of the rare subtypes were adenomatoid cystic/pigmented ChRCC (66/89, 74.2%), followed by multicystic ChRCC (10/89, 11.2%), and papillary ChRCC (9/89, 10.1%). In the control group, there were 62 (88.6%) classic and 8 (11.4%) eosinophilic ChRCC. There were no statistically significant differences between the study and control groups for age at diagnosis, gender distribution, tumor size, presence of tumor necrosis, presence of sarcomatoid differentiation, and adverse outcomes. No statistically significant differences were found in clinical outcome between the rare subtypes and classic/eosinophilic groups by tumor size, necrosis, and sarcomatoid differentiation. Further, no statistically significant differences were found in clinical outcome between the two groups, stratified by tumor size, necrosis, and sarcomatoid differentiation. Our findings corroborated previous studies that both sarcomatoid differentiation and tumor necrosis were significantly associated with poor clinical outcome in classic/eosinophilic ChRCC, and this was proven to be true for ChRCC with rare histologic subtypes as well. This study suggests that rare morphologic patterns in ChRCC without other aggressive features play no role in determining the clinical behavior of the tumor.
- Klíčová slova
- Chromophobe renal cell carcinoma, Grading, Kidney, Outcome, Subtypes, Survival,
- MeSH
- karcinom z renálních buněk * patologie MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- nádory ledvin * patologie MeSH
- nekróza MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- srovnávací studie MeSH
- Názvy látek
- nádorové biomarkery MeSH
AIMS: Formal depiction of granulomatous inflammation associated with renal neoplasms has mainly consisted of case reports. Herein, we investigate the clinicopathological features and potential significance of granulomas associated with renal tumours from a large multi-institutional cohort. METHODS AND RESULTS: One hundred and eleven study cases were collected from 22 institutions, including 57 partial nephrectomies and 54 radical nephrectomies. Patient ages ranged from 27 to 85 years (average = 60.1 years; male = 61%). Renal neoplasms included clear cell renal cell carcinoma (RCC; 86%), papillary RCC (8%), chromophobe RCC (3%), clear cell papillary RCC (1%), mixed epithelial stromal tumour (1%) and oncocytoma (1%). Granulomas were peritumoral in 36%, intratumoral in 24% and both in 40% of cases. Total granuloma count per case ranged from one to 300 (median = 15) with sizes ranging from 0.15 to 15 mm (mean = 1.9 mm). Necrotising granulomas were seen in 14% of cases. Histochemical stains for organisms were performed on 45% of cases (all negative). Sixteen cases (14%) had a prior biopsy/procedure performed, and eight patients had neoadjuvant immunotherapy or chemotherapy. Eleven patients (10%) had a confirmed diagnosis of sarcoidosis, including five in whom sarcoidosis was diagnosed after nephrectomy. CONCLUSION: Based on this largest case-series to date, peri-/intratumoral granulomas associated with renal neoplasms may be more common than initially perceived. The extent of granulomatous inflammation can vary widely and may or may not have necrosis with possible aetiologies, including prior procedure or immunotherapy/chemotherapy. Although a clinical association with sarcoidosis is infrequent it can still occur, and the presence of granulomas warrants mention in pathology reports.
- Klíčová slova
- carcinoma, granulomas, intratumoral, kidney, neoplasm, peritumoral, renal, sarcoid, sarcoid-like,
- MeSH
- dospělí MeSH
- granulom patologie MeSH
- karcinom z renálních buněk * patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin * patologie MeSH
- sarkoidóza * patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- zánět MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
A distinct renal tumor has recently been described as "high-grade oncocytic renal tumor" and "sporadic renal cell carcinoma with eosinophilic and vacuolated cytoplasm". The Genitourinary Pathology Society (GUPS) consensus proposed a unifying name "eosinophilic vacuolated tumor" (EVT) for this emerging entity. In this multi-institutional study, we evaluated 19 EVTs, particularly their molecular features and mutation profile, using next-generation sequencing. All cases were sporadic and none of the patients had a tuberous sclerosis complex. There were 8 men and 11 women, with a mean age of 47 years (median 50; range 15-72 years). Average tumor size was 4.3 cm (median 3.8 cm; range 1.5-11.5 cm). All patients with available follow-up data (18/19) were alive and without evidence of disease recurrence or progression during the follow-up, ranging from 12 to 198 months (mean 56.3, median 41.5 months). The tumors were well circumscribed, but lacked a well-formed capsule, had nested to solid growth, focal tubular architecture, and showed ubiquitous, large intracytoplasmic vacuoles, round to oval nuclei, and prominent nucleoli. Immunohistochemically, cathepsin K, CD117, CD10, and antimitochondrial antigen were expressed in all cases. Other positive stains included: PAX8, AE1/AE3 and CK18. CK7 was typically restricted only to rare scattered cells. Vimentin, HMB45, melan-A, and TFE3 were negative in all cases. All tumors showed retained SDHB. All cases (19/19) showed non-overlapping mutations of the mTOR pathway genes: TSC1 (4), TSC2 (7), and MTOR (8); one case with MTOR mutation showed a coexistent RICTOR missense mutation. Low mutational rates were found in all samples (ranged from 0 to 6 mutations/Mbp). Microsatellite instability and copy number variations were not found in any of the 17 analyzable cases. EVT represents an emerging renal entity that shows a characteristic and readily identifiable morphology, consistent immunohistochemical profile, indolent behavior, and mutations in either TSC1, TSC2, or MTOR genes.
- MeSH
- dospělí MeSH
- karcinom z renálních buněk * patologie MeSH
- ledviny patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory ledvin * patologie MeSH
- senioři MeSH
- TOR serin-threoninkinasy genetika MeSH
- variabilita počtu kopií segmentů DNA MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- MTOR protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
- TOR serin-threoninkinasy MeSH
Chromophobe renal cell carcinoma (ChRCC) accounts for 5% to 7% of all renal cell carcinomas. It was thought for many years that ChRCC exhibits a hypodiploid genome. Recent studies using advanced molecular genetics techniques have shown more complex and heterogenous pattern with frequent chromosomal gains. Historically, multiple losses of chromosomes 1, 2, 6, 10, 13, 17, and 21 have been considered a genetic hallmark of ChRCC, both for classic and eosinophilic ChRCC variants. In the last 2 decades, multiple chromosomal gains in ChRCCs have also been documented, depicting a considerably broader genetic spectrum than previously thought. Studies of rare morphologic variants including ChRCC with pigmented microcystic adenomatoid/multicystic growth, ChRCC with neuroendocrine differentiation, ChRCC with papillary architecture, and renal oncocytoma-like variants also showed variable chromosomal numerical aberrations, including multiple losses (common), gains (less common), or chromosomal changes overlapping with renal oncocytoma. Although not the focus of the review, The Cancer Genome Atlas (TCGA) data in ChRCC show TP53, PTEN, and CDKN2A to be the most mutated genes. Given the complexity of molecular genetic alterations in ChRCC, this review analyzed the existing published data, aiming to present a comprehensive up-to-date survey of the chromosomal abnormalities in classic ChRCC and its variants. The potential role of chromosomal numerical aberrations in the differential diagnostic evaluation may be limited, potentially owing to its high variability.
- MeSH
- chromozomální aberace * MeSH
- fosfohydroláza PTEN genetika MeSH
- geny p16 MeSH
- geny p53 MeSH
- karcinom z renálních buněk genetika patologie MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- nádory ledvin genetika patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- fosfohydroláza PTEN MeSH
- nádorové biomarkery MeSH
