PURPOSE: Inferior vena cava (IVC) involvement by renal cell carcinoma (RCC) is associated with a higher disease stage and is considered a risk factor for poor prognosis. This study aimed to investigate the role of the apparent diffusion coefficient (ADC) of MRI 3D texture analysis in the differentiation of solid and friable tumour thrombus in patients with RCC. MATERIALS AND METHODS: The study involved 27 patients with RCC with tumour thrombus in the renal vein or IVC, surgically treated with nephrectomy and thrombectomy and in whom preoperatively abdominal MRI including the DWI sequence was conducted. For 3D texture analysis, the ADC map was used, and the first-order radiomic features were calculated from the whole volume of the thrombus. All tumour thrombi were histologically classified as solid or friable. RESULTS: The solid and friable thrombus was detected in 51.9 % and 48.1 % of patients, respectively. No differences in mean values of range, 90th percentile, interquartile range, kurtosis, uniformity and variance were found between groups. Equal sensitivity and specificity (93 % and 69 %, respectively) of ADC mean, median and entropy in differentiation between solid and friable tumour thrombus, with the highest AUC for entropy (0.808), were observed. Applying the skewness threshold value of 0.09 allowed us to achieve a sensitivity of 86 % and a specificity of 92 %. CONCLUSIONS: In patients with RCC and tumour thrombus in the renal vein or IVC, the 3D texture analysis based on ADC-map allows for precise differentiation of a solid from a friable thrombus.
- Klíčová slova
- Diffusion-weighted imaging, Renal cell carcinoma, Texture analysis, Thrombus,
- MeSH
- difuzní magnetická rezonance metody MeSH
- dospělí MeSH
- karcinom z renálních buněk * diagnostické zobrazování patologie komplikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin * diagnostické zobrazování patologie komplikace MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- trombektomie metody MeSH
- trombóza * diagnostické zobrazování patologie MeSH
- vena cava inferior diagnostické zobrazování patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
a-Methylacyl coenzyme A racemase (AMACR) is traditionally considered to be a marker of papillary renal cell carcinoma. However, AMACR expression can be seen in other renal tumors. The aim of this study was to investigate AMACR immunoreactivity within the spectrum of clear cell renal cell neoplasms. Fifty-three clear cell renal epithelial tumors were used in assembling the following four cohorts: low grade (LG) clear cell renal cell carcinoma (CCRCC), high grade (HG) CCRCC, CCRCC with cystic changes, and multilocular cystic renal neoplasm of low malignant potential (MCRNLMP). Representative blocks were stained for AMACR, using two different clones (SP52 and OV-TL12/30). There were at least some AMACR immunoreactivity in 77.8 % and 68.9 % of CCRCCs (using SP52 and OV-TL12/30 clone, respectively). Moderate to strong positivity, or positivity in more than one third of the tumor (even weak in intensity) was detected in 46.7 % of CCRCCs using SP52 and in 48.9 % of CCRCC using OV-TL12/30 clone. The highest AMACR reactivity was observed in HG CCRCC (60 % by SP52 and 66.7 % by OV-TL12/30). Strong and diffuse AMACR positivity was detected in 8.9 % of all CCRCCs. AMACR immunoreactivity in MCRNLMP was 37.5 % (SP52 clone) and 25 % (OV-TL12/30 clone). We demonstrated relatively high expression rate of AMACR in CCRCC, while very variable in intensity and distribution. This finding may have diagnostic implications especially in limited samples (i.e., core biopsies), as AMACR positivity does not exclude the diagnosis of CCRCC.
- Klíčová slova
- AMACR, Clear Cell Renal Cell Carcinoma, Immunohistochemistry, Kidney, Multilocular Cystic Renal Neoplasm of Low Malignant Potential, Racemase,
- MeSH
- imunohistochemie metody MeSH
- karcinom z renálních buněk * patologie metabolismus diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * metabolismus MeSH
- nádory ledvin * patologie metabolismus diagnóza MeSH
- racemasy a epimerasy * metabolismus MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alpha-methylacyl-CoA racemase MeSH Prohlížeč
- nádorové biomarkery * MeSH
- racemasy a epimerasy * MeSH
Succinate dehydrogenase (SDH), formed by four subunits SDHA, SDHB, SDHC, SDHD, and an assembly factor SDHAF2, functions as a key respiratory enzyme. Biallelic inactivation of genes encoding any of the components, almost always in the presence of a germline mutation, causes loss of function of the entire enzyme complex (so-called SDH deficiency) and subsequent development of SDH-deficient neoplasms which include pheochromocytoma/paraganglioma, gastrointestinal stromal tumor, and renal cell carcinoma (RCC). These tumors may occur in the same patient or kindred. SDH-deficient RCC shows distinctive morphological features with vacuolated eosinophilic cytoplasm due to distinctive cytoplasmatic inclusions containing flocculent material. The diagnosis is confirmed by loss of SDHB on immunohistochemistry with positive internal control. The majority of tumors occur in the setting of germline mutations in one of the SDH genes, most commonly SDHB. The prognosis is excellent for low-grade tumors but worse for high-grade tumors with high-grade nuclei, sarcomatoid change, or coagulative necrosis. Awareness of the morphological features and low-threshold for applying SDHB immunohistochemistry help identify patients with SDH-deficient RCC and hereditary SDH-deficient tumor syndromes. In this review we summarize recent development on the clinical and genetic features, diagnostic approach, and pitfalls of SDH-deficient syndrome, focusing on SDH-deficient renal cell carcinomas.
- Klíčová slova
- Deficiency, Mutation, Renal cell carcinoma, Succinate dehydrogenase,
- MeSH
- dědičné nádorové syndromy * genetika MeSH
- karcinom z renálních buněk * genetika MeSH
- lidé MeSH
- nádory ledvin * genetika patologie MeSH
- sarkom * MeSH
- sukcinátdehydrogenasa genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- sukcinátdehydrogenasa MeSH
Low-grade oncocytic tumour (LOT) of the kidney has recently emerged as a potential novel tumour type. Despite similarity to oncocytoma or eosinophilic chromophobe renal cell carcinoma, it shows diffuse keratin 7 immunohistochemistry (IHC) and negative KIT (CD117), which differs from both. We aimed to identify the molecular characteristics of these tumours. Seventeen tumours (one male, 16 female, nine previously published) fitting the original description of this entity (solid eosinophilic cell morphology, often with areas of tumour cells loosely stretched in oedematous stroma, and the above IHC features) were analysed with a next-generation sequencing panel of 324 cancer-associated genes from formalin-fixed, paraffin-embedded tissue. All tumours harboured at least one alteration in either TSC1 (n = 7, 41%), TSC2 (n = 2, 12%), MTOR (n = 5, 29%) or PIK3CA (n = 4, 24%). Four tumours harboured a second alteration, including two NF2, one each in conjunction with MTOR and TSC2 alterations, one PTEN with TSC1 alteration and one tumour with both MTOR and TSC1 alterations. No other renal cancer-related or recurring gene alterations were identified. In addition to the previously described IHC findings, 16 of 16 were positive for GATA3. Eleven patients with follow-up had no metastases or recurrent tumours. Recurrent tuberous sclerosis/MTOR pathway gene alterations in LOT support its consideration as a distinct morphological, immunohistochemical and genetic entity. PIK3CA is another pathway member that may be altered in these tumours. Further study will be necessary to determine whether tumour behaviour or syndromic associations differ from those of oncocytoma and chromophobe carcinoma, warranting different clinical consideration.
- Klíčová slova
- PIK3CA, MTOR, TSC1, TSC2, low-grade oncocytic tumour, oncocytoma,
- MeSH
- fosfatidylinositol-3-kinasy třídy I genetika MeSH
- karcinom z renálních buněk * genetika MeSH
- ledviny MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mutace MeSH
- nádory ledvin * genetika MeSH
- oxyfilní adenom * genetika MeSH
- TOR serin-threoninkinasy genetika MeSH
- transkripční faktor GATA3 genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfatidylinositol-3-kinasy třídy I MeSH
- GATA3 protein, human MeSH Prohlížeč
- MTOR protein, human MeSH Prohlížeč
- PIK3CA protein, human MeSH Prohlížeč
- TOR serin-threoninkinasy MeSH
- transkripční faktor GATA3 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
The morphologic diversity of chromophobe renal cell carcinoma (ChRCC) is well-known. Aside from typical morphology, pigmented adenomatoid, multicystic and papillary patterns have been described. Ten cases of CHRCC composed of small cell population in various percentages were analysed, using morphologic parameters, immunohistochemistry and next-generation sequencing (NGS) testing. Patients were five males and five females, with age ranging from 40 to 78years. The size of tumors ranged from 2.2 cm to 11 cm (mean 5.17 cm). Small cell component comprised 10 to 80% of the tumor volume, while the remaining was formed by cells with classic ChRCC morphology. The immunohistochemical profile of the small cell component was consistent with typical ChRCC immunophenotype, with CD117 and CK7 positivity. Neuroendocrine markers were negative. Mutations of 13 genes were found: DCIER1, FGFR3, JAK3, SUFO, FAM46C, FANCG, MET, PLCG2, APC, POLE, EPICAM, MUTYH and AR. However, only the PLCG2 mutation is considered pathogenic.The small cell variant of ChRCC further highlights and expand upon existing morphologic heterogeneity spectrum. Recognition of small cell variant of CHRCC is not problematic in tumors, where the "classic" CHRCC component is present. However, in limited material (i.e., core biopsy), this may present a diagnostic challenge. Based on the limited follow-up data available, it appears that the small cell tumor component had no impact on prognosis, since there was no aggressive behavior documented. Awareness of this unusual pattern and applying additional sections to find classic morphology of ChRCC, as well as excluding neuroendocrine nature by immunohistochemistry, may help resolve difficult cases.
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- karcinom z renálních buněk * genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza genetika MeSH
- nádory ledvin * genetika patologie MeSH
- oxyfilní adenom * diagnóza genetika patologie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery 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
Clear cell renal cell carcinoma (CCRCC) is well known for intratumor heterogeneity. An accurate mapping of the tumor is crucial for assessing prognosis, and perhaps this can be linked to potential success/failure of targeted therapies. We assembled a cohort of 7 CCRCCs with prominent vasculature and microvascular hyperplasia (ccRCCPV), resembling those seen in high grade gliomas. A control group of classic CCRCC with no variant morphologies was also included. Both groups were analyzed for clinicopathologic, morphologic, immunohistochemical, and molecular genetic features. No statistically significant differences in mRNA expression of studied genes between the two groups were found. Using NGS panel Trusight Oncology 500 (TSO500), only one clinically significant gene mutation, VHL c.263G > A, p. (Trp88Ter), was found. TMB (Tumor Mutation Burden) and MSI (MicroSatellite Instability) were low, and no copy number variations (CNVs) were detected in the study cohort. Prominent microvascular hyperplasia in CCRCC is a rare phenomenon. From molecular genetic point of view, these tumors do not appear to be different from classic CCRCC. Prognostically, they also demonstrated similar clinical behaviors.
- Klíčová slova
- Clear cell renal cell carcinoma, Kidney, Microvascular hyperplasia, Vascular hyperplasia,
- MeSH
- hyperplazie genetika patologie MeSH
- karcinom z renálních buněk genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- nádorové biomarkery MeSH
- nádory ledvin genetika patologie MeSH
- prognóza MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery MeSH
