Family Translocation Renal Cell Carcinoma Research Articles

Clear cell and non-clear cell renal cell carcinoma in young adults: clinicopathological features, survival outcomes and prognostic factors.

Renal cell carcinoma (RCC) is infrequent among young adults. Few studies reported the outcome of RCC in young adults by pathological subtypes. The purpose of this study was to explore the clinicopathological features, survival outcomes and prognostic factors of young adult patients with clear cell (CCRCC) and non-clear cell renal cell carcinoma (NCCRCC). This study included young adult patients aged 18-40years who were diagnosed as renal cell carcinoma (RCC) between 2012 and 2022 at Peking University Third Hospital. All patients underwent either partial nephrectomy or radical nephrectomy, and some received adjuvant therapy. A comparative analysis was performed to investigate the differences in clinicopathological characteristics between the cohort of CCRCC and NCCRCC. Kaplan-Meier survival analysis was utilized to plot survival curves for young adults with RCC. The univariate and multifactorial prognostic analyses were conducted using the log-rank test and COX proportional hazards model. A total of 300 RCC patients aged 18-40years were performed, of which 201 were diagnosed with CCRCC (67%) and 99 were diagnosed with NCCRCC(33%). The NCCRCC included 29 cases (9.7%) of chromophobe RCC, 28 cases (9.3%) of MiT family translocation RCC, 22 cases (7.3%) of papillary RCC, 11 cases (3.7%) of low malignant potential multifocal cystic RCC, and 6 cases of unclassified RCC (2.0%), 2 cases of mucinous tubule and spindle cell carcinoma (0.7%), and 1 case of FH-deficient RCC (0.3%).The mean age was 33.4±6.1years old. The overall and progression free 5-year survival rate was 99.1 and 95.3%, respectively. The NCCRCC cohort demonstrated a statistically significant decrease in progression-free survival (PFS) rate when compared to the CCRCC cohort (p<0.001). There was no statistically significant difference observed in overall survival (OS) (p=0.069). Pathological stage was a significant independent predictor for OS (p=0.045). Pathological stage and nuclear grade were both independent predictors for PFS (p=0.020; p=0.005). The clinical and pathological features of young adults diagnosed with CCRCC exhibit notable distinctions from those of NCCRCC patients. The survival outcome was significantly influenced by the pathological stage, while both the nuclear grade and pathological stage had a significant impact on tumor progression. This study offered significant contributions to the understanding of the clinicopathological characteristics and prognostic determinants of renal cell carcinoma (RCC) in young adults.

Case – Long-term remission after repeated courses of palliative radiotherapy in a patient with metastatic MiT family translocation renal cell carcinoma

Case – Long-term remission after repeated courses of palliative radiotherapy in a patient with metastatic MiT family translocation renal cell carcinoma

The Mutant Menage- Mit Family Translocation Renal Cell Carcinoma

Microphthalmia associated transcription factor (MiT) family translocation renal cell carcinoma is neoplasm which enunciates genetic fusions within members of MiT family of transcription factors, especially TFE3 gene and TFEB gene. Neoplasm frequently incriminates the adult population ≤ 35 years of age with an intense female predilection. Tumefaction exhibits a papillary, solid or alveolar pattern of tumour configuration and is composed of clear cells or non-cohesive, pseudo stratified, eosinophilic epithelial cells. Tumour cells are pervaded with voluminous cytoplasm and pleomorphic nuclei of advanced grade. Neoplastic cells are intensely immune reactive to TFE3 or TFEB, PAX8, cathepsin K, CD10, alpha methyacyl CoA racemase (AMACR), vimentin or E-cadherin. Tumour cells appear immune non-reactive to cytokeratin, epithelial membrane antigen (EMA), carbonic anhydrase IX(CAIX), CD45, calretinin and smooth muscle actin(SMA). MiT family translocation renal cell carcinoma requires segregation from neoplasms such as clear cell papillary renal cell carcinoma, clear cell renal cell carcinoma, epithelioid angiomyolipoma, chromophobe renal cell carcinoma or papillary renal cell carcinoma. Neoplasm may be appropriately alleviated by cogent manoeuvers as surgical extermination of the neoplasm.

Renal cell carcinoma in the contralateral kidney with TFE3 gene translocation following chemotherapy for childhood nephroblastoma: A case report and literature review

Key Clinical MessageRenal cell carcinoma as a secondary malignant neoplasm is relatively rare; however, the possibility of secondary renal cell carcinoma following chemoradiotherapy for childhood nephroblastoma should be considered.AbstractThe occurrence of secondary renal cell carcinoma (RCC) following chemoradiotherapy for nephroblastoma is relatively rare, especially in microphthalmia transcription factor family translocation renal cell carcinoma. A 13‐year‐old Japanese male was referred to our department for treatment of a right kidney mass. The patient had undergone open left nephrectomy and adjuvant chemotherapy for nephroblastoma, 12 years before. Diagnostic imaging revealed a tumor in the right kidney and a lesion suspected to be metastasis in the left eighth rib. Chromophobe RCC or translocation RCC was suspected from the imaging pattern. TNM classification was cT1aN0M1, and the clinical stage was IV. Partial nephrectomy by robot‐assisted surgery for the right renal tumor and resection of the left eighth rib were performed. Pathologically, the renal tumor was diagnosed as translocation RCC, and the rib lesion demonstrated no evidence of malignancy. We are currently undergoing imaging follow‐up and the patient has been recurrence‐free for 15 months. In this study, we present a rare case of secondary translocation RCC after successful treatment of nephroblastoma.

"Oncocytoid Renal Cell Carcinomas After Neuroblastoma" Represent TSC -mutated Eosinophilic Solid and Cystic Renal Cell Carcinomas : Association With Prior Childhood Malignancy and Multifocality With Therapeutic Implications.

The concept of oncocytoid renal cell carcinoma in patients who have survived neuroblastoma as a distinct biologic entity has been controversial since its original description in 1999. This is in part because similar oncocytoid renal cell carcinomas have been described in association with other pediatric cancers, and also because other renal cell carcinoma subtypes (such as MiT family translocation renal cell carcinoma) have been described in children who have survived neuroblastoma. We identified an index case of a child who survived medulloblastoma and developed multifocal bilateral oncocytoid renal cell carcinomas with morphology and immunophenotype compatible with eosinophilic solid and cystic renal cell carcinoma (ESC RCC) and demonstrated that both neoplasms harbored distinctive mutations in the TSC1/TSC2 genes. Remarkably, the child's remaining bilateral multifocal renal neoplasms completely responded to MTOR inhibitor therapy without need for further surgery. To confirm our hypothesis that oncocytoid renal cell carcinomas after childhood cancer represent ESC RCC, we obtained formalin-fixed paraffin-embedded tissue blocks from 2 previously published cases of oncocytoid renal cell carcinoma after neuroblastoma, confirmed that the morphology and immunophenotype was consistent with ESC RCC, and demonstrated that both cases harbored somatic TSC gene mutations. Both expressed markers previously associated with neoplasms harboring TSC gene mutations, glycoprotein nonmetastatic B, and cathepsin K. Of note, one of these patients had 2 ESC RCC which harbored distinctive TSC2 mutations, while the background kidney of the other patient had multiple small cysts lined by similar oncocytoid cells which showed loss of TSC2 protein. We then reviewed 3 of 4 cases from the original 1999 report of oncocytoid renal cell carcinomas after neuroblastoma, found that all 3 demonstrated morphology (including basophilic cytoplasmic stippling) that is characteristic of ESC RCC, showed that all 3 overexpressed glycoprotein nonmetastatic B, and showed that both cases with adequate material demonstrated loss of TSC2 protein and expressed cytokeratin 20 and cathepsin K by immunohistochemistry. In summary, "oncocytoid renal cell carcinomas after neuroblastoma" represent ESC RCC which are often multifocal in patients who have survived childhood cancer, likely representing an incompletely characterized tumor predisposition syndrome. MTOR-targeted therapy represents an effective therapeutic option for such patients to preserve functional nephrons.

Vascular Expression of Prostate-specific Membrane Antigen (PSMA) in MiTF Family Translocation Renal Cell Carcinoma and Related Neoplasms.

Multiple studies have demonstrated prostate-specific membrane antigen (PSMA) expression in the neo-vasculature of non-prostate tumors including clear cell renal cell carcinoma (ccRCC). However, PSMA expression in rare renal tumors including MiTF family translocation renal cell carcinoma has not been previously characterized. We examined PSMA expression by immunohistochemistry in a series of MiTF family translocation renal cell carcinomas as well as in several genetically related tumors including alveolar soft part sarcoma and PEComas with TFE3 rearrangements. PSMA expression was also studied in several cases of ccRCC and papillary RCC. Overall, PSMA immunohistochemistry was performed in 61 samples from 58 patients. Vascular PSMA expression was seen with the highest frequency in ccRCC [88% (14/16)] (38% focal, 50% diffuse). Translocation RCC (tRCC) demonstrated the second highest frequency of PSMA expression [71% (22/28)] (57% focal, 14% diffuse), followed by alveolar soft part sarcoma [50% (4/8)] (38% focal, 12% diffuse). No PSMA expression was seen in PEComas with TFE3 rearrangement (0/3) or papillary RCC (0/6). PSMA expression was only present in tumor-associated neo-vasculature. A patient with oligometastatic tRCC underwent 68 Ga-PSMA-11 PET imaging which detected multiple putative metastatic lesions not detected on conventional computed tomography imaging performed 2 weeks prior, supporting the potential utility of PSMA imaging in tRCC. These findings have potential implications for the utility of PSMA guided diagnostic and therapeutic agents in both common and uncommon renal cell carcinoma subtypes as well as genetically related mesenchymal neoplasms.

Racial Disparities in MiT Family Translocation Renal Cell Carcinoma.

Racial disparities have been documented in the biology and outcome of certain renal cell carcinomas (RCCs) among Black patients. However, little is known about racial differences in MiT family translocation RCC (TRCC). To investigate this issue, we performed a case-control study using data from The Cancer Genome Atlas (TCGA) and the Chinese OrigiMed2020 cohort. A total of 676 patients with RCC (14 Asian, 113 Black, and 525 White) were identified in TCGA, and TRCC was defined as RCC with TFE3/TFEB translocation or TFEB amplification, leading to 21 patients with TRCC (2 Asian, 8 Black, 10 White, and 1 unknown). Asian (2 of 14 [14.3%] vs 10 of 525 [1.9%]; P = .036) and Black (8 of 113 [7.1%] vs 1.9%; P = .007) patients with RCC showed significantly higher prevalence of TRCC compared with White patients with RCC. The overall mortality rate of TRCC was slightly higher in Asian and Black patients compared with White patients (HR: 6.05, P = .069). OrigiMed2020 Chinese patients with RCC had a significantly higher proportion of TRCC with TFE3 fusions than TCGA White patients with RCC (13 of 250 [5.2%] vs 7 of 525 [1.3%]; P = .003). Black patients with TRCC were more likely to exhibit the proliferative subtype than White patients (6 of 8 [75%] vs 2 of 9 [22.2%]; P = .057) for those who had RNA-seq profiles. We present evidence of higher prevalence of TRCC in Asian and Black patients with RCC compared with White patients and show that these tumors in Asian and Black patients have distinct transcriptional signatures and are associated with poor outcomes.

Clinicopathologic Classification of Renal Cell Carcinoma in Patients ≤40 Years Old From Peru.

There are scant data on renal cell carcinoma (RCC) from relatively younger patients in South America using contemporary classification. Fifty-nine consecutively treated patients with RCC (≤40 years old) were assessed from the National Institute of Neoplastic Diseases in Peru from 2008 to 2020 (34 males; 25 females), age range of 13 to 40 years. Most common presenting symptoms were flank pain (n = 40), hematuria (n = 19), and weight loss (n = 12). Associated conditions included 4 patients with proven or presumed tuberous sclerosis and 1 patient with von Hippel Lindau syndrome, all with clear cell RCC. Tumor histopathology was clear cell RCC in 32 of 59 (54%), chromophobe RCC in 6 of 59 (10%), and 5 of 59 (8%) each of papillary RCC and MiT family translocation-associated RCC. Four of 59 (7%) were FH-deficient RCC and 2 of 59 (3%) remained unclassified. The remaining tumors were isolated examples of clear cell papillary renal cell tumor, eosinophilic solid and cystic RCC (ESC RCC), RCC with fibromyomatous stroma, sarcomatoid RCC, and sarcomatoid clear cell RCC. Of the 4 FH-deficient RCCs, none had the classic morphology. The 5 MiT family translocation RCCs had variable morphology. There were 41 tumors without recurrence or metastases, 3 tumors with local recurrence only, 8 tumors with metastases only, and 7 tumors with both local recurrence and metastases. The current study demonstrates the importance of special studies in accurately classifying RCC in younger individuals. The distribution of RCC subtypes in younger individuals is similar between 2 representative large institutions of the United States and Peru.

A novel VCP::TFE3 gene fusion resulting from t(X;9)(p11.23;p13.3) chromosome translocation in TFE3 rearranged renal cancer cell carcinoma.

Renal cell carcinoma (RCC) with rearrangement of transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3; TFE3-rearranged RCC) at Xp11.2 is a rare tumor entity but the most frequent among the microphthalmia transcription factor family translocation RCCs. Here, we report the identification of a new VCP::TFE3 fusion gene as the result of a t(X;9)(p11.23;p13.3) translocation identified by whole transcriptome sequencing. No other relevant molecular alteration was identified by whole exome sequencing. This case showed typical morphological features of TFE3-rearranged RCC with positive TFE3 immunostaining and positive TFE3 break-apart fluorescence in situ hybridization. MET was also overexpressed on immunohistochemistry. The patient had metastatic disease and was treated by surgery and five lines of therapy, including 24 months of stable disease on the mesenchymal epithelial transition (MET) inhibitor cabozantinib, with an overall survival of 7 years. In addition to expanding the spectrum of TFE3 rearrangement partners, this report highlights the complexity of these tumors and supports the development of translational programs in renal cancer.

Clear Cell Renal Cell Carcinoma with Focal Psammomatous Calcifications: A Rare Occurrence Mimicking Translocation Carcinoma.

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 tumors consistent with clear cell RCC that contain focal psammomatous calcifications. We identified clear cell RCCs with psammomatous calcifications from multiple institutions and performed immunohistochemistry and fluorescence and RNA in situ hybridization (FISH and RNA ISH). Twenty-one tumors were identified: 12 men, 9 women, ages 45 to 83 years. Tumor size was 2.3 to 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). Labeling for CA9 was usually 80-100% of the tumor cells (n=17/21) but was sometimes decreased in areas of eosinophilic cells (n=4). All (19/19) were positive for CD10. Most (19/20) were positive for AMACR (variable staining, 20-100%). Staining was negative for keratin 7, although 4 showed rare positive cells (4/20). Results were negative for cathepsin K (0/19), melan A (0/17), HMB45 (0/17), TFE3 (0/5), TRIM63 RNA-ISH (0/13), and TFE3 (0/19) and TFEB rearrangements (0/12). Seven of 19 (37%) showed chromosome 3p deletion. One (1/19) showed trisomy 7 and 17 without papillary features. 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.

Immune Checkpoint Therapy Combinations in Adult Advanced MiT Family Translocation Renal Cell Carcinomas.

There remains a paucity of data regarding the efficacy of immune checkpoint therapy (ICT) combinations ± vascular endothelial growth factor (VEGF) targeted therapy (TT) in translocation renal cell carcinoma (tRCC). This is a retrospective study of patients with advanced tRCC treated with ICT combinations at 11 centers in the US, France, and Belgium. Only cases with confirmed fluorescence in situ hybridization (FISH) were included. Objective response rates (ORR) and progression-free survival (PFS) were assessed by RECIST, and overall survival (OS) was estimated by Kaplan-Meier methods. There were 29 patients identified with median age of 38 (21-70) years, and F:M ratio 0.9:1. FISH revealed TFE3 and TFEB translocations in 22 and 7 patients, respectively. Dual ICT and ICT + VEGF TT were used in 18 and 11 patients, respectively. Seventeen (59%) patients received ICT combinations as first-line therapy. ORR was 1/18 (5.5%) for dual ICT and 4/11 (36%) for ICT + VEGF TT. At a median follow-up of 12.9 months, median PFS was 2.8 and 5.4 months in the dual ICT and ICT + VEGF TT groups, respectively. Median OS from metastatic disease was 17.8 and 30.7 months in the dual ICT and ICT + VEGF TT groups, respectively. In this retrospective study of advanced tRCC, limited response and survival were seen after frontline dual ICT combination therapy, while ICT + VEGF TT therapy offered some efficacy. Due to the heterogeneity of tRCC, insights into the biological underpinnings are necessary to develop more effective therapies.

MiT/TFE Family Renal Cell Carcinoma.

The microphthalmia-associated transcription factor/transcription factor E (MiT/TFE) family of transcription factors are evolutionarily conserved, basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors, consisting of MITF, TFEB, TFE3, and TFEC. MiT/TFE proteins, with the exception of TFEC, are involved in the development of renal cell carcinoma (RCC). Most of the MiT/TFE transcription factor alterations seen in sporadic RCC cases of MiT family translocation renal cell carcinoma (tRCC) are chimeric proteins generated by chromosomal rearrangements. These chimeric MiT/TFE proteins retain the bHLH-Zip structures and act as oncogenic transcription factors. The germline variant of MITF p.E318K has been reported as a risk factor for RCC. E 318 is present at the SUMOylation consensus site of MITF. The p.E318K variant abrogates SUMOylation on K 316, which results in alteration of MITF transcriptional activity. Only a few cases of MITF p.E318K RCC have been reported, and their clinical features have not yet been fully described. It would be important for clinicians to recognize MITF p.E318K RCC and consider MITF germline testing for undiagnosed familial RCC cases. This review outlines the involvement of the MiT/TFE transcription factors in RCC, both in sporadic and hereditary cases. Further elucidation of the molecular function of the MiT/TFE family is necessary for better diagnosis and treatment of these rare diseases.

A case of TFE3 translocation renal cell carcinoma with rare morphological features and literature review.

TFE3 translocation renal cell carcinoma (RCC) is a rare tumor that represents approximately 1% of RCC. It was classifed as a member of MiT family translocation RCCs by the World Health Organization in 2016. It is characterized by Xp11 translocation gene fusions involving TFE3. The diagnosis of TFE3 translocation RCC is based on immunohistochemical analysis and TFE3 break apart probes in FISH analysis, rather than histological characteristics and imaging examination. To determine the clinico-pathological, immuno-phenotypic, and cytogenetic characteristics of TFE3 translocation RCC. The clinical data of a 52-year-old-female patient with TFE3 translocation RCC exhibiting rare morphological characteristics was analyzed, and the tumor tissues were probed using histopathological staining, immunohistochemistry, and fluorescence in situ hybridization (FISH). In addition, the relevant literature was reviewed. This case is a TFE3 translocation RCC with rare morphological features. It composed of two types of tumor cells. TFE3 and pax-8 were diffusely and strongly expressed in both tumor cells, and they were partially positive for CAIX, RCC, CK, EMA, CD10, Vim, Melan-A, and p504s. Only 2% of the cells were positive for the proliferation marker Ki-67, and the tumor was negative for CK7, CD117, Inhibin-α, HBM45, and p53. FISH showed a positive signal for TFE3 translocation. This case was a TFE3 translocation RCC with rare morphological features. Through this case report, we emphasize the importance of in situ detection of TFE3 gene translocation and protein in TFE3 translocation RCC.

Proteogenomic characterization of MiT family translocation renal cell carcinoma

Microphthalmia transcription factor (MiT) family translocation renal cell carcinoma (tRCC) is a rare type of kidney cancer, which is not well characterized. Here we show the comprehensive proteogenomic analysis of tRCC tumors and normal adjacent tissues to elucidate the molecular landscape of this disease. Our study reveals that defective DNA repair plays an important role in tRCC carcinogenesis and progression. Metabolic processes are markedly dysregulated at both the mRNA and protein levels. Proteomic and phosphoproteome data identify mTOR signaling pathway as a potential therapeutic target. Moreover, molecular subtyping and immune infiltration analysis characterize the inter-tumoral heterogeneity of tRCC. Multi-omic integration reveals the dysregulation of cellular processes affected by genomic alterations, including oxidative phosphorylation, autophagy, transcription factor activity, and proteasome function. This study represents a comprehensive proteogenomic analysis of tRCC, providing valuable insights into its biological mechanisms, disease diagnosis, and prognostication.

1461P Impact of first-line (1L) therapy on outcomes of adult patients (pts) with metastatic MiT family translocation renal cell carcinomas (TRCC) treated in the contemporary immune checkpoint therapy (ICT) era

TRCC represent a rare and aggressive subgroup of RCC. While 1L therapy recommendations and clinical prognostication of pts with clear-cell RCC are well-known, data on TRCC clinical behavior are limited. TRCC is reported to be an immune cold tumor and the data surrounding 1L ICT is scarce.

Hereditary Renal Cell Carcinoma

BACKGROUND: Hereditary renal cell carcinoma (RCC) is a complex and rapidly evolving topic as there is a growing body of literature regarding inherited syndromes and mutations associated with an increased risk of RCC. OBJECTIVES: We sought to systematically review 13 hereditary syndromes associated with RCC; von Hippel-Lindau Disease associated RCC (VHLRCC), BAP-1 associated clear cell RCC (BAPccRCC), Familial non-von Hippel Lindau clear cell RCC (FccRCC), Tuberous Sclerosis Complex associated RCC (TSCRCC), Birt-Hogg-Dub e ´ Syndrome associated RCC (BHDRCC), PTEN Hamartoma Tumor Syndrome associated RCC (PHTSRCC), Microphthalmia-associated Transcription Family translocation RCC (MiTFtRCC), RCC with Chromosome 6p Amplification (TFEBRCC), Autosomal Dominant Polycystic Kidney Disease associated RCC (ADPKDRCC), Hereditary Leiomyomatosis associated RCC (HLRCC), Succinate Dehydrogenase RCC (SDHRCC), Hereditary Papillary RCC (HPRCC), and ALK-Rearrangement RCC (ALKRCC). RESULTS: Hereditary RCC is generally associated with an early age of onset, multifocal and/or bilateral lesions, and aggressive disease course. VHLRCC, BAPccRCC, FccRCC, and certain mutations resulting in SDHRCC are associated with clear cell RCC (ccRCC). HPRCC is associated with Type 1 papillary RCC. HLRCC is associated with type 2 papillary RCC. BHDRCC is associated with Chromophobe RCC. TSCRCC, PHTSRCC, MiTFtRCC, TFEBRCC, ADPKDRCC, certain SDHRCC and ALKRCC have variable histology. CONCLUSIONS: There has been tremendous advancement in our understanding of the pathophysiology of hereditary RCC. Ongoing research will refine our understanding of hereditary RCC and its therapeutic targets.

Transcription factor E3 renal cell carcinoma presenting as secondary hypertension.

Microphthalmia-associated transcription factor family (transcription factor E3 or transcription factor EB) translocation renal cell carcinomas (RCCs) are rare neoplasms. These renal neoplasms can be either asymptomatic and incidentally discovered on imaging or symptomatic, with the most common presenting symptoms being hematuria, pain, and abdominal mass, or paraneoplastic event. In conventional RCCs, hypertension is considered a risk factor and a possible paraneoplastic event, whereas, in translocation RCCs, prior exposure to cytotoxic chemotherapy is the only known risk factor, and hypertension as an isolated associated paraneoplastic event has never been reported. Interestingly, hypertension as the only presenting symptom in RCC is extremely rare. We report a case of transcription factor E3 positive RCC in a young adult presenting only with hypertension that normalized after radical nephrectomy. To the best of our knowledge, this is the first reported case of hypertension secondary to microphthalmia-associated transcription translocation RCC.

A Retrospective Study of Lymph Node Dissection for Renal Cell Carcinoma

We retrospectively analyzed the effect of lymph node dissection (LND) in patients with renal cell carcinoma (RCC). Of 151 patients who underwent nephrectomy for RCC, 86 underwent LND. No distant metastasis (M0) was present in 71 patients, although distant metastasis (M1) was present in 15. Three (4.2%) and eight (53%) patients in the M0 and M1 groups, respectively, were clinical N-stage positive. Two (2.8%) and three (20%) patients in the M0 and M1 groups, respectively, were pathological N-stage positive. Both pathological N stage-positive patients in the M0 group were pathologically diagnosed with microphthalmia transcription family translocation RCC. The clinical and pathological positive node areas exhibited concordance in all three pathological N stage-positive patients in the M1 group. Chylous leakage occurred in 16 (19%) patients in the LND group (p＜0.05). Extended LND was a statistically significant risk factor for chylous leakage in the multivariate analysis. Only limited cases should undergo LND, owing to the low frequency of positive pathological lymph node metastasis, and high complication rate.

Advanced nccRCC: what therapeutic options in 2022?

Non-clear-cell renal cell carcinomas (nccRCC) represent around 25% of all renal cancers and are a very heterogeneous group of tumours in terms of both biological features and prognosis. Papillary renal cell carcinomas (pRCC) are the most frequent subtype with 15% to 20% of all kidney cancers. Improved biological knowledge of these tumours has led to better identification of each subtype. Among pRCC, some exhibit mutations of the MET oncogene and others mutations of the gene coding for fumarate hydratase. The management of nccRCC, in particular the pRCC subtype, has evolved considerably in recent times, spearheaded by the advent of targeted therapies including anti-angiogenics but also new immunotherapy agents. Several studies have in the last few years prompted a new standard of care for these nccRCC. We propose to present throughout this article the latest available efficacy data on different compounds assessed in the treatment of the most frequent nccRCC, including the pRCC, chromophobe carcinoma, collecting duct carcinoma, MiT family translocation renal cell carcinoma and renal medullary carcinoma subtypes.

Immuno-oncology (IO) combinations +/- VEGF targeted therapy (VEGF TT) in patients (pts) with advanced mit family translocation renal cell carcinomas (tRCC): Results from an international multicenter study.

343 Background: IO combinations are standard of care for first-line therapy of clear-cell RCC; however, non-clear cell histologies including tRCC were not included in the registrational trials. We previously reported a modest efficacy (objective response rate [ORR] &lt;20%) with IO monotherapy (PD-1 blockade) in tRCC (Boilève et al, JITC. 2018). The efficacy of IO combinations +/- VEGF TT has not been reported. Methods: This is a retrospective, international, multicenter study of pts with tRCC treated with IO-IO or IO+VEGF TT at 11 centers in the US, France, and Belgium. Only pts with confirmed TFE3 or TFEB translocation by fluorescent-in-situ hybridization (FISH) were included. ORR and progression-free survival (PFS) were assessed by RECIST. Overall survival (OS) was assessed by Kaplan-Meier methods. OS was measured from initiation of therapy till death or last follow up. We also assessed the association between OS and baseline prognostic variables. Results: 29 patients with metastatic tRCC were included in this analysis. Median age at starting therapy was 38 (IQR 27, 53) years. Female:Male ratio was 0.9:1. FISH revealed a translocation involving TFE3 and TFEB in 22 and 7 patients, respectively. Most frequent metastatic sites at diagnosis were lungs (76%), liver (52%), retroperitoneal adenopathy (48%), and bone (38%). IMDC risk at diagnosis was favorable (31%), intermediate (45%) and poor (24%). Combinations of IO+VEGF TT and anti-PD1 (L1) + anti-CTLA-4 (IO+IO) were used in 11 and 18 pts, respectively. 17 (59%) pts received IO combinations as 1L, 7 (24%) pts as 2L and 5 (17%) pts as ≥3L. ORR in the IO+IO group was 1/18 (5.5%), while in IO+VEGF TT group was 4/11 (36%). For 20 (69%) pts, progressive disease was the best overall response. At a median follow-up of 12.9 months (mo), median PFS was 3.2 mo and median OS was 13.5 mo for all 29 pts (Table). Median PFS in the IO+IO group was 2.8 mo, and 5.4 mo in IO+VEGF TT group (HR=0.81, 95% CI: 0.35-1.84). Conclusions: In this small retrospective study of tRCC, IO+IO therapy produced modest activity based on low ORR and short PFS while IO+VEGF TT produced numerically higher ORR and longer PFS. Insights into the biological basis of tRCC are necessary to develop more effective therapies for this rare and aggressive RCC variant.[Table: see text]