Succinate Dehydrogenase-deficient Renal Cell Research Articles

Succinate dehydrogenase A deficient renal cell carcinoma: A rare renal tumor distinct from typical Succinate dehydrogenase deficient renal cell carcinoma

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype of RCC classified as a molecularly defined RCC in the fifth edition of the WHO. Most gene alterations in patients with SDH-deficient RCC involve the SDHB subunit, with less involvement of the SDHC, SDHA, and SDHD subunits. Four cases of SDHA-deficient RCC have been reported in the literature, of which one case was associated with an NF2 gene mutation. Herein, we report six novel SDHA-deficient RCC cases, including two cases with NF2 gene mutations. In contrast to the typical morphology of SDH-deficient RCC, the six tumors mainly displayed glandular, sheet-like, or papillary growth patterns with prominent nucleoli (Grades 2–3), among which two cases with NF2 mutations had prominent nucleoli (Grade 3), large transparent vacuoles in the cytoplasm, and a large number of lymphocytes in the stroma. Six tumors showed negative immunohistochemical staining for SDHA and SDHB, and three cases presented with high expression of PD-L1. Second-generation sequencing revealed novel pathogenic somatic SDHA gene mutation and NF2 gene mutations in six and two tumors, respectively. Follow-up data were collected for the six patients with a follow-up time ranging from 7 to 268 months, and all six patients have survived to date. One patient received targeted therapy for tumor metastasis to the lungs after seven months, and another patient with an NF2 gene mutation received immunotherapy for lymph node metastasis revealed during surgery. SDHA-deficient RCCs with NF2 gene mutations have the ability to metastasize but might respond well to immunotherapy. For the first time, we report the largest number of SDHA-deficient RCC cases and comprehensively investigate their clinicopathological and molecular features to provide important guidance for diagnosis and clinical immunotherapy.

P10 - Succinate dehydrogenase deficient renal cell carcinoma: Comprehensive molecular profiling suggests improved diagnostic and therapeutic strategies

P10 - Succinate dehydrogenase deficient renal cell carcinoma: Comprehensive molecular profiling suggests improved diagnostic and therapeutic strategies

Renal Oncocytoma With Both Lymphovascular Invasion and Prominent Intracytoplasmic Vacuole-Like Spaces: A Case Report and Review of the Literature

Here we report a case of renal oncocytoma in a 68 year-old male. The diagnosis was initially made on a needle biopsy 6 years prior to the partial nephrectomy. The case is unique that in addition to the gross and microscopic features commonly seen in renal oncocytomas, both lymphovascular invasion and prominent intracytoplasmic vacuole-like spaces are also present in this tumor. Although vascular invasion is increasingly recognized as compatible with renal oncocytoma, intracytoplasmic vacuoles are a rare and unusual finding that may lead to diagnostic difficulty. The diagnosis of renal oncocytoma was confirmed after immunohistochemistry was performed to argue against succinate dehydrogenase deficient renal cell carcinoma (RCC) and chromophobe RCC. This case highlights the importance for practicing pathologists to recognize the rare co-occurrence of lymphovascular invasion and large intracytoplasmic vacuole-like spaces in renal oncocytoma. Other differential diagnoses may include emerging renal tumor entities, such as the recently-proposed eosinophilic vacuolated tumor.

Clinicopathological characterisation of renal cell carcinoma in young adults: a contemporary update and review of literature.

Renal cell carcinomas are relatively rare in children and young adults. While well characterised in adults, the morphological and molecular characterisation of these tumours in young patients is relatively lacking. The objective of this study was to explore the spectrum of renal cell carcinoma (RCC) subtypes in children and young adults and to determine their clinico-pathological, immunohistochemical and molecular characteristics by evaluating a large retrospective cohort of renal cell carcinoma patients age 30years or younger. Sixty-eight cases with confirmed diagnosis of renal cell carcinoma at age 30years or younger were identified at our institution. Clear cell carcinoma accounted for the most common subtype seen in this age group. Translocation renal cell carcinoma and rare familial syndrome subtypes such as succinate dehydrogenase deficient renal cell carcinoma and tuberous sclerosis complex-associated renal cell carcinoma were found relatively more frequently in this cohort. Despite applying the 2016 WHO classification criteria, a high proportion of the tumours in our series remained unclassified. Our results suggest that renal cell carcinoma in children and young adults is a relatively rare disease that shares many histological similarities to renal cell carcinoma occurring in adults and yet demonstrate some unique clinical-pathological differences. Microphthalmia-associated transcription (MiT) family translocation RCC and rare familial syndrome subtypes are relatively more frequent in the paediatric and adolescent age groups than in adults. Clear cell RCC still accounted for the most common subtype seen in this age group. MiT family translocation RCC patients presented with advanced stage disease and had poor clinical outcomes. The large and heterogeneous subgroup of unclassified renal cell carcinoma contains phenotypically distinct tumours with further potential for future subcategories in the renal cell carcinoma classification.

Succinate Dehydrogenase–Deficient Renal Cell Carcinoma With Sarcomatoid Features

Abstract Succinate dehydrogenase (SDH) complex deficiency syndrome is an autosomal dominant syndrome with mutations in the SDH gene characterized by multiple tumor types, including paragangliomas, pheochromocytomas, gastrointestinal stromal tumors, thyroid tumors, testicular seminoma, neuroblastomas, and, less commonly, renal cell carcinoma. SDH-deficient renal cell carcinoma is a distinct and rare subtype of renal cell carcinoma, typically with a good prognosis, that demonstrates histologic features including cytoplasmic inclusions and vacuoles with a loss of SDH subunit B immunostaining. We present a case of succinate dehydrogenase–deficient renal cell carcinoma with sarcomatoid features in a 24-year-old male who initially presented with hematuria and flank pain. An MRI of the abdomen showed a large enhancing mass in the upper pole of the kidney. He underwent a radical nephrectomy and was found to have an 11.0 × 10.5 × 10.2-cm variegated and lobular mass in the upper pole of the kidney. Microscopic examination showed sheets of cells with cleared out cytoplasm, cytoplasmic inclusions, and vacuoles. Areas of the mass showed sarcomatoid features and necrosis. The mass extended into the pelvicalyceal system and metastasized to the adrenal gland. An SDH B immunostain was performed on the specimen and was negative, confirming the diagnosis of SDH-deficient renal cell carcinoma. Subsequently, the patient underwent genetic testing and was found to have an SDHB germline mutation.