Update on selected oncocytic renal cell tumors

Advances in immunohistochemical and molecular technologies have led to the identification of various new renal cell carcinoma (RCC) subtypes since the 2016 WHO classification. Among these, oncocytic tumors, characterized by cells with abundant eosinophilic cytoplasm, pose significant diagnostic challenges due to their overlapping histological features. Key oncocytic RCCs include renal oncocytoma, chromophobe RCC, and others such as succinate dehydrogenase-deficient RCC (SDH-RCC), hybrid oncocytic/chromophobe renal tumors (HOCTs), and oncocytic papillary renal neoplasm with reverse polarity. Recent studies have identified new oncocytic entities, including eosinophilic solid and cystic RCC (ESC-RCC), eosinophilic vacuolated tumor (EVT), and low-grade oncocytic tumor (LOT).

EVT

EVT, initially described as a "high-grade oncocytic tumor," has now been recognized by the WHO as an eosinophilic vacuolated tumor. Approximately 60 cases have been reported, predominantly affecting women (M

ratio 1:1.3) with a mean age of 49 years. EVTs typically present sporadically but can be associated with tuberous sclerosis complex (TSC). Histologically, EVTs exhibit a distinctive eosinophilic and vacuolated cytoplasm and harbor mutations in TSC1, TSC2, and/or MTOR genes. Clinically, these tumors have a favorable prognosis with low metastatic potential.

LOT

LOT is characterized by its indolent behavior and distinct histopathological features, including a low-grade nuclear morphology and a solid growth pattern. Immunohistochemically, LOTs are usually positive for CK7 and negative for CD117, distinguishing them from chromophobe RCC. Molecular analyses have not identified specific genetic mutations, but their unique morphology warrants a separate classification. Clinical outcomes for LOT patients are excellent, with minimal risk of progression or metastasis.

ESC-RCC

ESC-RCC, a recently described entity, is associated with TSC mutations and presents with a mixed solid and cystic architecture. Patients range from young to middle-aged adults, with a slight female predominance. Histologically, ESC-RCCs display cells with eosinophilic cytoplasm and variable cystic changes. Immunohistochemical profiles typically include positivity for CD117 and CK7. ESC-RCCs generally have a benign clinical course, but a small subset may exhibit aggressive behavior, necessitating careful long-term follow-up.

Low-Grade Oncocytic FH-Deficient RCC

Low-grade oncocytic fumarate hydratase (FH)-deficient RCC is a rare variant that shares morphological similarities with other oncocytic tumors but is characterized by FH deficiency. These tumors exhibit a low-grade oncocytic morphology and have been linked to hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Immunohistochemical staining for 2-succinocysteine (2SC) and FH can aid in diagnosis. Despite their benign appearance, FH-deficient RCCs can behave aggressively, underscoring the importance of recognizing this entity for appropriate management.

HOCTs

HOCTs are composite tumors containing features of both oncocytoma and chromophobe RCC. These tumors are typically sporadic and present a diagnostic challenge due to their mixed histological characteristics. Immunohistochemically, HOCTs show variable expression of markers typical of both parent tumors. Clinical outcomes are generally favorable, with low recurrence and metastasis rates, supporting the classification of HOCTs as low-risk tumors.

Conclusions

The identification and characterization of these new oncocytic RCC entities have significant implications for diagnosis and management. Accurate classification based on histopathological, immunohistochemical, and molecular features is crucial for prognostication and therapeutic decision-making. Future studies are needed to further elucidate the genetic and clinical landscape of these tumors, ultimately improving patient outcomes.

Full text

https://www.xiahepublishing.com/2771-165X/JCTP-2022-00032

The study was recently published in the Journal of Clinical and Translational Pathology.

Journal of Clinical and Translational Pathology (JCTP) is the official scientific journal of the Chinese American Pathologists Association (CAPA). It publishes high quality peer-reviewed original research, reviews, perspectives, commentaries, and letters that are pertinent to clinical and translational pathology, including but not limited to anatomic pathology and clinical pathology. Basic scientific research on pathogenesis of diseases as well as application of pathology-related diagnostic techniques or methodologies also fit the scope of the JCTP.

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