The Evolving Concept of Renal Neoplasia: Impact of Emerging Molecular and Electron Microscopic Studies

Abstract

The classification of renal tumors has evolved from one that initially encompassed only 2 types of tumors, i.e., clear and granular cell carcinomas, to the markedly expanded recent classification that incorporates new entities, some of which are primarily defined by specific molecular abnormalities. Despite these advances, a single tumor category, clear cell carcinoma, still incorporates the majority (approximately 70%) of renal tumors. It is, however, postulated that this single category is likely to encompass several different tumor types that are, at present, undifferentiated. Electron microscopic studies have been pivotal in defining the spectrum of oncocytoma-chromophobe renal cell carcinoma. Cytoplasmic eosinophilia found in some renal cell carcinomas currently classified as clear cell type is under intense study. Tumors that have recently emerged from this group include tumors with translocations involving chromosome Xp11.2, carcinomas associated with neuroblastoma and epithelioid angiomyolipoma. The spectrum of renal tumors seen in younger patients is wider than among older patients, with rare and unusual tumors being more likely seen in younger patients. The author concludes that although the routine application of electron microscopy to kidney tumor diagnosis may not be practical, systematic ultrastructural studies of these tumors may aid in the definition of new entities.

Distinct Cytoplasmic Expression of KL-6 Mucin in Chromophobe Renal Cell Carcinoma: A Comparative Immunohistochemical Study with Other Renal Epithelial Cell Tumors

“…Furthermore, this pattern of expression was similar to that in intercalated cells located in the renal collecting tubules, confirming the concept that chromophobe RCC is histologically related to the renal distal nephron epithelium, especially the intercalated cells [13]. …”

Mitochondria with Tubulovesicular Cristae in Renal Oncocytomas

“…The differential diagnosis is based on the overall cytologic aspect of the tumors, the absence or only exceptional presence of clear microvesicles in oncocytoma [25], and the appearance of the mitochondria [4,7,22,23]. Most oncocytomas show packed mitochondria with lamellar, piled cristae, and CRCC exhibited in the overwhelming majority of cases mitochondria with tubulovesicular cristae [4,7,22,23,26].…”

“…Differentiated gene abnormalities [18], transcription factor expression [19], and microRNa profiles are currently being described in human kidney tumors [20]. Despite of these advances and since the detailed description of Thoenes et al [21] of the ultrastructural appearance of renal tumors, electron microscopy continues to be an easy to perform, low-cost, and useful tool in the diagnosis of kidney tumors [22][23][24].…”

Ancillary Diagnostic Techniques in the Evaluation of Adult Epithelial Renal Neoplasms

“…Neoplasms with proximal tubular differentiation express CD10, whereas those with distal tubular differentiation exhibit kidney-specific cadherin expression. [42][43][44] The role of cytogenetics and molecular markers in the evaluation of these neoplasms continues growing, 17,45-48 but its use is compromised by reduced accessibility to these techniques in smaller practices and relative high cost. 41 The combination of several immunohistochemical markers may be used to address the differential diagnosis of epithelial renal tumors, but significant overlap is often present, preventing a clear separation of a significant percentage of these.…”

“…For example, granules/ crystalline inclusions may be present in the cytoplasm of tumor cells mimicking those seen in alveolar soft part (ASP) sarcomas, 44 suggesting that this large category of clear cell tumors could be segregated into different clinically significant subtypes in the future. Nevertheless, the classic features associated with clear cell carcinomas with intracytoplasmic glycogen and fat intimately together in the neoplastic cells and proximal tubule-like microvillous surface differentiation are diagnostic and extremely specific for these RCCs.…”