Clinicopathological and molecular comparison of eosinophilic solid and cystic renal cell carcinoma and TFEB-amplified renal cell carcinoma: a comprehensive study of 15 cases.

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) and TFEB-amplified renal cell carcinoma (TFEB-amplified RCC, a subset of TFEB-altered RCC) are rare eosinophilic renal cell tumours that can be difficult to distinguish on the basis of morphology and immunohistochemistry alone. In this study, we compared the clinicopathological and molecular features of these entities to identify distinguishing characteristics. Nine cases of ESC-RCC and six cases of TFEB-amplified RCC from our institutional archives were evaluated for clinical, morphological, immunohistochemical and molecular features. Despite morphological overlap, each entity exhibited somewhat distinctive features. ESC-RCC frequently exhibited solid and cystic architecture with tightly packed tubules, flocculent to coarsely granular cytoplasm with basophilic stippling and prominent admixed macrophages. In comparison, TFEB-amplified RCC more frequently demonstrated solid growth of pseudopapillae and loose tubules, dense eosinophilic granular cytoplasm without basophilic stippling, focally apical nuclei and extracellular magenta globules. However, neither morphology nor immunohistochemistry was sufficiently specific to completely distinguish these entities. Ancillary molecular testing identified pathogenic TSC1 or TSC2 gene variants in ESC-RCC and TFEB gene locus amplification in TFEB-amplified RCC. Although ESC-RCC and TFEB-RCC share overlapping morphological and immunohistochemical features, each demonstrates somewhat characteristic histological findings. Definitive distinction requires molecular testing to identify the underlying molecular alterations. As molecular testing assumes an increasingly important role in RCC diagnosis and classification, recognition of these rare entities and their overlapping and distinguishing features is essential for appropriate testing and accurate diagnosis.