Eosinophilic solid and cystic renal cell carcinoma mimicking epithelioid angiomyolipoma: series of 4 primary tumors and 2 metastases

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel entity of rare tumors with rather unique morphology and immunohistochemical profile. Until recently these tumors were characterized by indolent behavior. Herein, we describe a series of six primary and metastatic ESC-RCCs morphologically and immunophenotypically mimicking epithelioid angiomyolipoma (eAML). Retrospective review of unclassified RCCs with oncocytic phenotype yielded several candidate cases, 4 of which fulfilled diagnostic criteria after additional work-up. Three female patients and one male (median age 46) presented with unifocal tumors ranging from 1.5 cm to 20.5 cm (median 5 cm). On follow-up (median 32 months), 2 younger patients had no signs of tumor recurrence, but older patients presented with advanced disease. A 50 year-old female developed numerous bone metastases and tumor progression despite aggressive treatment. Two of these metastases were analyzed showing morphology and immunoprofile similar to the primary tumor. 50 year-old male had locally aggressive tumor invading adrenal gland and retroperitoneum. All cases exhibited ESC-like architecture of solid sheets, tight nests and variably sized cysts with hobnailed lining, as well as foci of diffuse growth with poorly cohesive brightly eosinophilic cells. Characteristic cytoplasmic stippling and coarse granularity was present in all cases including compact cytoplasmic “Leishmaniasis-like” globules. Due to high suspicion of eAML, immunostaining panels included melanocytic markers, cytokeratins and RCC-specific markers. All ESC-RCC were positive for CK20 and melanocytic markers Melan-A, Cathepsin-K or HMB45, as well as PAX8, whereas EMA, pan-cytokeratin, CK7, CKIT, CD10, CAIX were negative. Comparison with 5 eAML cases including 2 malignant tumors showed similar morphology and immune reactivity except for more frequent expression of HMB45 and lack of PAX8 positivity. In conclusion, we report 2 cases of aggressive ESC-RCC course including widespread bone metastases in addition to 2 typical indolent tumors. ESC-RCC and eAML could present with overlapping morphology and immunophenotype causing diagnostic difficulty and expanding our understanding of these rare tumors.