Eosinophilic, solid and cystic (ESC) renal cell carcinoma (RCC) is characterized by a solid and cystic architecture with cells showing abundant eosinophilic cytoplasm with hobnail arrangement and a cytokeratin 7-negative/cytokeratin 20-positive immunophenotype. Recent studies have suggested that bi-allelic events affecting TSC genes might play an important role for such tumors. However, only indirect evidence of the clonal origin of TSC mutation has been gathered so far. Therefore, in this paper we aimed to perform multi-regional tumor sampling molecular analysis in four ESC RCC cases that had been completely embedded, three sporadic and one occurring in a patient with tuberous sclerosis complex (TSC). Histologically, the 4 cases showed cystic and solid architecture and cells with abundant eosinophilic cytoplasm with cytoplasmic stippling and round to oval nuclei. Immunohistochemistry showed at least focal expression of cytokeratin 20 in all tissue samples and negative cytokeratin 7, as well as diffuse positivity for S100A1 and at least focal expression of cathepsin K in three out of four cases. The sporadic cases showed the same somatic TSC1 mutations in all tissue samples analyzed, while the TSC-associated case showed the same TSC1 alteration in both normal tissue and all tumor samples analyzed, proving the germline nature of the alteration. In conclusion, our data demonstrate that clonal TSC loss is a key event in ESC RCC and support considering ESC RCC as an entity given its distinct morphologic, immunophenotypical and molecular characteristics.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2021 May 14 [Epub ahead of print]
Enrico Munari, Giulio Settanni, Anna Caliò, Diego Segala, Sara Lonardi, Silvia Sandrini, Paola Vacca, Nicola Tumino, Marcella Marconi, Matteo Brunelli, Stefano Gobbo, George J Netto, Lorenzo Moretta, Giuseppe Zamboni, Guido Martignoni
Department of Pathology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy., Department of Diagnostics and Public Health, University of Verona, Verona, Italy., Pathology Unit, ASST-Spedali Civili, Brescia, Italy., Immunology Area, IRCCS Bambino Gesù Children's Hospital, Rome, Italy., Pathology Unit, Pederzoli Hospital, Peschiera del Garda, Verona, Italy., Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA., Department of Diagnostics and Public Health, University of Verona, Verona, Italy. .