FINAL DIAGNOSIS
Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC).
DISCUSSION
Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) has been recently introduced as an emerging RCC entity, which is not included in the 2016 WHO classification, with well-defined clinical, pathological, immunohistochemical and genetic/molecular features. ESC-RCC is usually a sporadic and non-syndromic neoplasm, although a subset has been documented in the setting of tuberous sclerosis complex (TSC) [1,2]. Following the initial study by Trpkov et al., several papers from different institutions were published, providing further support to the concept of ESC-RCC as a novel entity [3]. Sporadic ESC-RCC usually affects middle-age or older women and is typically associated with indolent clinical behavior [4].
ESC-RCC is usually an unencapsulated tumor with mixed macrocystic (multifocal and varying in size) and solid patterns [3]. Rare cases display an almost exclusively solid growth with only rare, if any, identifiable microscopic cysts. The case described here is most likely an example with almost exclusively solid growth pattern although as previously noted the fragmented nature of the specimen limited the identification of cystic areas. ESC-RCC is characterized by a hobnail arrangement of the epithelial component lining of the cysts, intermixed with more cellular trabeculae, nests and compact acini, as well as solid areas [3]. The neoplastic cells typically display voluminous eosinophilic cytoplasm, with intracytoplasmic vacuolization and coarse cytoplasmic granules (''stippling''), reminiscent of "leishmania bodies", representing aggregates of rough endoplasmic reticulum [4]. Scattered aggregates of foamy histiocytes and lymphocytes are often present. Of note, a unique case of ESC-RCC with melanin production was recently published [5].
ESC-RCC has a characteristic immunohistochemical profile with positivity for CK20 (diffuse or patchy, as in our case), PAX8, AE1/AE3, CK8/18, Cathepsin K (diffuse or focal), vimentin, and negative for CK7 (or focal positive), CD117, CAIX, HMB45 and Melan A [3,6-8]. The differential diagnosis is wide encompassing renal tumors with eosinophilic cells, including oncocytoma, eosinophilic variant of chromophobe renal cell carcinoma, low-grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), hybrid oncocytic/chromophobe tumor (HOCT), succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC), MiT family translocation renal cell carcinoma (MiTF RCC), and epithelioid angiomyolipoma, among others. However, the combination of characteristic morphologic features with its rather unusual immunohistochemical profile [CK20 and Cathepsin K (+)/CK7 and CD117 (-)] are generally adequate for the diagnosis.
ESC-RCC harbors TSC1 and TSC2 mutations and recurrent mutually exclusive somatic biallelic loss of TSC1/2 is considered as a molecular marker of this entity [9-11]. An absence of germline TSC1/2 aberration in matched non-neoplastic renal parenchyma distinguishes ESC-RCC from its syndromic counterpart (TSC-RCC). Additionally, karyotype profiling of ESC-RCC showed common and recurring genomic changes as copy number (CN) gains at 16p13-16q23, 7p21-7q36, 13q14, 19p12 and CN losses at Xp11.21 and 22q11; loss of heterozygosity (LOH) has been identified at 16p11.2-11.1, Xq11-13, Xq13-21, 11p11, 9q21-22, and 9q33 [6]. These data regarding the genetic landscape of ESC-RCC could have significant translational impact as these patients may be candidates for mTOR pathway-targeted therapy.
REFERENCES
Contributed by Dimitrios Korentzelos, MD and Gabriela M Quiroga-Garza, MD