A variety of epithelial renal neoplasms have been identified both in patients with tuberous sclerosis complex (TSC) and in the nonsyndromic setting associated with somatic mutations in TSC family genes. ¹ One of these such tumors is the eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), which represents a relatively compact and distinct morpho-molecular entity, characterized  by TSC2 or TSC1 mutations. ^2,3 

Approximately 10% of ESC RCCs occur in patients with documented Tuberous Sclerosis (TCS) syndrome OMIM:191100, but the great majority are sporadic.

Patients with ESC-RCC are usually asymptomatic (i.e., the tumors are found incidentally), with a very strong female predominance.

ESC-RCC is a well circumscribed, typically unilateral and solitary, but not encapsulated, yellow-tan/gray lesion.  ESC-RCC is comprised of variable amounts of solid and cystic growth.  Variable radiologic appearances have reported, according to the proportion of solid and cystic components. ^3-5

ESC-RCC is comprised of predominantly eosinophilic cells with small regular nuclei and moderate to voluminous cytoplasm (i.e. low nuclear to cytoplasmic ratio); however, focal clear cell and vacuolated cytoplasm may be present.  Tumors typically lack necrosis and basophilic stippling within the cytoplasm is frequently present.  Morphological features cannot distinguish of ESC-RCCs found in TSC and non-TSC patients.

In contrast to other RCC subtypes, ESC-RCC demonstrates focal to diffuse CK20 expression in ~80% of cases. ESC RCC is consistently negative for CD117 (KIT) and CAIX; CK7 is typically very focal or negative in ESC-RCC.  Cathepsin K has also been shown to be expressed in a subset of ESC-RCC.

Generally, the great majority of ESC RCCs show indolent behavior, although rare cases (

ESC-RCCs show a molecular karyotype (Whole Genome Copy Number Analysis) profile of common and recurring genomic changes, including a copy number (CN) gains at 16p13-16q23, 7p21-7q36, 13q14, and 19p12 and CN losses at Xp11.21 and 22q11. Loss of heterozygosity (LOH) alterations were also  identified at 16p11.2-11.1, Xq11-13, Xq13-21, 11p11, 9q21-22, and 9q33. However , these molecular alterations are neither pathognomonic nor specific for ESC-RCC, but  many genes residing in the above  CN gains, losses, or LOH regions are known to play a role in cancer-related pathways. ²

Next generation sequencing (NGS) on ESC-RCCs revealed recurrent and mutually exclusive somatic bi-allelic loss or mutations in of TSC gene family, including TSC2 and TSC1 in pediatric and adults populations. ^7-10  Despite the common genetic background, it appears that the tumors with TSC/mTOR mutations represent a diverse group of distinct renal neoplasms. ¹¹