Tubulocystic (TC) renal cell carcinoma (RCC) is a distinct RCC subtype that has characteristic cystic architecture, eosinophilic cytology and large prominent nucleoli. An absence of solid growth (i.e., a mural nodule is required to make this diagnosis in its ‘pure’ form.  TC-RCC has been reported to occur in association with many subtypes of renal cell carcinoma, most frequently papillary RCC, but also fumarate hydratase (FH)-deficient RCC and occasionally collecting duct carcinoma.

Rare,

Mainly incidental finding, more commonly in men, often small size at presentation (mean 2 cm).

Well circumscribed and unencapsulated; frequently a multicystic gross appearance that has been compared with bubble wrap.

Composed of tightly packed tubules and cysts of varying size, lined by cuboidal cells containing abundant eosinophilic cytoplasm with large nuclei with prominent nucleoli.   Nuclear grade (i.e., Fuhrman, ISUP or WHO) is not assigned to this tumor type. The entity TC-RCC should be diagnosed only when present as a “pure” form, using well defined strict morphological criteria including an absence of any solid growth; the presence of papillary, poorly differentiated, or other architectural patterns exclude a tumor from diagnostic assignment of ‘pure’ TC-RCC.

FH is intact (i.e., positive) in ’pure’ TC-RCC.

Rarely progresses, recurs, or metastasizes.

Some initial cytogenetic approaches appear to give contradictory results, suggesting genetic genomic overlap between TC-RCC and PRCC because common gains in chromosomes 7 and 17 and loss of Y chromosome ¹, or only trisomy 17. ^2,3 However, recent studies have failed to confirm such relationship mainly for excluding any tumour tubulocystic and papillary morphology.^3,4 Chromosome 9 loss (and Y, in male) and chromosome 17 gain were consistently identified across all “pure” TC-RCC by copy number analysis .^5,6

No mutations characteristic of the other RCC types were found , but  a few mutational profiles were reported:  mutations in the ABL1 and PDGFRA genes  present in >60% of TC-RCC ⁷ and  mutations in chromatin modifying genes KMT2C and KDM5C, as well as other oncogenic mutations involving DNA repair and DNA damage response genes,  such as PMS2, RAD21 and TP53. ⁸