Renal Cell Carcinoma in Tuberous Sclerosis Complex

Abstract

Renal cell carcinoma (RCC) occurs in 2-4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathological and molecular features, enabling separation of these 46 tumors into three groups. The largest subset of tumors (n=24) had a distinct morphological, immunological and molecular profile, including prominent papillary architecture and uniformly deficient SDHB expression prompting the novel term “TSC-associated papillary RCC.” The second group (n=15) was morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT) while the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated papillary RCCs (PRCC) had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were the International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCC showed strong, diffuse labeling for CA-IX (100%), CK7 (94%), vimentin (88%), CD10 (83%), and were uniformly negative for succinate dehydrogenase subunit B (SDHB), TFE3 and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes which may help to expand the morphologic spectrum of TSC-associated RCC.

Structured assessment and followup for patients with hereditary kidney tumour syndromes

“…Renal cell carcinoma is associated with the TSC in 2-3% of patients. 49 Extrarenal manifestations should not be overlooked when treating this condition. These are listed in Table 1.…”

Hamartomas from head to toe: an imaging overview

“…Renal cell carcinoma is seen in 2-4% of patients with TSC. 64 A recent study by Yang et al 67 showed that approximately one-half of these neoplasms are of papillary architecture (TSCassociated papillary renal cell carcinoma) and nearly one-third of the neoplasms were found to be a similar to a hybrid oncocytic/chromophobe tumour. The remaining neoplasms were deemed unclassifiable.…”

A family case with germlineTSC1and mtDNA mutations developing bilateral eosinophilic chromophobe renal cell carcinomas without other typical phenotype of tuberous sclerosis

“…Bilateral chRCCs have rarely been reported, but occasionally occur in patients with Birt-Hogg-Dubé syndrome (BHDS),3 Cowden syndrome (CS)4 or tuberous sclerosis complex (TSC) 5. BHDS is an autosomal dominant disease characterised by fibrofolliculomas, pneumothorax and renal cancers 6.…”