Renal cell carcinoma in tuberous sclerosis complex.
Renal cell carcinoma (RCC) occurs in 2% to 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, pathologic, and molecular features, enabling separation of these 46 tumors into 3 groups. The largest subset of tumors (n=24) had a distinct morphologic, immunologic, and molecular profile, including prominent papillary architecture and uniformly deficient succinate dehydrogenase subunit B (SDHB) expression prompting the novel term "TSC-associated papillary RCC (PRCC)." The second group (n=15) were morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT), whereas the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated PRCCs 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 International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCCs showed strong, diffuse labeling for carbonic anhydrase IX (100%), CK7 (94%), vimentin (88%), and CD10 (83%) and were uniformly negative for 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.
Departments of *Pathology **Urology ††Carol and James Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital ‡‡Division of Translational Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston ∥Department of Pathology, University of Massachusetts Medical School, Worcester, MA †Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou §Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, PR China ‡Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN #Department of Medicine, Division of Genomic Medicine, Institute for Human Genetics, University of California, San Francisco, CA ¶Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland.
Ping
P
Yang
Kristine M
KM
Cornejo
Peter M
PM
Sadow
Liang
L
Cheng
Mingsheng
M
Wang
Yu
Y
Xiao
Zhong
Z
Jiang
Esther
E
Oliva
Sergiusz
S
Jozwiak
Robert L
RL
Nussbaum
Adam S
AS
Feldman
Elahna
E
Paul
Elizabeth A
EA
Thiele
Jane J
JJ
Yu
Elizabeth P
EP
Henske
David J
DJ
Kwiatkowski
Robert H
RH
Young
Chin-Lee
CL
Wu
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000145:classification / Q000209:etiology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002648:Child; D002681:China; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000737:chemistry / Q000145:classification / Q000209:etiology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011044:Poland; D011237:Predictive Value of Tests; D011379:Prognosis; D009626:Terminology as Topic; D014402:Tuberous Sclerosis / Q000150:complications* / Q000401:mortality; D047368:Tumor Burden; D014481:United States; D055815:Young Adult
D014408:Biomarkers, Tumor