Renal cell carcinoma in tuberous sclerosis complex

Ping Yang, Kristine M. Cornejo, Peter M. Sadow, Liang Cheng, Mingsheng Wang, Yu Xiao, Zhong Jiang, Esther Oliva, Sergiusz Jozwiak, Robert L. Nussbaum, Adam S. Feldman, Elahna Paul, Elizabeth A. Thiele, Jane J. Yu, Elizabeth P. Henske, David J. Kwiatkowski, Robert H. Young, Chin Lee Wu

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)895-909
Number of pages15
JournalAmerican Journal of Surgical Pathology
Volume38
Issue number7
DOIs
StatePublished - Jul 2014

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Tuberous Sclerosis
Renal Cell Carcinoma
Neoplasms
Glandular and Epithelial Neoplasms
Succinate Dehydrogenase
Kidney Neoplasms
Chromosome Deletion
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 7
Vimentin
Pathology
Kidney

Keywords

  • hybrid oncocytic/chromophobe tumor
  • immunohistochemistry
  • molecular genetics
  • renal cell carcinoma
  • succinate dehydrogenase
  • tuberous sclerosis complex

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

Renal cell carcinoma in tuberous sclerosis complex. / Yang, Ping; Cornejo, Kristine M.; Sadow, Peter M.; Cheng, Liang; Wang, Mingsheng; Xiao, Yu; Jiang, Zhong; Oliva, Esther; Jozwiak, Sergiusz; Nussbaum, Robert L.; Feldman, Adam S.; Paul, Elahna; Thiele, Elizabeth A.; Yu, Jane J.; Henske, Elizabeth P.; Kwiatkowski, David J.; Young, Robert H.; Wu, Chin Lee.

In: American Journal of Surgical Pathology, Vol. 38, No. 7, 07.2014, p. 895-909.

Research output: Contribution to journalArticle

Yang, P, Cornejo, KM, Sadow, PM, Cheng, L, Wang, M, Xiao, Y, Jiang, Z, Oliva, E, Jozwiak, S, Nussbaum, RL, Feldman, AS, Paul, E, Thiele, EA, Yu, JJ, Henske, EP, Kwiatkowski, DJ, Young, RH & Wu, CL 2014, 'Renal cell carcinoma in tuberous sclerosis complex', American Journal of Surgical Pathology, vol. 38, no. 7, pp. 895-909. https://doi.org/10.1097/PAS.0000000000000237
Yang, Ping ; Cornejo, Kristine M. ; Sadow, Peter M. ; Cheng, Liang ; Wang, Mingsheng ; Xiao, Yu ; Jiang, Zhong ; Oliva, Esther ; Jozwiak, Sergiusz ; Nussbaum, Robert L. ; Feldman, Adam S. ; Paul, Elahna ; Thiele, Elizabeth A. ; Yu, Jane J. ; Henske, Elizabeth P. ; Kwiatkowski, David J. ; Young, Robert H. ; Wu, Chin Lee. / Renal cell carcinoma in tuberous sclerosis complex. In: American Journal of Surgical Pathology. 2014 ; Vol. 38, No. 7. pp. 895-909.
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AU - Oliva, Esther

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AU - Paul, Elahna

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