Tubulocystic renal cell carcinoma: a distinct clinicopathologic entity with a characteristic genomic profile

Judy Sarungbam, Rohit Mehra, Scott A. Tomlins, Steven C. Smith, Gowtham Jayakumaran, Hikmat Al Ahmadie, Anuradha Gopalan, Sahussapont J. Sirintrapun, Samson W. Fine, Yanming Zhang, Mahul B. Amin, Victor E. Reuter, Ying Bei Chen, Satish K. Tickoo

Research output: Contribution to journalArticle

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Abstract

Tubulocystic renal cell carcinoma, a unique tumor, was recently included as a new entity in the World Health Organization classification of renal tumors. It has variably been reported to be related to other renal cell carcinomas, including papillary renal cell carcinoma, fumarate hydratase-deficient carcinoma, and others, likely because many such carcinomas may show variable amounts of tubulocystic architecture. The published data characterizing the molecular features of these tumors are inconsistent. We studied nine “pure” tubulocystic renal cell carcinomas, as defined by International Society of Urologic Pathologists (ISUP) and World Health Organization (WHO), by targeted next-generation sequencing, and fluorescence in situ hybridization for X and Y chromosomes, to investigate if these show any unique characteristics or any overlap with known mutational/molecular profiles or copy number alterations in other subtypes of renal cell carcinoma. All nine tubulocystic carcinomas demonstrated combined losses at chromosome 9 and gains at chromosome 17, as well as, loss of chromosome Y (in 5/5). None of the tumors showed mutational profiles characteristic of other renal neoplasms, including those seen in fumarate hydratase-deficient renal cell carcinoma. Recurrent mutations in chromatin-modifying genes, KMT2C and KDM5C, were detected in two of nine tumors. Thus, tubulocystic renal cell carcinoma, if defined strictly, at the clinical and pathologic level, demonstrates genomic features distinct from other subtypes of renal cell carcinoma. These findings support the contention that tubulocystic renal cell carcinoma should be diagnosed only using strict morphological criteria and only when presenting in a “pure” form; presence of variable papillary, poorly differentiated, or other architectural patterns most likely do not belong to the category of tubulocystic renal cell carcinoma.

Original languageEnglish (US)
JournalModern Pathology
DOIs
StateAccepted/In press - Jan 1 2019

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Renal Cell Carcinoma
Fumarate Hydratase
Y Chromosome
Neoplasms
Carcinoma
Chromosomes, Human, Pair 9
Chromosomes, Human, Pair 17
Kidney Neoplasms
X Chromosome
Fluorescence In Situ Hybridization
Chromatin
Kidney
Mutation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Sarungbam, J., Mehra, R., Tomlins, S. A., Smith, S. C., Jayakumaran, G., Ahmadie, H. A., ... Tickoo, S. K. (Accepted/In press). Tubulocystic renal cell carcinoma: a distinct clinicopathologic entity with a characteristic genomic profile. Modern Pathology. https://doi.org/10.1038/s41379-018-0185-5

Tubulocystic renal cell carcinoma : a distinct clinicopathologic entity with a characteristic genomic profile. / Sarungbam, Judy; Mehra, Rohit; Tomlins, Scott A.; Smith, Steven C.; Jayakumaran, Gowtham; Ahmadie, Hikmat Al; Gopalan, Anuradha; Sirintrapun, Sahussapont J.; Fine, Samson W.; Zhang, Yanming; Amin, Mahul B.; Reuter, Victor E.; Chen, Ying Bei; Tickoo, Satish K.

In: Modern Pathology, 01.01.2019.

Research output: Contribution to journalArticle

Sarungbam, J, Mehra, R, Tomlins, SA, Smith, SC, Jayakumaran, G, Ahmadie, HA, Gopalan, A, Sirintrapun, SJ, Fine, SW, Zhang, Y, Amin, MB, Reuter, VE, Chen, YB & Tickoo, SK 2019, 'Tubulocystic renal cell carcinoma: a distinct clinicopathologic entity with a characteristic genomic profile', Modern Pathology. https://doi.org/10.1038/s41379-018-0185-5
Sarungbam, Judy ; Mehra, Rohit ; Tomlins, Scott A. ; Smith, Steven C. ; Jayakumaran, Gowtham ; Ahmadie, Hikmat Al ; Gopalan, Anuradha ; Sirintrapun, Sahussapont J. ; Fine, Samson W. ; Zhang, Yanming ; Amin, Mahul B. ; Reuter, Victor E. ; Chen, Ying Bei ; Tickoo, Satish K. / Tubulocystic renal cell carcinoma : a distinct clinicopathologic entity with a characteristic genomic profile. In: Modern Pathology. 2019.
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