Synapse - Adverse histology, homozygous loss of CDKN2A/B, and complex genomic alterations in locally advanced/metastatic renal mucinous tubular and spindle cell carcinoma

Adverse histology, homozygous loss of CDKN2A/B, and complex genomic alterations in locally advanced/metastatic renal mucinous tubular and spindle cell carcinoma Journal Article

Authors:	Yang, C.; Cimera, R. S.; Aryeequaye, R.; Jayakumaran, G.; Sarungbam, J.; Al-Ahmadie, H. A.; Gopalan, A.; Sirintrapun, S. J.; Fine, S. W.; Tickoo, S. K.; Epstein, J. I.; Reuter, V. E.; Zhang, Y.; Chen, Y. B.
Article Title:	Adverse histology, homozygous loss of CDKN2A/B, and complex genomic alterations in locally advanced/metastatic renal mucinous tubular and spindle cell carcinoma
Abstract:	Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma with characteristic histologic features and chromosomal alterations. Although typically indolent, a small subset of cases has been reported to exhibit aggressive clinical behavior. We retrospectively identified 33 patients with MTSCC, consisting of 10 cases of locally advanced/metastatic MTSCC (pT3 or N1 or M1) and 23 kidney-confined MTSCC (pT1/T2) without disease recurrence or progression. Utilizing a single-nucleotide polymorphism array and a targeted next-generation sequencing platform, we examined genome-wide molecular alterations in 24 cases, including 11 available samples from 8 patients with locally advanced/metastatic MTSCC. Ten patients with locally advanced/metastatic MTSCC were 8 females (80%) and 2 males (20%). At nephrectomy, 7 of these 10 cases (70%) were pT3 or pN1 while the remaining 3 (30%) were pT1/T2. Eight patients (80%) developed metastases and common sites included lymph node (4, 40%), bone (4, 40%), and retroperitoneum (3, 30%). Four patients died of disease (40%) during follow-up. Locally advanced/metastatic MTSCCs shared typical MTSCC genomic profiles with loss of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22, while some exhibited additional complex genomic alterations, most frequently a relative gain of 1q (7/8). Homozygous loss of CDKN2A/B was observed in 3 (38%) locally advanced/metastatic MTSCCs. Tumor necrosis, solid nested/sheet pattern, irregular trabecular/single-file infiltration in a desmoplastic stroma, lymphovascular space invasion, and increased mitotic activity were associated with locally advanced/metastatic MTSCCs (all p < 0.05). Our findings reveal that MTSCCs with aggressive clinical behavior have progressed through clonal evolution; CDKN2A/B deletion and additional complex genomic abnormalities may contribute to this process. Recognizing the morphologic presentation of high-grade MTSCC and evaluating adverse histologic features seen in these tumors can help establish a definitive diagnosis and stratify patients for treatment and prognostication. © 2020, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
Journal Title:	Modern Pathology
Volume:	34
Issue:	2
ISSN:	0893-3952
Publisher:	Nature Research
Date Published:	2021-02-01
Start Page:	445
End Page:	456
Language:	English
DOI:	10.1038/s41379-020-00667-9
PUBMED:	32879414
PROVIDER:	scopus
PMCID:	PMC7855055
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85090089828&doi=10.1038%2fs41379-020-00667-9&partnerID=40&md5=809b88d3a1734f605c5d03648fcb3d5b
Notes:	Article -- Export Date: 1 February 2021 -- Source: Scopus