Sarcomatoid Yolk Sac Tumor Harbors Somatic Mutations That Are Otherwise Rare in Testicular Germ Cell Tumors.

TitleSarcomatoid Yolk Sac Tumor Harbors Somatic Mutations That Are Otherwise Rare in Testicular Germ Cell Tumors.
Publication TypeJournal Article
Year of Publication2022
AuthorsAcosta AM, Al-Obaidy KI, Sholl LM, Dickson BC, Lindeman NI, Hirsch MS, Collins K, Fletcher CD, Idrees MT
JournalAm J Surg Pathol
Date Published2022 May 01
KeywordsBiomarkers, Tumor, Endodermal Sinus Tumor, Humans, Male, Mutation, Neoplasms, Germ Cell and Embryonal, Sarcoma, Soft Tissue Neoplasms, Testicular Neoplasms, Tumor Suppressor Protein p53

In testicular germ cell tumors (TGCTs), components with nonspecific sarcomatous features that express keratins and glypican 3 are classified as sarcomatoid yolk sac tumor (SYST). SYST is most frequently seen in metastatic sites after chemotherapy. Like so-called "somatic-type" malignancies arising in TGCTs, SYST is markedly resistant to systemic therapy and has a more aggressive clinical course than conventional types of TGCT. However, the clinicopathologic and molecular features of SYST remain incompletely described. This study evaluated a multi-institutional series of 20 SYSTs using massively parallel sequencing and p53 immunohistochemistry. The histologic and clinical characteristics of the cases were also assessed, including analyses of disease-specific outcomes. DNA sequencing identified somatic mutations in 12/20 cases (60%), including recurrent TP53 and RIF1 mutations (present in 4/20 cases, 20% each). In 3 of the 4 SYST with TP53 mutations, there was molecular evidence of loss of heterozygosity. Immunohistochemistry demonstrated diffuse overexpression of p53 protein in 3/4 (75%) cases with TP53 mutations. The remaining TP53-mutant case demonstrated multifocal overexpression of p53, suggestive of subclonal inactivation of the gene. Overexpression of p53 protein was not seen in any of 15 TP53 wild-type cases evaluated by immunohistochemistry. A subset of 4 cases underwent RNA sequencing (fusion panel), which demonstrated the absence of oncogenic gene fusions. A 2-tiered grading system based on 3 histologic parameters (cellularity, number of mitoses, and necrosis) demonstrated that high-grade SYSTs have a higher risk of disease-specific death compared to low-grade tumors. The risk of disease-specific mortality was also higher in SYSTs with somatic mutations. In conclusion, this study demonstrated that 60% of SYSTs harbor somatic oncogenic mutations that are otherwise rare in TGCTs, and the presence of these mutations is associated with an aggressive clinical course. In addition, the results presented herein suggest that grading SYSTs may be clinically relevant.

Alternate JournalAm J Surg Pathol
PubMed ID35034041
Related Faculty: 
Neal Lindeman, M.D.

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