Fluorescence in-situ hybridization assessment of spindle cell-rich testicular sex cord stromal tumors demonstrates multiple chromosomal gains across histologic subtypes

Andres Martin Acosta; Christopher D M Fletcher; Lynette M Sholl; Geert Jlh van Leenders; Esther Oliva; Kristine M Cornejo; Federico Repetto; Katrina Collins; Muhammad T Idrees; Michelle S Hirsch; Kiril Trpkov; Thomas M Ulbright; Julia A Bridge

doi:10.1016/j.humpath.2024.105652

Fluorescence in-situ hybridization assessment of spindle cell-rich testicular sex cord stromal tumors demonstrates multiple chromosomal gains across histologic subtypes

Hum Pathol. 2024 Aug 30:153:105652. doi: 10.1016/j.humpath.2024.105652. Online ahead of print.

Affiliations

¹ Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: anmaacos@iu.edu.
² Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³ Department of Pathology, Erasmus Medical Center, Erasmus University, Rotterdam, Netherlands.
⁴ Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Favaloro University, Buenos Aires, Argentina.
⁶ Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
⁷ Diagnostic and Molecular Pathology, Alberta Precision Laboratories and University of Calgary, Calgary, Alberta, Canada.
⁸ Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA; FISH and Cytogenetics Laboratory, ProPath, Dallas, TX, USA.

PMID: 39218045
DOI: 10.1016/j.humpath.2024.105652

Abstract

Spindle cell-rich testicular sex cord-stromal tumors (TSCSTs) comprise a group that includes mostly (but not exclusively): myoid gonadal stromal tumor (MGST), adult granulosa cell tumor (AGCT), and unclassified TSCST. These entities demonstrate histopathologic overlap, and prior genomic studies have failed to identify specific oncogenic drivers. Results of DNA sequencing suggest that different types of spindle cell-rich TSCSTs harbor a recurrent pattern of chromosomal gains. However, these results have not been validated by alternative methods and the extent of these changes within individual tumors remains unknown. We used a combination of commercially available fluorescence in-situ hybridization (FISH) probes (3q11.2, 6p24.3, 6q11.1, 6q23, 7q11.21-q11.22, 9p21.3, 11q13.3, 17p11.2) to enumerate a subset of chromosomes identified as altered (gained) in prior studies. We analyzed 10 cases (3 MGST, 4 unclassified TSCST, 3 AGCT), including 7 that had been previously sequenced. FISH demonstrated gains of chromosomes 3, 6, 7, 9, and 11 above the pre-established threshold (25%) in 50%, 80%, 70%, 20%, and 40% of cases, respectively, with gains of chromosome 17 being present in only 1 unclassified TSCST. The proportion of cells with chromosomal gains ranged from 26% to 60%. Tumors with available copy number data from prior genomic analyses showed a partial discordance between FISH and sequencing results. This study demonstrates that spindle-cell rich TSCSTs harbor a recurrent pattern of chromosomal gains, which are present in variable subsets of neoplastic cells. Further studies are needed to determine if these chromosomal changes represent a mechanism relevant for oncogenesis or a secondary event.

Keywords: Adult granulosa cell tumor; Myoid gonadal stromal tumor; Sex cord-stromal tumor; Testis; Unclassified sex cord-stromal tumor.