PMID- 35933574 OWN - NLM STAT- MEDLINE DCOM- 20221215 LR - 20230807 IS - 1936-0568 (Electronic) IS - 1936-055X (Print) IS - 1936-055X (Linking) VI - 16 IP - 4 DP - 2022 Dec TI - GLI1-Altered Soft Tissue Tumors of the Head and Neck: Frequent Oropharyngeal Involvement, p16 Immunoreactivity, and Detectable Alterations by DDIT3 Break Apart FISH. PG - 1146-1156 LID - 10.1007/s12105-022-01476-z [doi] AB - BACKGROUND: GLI1 is a transcription factor protein that has recently gained recognition in a morphologically distinct group of epithelioid soft tissue tumors characterized by GLI1 fusions or amplifications. The head and neck region, particularly the tongue, is a common location for GLI1-altered tumors. DDIT3 break apart fluorescence in situ hybridization (FISH), commonly used to identify translocations in myxoid/round cell liposarcoma, has been used as a surrogate test to detect both fusions and amplifications of the 12q13.3 region encompassing DDIT3 and GLI1 gene loci. METHODS: We herein report 5 cases of GLI1-altered soft tissue tumors. Three arose in the oropharynx (base of tongue/vallecula, tonsil) and two arose in the tongue. Given the frequent oropharyngeal location and epithelioid morphology, p16 immunohistochemistry was performed on cases with available material. Commercially available DDIT3 break apart FISH, custom GLI1 specific FISH, and RNA sequencing were performed on select cases. RESULTS: Two cases showed amplification using DDIT3 FISH which was confirmed using GLI1 specific FISH. The remaining cases harbored ACTB::GLI1, one of which showed rearrangement of the 12q13.3 region by DDIT3 FISH with absence of amplification by GLI1 specific FISH. STAT6 immunoexpression was positive in the GLI1-amplified cases and negative in the GLI1-rearranged cases while MDM2 expression was positive in the 4 cases tested. CDK4 expression was strong and diffuse in the GLI1-amplified cases. p16 immunohistochemistry showed strong nuclear and cytoplasmic staining in 50-70% of tumor cells in all four tested cases. CONCLUSION: Here we show that GLI1-altered soft tissue tumors are frequently positive for p16 and can occur in tonsillar regions of the oropharynx. As such, positive p16 immunohistochemistry alone cannot be used as evidence for the diagnosis of HPV-related squamous cell carcinoma as strong and diffuse p16 expression may also occur in GLI1-altered soft tissue tumors. Commercially available DDIT3 break apart FISH, which is readily available in many cytogenetic laboratories, may be useful as a sensitive surrogate test for GLI1 fusions and amplifications. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Palsgrove, Doreen N AU - Palsgrove DN AUID- ORCID: 0000-0001-9640-2482 AD - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA. doreen.palsgrove@utsouthwestern.edu. AD - UT Southwestern Medical Center, Clements University Hospital UH04.234, 6201 Harry Hines Boulevard, Dallas, TX, 75390, USA. doreen.palsgrove@utsouthwestern.edu. FAU - Rooper, Lisa M AU - Rooper LM AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Stevens, Todd M AU - Stevens TM AD - Department of Pathology, University of Kansas Medical Center, Kansas City, KS, USA. FAU - Shin, Christina AU - Shin C AD - Histopathology Department, Middlemore Hospital, Auckland, New Zealand. FAU - Damm, Douglas D AU - Damm DD AD - Pathology and Cytology Laboratories, Lexington, KY, USA. FAU - Gagan, Jeffrey AU - Gagan J AD - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Bridge, Julia A AU - Bridge JA AD - ProPath, Dallas, TX, USA. FAU - Thompson, Lester D R AU - Thompson LDR AD - Head and Neck Pathology Consultations, Woodland Hills, CA, USA. FAU - Koduru, Prasad R AU - Koduru PR AD - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Bishop, Justin A AU - Bishop JA AD - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA. LA - eng PT - Journal Article DEP - 20220806 PL - United States TA - Head Neck Pathol JT - Head and neck pathology JID - 101304010 RN - 0 (DDIT3 protein, human) RN - 147336-12-7 (Transcription Factor CHOP) RN - 0 (GLI1 protein, human) RN - 0 (Zinc Finger Protein GLI1) SB - IM MH - Humans MH - Adult MH - In Situ Hybridization, Fluorescence MH - *Soft Tissue Neoplasms/genetics MH - *Head and Neck Neoplasms/genetics MH - Transcription Factor CHOP MH - Zinc Finger Protein GLI1 PMC - PMC9729462 OTO - NOTNLM OT - DDIT3 OT - FISH OT - GLI1 OT - Oropharynx OT - p16 COIS- All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. EDAT- 2022/08/07 06:00 MHDA- 2022/12/15 06:00 PMCR- 2023/08/06 CRDT- 2022/08/06 23:32 PHST- 2022/05/19 00:00 [received] PHST- 2022/07/07 00:00 [accepted] PHST- 2022/08/07 06:00 [pubmed] PHST- 2022/12/15 06:00 [medline] PHST- 2022/08/06 23:32 [entrez] PHST- 2023/08/06 00:00 [pmc-release] AID - 10.1007/s12105-022-01476-z [pii] AID - 1476 [pii] AID - 10.1007/s12105-022-01476-z [doi] PST - ppublish SO - Head Neck Pathol. 2022 Dec;16(4):1146-1156. doi: 10.1007/s12105-022-01476-z. Epub 2022 Aug 6.