Benjamin Livingston Farah¹, Sze Jet Aw², Jacqueline Siok Gek Hwang¹, Timothy Tay Kwong Yong¹
1) Department of Anatomical Pathology, Division of Pathology, Singapore General Hospital, Singapore.
2) Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore.

A SOX-10 positive GLI1-altered mesenchymal tumour of the pleura with a novel fusion; expanding the possibilities of an emerging entity. 

GLI1-altered mesenchymal tumours are an emerging entity defined by alterations of the GLI1 gene¹. They show a variety of histomorphological patterns and consistently show immunoreactivity to S100 and CD56, with SOX10 being negative^1,2,3. Most cases are benign, with malignant behaviour described in a subset¹. Here we report a case of an incidentally identified GLI1-altered tumour arising from the pleura of a young female patient. Core biopsy was performed, and the tumour was noted to be comprised of round-to-ovoid cells growing in nests, trabeculae, and with tubule formation; intermixed larger, epithelioid cells with clear cytoplasm were noted. Nuclear atypia was mild; significant mitotic activity was not present. Interestingly, the tumour showed strong, diffuse CD56 and SOX10 immunoreactivity, with only patchy, weaker S100 staining noted. A NCOR2 (exon 7) :: GLI1 (exon 6) gene fusion was identified on a next-generation sequencing assay, establishing the diagnosis. In addition to the unexpected SOX10 immunoreactivity, this is the first description of this particular fusion; a previous work had described fusion between these two genes with different exons involved. This case highlights the challenges in diagnosing GLI1-altered mesenchymal tumours, and expands the possible immunoprofiles and gene fusions seen in these cases. 

References:
1. Liu J, Mao R, Lao IW, Yu L, Bai Q, Zhou X, Wang J. GLI1-altered mesenchymal tumor: a clininicopathological and molecular analysis of ten additional cases of an emerging entity. Virchows Arch. 2022 May;480(5):1087-1099. doi: 10.1007/s00428-021-03224-0. Epub 2021 Nov 15. PMID: 34779913.

2. Klubíčková N, Kinkor Z, Michal M, Baněčková M, Hájková V, Michálek J, Pink R, Dvořák Z, Michal M, Leivo I, Skálová A. Epithelioid Soft Tissue Neoplasm of the Soft Palate with a PTCH1-GLI1 Fusion: A Case Report and Review of the Literature. Head Neck Pathol. 2022 Jun;16(2):621-630. doi: 10.1007/s12105-021-01388-4. Epub 2021 Oct 16. PMID: 34655412.

3. Aivazian K, Mahar A, Jackett LA, Kimble RM, Scolyer RA. GLI activated epithelioid cell tumour: report of a case and proposed new terminology. Pathology. 2021 Feb;53(2):267-270. doi: 10.1016/j.pathol.2020.07.013. Epub 2020 Oct 6. PMID: 33032812.

Author Contribution:
BLF, JSGH, TTKY reported the case, and consulted/reviewed the relevant literature. SJA reported the molecular assay and consulted/reviewed the relevant literature. Abstract was drafted by BLF and critically edited by all.