PMID- 37468653 OWN - NLM STAT- MEDLINE DCOM- 20230810 LR - 20230810 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) VI - 483 IP - 2 DP - 2023 Aug TI - Novel NONO::TFE3 fusion and ALK co-expression identified in a subset of cutaneous microcystic/reticular schwannoma. PG - 237-243 LID - 10.1007/s00428-023-03605-7 [doi] AB - Microcystic/reticular schwannoma (MRS) is a benign variant of schwannoma with a predilection for the gastrointestinal tract and skin. To date, genetic characterization of this tumor is limited. Prompted by the identification of TFE3::NONO fusion and ALK overexpression in an index case of MRS, a cohort of tumors was collected from institutional and consultation archives of two institutions. Next-generation sequencing (NGS), TFE3 fluorescence in situ hybridization (FISH), and TFE3 and ALK immunohistochemistry were performed, while clinicopathologic variables were documented. Eighteen MRS cases were identified (35 to 85 years) arising in the skin (n=8), gastrointestinal tract (n=5), adrenal gland (n=3), abdominal wall (n=1), and unknown site (n=1). Tumors showed a circumscribed to multinodular to plexiform low-power architecture with variable amounts of microcystic/reticular and solid schwannian components. Mitotic figures were scarce (0-1/10 HPFs), and atypia was absent. S100 protein and/or SOX10 immunoreactivity was noted in the microcystic/reticular and schwannian areas of all cases. NGS performed on two cutaneous tumors yielded NONO exon 12 fusion with TFE3 exon 4, and these lesions also showed HMB45 and ALK expression. Two additional cases showed ALK expression (1 weak), while a third was positive for TFE3, but these cases failed to show ALK or TFE3 rearrangement by FISH/NGS. There were no morphologic variables that correlated with the presence of NONO::TFE3. We identified a subset of microcystic/reticular schwannomas with NONO::TFE3 fusions and ALK co-expression, adding to the cohort of mesenchymal neoplasms that show ALK overexpression without rearrangement of the ALK gene. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Fritchie, Karen J AU - Fritchie KJ AUID- ORCID: 0009-0009-3831-7496 AD - Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 2119 E 93rd Street, L15, Cleveland, OH, 44195, USA. fritchk@ccf.org. FAU - Dermawan, Josephine K AU - Dermawan JK AD - Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 2119 E 93rd Street, L15, Cleveland, OH, 44195, USA. FAU - Astbury, Caroline AU - Astbury C AD - Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 2119 E 93rd Street, L15, Cleveland, OH, 44195, USA. FAU - Sharma, Anurag AU - Sharma A AD - Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 2119 E 93rd Street, L15, Cleveland, OH, 44195, USA. FAU - Bakhshwin, Ahmed AU - Bakhshwin A AD - Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 2119 E 93rd Street, L15, Cleveland, OH, 44195, USA. FAU - Fuller, Lanisha AU - Fuller L AD - Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 2119 E 93rd Street, L15, Cleveland, OH, 44195, USA. FAU - Agrawal, Shruti AU - Agrawal S AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA. AD - Department of Dermatology, Mayo Clinic, Rochester, MN, 55905, USA. FAU - Wieland, Carilyn N AU - Wieland CN AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA. AD - Department of Dermatology, Mayo Clinic, Rochester, MN, 55905, USA. FAU - Greipp, Patricia T AU - Greipp PT AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA. FAU - Azzato, Elizabeth M AU - Azzato EM AD - Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 2119 E 93rd Street, L15, Cleveland, OH, 44195, USA. FAU - Folpe, Andrew L AU - Folpe AL AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA. FAU - Billings, Steven D AU - Billings SD AD - Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 2119 E 93rd Street, L15, Cleveland, OH, 44195, USA. LA - eng PT - Journal Article DEP - 20230719 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 RN - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - 0 (TFE3 protein, human) RN - 0 (NONO protein, human) RN - 0 (DNA-Binding Proteins) RN - 0 (RNA-Binding Proteins) SB - IM MH - Humans MH - In Situ Hybridization, Fluorescence MH - *Neurilemmoma/genetics/pathology MH - *Skin Neoplasms/genetics MH - *Cysts MH - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics MH - Receptor Protein-Tyrosine Kinases/genetics MH - DNA-Binding Proteins/genetics MH - RNA-Binding Proteins/genetics OTO - NOTNLM OT - ALK-D5F3 OT - Microcystic OT - NONO OT - Reticular OT - Schwannoma OT - TFE3 EDAT- 2023/07/20 01:07 MHDA- 2023/08/10 06:43 CRDT- 2023/07/19 23:28 PHST- 2023/04/25 00:00 [received] PHST- 2023/07/12 00:00 [accepted] PHST- 2023/07/09 00:00 [revised] PHST- 2023/08/10 06:43 [medline] PHST- 2023/07/20 01:07 [pubmed] PHST- 2023/07/19 23:28 [entrez] AID - 10.1007/s00428-023-03605-7 [pii] AID - 10.1007/s00428-023-03605-7 [doi] PST - ppublish SO - Virchows Arch. 2023 Aug;483(2):237-243. doi: 10.1007/s00428-023-03605-7. Epub 2023 Jul 19.