Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 2119 E 93rd Street, L15, Cleveland, OH, 44195, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
Virchows Arch. 2023 Aug;483(2):237-243. doi: 10.1007/s00428-023-03605-7. Epub 2023 Jul 19.
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.
微囊/网状施万细胞瘤（MRS）是一种具有胃肠道和皮肤偏好的良性施万细胞瘤变体。迄今为止，对这种肿瘤的遗传特征描述有限。在首例 MRS 中鉴定出 TFE3::NONO 融合和 ALK 过表达后，我们从两个机构的机构和咨询档案中收集了一组肿瘤。进行了下一代测序（NGS）、TFE3 荧光原位杂交（FISH）以及 TFE3 和 ALK 免疫组织化学检测，同时记录了临床病理变量。鉴定出 18 例 MRS 病例（年龄 35 至 85 岁），分别发生在皮肤（n=8）、胃肠道（n=5）、肾上腺（n=3）、腹壁（n=1）和未知部位（n=1）。肿瘤具有界限清楚至多结节至丛状的低倍结构，具有不同数量的微囊/网状和实性施万成分。有丝分裂象稀少（0-1/10 HPFs），无异型性。所有病例的微囊/网状和施万氏区域均可见 S100 蛋白和/或 SOX10 免疫反应性。对两个皮肤肿瘤进行的 NGS 显示 NONO 外显子 12 与 TFE3 外显子 4 融合，这些病变还显示 HMB45 和 ALK 表达。另外两个病例显示 ALK 表达（1 例弱阳性），而第三个病例 TFE3 阳性，但这些病例通过 FISH/NGS 未显示 ALK 或 TFE3 重排。没有与 NONO::TFE3 存在相关的形态学变量。我们鉴定了一组具有 NONO::TFE3 融合和 ALK 共表达的微囊/网状施万细胞瘤，增加了一组显示 ALK 过表达而 ALK 基因无重排的间叶性肿瘤。
