EMA-Positive Superficial ALK-Rearranged Myxoid Spindle Cell Neoplasm Masquerading as Perineurioma/Hybrid Nerve Sheath Tumor.
Journal
The American Journal of dermatopathology
ISSN: 1533-0311
Titre abrégé: Am J Dermatopathol
Pays: United States
ID NLM: 7911005
Informations de publication
Date de publication:
01 Sep 2024
01 Sep 2024
Historique:
medline:
16
8
2024
pubmed:
16
8
2024
entrez:
16
8
2024
Statut:
ppublish
Résumé
Superficial anaplastic lymphoma kinase (ALK)-rearranged myxoid spindle cell neoplasm (SAMS) is a recently described entity which coexpresses ALK, CD34, and commonly S100. These neoplasms are characterized morphologically by concentric spindle cell whorls and cords and are commonly set in an abundant myxoid to myxocollagenous stroma, thus mimicking perineurioma or hybrid nerve sheath tumor. EMA immunostain has been reported to be negative in SAMS which helps in excluding the latter entities. Herein, we report the first EMA-positive SAMS of the right leg in a 37-year-old female patient masquerading as perineurioma/hybrid nerve sheath tumor. The tumor morphologically was comprised of spindle cells arranged in loose whorls and short fascicles set in myxoid to collagenous stroma and coexpressed CD34 and EMA, reminiscent of perineurioma. S100 showed focal staining. ALK immunostain was subsequently performed and was positive. ALK gene rearrangement was identified by fluorescence in situ hybridization break-apart assay and was further confirmed by next-generation sequencing-based RNA sequencing demonstrating FLNA::ALK fusion, thus supporting the diagnosis of SAMS. In conclusion, EMA can be expressed in SAMS, thus posing as a diagnostic pitfall. ALK immunostain and molecular studies are essential for confirming the diagnosis of SAMS and excluding potential mimickers, particularly perineurioma or hybrid nerve sheath tumor.
Identifiants
pubmed: 39150182
doi: 10.1097/DAD.0000000000002734
pii: 00000372-202409000-00007
doi:
Substances chimiques
Anaplastic Lymphoma Kinase
EC 2.7.10.1
ALK protein, human
EC 2.7.10.1
Biomarkers, Tumor
0
Mucin-1
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
597-600Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
Références
Shiota M, Fujimoto J, Semba T, et al. Hyperphosphorylation of a novel 80k Da protein-tyrosine kinase similar to Ltkina humanKi-1 lymphoma cellline, AMS3. Oncogene. 1994;9:1567–1574.
Lin JJ, Riely GJ, Shaw AT. Targeting ALK: precision MedicineTakes on drug resistance. CancerDiscov. 2017;7:137–155.
Galea LA, Hildebrand MS, Witkowski T, et al. ALK-rearranged renal cell carcinoma with TPM3::ALK gene fusion and review of the literature. Virchows Arch. 2023;482:625–633.
Choi YL, Takeuchi K, Soda M, et al. Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res. 2008;68:4971–4976.
Sugawara E, Togashi Y, Kuroda N, et al. Identification of anaplastic lymphoma kinase fusions in renal cancer: large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method. Cancer. 2012;118:4427–4436.
Fischer GM, Papke DJ Jr. Gene fusions in superficial mesenchymal neoplasms: emerging entities and useful diagnostic adjuncts. Semin Diagn Pathol. 2023;40:246–257.
Dermawan JK, Azzato EM, Goldblum JR, et al. Superficial ALK-rearranged myxoid spindle cell neoplasm: a cutaneous soft tissue tumor with distinctive morphology and immunophenotypic profile. Mod Pathol. 2021;34:1710–1718.
Suurmeijer AJH, Dickson BC, Swanson D, et al. A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes. Genes Chromosomes Cancer. 2018;57:611–621.
Davis JL, Lockwood CM, Stohr B, et al. Expanding the spectrum of pediatric NTRKrearranged mesenchymal tumors. Am J Surg Pathol. 2019;43:435–445.
Agaram NP, Zhang L, Sung YS, et al. Recurrent NTRK1 gene fusions define a novel subset of locally aggressive lipofibromatosis-like neural tumors. Am J Surg Pathol. 2016;40:1407–1416.
Kao YC, Suurmeijer AJH, Argani P, et al. Soft tissue tumors characterized by a wide spectrum of kinase fusions share a lipofibromatosis-like neural tumor pattern. Genes Chromosomes Cancer. 2020;59:575–583.
Davis JL, Vargas SO, Rudzinski ER, et al. Recurrent RET gene fusions in paediatric spindle mesenchymal neoplasms. Histopathology. 2020;76:1032–1041.
Antonescu CR, Dickson BC, Swanson D, et al. Spindle cell tumors with RET gene fusions exhibit a morphologic spectrum akin to tumors with NTRK gene fusions. Am J Surg Pathol. 2019;43:1384–1391.
Kao YC, Fletcher CDM, Alaggio R, et al. Recurrent BRAF gene fusions in a subset of pediatric spindle cell sarcomas: expanding the genetic spectrum of tumors with overlapping features with infantile fibrosarcoma. Am J Surg Pathol. 2018;42:28–38.
Lopez-Nunez O, Surrey LF, Alaggio R, et al. Novel PPP1CB-ALK fusion in spindle cell tumor defined by S100 and CD34 coexpression and distinctive stromal and perivascular hyalinization. Genes Chromosomes Cancer. 2020;59:495–499.
Kao YC, Lee PH, Wu CL, et al. Superficial ALK-rearranged myxoid spindle cell neoplasm with a novel FMR1-ALK fusion gene. Mod Pathol. 2022;35:438–441.
Kasago I, Aypar U, Sukhadia P, et al. A novel case of cutaneous myxoid spindle cell neoplasm with FMR1-ALK gene fusion and CD34/S100 co-expression. J Cutan Pathol. 2023;50:505–510.
Sheng SJ, Li JM, Fan QH, et al. Case report: ALK-rearranged spindle and epithelioid cell neoplasms with S100 and CD34 co-expression: additional evidence of kinase fusion-positive soft tissue tumors. Front Oncol. 2022;12:1007296.
Gestrich CK, Davis JL, Biederman L, et al. ALK-rearranged epithelioid mesenchymal neoplasm: expanding the spectrum of tyrosine kinase-altered mesenchymal tumors. Mod Pathol. 2023;36:100334.
Wong V, Pavlick D, Brennan T, et al. Evaluation of a congenital infantile fibrosarcoma by comprehensive genomic profiling reveals an LMNA-NTRK1 gene fusion responsive to Crizotinib. J Natl Cancer Inst. 2016;108:djv307–3.
Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378:731–739.