LMNA-NTRK1 rearranged mesenchymal tumor (lipofibromatosis-like neural tumor) mimicking pigmented dermatofibrosarcoma protuberans.
LMNA
NTRK
NTRK1
lipofibromatosis-like neural tumor
Journal
Journal of cutaneous pathology
ISSN: 1600-0560
Titre abrégé: J Cutan Pathol
Pays: United States
ID NLM: 0425124
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
21
04
2020
revised:
21
05
2020
accepted:
22
05
2020
pubmed:
11
6
2020
medline:
7
10
2021
entrez:
11
6
2020
Statut:
ppublish
Résumé
We present the case of a 31-year-old female with a 1.5 cm pigmented nodule on the scalp. Histopathological examination revealed a proliferation of relatively bland spindle cells and pigmented dendritic cells, with interspersed lymphoid follicles diffusely infiltrating the adipose tissue. The microscopic differential diagnosis included pigmented dermatofibrosarcoma protuberans (DFSP). The spindle cells showed S-100 and CD34 labeling but were negative for SOX-10. Immunohistochemical stain for pan-TRK was positive, while fluorescence in-situ hybridization for PDGFB gene rearrangement was negative. Targeted RNA sequencing revealed an LMNA-NTRK1 (exon2/exon10) fusion. This molecular result coupled with the histopathological findings and immunohistochemical profile supported the diagnosis of the recently characterized NTRK-rearranged spindle cell neoplasm termed "lipofibromatosis-like neural tumor (LPF-NT)." These neoplasms typically occur in superficial soft tissue and are characterized by a distinctive immunoprofile (CD34+, S-100+, SOX10-). Histopathological differential diagnosis for LPF-NT tumors includes lipofibromatosis, DFSP, low-grade malignant peripheral nerve sheath tumor, and spindle cell/desmoplastic melanoma. The pigmented dendritic cells reminiscent of pigmented DFSP and lymphoid follicles noted in our case have not been previously reported in LPF-NT, thus expanding the morphological spectrum of this entity. LMNA-NTRK1 fusion serves both as a diagnostic and therapeutic biomarker, as cases with advanced disease may be amenable to targeted therapy using tyrosine kinase inhibitors.
Substances chimiques
LMNA protein, human
0
Lamin Type A
0
NTRK1 protein, human
0
Oncogene Proteins, Fusion
0
Receptor, trkA
EC 2.7.10.1
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
290-294Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
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(10):1407-1416.
Lao IW, Sun M, Zhao M, Yu L, Wang J. Lipofibromatosis-like neural tumour: a clinicopathological study of ten additional cases of an emerging novel entity. Pathology. 2018;50(5):519-523.
Bartenstein DW, Coe TM, Gordon SC, et al. Lipofibromatosis-like neural tumor: case report of a unique infantile presentation. JAAD Case Rep. 2018;4(2):185-188.
Hung YP, Fletcher CD, Hornick JL. Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumor, and histologic mimics. Histopathology. 2018;73(4):634-644.
Suurmeijer AJ, 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 Canc. 2018;57(12):611-621.
Fetsch JF, Miettinen M, Laskin WB, Michal M, Enzinger FM. A clinicopathologic study of 45 pediatric soft tissue tumors with an admixture of adipose tissue and fibroblastic elements, and a proposal for classification as lipofibromatosis. Am J Surg Pathol. 2000;24(11):1491-1500.
Miettinen MM, Antonescu CR, Fletcher CDM, et al. Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1-a consensus overview. Hum Pathol. 2017;67:1-10.
Blokhin E, Pulitzer M, Busam KJ. Immunohistochemical expression of p16 in desmoplastic melanoma. J Cutan Pathol. 2013;40(9):796-800.
Xu Z, Yibulayin F, Shi P, Feng L. Desmoplastic melanoma versus spindle cell melanoma: incidence and survival, 1973 to 2017. Medicine. 2018;97(29):e11563.
Fattoruso SI, Visca P, Lopez M. Molecular approach in the treatment of dermatofibrosarcoma protuberans. Clin Ter. 2008;159(5):361-367.
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(10):1384-1391.
Antonescu CR. Emerging soft tissue tumors with kinase fusions: an overview of the recent literature with an emphasis on diagnostic criteria. Genes Chromosomes Canc. 2020;59(8):437-444. https://doi.org/10.1002/gcc.22846. [Epub ahead of print].
Haller F, Knopf J, Ackermann A, et al. Paediatric and adult soft tissue sarcomas with NTRK1 gene fusions: a subset of spindle cell sarcomas unified by a prominent myopericytic/haemangiopericytic pattern. J Pathol. 2016;238(5):700-710.
Michal M, Hájková V, Skálová A, Michal M. STRN-NTRK3-rearranged mesenchymal tumor of the uterus: expanding the morphologic spectrum of tumors with NTRK fusions. Am J Surg Pathol. 2019;43(8):1152-1154.
So YK, Chow C, To KF, Chan JK, Cheuk W. Myxoid spindle cell sarcoma with LMNA-NTRK fusion: expanding the morphologic spectrum of NTRK-rearranged tumors. Int J Surg Pathol. 2020;1-5. https://doi.org/10.1177/1066896920905888. [Epub ahead of print].
Chiang S, Cotzia P, Hyman DM, et al. NTRK fusions define a novel uterine sarcoma subtype with features of fibrosarcoma. Am J Surg Pathol. 2018;42(6):791-798.
Nakagawara A. Trk receptor tyrosine kinases: a bridge between cancer and neural development. Cancer Lett. 2001;169(2):107-114.
Vaishnavi A, Capelletti M, Le AT, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013;19(11):1469-1472.
Olson N, Rouhi O, Zhang L, et al. A novel case of an aggressive superficial spindle cell sarcoma in an adult resembling fibrosarcomatous dermatofibrosarcoma protuberans and harboring an EML4-NTRK3 fusion. J Cutan Pathol. 2018;45(12):933-939.
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(8):731-739.