LMNA‐NTRK1 rearranged mesenchymal tumor (lipofibromatosis‐like neural tumor) mimicking pigmented dermatofibrosarcoma protuberans

Abstract

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.

Dermal lipofibromatosis‐like neural tumor

“…In our series, mean age is 44.8 years as our patients are teenagers and adults (two of them older than 65), while most of the previous series on these tumors are pediatric‐based and involve soft tissue. Regarding peculiar histopathological features, one of our cases presented more dense lymphoid aggregates as in the one mimicking the pigmented variant of dermatofibrosarcoma (DFSP) (so‐called Bednar tumor) 3 . Here, it is important to notice than DFSP are expected to be negative with pan‐NTRK immunohistochemical antibodies.…”

“…COL1A1‐PDGFB fusion transcript can be detected. It is possible to find a scarce expression of S100 (and of Melan‐A) in the pigmented dendritic cells in Bednar tumor 3 …”

“…We have found just two previously published cases showing histopathological features similar to our reported cases with a predominantly dermal location. The first one, appearing in a 31‐year‐old female, and presenting pigmented dendritic cells and lymphoid nodules as peculiar histopathological findings (immunohistochemically positive to CD34, S100, and pan‐TRK and with a LMNA‐NTRK1 fusion by targeted sequencing) 3 ; and the other one, a congenital CD34+ dermo‐hypodermal spindle‐cell neoplasm harboring a novel KHDRBS1‐NTRK3 fusion gene 4 described by the authors as “a dissecting dermo‐hypodermal proliferation of monotonous spindle cells arranged in a fascicular and storiform pattern.” 4 There are no reported data on S100 immunostaining in the second case 4 …”

“…2 These LPF-NT tumors present some peculiar immunohistochemical features such as S100 expression, SOX10 negativity, and a positive neurotrophic tyrosine kinase receptor 1 (NTRK1) gene rearrangement with LaminA/C (LMNA) gene. 2,3 We present five additional cases with unusual histopathologic findings as they are dermal-based, thus expanding the morphological spectrum of this entity.…”

“…These neoplasms are composed of a cellular proliferation of mildly atypical CD34+ spindle cells with an infiltrative pattern, first described by Agaram et al in 2016 2 . These LPF‐NT tumors present some peculiar immunohistochemical features such as S100 expression, SOX10 negativity, and a positive neurotrophic tyrosine kinase receptor 1 ( NTRK1 ) gene rearrangement with LaminA/C ( LMNA ) gene 2,3 …”