Desmoplastic stromal changes in cutaneous neural granular cell tumors: An under‐recognized histopathologic feature of diagnostic and prognostic importance

Abstract

Background: Granular cell tumors (GCTs) are uncommon mucocutaneous and soft tissue neoplasms with distinctive histopathologic appearance but controversial histogenesis. Herein, we report a variant of cutaneous GCT featuring extensive desmoplastic stroma which may result in diagnostic difficulties with mesenchymal proliferations, particularly a dermatofibroma.Methods: Following a recent case of GCT with prominent stromal desmoplasia, we reviewed all cases diagnosed as GCT during the past 10 years accessioned at the dermatopathology unit in a tertiary university hospital.Results: Three additional cases with a similar excessive connective tissue were identified out of a total of 49 GCTs. Cytoplasmic granularity was often subtle and focal, S100 expression was weak, and nuclei had a tendency to show spindling in tumor cells entrapped within the desmoplastic areas. Of note, nuclear spindling is one of the criteria used to diagnose an atypical/malignant GCT. Conclusion:We propose the term "desmoplastic GCT" for these tumors, which not only appropriately addresses the stromal changes but also raises an awareness of GCT being one of the cutaneous tumors which may show stromal desmoplasia. Differential diagnostic difficulties apart, awareness of this phenomenon is important so that desmoplasia and resultant spindling are not linked with potential aggressive behavior. K E Y W O R D Scutaneous neoplasms, desmoplasia, diagnostic criteria, granular cell tumor, prognosis

Atypical cytological presentation of granular cell tumour: Tumour‐associated fibrosis may affect fine‐needle aspiration cytology accuracy

“…Tumour‐associated fibrosis is a variable component of benign and malignant tumour microenvironment, affecting its prognosis 30 , 31 . Cells producing fibrosis are fibroblasts and mesenchymal stem cells (MSCs), depending on their independence or association with tumoural cells 2 , 29‐33 . Tumour‐associated fibroblasts and tumour‐associated MSCs have unique molecular profiles, which facilitate tumour cell communication, influence extracellular matrix deposition, and the immune system action 30 , 31 .…”

“…Tumour‐associated fibroblasts and tumour‐associated MSCs have unique molecular profiles, which facilitate tumour cell communication, influence extracellular matrix deposition, and the immune system action 30 , 31 . In contrast, normal tissue fibroblasts and MSCs are important in restraining cancer initiation, influencing epithelial cell differentiation, and limiting cancer cell invasion 32 , 33 . In case of GCT, the induction to fibrogenesis and its amount is variable and variably reported and quantified depending on different factors including the sites of onset 25‐33 .…”

“…According to the literature, fibrosis seems to be scanty or absent in GCT of the gastrointestinal tract where there is a prevalence of peri‐tumoural lymphoid infiltrate in the gastric and intestinal sites 29 . Conversely, fibrosis in mammary and cutaneous GCT may be preponderant and may cause diagnostic problems on histological samples too 25 , 32 , 33 . Therefore the minimal or absent fibrosis in gastrointestinal cases of the present series (cases 4, 6) when compared to the other sites, is consistent with these data.…”