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

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.

Hailey-Hailey Disease With Coexistent Herpes Virus Infection: Insights Into the Diagnostic Conundrum of Herpetic/Pseudoherpetic Features in Cutaneous Acantholytic Disorders.

The specific histopathologic diagnosis of a primary acantholytic disorder takes into account the distribution and extent of acantholysis, presence or absence of dyskeratosis, nature of the dermal inflammatory cell infiltrate, and immunofluorescence findings. Herpes virus infection is a common cause of secondary acantholysis where distinctive viral cytopathic changes aid in making it a clear-cut diagnosis in majority of cases. We present a case of coexistence of Hailey-Hailey disease and herpes simplex virus infection to compare and contrast their histopathologic features. This is imperative because acantholytic cells from primary acantholytic disorders may occasionally show cytological features traditionally associated with herpes virus infection (pseudoherpetic changes). The objective of this article is to create a greater awareness of pseudoherpetic changes and also to explore the clinical significance of coexistence of a primary acantholytic disorder and herpes virus infection, as in this case.

Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells.

BACKGROUND: Mutations in the gene encoding filaggrin (FLG), an epidermal structural protein, are the strongest risk factor identified for the development of atopic dermatitis (AD). Up to 50% of patients with moderate-to-severe AD in European populations have FLG-null alleles compared with a general population frequency of 7% to 10%. OBJECTIVE: This study aimed to investigate the relationship between FLG-null mutations and epidermal antigen-presenting cell (APC) maturation in subjects with and without AD. Additionally, we investigated whether the cis isomer of urocanic acid (UCA), a filaggrin breakdown product, exerts immunomodulatory effects on dendritic cells. METHODS: Epidermal APCs from nonlesional skin were assessed by using flow cytometry (n = 27) and confocal microscopy (n = 16). Monocyte-derived dendritic cells from healthy volunteers were used to assess the effects of cis- and trans-UCA on dendritic cell phenotype by using flow cytometry (n = 11). RESULTS: Epidermal APCs from FLG-null subjects had increased CD11c expression. Confocal microscopy confirmed this and additionally revealed an increased number of epidermal CD83(+) Langerhans cells in FLG-null subjects. In vitro differentiation in the presence of cis-UCA significantly reduced costimulatory molecule expression on monocyte-derived dendritic cells from healthy volunteers and increased their ability to induce a regulatory T-cell phenotype in mixed lymphocyte reactions. CONCLUSIONS: We show that subjects with FLG-null mutations have more mature Langerhans cells in nonlesional skin irrespective of whether they have AD. We also demonstrate that cis-UCA reduces maturation of dendritic cells and increases their capacity to induce regulatory T cells, suggesting a novel link between filaggrin deficiency and immune dysregulation.