Subtlety of Granulomatous Mycosis Fungoides: A Retrospective Case Series Study and Proposal of Helpful Multimodal Diagnostic Approach With Literature Review

Abstract

Granulomatous mycosis fungoides (GMF) harbors a worse prognosis compared with classic MF and remains a significant diagnostic dilemma. We analyzed clinicopathologic, immunophenotypic, and molecular characteristics of GMF to develop a diagnostic algorithm. Our methodology involved a retrospective case series study of patients with GMF from our database between 2014 and 2020. A total of 8 patients with 9 biopsies of GMF were identified. Skin manifestations had variable clinical phenotype. Histologically, all cases demonstrated atypical CD4⁺ T-cell infiltrate with scant in 50% (n = 4), focal 37.5% (n = 3), and absent 25% (n = 2) epidermotropism. Granuloma formation was seen in 77.8% biopsies (n = 7) with sarcoid-type granulomas in 57.1% (n = 4) and granuloma annulare-like type in 42.9% (n = 3). In 66.7% of biopsies (n = 6), the CD4:CD8 ratio was >4:1 and 66.6% (n = 6) of biopsies showed ≥50% loss of CD7 expression. T-cell receptor gene rearrangement studies performed on biopsy sections were positive in all biopsies (n = 6), whereas peripheral blood T-cell receptor gene rearrangement studies did not identify clonality. In conclusion, GMF has subtle or absent epidermotropism and variable granulomatous reaction; thus, the diagnosis requires a multimodal approach, and our proposed algorithm provides a framework to approach this diagnostic challenge.