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.

Cutaneous Manifestations of Sarcoid: Clinical Presentation and Histopathology

“…Metastatic Crohn's disease can show small granulomas distant from primary lesions of the disease [25]. Melkersson-Rosenthal syndrome and granulomatous cheilitis can also show small collections of epithelioid cells, often with adjacent lymphangiectasia [26]. Deep folliculitides, such as hidradenitis suppurativa, though often showing foreign body granulomas, can sometimes have a sarcoidal pathology as well.…”

Differential Upregulation of Th1/Th17-Associated Proteins and PD-L1 in Granulomatous Mycosis Fungoides

“…Granulomatous formation can occur in up to 2% of all cutaneous lymphomas, and it is reported in a broad variety of them [ 1 , 2 ]. Granulomatous mycosis fungoides (GMF) is an unusual variant of mycosis fungoides (MF) and represents the most common form of granulomatous primary cutaneous T-cell lymphoma [ 1 ].…”

“…Large cell transformation (LCT) is characterized by the transformation of small neoplastic lymphocytes to large and clonally identical forms and is accepted as a worse prognosis factor [ 5 ]. Although both GMF and MF appear to have a similar rate of LCT, GMF appears to portend a worse prognosis [ 2 , 5 ]. Disease progression in GMF has been reported to be as high as 46%, in contrast to 30% in classic MF, and is comparable to that reported for MF with LCT [ 6 , 7 ].…”

“…Our knowledge about the biology, epidemiology, and clinicopathologic features of GMF is currently restricted to information obtained from a few case series and reports [ 1 , 2 , 7 , 13 , 14 , 15 , 16 ]. Importantly, the composition of the immune checkpoint (IC) landscape and status of other biomarkers that are expressed by the neoplastic lymphocytes in GMF and that could be implicated in its reported different behavior is unknown.…”