Age-related histopathological and immunophenotypic variations in early-stage mycosis fungoides: a multicentre retrospective study in Türkiye.
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OBJECTIVES: Early-stage mycosis fungoides (MF) is diagnostically challenging due to overlap with inflammatory dermatoses. Age-related immunological and cutaneous changes may modify histopathological presentation. We aimed to compare clinical, histopathological and immunophenotypic features of early-stage MF between geriatric and non-geriatric patients. DESIGN: Multicentre retrospective cross-sectional study. SETTING: Dermatology departments of tertiary centres in Türkiye. PARTICIPANTS: A total of 541 patients diagnosed with early-stage MF were included and stratified into geriatric (≥65 years) and non-geriatric (18-64 years) groups. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were age-related differences in histopathological and immunohistochemical features. Secondary outcomes included clinical characteristics and quality of life measures. Primary endpoints were prespecified a priori (epidermotropism, basilar lymphocytes, epidermal atrophy, dermal lymphocytic infiltration, papillary dermal fibrosis and CD4-dominant versus CD8(+)/CD4(-) phenotypes); all other comparisons were considered exploratory. RESULTS: The geriatric group had a higher proportion of males (59.5% vs 47.1%; p=0.004), while lesion type, duration, surface involvement and Dermatology Life Quality Index scores did not differ between groups. Histopathologically, epidermotropism (81.3% vs 63.3%), basilar lymphocytes (57.1% vs 45.7%), epidermal atrophy (26.6% vs 13.8%), dermal lymphocytic infiltration (75.8% vs 58.5%) and papillary dermal fibrosis (55.2% vs 38.4%) were more frequent in geriatric patients (all p<0.05). Plasma cells (13.5% vs 6.2%) and eosinophils (21.8% vs 13.8%) were also increased. A CD4-dominant phenotype was more common in geriatric patients (70.2% vs 60.6%; p=0.043), whereas a CD8-positive/CD4-negative phenotype was more frequent in non-geriatric patients (8.5% vs 2.6%; p=0.012). However, histopathological and immunohistochemical variables were extracted from existing routine pathology reports without central slide re-review, harmonised scoring criteria or adjudication; therefore, the reported frequencies may partly reflect intercentre/interobserver reporting practices and temporal changes in diagnostic work-up (eg, immunohistochemistry panels and reporting terminology) in addition to biological differences. CONCLUSIONS: Although clinical characteristics were comparable across age groups, geriatric patients showed differences in reported histopathological and immunophenotypic features; these observations may facilitate clinicopathological recognition of early-stage MF in older individuals. However, some features (particularly epidermal atrophy and superficial/papillary fibrosis) are not MF-specific and may partly reflect background age- and site-related changes.