IgM Immunohistochemical Expression is a Potential Risk Factor for Extracutaneous Dissemination in Patients With Primary Cutaneous Follicle Center Lymphoma

Primary cutaneous follicle center lymphoma (PCFCL) is a type of cutaneous B-cell lymphoma with an indolent behavior and a 5-year disease-specific survival of 95%. Given the difficulty of identifying patients at risk for developing extracutaneous dissemination (ECD), this study aimed to identify predictors in the clinical presentation, histopathology, immune phenotype, and genetic profile of PCFCL patients by comparing those who developed ECD with those whose disease remained skin limited (SL) during follow-up. After review of clinical data and histopathology, a total of 13 ECD-PCFCL patients and 15 SL-PCFCL patients with varying treatments were included from the Dutch Cutaneous Lymphomas Registry. At diagnosis, all patients presented with classic PCFCL lesions on the trunk or head-and-neck region, and histology indicated a predominance of centrocytes admixed with centroblasts. IgM expression was significantly more frequent in ECD-PCFCL (54%) than in SL-PCFCL (7%; P =0.006). Targeted next-generation sequencing (NGS) with a 200 B-cell lymphoma-related gene panel demonstrated known PCFCL-like mutations in both groups. In addition, ECD-PCFCL demonstrated an enrichment of mutations associated with the activated B-cell genotype, including MYD88 (n=2), and some unique mutations, such as in ERBB4 (n=4). In conclusion, this study identified IgM expression at diagnosis as a potential biomarker for extracutaneous spread in PCFCL. In IgM-positive cases, genetic testing may be warranted. Patients with uncommon mutational profiles, such as those resembling the ABC-DLBCL genotype, may particularly benefit from closer follow-up and consideration of more aggressive treatment, including immuno-polychemotherapy. As these observations were made in a limited number of patients, our results require validation in an independent cohort.