Track

Case Reports

Abstract

Primary cutaneous follicle center lymphoma (PCFCL) is a low-grade B-cell lymphoma (BCL) with germinal center phenotype, limited to the skin at diagnosis. Diagnosing PCFCL can be challenging; molecular techniques (e.g., B-cell clonality studies [BIOMED-2], next-generation sequencing [NGS]) can aid in diagnosis. Comparing molecular signatures of BCLs at different sites or time points within a single patient may shed light on disease mechanisms and guide treatment. There is limited literature on clonal identity and evolution in cutaneous BCLs; most studies report identical clones in same-site recurrences. We report a novel case of same-site multiply recurrent PCFCL exhibiting clonal evolution over 9 years. A 24-year-old man presented with a one-year history of an enlarging nodule on the frontal scalp. Biopsy revealed a low-grade BCL of follicle center phenotype with positive B-cell clonality, confirming PCFCL. Despite treatment, he experienced 2 recurrences on the scalp over 9 years. Molecular analysis revealed distinct B-cell receptor clones via BIOMED-2, suggesting clonal evolution. NGS performed on the recurrences identified a shared variant of unknown significance (VUS) in the NOTCH2 gene, indicating a common genetic origin despite clonal divergence. In addition, the most recent recurrence showed a Bruton tyrosine kinase VUS further suggesting clonal evolution. PCFCL are known to exhibit somatic hypermutation, which may confound the determination of clonal relationships using BIOMEDs. This case highlights that clonal evolution can occur within the same site while retaining a shared genetic "fingerprint." The clinical presentation, combined with NGS data, was crucial in establishing the relationship between these seemingly distinct clones.