Pediatric-Type Follicular Lymphoma of the Conjunctiva

Pediatric-type follicular lymphoma (PTFL) is a rare and indolent B-cell lymphoma that largely affects children and young adults. Although typically nodal, rare similar lesions have been reported in the conjunctiva, but differential diagnosis with follicular hyperplasia and other low-grade B-cell lymphomas is challenging. We identified 22 B-cell-derived conjunctival lesions in patients aged 7 to 33 years. All biopsies were characterized using morphologic, immunophenotypic, and molecular criteria. Cases showed a marked male predominance (20 males and 2 females). Final diagnoses included PTFL (n=8), PTFL with marginal zone differentiation (n=3), extranodal marginal zone lymphoma (EMZL, n=8), and reactive hyperplasia (n=3). PTFL cases showed expanded serpiginous follicles with a starry-sky appearance, high Ki67 proliferation index, CD10 and BCL6 positivity, and absence of BCL2 expression. Clonality studies were performed in all cases, revealing clonal immunoglobulin gene (IG) rearrangements in 18 cases and a polyclonal pattern in 4. Next-generation sequencing (NGS) provided confirmatory evidence for PTFL with detection of MAP2K1 mutations in 5/7 (71.4%) cases tested, observed in cases both with and without marginal zone differentiation. Our findings broaden the clinical and anatomic spectrum of PTFL. Like nodal PTFL, cases in the conjunctiva may show evidence of MZ differentiation, confirming that this is a spectrum of one disease. Integrated histologic and molecular assessment is key to accurate diagnosis of pediatric conjunctival lymphoid proliferations.