Follicle Center Lymphoma (FCL) of the Lower Female Genital Tract (LFGT)

Abstract

Primary cutaneous follicle center lymphoma has been distinguished from nodal follicular lymphoma (FL) based on genomic and clinical features. The nature of other extranodal FLs is not well defined. We report 15 cases of follicle center lymphoma involving the lower female genital tract. Cases were evaluated using an immunohistochemical panel for B-cell lymphoma, B-cell clonality, fluorescence in situ hybridization for BCL2 gene rearrangement, and next-generation sequencing. All patients had localized disease with no evidence of bone marrow involvement. Most cases (12/15, 80%) had a follicular pattern, at least focally. Large centrocytes were a prominent feature leading to concern for diffuse large B-cell lymphoma by referring pathologists. Neoplastic cells were positive for CD20 and BCL-6, while BCL-2 was positive in 2/15 (13%) cases. Fluorescence in situ hybridization for BCL2 gene rearrangement was negative in 10/11 (91%) cases. Next-generation sequencing performed in 10 cases revealed TNFRSF14 as the most frequently mutated gene in 6/10 (60%) cases. No case had CREBBP or KMT2D mutations as seen in nodal FL. None of the patients had progressive disease with durable complete remission achieved in 10/12 (83%) cases. The median follow-up period was 7.8 years (range: 0.2 to 20.5 y) with a 5-year overall survival of 100%. We conclude that follicle center lymphoma of the lower female genital tract is a novel variant of primary cutaneous follicle center lymphoma. Despite a frequent component of large cells, it is characterized by localized disease and low risk for dissemination. Awareness and recognition are important to distinguish these lesions from aggressive B-cell lymphomas.

B- and T-/NK-Cell Lymphomas in the 2022 International Consensus Classification of Mature Lymphoid Neoplasms and Comparison with the WHO Fifth Edition

“…Most cases occur in the head and area or upper trunk. However, similar lesions have been reported in the uterine c and vagina, involving mucosal and cutaneous sites [12].…”

Cutaneous B‐cell lymphomas: 2023 update on diagnosis, risk‐stratification, and management

“…17 Therefore, the genetic landscape may help distinguish PCFCL from secondary cutaneous FL. A novel variant involving the lower female genital tract (cervix and/or vagina) was recently described, 18 sharing immunophenotypic (e.g., >80% Bcl-2 negative), genetic (e.g., no CREBBP, KMT2D mutations were identified), and clinical characteristics (localized disease with 100% 5-year overall survival) with PCFCL.…”

The clinical and molecular taxonomy of t(14;18)-negative follicular lymphomas

“… 35 Two of these features support systemic disease. Interestingly, the mutational profile of PCFCL is similar to other extranodal t(14;18)-negative FLs, 41 , 69 , 70 , 71 suggesting that inactivation of TNFRSF14 might play a role in the development of t(14;18)-negative lymphomas. The exact mechanism of TNFRSF14 mutations promoting FL lymphomagenesis remains to be elucidated.…”

“…Recently, a group of FCLs of the lower female genital tract presenting in the uterine cervix and vagina was reported. 70 These cases shared many features with PCFCL and was proposed as a novel variant of PCFCL. The most frequent mutated gene was TNFRSF14 (60%), with no mutations in chromatin modifying genes.…”

“… Comparison of mutational landscape between t(14;18)-positive and t(14;18)-negative FL entities. Frequencies of recurrently mutated genes in 100 t(14;18)-positive FL ( BCL2 -pos FL), 17 31 duodenal-type FL (DTFL), 15 74 nodal t(14;18)-negative cases, 32 , 36 , 37 , 38 31 PCFCL, 34 , 35 10 lower female genital tract (LFGT) FL, 70 7 thyroid BCL2 -neg FL, 71 81 PTFL, 40 , 82 , 84 and 17 LBCL- IRF4. 91 Color gradient depicted per the percentage of mutated cases for each gene: dark red, 100%: dark green, 0%.…”