Incidence, clinicopathological features and genetics of in‐situ follicular neoplasia: a comprehensive screening study in a Japanese cohort

• Published in: Histopathology Vol. 80; no. 5; pp. 820 - 826
• Main Authors: Oishi, Naoki, Segawa, Takahiro, Miyake, Kunio, Mochizuki, Kunio, Kondo, Tetsuo
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2022
• Subjects: Aged; BCL2; Carcinoma in Situ - epidemiology; Carcinoma in Situ - genetics; Carcinoma in Situ - pathology; Cell proliferation; CREBBP; Early Detection of Cancer; Female; follicular lymphoma; Follow-Up Studies; Germinal centers; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Incidence; Inflammation; in‐situ follicular B‐cell neoplasm; in‐situ follicular neoplasia; Japan - epidemiology; Lymph nodes; Lymph Nodes - pathology; Lymphocytes B; Lymphoma; Lymphoma, Follicular - epidemiology; Lymphoma, Follicular - genetics; Lymphoma, Follicular - pathology; Male; Middle Aged; Prevalence; Solid tumors; Japan; Europe; in-situ follicular neoplasia; BCL2; in-situ follicular B-cell neoplasm; CREBBP; follicular lymphoma
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.14617

Aims In‐situ follicular neoplasia (ISFN) is a histologically recognizable neoplastic proliferation of follicular lymphoma (FL)‐like B cells confined to the germinal centres. While some ISFNs are associated with overt FL, others are incidentally identified as isolated or pure forms in individuals without evidence of overt FL. The prevalence of incidentally found isolated ISFN is approximately 3% in Europe; however, no screening study has been conducted in Asia. To investigate the incidence and clinicopathological characteristics of ISFNs in the Japanese population, we conducted histopathological screening of the lymph nodes (LNs) resected for solid tumours or inflammatory conditions. Methods and results We screened for ISFN in 5700 LNs from 340 individuals using immunohistochemistry for BCL2 and identified seven ISFNs, with an incidence of 2.1%. The median age of the individuals with ISFN was 67 years, none of whom developed overt FL, with a median follow‐up of 59 months. Next‐generation sequencing was performed in five ISFNs, and 10 variants in seven FL‐associated genes were identified. The identified variants included HIST1H1E (n = 2), ARID1A (n = 2), KMT2D (n = 1), CARD11 (n = 1), BCL7A (n = 1), CREBBP (n = 1) and TNFRSF14 (n = 1). Conclusions The incidence of isolated ISFN in the Japanese population is not significantly different from that in Europe, presumably reflecting the recent increase in FL in Japan. These incidentally found ISFNs have a low potential to transform into overt FL. Although mutations of FL‐associated genes are already present in ISFNs, further molecular studies are needed to identify driver genes leading to the transformation of ISFN to overt FL. By immunohistochemical screening of 5700 LNs from 340 individuals, isolated in‐situ follicular neoplasia (ISFN) was identified in 2.1% of Japanese population. Next‐generation sequencing identified variants involving HIST1H1E, ARID1A, KMT2D, CARD11, BCL7A, CREBBPand TNFRSF14in ISFNs.