Follicular lymphoma with signet ring cell morphology: Clinicopathologic analysis of 31 cases

We report 31 cases of follicular lymphoma (FL) with signet ring (SR) cells, representing <0.05% of FLs diagnosed at our institution. The cohort includes 16 women and 15 men with a median age of 65 years (range, 26-87). All patients presented with lymphadenopathy. Twenty-three (74%) patients had advanced stage disease and 8 (26%) had localized (stage I or II) disease. Twenty-one (68%) patients underwent excisional biopsy, 8 core needle biopsy and 2 fine needle aspiration. All 29 neoplasms with biopsy specimens had a follicular pattern, at least in part, but 9 had diffuse areas. These neoplasms were grade 1-2 in 19 cases and grade 3A in 10 cases. In addition, 1 patient had FL grade 1-2 in the nasopharynx and FL grade 3A FL in a regional lymph node and 1 patient had FL grade 3A (25% of the specimen) associated with diffuse large B-cell lymphoma. We semi-quantified the percentage of SR cells as follows: 5-10% in 3 cases, 11-25% in 8, 26-50% in 9, 51-75% in 10 and > 75% in 1 neoplasm. Immunophenotypic analysis using immunohistochemistry was performed in all cases and flow cytometry immunophenotypic analysis was performed in 24 cases. All neoplasms were positive for pan-B-cell markers and lacked T-cell antigens. CD10 was positive in 28 of 30 (93%) cases, and BCL2 and BCL6 were positive in all 20 and 18 cases assessed, respectively. IGH::BCL2 was detected in all 10 cases tested by fluorescence in situ hybridization. Targeted next-generation sequencing analysis performed successfully on 4 cases identified recurrent mutations in genes often involved in FL, such as KMT2D and TNFRSF14. In conclusion, in this retrospective study we provide the largest case series of FL-SR. We show that SR cells can be numerous in FL, but otherwise these cases resemble classic FL. We also provide results of next generation sequencing data on 4 cases which heretofore has not been reported.