Flow cytometric, gene rearrangement, and karyotypic analyses of 110 cases of primary thyroid lymphoma: a single-institutional experience in Japan

Abstract

Ancillary studies for primary nodal lymphomas have been well documented; however, studies of primary thyroid lymphoma (PTL) are limited. Here, we aimed to clarify the clinicopathological, flow cytometric, gene rearrangement, and karyotypic characteristics of PTL by investigation of a large series at a single institute. We performed flow cytometric, IgH rearrangement, and karyotypic analyses of 110 PTL tissues surgically resected at Kuma Hospital between January 2012 and April 2017. All PTLs were of B-cell origin, including mucosa-associated lymphoid tissue lymphoma (MALTL; 89 patients, 80.9%), diffuse large B-cell lymphoma (DLBCL; 18 patients, 16.4%), and follicular lymphoma (FL; three patients, 2.7%). In 96 (87.3%) patients, anti-thyroid antibodies were positive. For flow cytometry using aspirated and resected materials, light chain restriction was observed in 73.7% and 69.2% of examined cases, respectively. Heavy chain JH DNA rearrangement was observed in 65.4% of PTLs (58.1% of MALTL cases, 100% of DLBCL cases, and 100% of FL cases). Chromosomal abnormalities were detected in 49.0% of PTLs, and translocation was most frequently detected (24.0%), followed by addition (20.8%) and trisomy (18.8%). The most frequent (9.4%) karyotype was t(3;14)(q27;q32). Both FLs harbored t(14;18) (q32;q21), and the karyotype was not detected in patients with MALTL and DLBCL. The negative rate for all three examinations was 3.8%. We concluded that thyroid MALTL was cytogenetically different from that in other organs. Our results suggested that pre-operative flow cytometry analysis using aspirated materials was as reliable as that using resected materials.

Thyroid lymphoproliferative lesions in Asia

“…Interestingly, of all the PTLs, while DLBCL was the most frequent (71.9%; including DLBCL transformed from low-grade NHL) subtype in western literature, MALT lymphoma was the commonest (41.1%) in Asian studies. Some recent studies have subclassified DLBCL into germinal and post-germinal center type (12,14,18,26). Other rare subtypes of PTL reported include follicular lymphoma (FL), chronic 2).…”

“…A study from Asia compared the cytomorphology of PTL on LBC with that of conventional smears. This study was not included in the analysis in this review because of overlapping study period with another study published from the same institute (14). The authors reported that on LBC large elongated swollen nuclei act as a clue to differentiate PTL from non-neoplastic lymphoid cells and that lymphoglandular bodies are not reliable for diagnosing PTL (49).…”

“…Flowcytometry (FC) is a reliable method for evaluation of patients suspected to have PTL. The National Cancer Institute (NCI)-sponsored Thyroid Fine Needle Aspiration State of the Science Conference concluded that FC is useful for immunophenotyping of clinically suspected cases of PTL ( 52), as has also been documented in some Asian and Western studies (14,15,17,28,29,(39)(40)(41)43,45). Hirokawa et al tried to establish a diagnostic algorithm based on findings of USG, FNAC and FC.…”

“…Two studies, one from the USA (43) and the other from Japan ( 14) have documented use of tissue samples in FC for PTL management. While the former used frozen specimens for FC (43), the latter have just mentioned resection specimens as the material used (14). Suzuki et al performed FC on a large number of aspirated and resected materials and found nearly similar detection rates (73.7% and 69.2% respectively) of light chain restriction from both types of materials (14).…”

“…Molecular testing: use of molecular methods as an ancillary technique in PTL diagnosis and management has also been discussed in some studies (11,14,15,17,26,28,29,39,40,43,44,46), more commonly in those from the West (Table 3). Majority of these methods were performed from surgical tissue specimens except two studies where FNA material was used (29,40).…”