Syncytial variant of nodular sclerosis Hodgkin lymphoma: an under-emphasized variant

Abstract

Syncytial variant nodular sclerosis Hodgkin lymphoma (HL) is a variant that was described over 40 years ago but has received relatively little attention in the literature. Earlier studies emphasized the predominance of Hodgkin (also known as lacunar) and Reed-Sternberg (HRS) cells in this variant. Here we emphasize that the HRS cells in syncytial variant nodular sclerosis HL have a cohesive appearance, form confluent sheets, and have an immunophenotype typical of classic HL. Cases of syncytial variant nodular sclerosis HL are also commonly associated with necrosis and granulocytes in the background. Patients with syncytial variant nodular sclerosis HL tend to be young adults who present with lymphadenopathy (most often cervical) and/or a mediastinal mass. The few studies of syncytial variant nodular sclerosis HL available in the literature have suggested that this variant is associated with a higher frequency of B-type symptoms and advanced-stage disease, and one study has suggested that patients have a shorter progression-free survival than patients with typical nodular sclerosis HL. However, currently patients with syncytial variant nodular sclerosis HL are treated similarly to patients with typical nodular sclerosis HL. The large number of neoplastic cells in syncytial variant nodular sclerosis HL cases presents a diagnostic challenge, and the differential diagnosis includes non-Hodgkin lymphomas, other types of classic HL, gray zone lymphoma, thymoma and metastatic neoplasms to the mediastinum including germ cell tumors, carcinomas, and melanoma.