Sinonasal B-cell lymphomas: A nationwide cohort study, with an emphasis on the prognosis and the recurrence pattern of primary diffuse large B-cell lymphoma

Abstract

Lymphomas of the nasal cavity and paranasal sinuses (NPS) are rare. Knowledge on sinonasal B-cell lymphoma (SNBCL) primarily comes from case series or single-center studies on small cohorts. We sought to determine the subtype distribution, clinical characteristics, disease behavior, and prognosis on a nationwide scale, with an emphasis on prognostic factors for the most common sinonasal lymphoma, primary sinonasal diffuse large B-cell lymphoma (PSDLBCL). We collated all data from medical records and national databases on patients registered with SNBCL from 1980 through 2018 in the national pathology registry and collected all tissue samples for validation of diagnosis. We included 205 patients and found 10 different subtypes of lymphoma. Diffuse large B-cell lymphoma (DLBCL) was the predominant subtype (80%). The incidence of SNBCL was 0.14/100,000 person-years. The five-year progression-free survival (PFS) and overall survival rates for PSDLBCL were 50% and 56%, respectively. For PSDLBCL, Rituximab showed a statistically significant effect (Hazard Ratio 0.22, p < 0.001), whereas consolidative radiotherapy combined with immunochemotherapy was of limited value (PFS, p = 0.93). When treatment failure occurred, DLBCL showed a distinct pattern of recurrence/dissemination to the NPS, skin, breast, central nervous system (CNS), and/or testis. Collectively, DLBCL comprised a clear majority of SNBCLs, although nine other subtypes were represented. Data showed that immunochemotherapy increased survival for PSDLBCL and that the addition of radiotherapy did not benefit patients. Furthermore, treatment failure for sinonasal DLBCL showed a possible common pathogenesis with primary extranodal lymphomas of specific locations (e.g., CNS, skin, breast, and testis).

Keywords: lymphoma; nose neoplasms; paranasal neoplasms; prognosis; treatment.

FIGURE 1

Subtype distribution of primary sinonasal lymphomas and recurrence/dissemination pattern for primary sinonasal diffuse large B‐cell lymphoma (PSDLBCL). (A) A clear majority of the primary lymphomas are of the subtype diffuse large B‐cell lymphomas (DLBCL). HGBCL, high‐grade B‐cell lymphoma (NOS); HGBCL (double hit) (HGBCLDH), high‐grade B‐cell lymphoma, HGBCL (double hit); PBL, plasmablastic lymphoma. “Other” is patients with follicular, lymphoplasmacytic, or Burkitt lymphoma (BL). (B) Diagram of sites of recurrence and sites of dissemination in the case of refractory primary sinonasal DLBCL

FIGURE 2

Patients with primary diffuse large B‐cell lymphoma (DLBCL) treated with chemotherapy and immunochemotherapy, stratified by immunotherapy and radiotherapy, respectively (A–D) Patients receiving chemotherapy, stratified by immunotherapy. (A) overall survival (OS). (B) progression‐free survival (PFS). (C) absolute risk (AR) of dying from primary sinonasal diffuse large B‐cell lymphoma (PSDLBCL) (p = 0.01). (D) Relative survival ratio, that is, the ratio of mortality compared with the background population adjusted for age, calendar year and sex (p = 0.07). (E–H) Patients receiving immunochemotherapy, stratified by consolidative radiotherapy. (E) OS (F) PFS. (G) AR of dying from PSDLBCL. (H) Relative survival ratio (p = 0.95). Dotted vertical line indicates median survival. C, chemotherapy (chop or chop‐like); IC, immunochemotherapy; RT, radiotherapy