Risk of non-Hodgkin lymphoma in sarcoidosis patients with salivary gland involvement: A retrospective cohort study.

Abstract

e19060 Background: Sarcoidosis is an inflammatory disease characterized by non-caseating granulomas that most commonly affect the lungs and intrathoracic lymph nodes but may virtually involve any organ system. Salivary gland sarcoidosis is a rare manifestation of systemic sarcoidosis and may clinically mimic Sjogren's syndrome. While salivary gland disease is a well-established risk factor for non-Hodgkin lymphoma (NHL) in Sjogren's syndrome, its association with NHL in sarcoidosis remains poorly characterized. This study aims to assess whether salivary gland involvement in sarcoidosis is associated with an increased risk of NHL and other hematological malignancies. Methods: We conducted a retrospective cohort study using TriNetX, a multi-institutional, de-identified EHR database. The study population included adult patients (≥18 years) with sarcoidosis. The exposure cohort was comprised of patients with salivary gland involvement while the control group was comprised of patients without salivary gland involvement. Patients with Sjogren's syndrome and prior hematological malignancies were excluded. One-to-one propensity score matching was performed based on age, sex, race, and medication exposures to glucocorticoids and antineoplastics. The primary outcome was defined as the development of NHL. The secondary outcome was defined as the development of any hematological malignancy. Results: After matching, 2,093 patients were included per cohort. NHL occurred in 25 patients in the exposure cohort and 11 patients in the control cohort with a risk ratio of 2.27 (95% CI 1.12-4.61) and an odds ratio of 2.29 (95% CI 1.12- 4.66). Overall hematological malignancies occurred in 47 patients in the exposure cohort and 18 patients in the control cohort with a risk ratio of 2.61 (95% CI 1.52-4.48) and an odds ratio of 2.65 (95% CI 1.53- 4.58). Conclusions: Salivary gland involvement in sarcoidosis is associated with a 2.3-fold increased risk of NHL and a 2.6-fold increased risk of overall hematological malignancies, although the absolute risk remains low at 1.19% and 2.25% respectively. These results suggest chronic salivary gland inflammation in sarcoidosis may drive carcinogenesis through persistent B-cell activation as is well described in Sjogren’s syndrome. Collectively, the findings highlight salivary gland involvement as a clinically meaningful risk marker in sarcoidosis patients, supporting targeted surveillance and lower biopsy thresholds in this population.