Malignant Lymphoma in Primary Sjögren Syndrome: Incidence and Risk Factors.

Primary Sjögren Symdrome (PSS) is the second common systemic autoimmune rheumatic disease whose main histological feature is a focal infiltration of the exocrine glands by activated B and T lymphocytes. PSS is considered a benign autoimmune condition with a chronic indolent course. However, several reports have noted an increased incidence of malignant lymphoma with an estimated risk of up to 44 times greater than in the normal population. The aims of the present study are to assess the cumulative incidence of lymphoma in patients diagnosed of PSS, as well as to identify risk factors for developing this condition.

All patients diagnosed since 1988 and followed-up for longer than 2 years at our institution, were included. The pathological, immunological, and clinical features of each case of PSS were retrospectively examined. These data were cross-examined with the cumulative incidence of lymphoma in this group of patients, in order to determine common findings in patients later developing lymphoid malignancies.

272 patients had been diagnosed as having a PSS in this time period, of which 244 [9 males, 235 females; median age 58 years (range 17 to 88)] had been followed for more than 2 years. After a median follow up of 9.6 years, 11 (4.5%) patients developed a lymphoma, after 6 to 171 months from diagnosis. The cumulative risk for developing lymphoma at 5, 10 and 15 years was 3.4, 4.1, and 9.3%, respectively. Risk factors associated with the development of lymphoma were skin purpura/vasculitis, lymphopenia and low levels of C3 and C4 complement fractions. Low levels of C3 and C4 were also found to be associated with an earlier development of lymphoma. Conversely, skin purpura/vasculitis and lymphopenia were both associated with the development of lymphoma at a later stage. The hystological analysis showed mucosal-associated lymphoid tissue lymphoma in 5 patients, diffuse large B cell in 3, and follicular lymphoma in 3 cases. Clinically, lymphomas had extranodal presentation in 8 out of the 11 cases, involving the salivary glands in 5, lacrimal glands in 1, and soft tissues and lung in 1 case, respectively. Only 3 patients had received immunosuppressive therapy prior to the diagnosis of lymphoma, and EBV was not found in the histological examination of any of these cases.

Patients with PSS are at a higher risk for developing lymphoma. Our study suggests low levels of C3 or C4, as well as the presence of purpura or lymphopenia delimitates a group of patients at a higher risk, so that such patients may benefit from a closer follow up.

No relevant conflicts of interest to declare.