The diverse hematologic manifestations of primary Sjögren syndrome (pSS) have 
not been systematically investigated, and their prognostic relevance remains 
unclear. We conducted a retrospective study of 536 consecutive patients followed 
in our institution to assess the prevalence of hematologic abnormalities and 
their associations with various disease manifestations in pSS. We also aimed to 
identify risk factors for the development of non-Hodgkin lymphoma (NHL) overall 
and by subtype. Anemia of chronic disease and hypergammaglobulinemia were the 
most prevalent hematologic manifestations encountered at diagnosis and during 
the course of pSS. Univariate analysis between cytopenias and glandular 
manifestations revealed a statistically significant correlation between 
lymphocytopenia and parotid gland enlargement (p = 0.002), as well as between 
neutropenia and xerostomia (p = 0.019). Anemia, lymphocytopenia, 
thrombocytopenia, hypergammaglobulinemia, the presence of monoclonal serum 
proteins, and cryoglobulinemia correlated significantly with the presence of 
extraglandular symptoms such as palpable purpura, lymphadenopathy, and 
splenomegaly. Lymphoma was diagnosed in 7.5% (95% confidence interval [CI], 
5.4%-10%) of patients. Marginal zone B-cell lymphomas (MZBCLs) were the 
predominant histologic type (65%; 95% CI, 48.3%-79.4%), while diffuse large 
B-cell lymphomas (DLBCLs) accounted for 17.5% (95% CI, 7.3%-32.8%) of all cases. 
The development of NHL in patients with pSS could be predicted by the presence 
of simple clinical and laboratory factors at diagnosis: neutropenia (p = 0.041), 
cryoglobulinemia (p = 0.008), splenomegaly (p = 0.006), lymphadenopathy (p = 
0.021), and low C4 levels (p = 0.009). Patients carrying any of these factors 
had a more than 5-fold increased risk of NHL compared to patients with no risk 
factors at all. The above set of disease characteristics could predict 
subsequent development of MZBCL; the presence of lymphocytopenia (p = 0.044) at 
diagnosis served as a risk factor for the development of a non-MZBCL, most 
commonly DLBCL. Anemia of chronic disease and hypergammaglobulinemia are common 
hematologic manifestations at diagnosis and during the course of pSS. 
Neutropenia and cryoglobulinemia at diagnosis are significantly associated with 
an increased risk of lymphoma development.