T-cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disorder characterized by a persistent increase in the number of large granular lymphocytes (LGLs), neutropenia, and splenomegaly. Clinical manifestations of T-LGLL in the setting of rheumatoid arthritis (RA) are often identical to those in which one would suspect Felty's syndrome (FS). These disorders are distinguished by the presence of T-cell clonality, which is present in T-LGLL but not in FS. Mutations in the signal transducer and activator of transcription 3 (STAT3) and 5b (STAT5b) genes can be used as molecular markers of T-LGLL, but their prevalence in FS is unknown.Eighty-one patients with RA and unexplained neutropenia or/and an increase in the number of LGLs above 2 × 10⁹/L were stratified into RA-associated T-LGLL (N = 56) or FS (N = 25) groups based on the presence or absence of T-cell clonality. STAT3 and STAT5b gene mutations were assessed in each group by means of allele-specific polymerase chain reaction assays. Clinical, immunological, laboratory data and the results of immunophenotyping of blood and bone marrow lymphocytes were also evaluated.Mutations of the STAT3 gene and an increase in the number of LGLs above 2 × 10⁹/L were detected in RA-associated T-LGLL, but not in FS (39% vs 0% and 21% vs 0%, respectively). Mutations in the STAT5b gene were not observed in either group. Expression of CD57, CD16, and CD5^−/dim on CD3⁺CD8⁺ T-lymphocytes was observed in both RA-associated T-LGLL and FS.STAT3 gene mutations or LGL counts over 2 × 10⁹/L in RA patients are indicative of T-LGLL.

The occurrence of diffuse large B-cell lymphoma (DLBCL) in the course of Sjogren’s syndrome (SS) is considered to be equally related either to the development of DLBCL de novo or to the transformation from marginal zone lymphoma (MZL). However, the question of possible clonal relationship between MZL and DLBCL in the group of SS patients remains open. Here we present the data concerning 194 patients with lymphoma complicated SS followed up at Nasonova Research Institute of Rheumatology during the last 22 years. Molecular analysis of tumor cells was performed for 6 SS patients who had developed both MZL and DLBCL. To assess clonal relationship between each of the tumor pairs immunoglobulin heavy chain (IGH) gene rearrangements were identified according BIOMED-2 protocol by means of multiplex polymerase chain reaction followed by GeneScan fragment analysis. Despite different localization MZL and DLBCL were clonally related in five tumor pairs. The median time to transformation was 11 months (range 0–78 months). MZL and DLBCL were clonally related in most cases from our cohort of SS patients. No statistically significant difference in survival between patients with DLBCL transformed from MZL and patients with de novo DLBCL was found in the cohort of SS patients investigated.

Aim: Patients with primary Sjögren's syndrome (pSS) have an increased risk of developing diffuse large B‐cell lymphoma (DLBCL), which is an aggressive and heterogeneous non‐Hodgkin lymphoma. This study aimed to characterize DLBCLs in patients with pSS.Method: We identified 18 patients with DLBCL and pSS over a 22‐year period. Based on the 2016 WHO guidelines, we characterized DLBCL based on immunohistochemical tests using a broad panel of antibodies, and an Epstein‐Barr virus (EBV) test using in situ hybridization.Results: The median time from initial pSS symptom onset to the DLBCL diagnosis was 20.5 years and the median time from the pSS diagnosis until the DLBCL diagnosis was 14 years. After the lymphoma diagnosis, the median overall survival was 3 months (range: 0‐212 months) and the 5‐year overall survival rate was 37.5%. Thirteen DLBCLs were re‐classified as DLBCL, not otherwise specified (NOS) in nine cases; EBV‐positive DLBCL, NOS in two cases; and T‐cell/histiocyte‐rich large B‐cell lymphoma in two cases. Five cases of DLBCLs were not re‐classified because their EBV status was unknown. The Hans algorithm, which uses a combination of staining for CD10, BCL6, and MUM1, was used to classify the DLBCLs into the germinal center B‐cell (GCB) subtype for three cases and the non‐GCB subtype for nine cases.Conclusion: These results indicate that DLBCL tends to occur late in pSS cases and is mainly related to the non‐GCB subtype of DLBCL.

A persistently increased T-cell large granular lymphocyte (T-LGL) count in the blood of more than 2 × 10⁹/L for at least 6 months is necessary for a reliable diagnosis of T-LGL leukemia. In cases with LGL counts of approximately 0.5–2 × 10⁹/L, a diagnosis of T-LGL leukemia can be made if clonal rearrangement of T-cell receptor (TCR) genes is present and if the patient shows typical manifestations of T-LGL leukemia, such as cytopenia, splenomegaly, or concomitant autoimmune disease. However, in cases with LGL counts of less than 0.5 × 10⁹/L, the diagnosis of T-LGL leukemia is questionable (termed as “gray-zone” cases). Although mutations in signal transducer and activator of transcription 3 (STAT3) gene are the molecular hallmark of T-LGL leukemia, their diagnostic value in the “gray-zone” cases of T-LGL leukemia has not been evaluated – our study has been aimed to examine the prevalence of STAT3 mutations in these cases. Herein, we describe 25 patients with autoimmune rheumatic diseases, neutropenia, clonal rearrangement of TCR genes, and circulating LGL count of less than 0.5 × 10⁹/L. Splenomegaly was observed in 19 (76%) patients. Mutations in the STAT3 were detected in 56% of patients using next-generation sequencing. Importantly, in 3 patients, no involvement of the blood and bone marrow by malignant LGLs was noted, but examination of splenic tissue revealed infiltration by clonal cytotoxic T-lymphocytes within the red pulp, with greater prominence in the cords. We suggest using the term “splenic variant of T-LGL leukemia” for such cases.

Sjögren’s syndrome (SS) has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats. Contrast-enhanced computed tomography scan (CT-scan) of the abdomen revealed multiple low density foci with homogeneous structure and clear contours in both lobes of the liver. Histologically, proliferation of medium sized lymphoma cells with round-oval and slightly irregular nuclei with fine chromatin was shown. Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL). To exclude secondary liver lesion by non-Hodgkin lymphoma, chest and small pelvis CT-scan, endoscopy of upper and lower gastrointestinal tract and study of bone marrow were performed. After 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the complete remission was achieved, which persists after 45 months of follow-up. Primary hepatic lymphomas are extremely rare, and previously only low-grade hepatic lymphomas have been described in SS. To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS.