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: to propose diagnostic algorithm of IgG4-related disease (IgG4-RD). Materials and methods. One center retrospective research. 52 pts with IgG4-RD were included. The diagnosis was proved histologically and immunohistochemically. 48 out of 52 pts received treatment. Treatment included one of the following schemes (along with low oral glucocorticoids): rituximab monotherapy, cyclophosphamide monotherapy or their combination. Results. The mean age was 47.4±5.9 years, the mean age of the disease onset was 43.9±16.0 years. Median time before the diagnosis was 24 months. The most often sites of IgG4-RD were lacrimal (63.5%), salivary (46.2%) glands, lungs (48%), lymph nodes (34.6%) and retroperitoneum (17.3%). In clinical picture the leading complain was organ enlargement, but not its dysfunction. Pain was characteristic for retroperitoneum localization. In 56.8% of pts with IgG4-related syalo - and/or dacryoadenitis there was association with ear - nose - throat organs affection. In 4 pts (7.7%) IgG4-RD was combined with some malignant disease, including MALT-lymphoma of lacrimal glands. Irreversible organ damage as an IgG4-RD outcome had 15.4% of pts. The main laboratory markers of IgG4-RD were ESR elevation (38.5%), blood eosinophilia (9.6%), immunological disturbances (serum total IgG and IgG4 elevation, IgE elevation, antinuclear antibodies, rheumatoid factor detection, hypocomplementemia). Serum IgG4 level >1.35 g/l was elevated in 88% of pts and correlated with the number of affected organs (Spearman correlation coefficient 0.39, Student’s test, р=0.0056). Monoclonal serum secretion and B-cell clonality in the tissue was detected in 4 (23.5%) out of 17 pts, but not all of them had both signs. Conclusion. Based on the analysis of clinical and laboratory characteristics of IgG4-RD a diagnostic algorithm was proposed that enhances the detection and examination of the patients with suspected IgG4-RD.

Results of a cytogenetic and morphological study of 60 malignant lymphomas (ML) are presented. The most often observed chromosome abnormalities were rearrangements involving 14q32, 11q13, 11q21-23, 6q15, 6q21, 12p11-12, 17p11-12, and extra chromosomes 18, 3, 21 and 7. Translocations involving 14q32, leading to the appearance of marker 14q+, were noted in 41% of the tumors. Strict correlations between karyotype and morphology of ML were not seen. However, rearrangements of 11q were mostly found in low-grade tumors and markers 6q- in high-grade tumors. The absence of t(14;18), which is regarded to be the most common abnormality in ML, and an unusually high incidence of t(11;14) in our series confirm the uneven geographical distribution of ML with these translocations. Chromosome abnormalities in ML and acute lymphoblastic leukemia are compared.

We present an exceptionally rare case of co-occurrence of Rosai–Dorfman disease (RDD) and nodal marginal zone lymphoma (NMZL) in a 60-year-old Caucasian female with a 20-year course of Sjögren's syndrome (SS). In response to treatment for lymphoma, the patient presented a short positive response, followed by a rapid progression of the disease accompanied by the development of the peripheral facial nerve palsy. We failed to detect Epstein–Barr virus (EBV) in the NMZL/RDD sample by EBV-encoded RNA (EBER) in situ hybridization but identified genomic DNA of EBV by polymerase chain reaction. A second biopsy revealed EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified. The identical clonal immunoglobulin heavy chain gene rearrangements in the NMZL and DLBCL pointed to their clonal relationship. Though the role of EBV in the pathogenesis of some lymphomas is well-known, there have been only few cases of EBV-induced transformation of low-grade B-cell lymphoma into high-grade lymphoma and no cases of a patient with an NMZL background. To our knowledge, this is the first report of a concomitant occurrence of RDD and NMZL in a SS patient.