Prevalence of STAT3 mutations in patients with rheumatoid arthritis-associated T-cell large granular lymphocytic leukaemia and Felty syndrome.

OBJECTIVES: Neutropenia is a key presentation of Felty syndrome (FS) and rheumatoid arthritis (RA)-associated T-cell large granular lymphocytic (T-LGL) leukaemia. Clonal rearrangement of T-cell receptor (TCR) gene supports the diagnosis of T-LGL leukaemia but not FS. Mutations in the signal transducer and activator of transcription 3 (STAT3) gene are highly specific for T-LGL leukaemia, but their prevalence in FS remains poorly clarified. METHODS: The study included 100 patients with RA and unexplained neutropenia. TCR rearrangements were examined in blood (100 cases), bone marrow (47 cases), and spleen (12 cases) using the BIOMED-2 protocol. Patients were stratified into RA-associated T-LGL leukaemia cohort if a clonal TCR rearrangement was identified in any of the tested patient samples, and into FS cohort in other cases. Mutations in the STAT3 were examined using next-generation sequencing (NGS) technology in blood (100 cases), bone marrow (37 cases), and spleen (7 cases). RESULTS: STAT3 mutations were identified in 71% (49/69) patients with RA-associated T-LGL leukaemia and in 10% (3/31) patients with FS (p=4.7×10-8). Three samples from the RA-associated T-LGL leukaemia cohort and 5 samples from the FS cohort had STAT3 mutations in the absence of clonal TCR rearrangement. CONCLUSIONS: The results suggest that STAT3 mutations are significantly less common in FS than in RA-associated T-LGL leukaemia. Moreover, NGS can detect clones undetectable by fragment analysis. We speculate that in patients with RA and neutropenia, the detection of STAT3 mutations can point to T-LGL leukaemia even in the absence of clonal TCR rearrangement.

Clinical Study of the Relationship between Sjögren Syndrome and T-Cell Large Granular Lymphocytic Leukemia: Single-Center Experience.

The relationship between Sjögren syndrome (SS) and T-cell large granular lymphocytic (T-LGL) leukemia remains unclear. In this paper, we report for the first time a large case series of 21 patients with primary and secondary SS associated with T-LGL leukemia. Our results suggest the importance of considering T-LGL leukemia in the diagnostic evaluation of SS patients, particularly when neutropenia occurs. We also postulate that elevated antinuclear antibody titers in patients with T-LGL leukemia indicate the need for the clinical assessment of SS. To assess whether SS affects the frequency of the signal transducer and activator of transcription 3 (STAT3) gene mutations in T-LGL leukemia, we examined STAT3 mutations by next-generation sequencing in two cohorts of patients: with SS-associated T-LGL leukemia and T-LGL leukemia in the setting of rheumatic diseases but without SS. While our results suggest that SS, per se, is not associated with an increased frequency of STAT3 mutations in T-LGL leukemia, further studies are needed to better assess the role of the STAT pathway in the development of concomitant SS and T-LGL leukemia.

Analysis of a single-institution cohort of patients with Felty's syndrome and T-cell large granular lymphocytic leukemia in the setting of rheumatoid arthritis.

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.

Clonal relationship of marginal zone lymphoma and diffuse large B-cell lymphoma in Sjogren's syndrome patients: case series study and review of the literature.

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.

Behçet's disease and comorbidity: internal case reports and literature review.

The aim of this study was to determine the clinical characteristics of two patients with malignancy related to Behçet's disease. We reviewed literary-reported cases of Behçet's disease related to myelodysplastic syndrome, neoplasm and leukemia. Our own observation included two cases of comorbid conditions of Behçet's disease. The first patient with Behçet's disease had been examined concurrent development of intestinal tumor. The second one was diagnosed to have chromic myeloleukemia. The malignant transformation of Behçet's disease patients, both solid and hematological, is rather rare. Further accumulation of relevant date and its analysis will allow to find out the relationship between malignant disease and chemotherapy in Behçet's disease.

Aleukemic variant of T-cell large granular lymphocyte leukemia in patients with rheumatoid arthritis - diagnostically challenging subtype.

INTRODUCTION: The typical clinical manifestations of T-cell large granular lymphocyte (T-LGL) leukemia are an increase in the number of large granular lymphocytes (LGLs) in the blood > 2000 cells/µL, neutropenia, and splenomegaly. In rare cases of so-called 'aleukemic' T-LGL leukemia, the number of LGLs is <400-500 cells/µL. In patients with rheumatoid arthritis (RA), distinguishing T-LGL leukemia with low tumor burden in the blood and bone marrow from Felty syndrome (FS) poses diagnostic challenges. AREAS COVERED: This review aimed to describe the basic characteristics and variants of aleukemic T-LGL leukemia, with a special focus on aleukemic T-LGL leukemia with massive splenomegaly (splenic variant of T-LGL leukemia) and differential diagnosis of such cases with hepatosplenic T-cell lymphoma. The significance of mutations in the signal transducer and activator of transcription 3 (STAT3) gene for distinguishing aleukemic RA-associated T-LGL leukemia from FS is discussed, along with the evolution of the T-LGL leukemia diagnostic criteria. PubMed database was used to search for the most relevant literature. EXPERT OPINION: Evaluation of STAT3 mutations in the blood and bone marrow using next-generation sequencing, as well as a comprehensive spleen study, may be necessary to establish a diagnosis of aleukemic RA-associated T-LGL leukemia.

Combination of Sjögren's syndrome and anti-Ku syndrome complicated by the development of mucosa-associated lymphoid tissue lymphoma: case review and systematic review of the literature.

The frequency of antibodies to Ku varies in various autoimmune diseases. In 2019, Spielmann et al. identified two types of anti-Ku syndrome based on a hierarchical clustering analysis. Sjögren's syndrome occurs both in the first type of anti-Ku syndrome and in the second type. Despite the fact that increased tissue expression of Ku proteins was noted in lymphocytic cells with focal sialoadenitis of the minor salivary glands in patients with primary Sjogren's syndrome, only 49 cases of a combination of anti-Ku antibodies and manifestations of Sjogren's syndrome have been described in the literature. Some researchers examined patients for the presence of Sjogren's syndrome only if they had anti-Ro or anti-La antibodies, although in the literature, there are descriptions of Sjogren's syndrome in the presence of only isolated anti-Ku antibodies, as in our case. Literature data on glandular and extraglandular manifestations of Sjögren's syndrome in anti-Ku-positive patients are limited. Below, we present the first case of Sjögren's syndrome in combination with the first type of anti-Ku syndrome complicated by the development of mucosa-associated lymphoid tissue (MALT) lymphoma. The article also provides a systematic review of the literature on the association of Sjögren's syndrome with anti-Ku antibodies.

STAT3 mutations in "gray-zone" cases of T-cell large granular lymphocytic leukemia associated with autoimmune rheumatic diseases.

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.

Analysis of prognostic factors in diffuse large B-cell lymphoma associated with rheumatic diseases.

OBJECTIVE: The risk of developing diffuse large B-cell lymphoma (DLBCL) is increased in many rheumatic diseases (RDs). It is possible that RD-associated DLBCL is a distinct subset within the category of 'DLBCL', exhibiting characteristic biological features and clinical behaviour. However, information on RD-associated DLBCL is limited. METHODS: We searched the V.A. Nasonova Research Institute of Rheumatology (Russia) database from 1996 to 2021 for patients with RDs and coexisting DLBCL. Prognostic factors including the International Prognostic Index (IPI), bulk disease and c-MYC/8q24 gene rearrangements were analysed. Furthermore, we stratified DLBCLs as germinal centre B-cell (GCB) subtype and non-GCB subtype based on Hans' immunohistochemical algorithm and also examined Epstein-Barr virus (EBV) status. RESULTS: Twenty-seven patients with RD-associated DLBCL were identified. Twenty patients had primary Sjogren's syndrome, three had systemic lupus erythematosus, two had rheumatoid arthritis and two had systemic sclerosis. Secondary Sjogren's syndrome was found in four patients. The median age at the time of diagnosis of DLBCL was 59 years with a female predominance (26:1). Based on IPI, 16 patients were assigned to the intermediate-high and high-risk groups. Bulk disease was detected in 29% of patients. Of the 20 examined cases, 4 (20%) were classified as the GCB subtype and 16 (80%) were classified as the non-GCB subtype. EBV was detected in 2 of the 21 tested cases (10%), and the c-MYC/8q24 gene rearrangement was not found in any of the 19 examined cases. After the lymphoma diagnosis, the median overall survival (OS) was 10 months (range: 0-238 months). CONCLUSIONS: Except for the more common non-GCB subtype, we did not identify any other prognostic factor that could influence the prognosis of patients with RD-associated DLBCL. We believe that short OS in our patients was predominantly associated with decreased tolerance to lymphoma treatment.

The non-leukemic T cell large granular lymphocytic leukemia variant with marked splenomegaly and neutropenia in the setting of rheumatoid arthritis - Felty syndrome and hepatosplenic T cell lymphoma mask.

T cell large granular lymphocytic (T-LGL) leukemia is a rare type of mature T cell neoplasm. The typical features of T-LGL leukemia include an increased number of large granular lymphocytes in the peripheral blood, cytopenia (most commonly neutropenia), and mild-to-moderate splenomegaly. Up to 28% of patients with T-LGL leukemia have rheumatoid arthritis (RA). This study reports ten atypical cases (seven women and three men, median age 60.5 years) of RA-associated T-LGL leukemia presenting with lymphopenia, severe neutropenia, and marked splenomegaly. The weight of the spleens ranged from 892 to 2100 g (median 1100 g). Bone marrow histology and differential counts of bone marrow aspirates revealed no peculiarities in nine of ten cases. The red pulp of the spleen was expanded and showed moderate to strong infiltration by medium-sized slightly pleomorphic lymphocytes in nine cases and subtle infiltration in one. Although lymphocytic infiltration involved both cords and sinusoids, it was more apparent within the splenic cords. The white pulp was preserved and contained prominent germinal centers in eight patients and was atrophic in two patients. Immunohistochemically, malignant lymphocytes were CD3+, CD43+, and CD4- in all cases and TIA-1+ in nine out of ten. TCRαß positivity and TCRγδ positivity was observed in six and four cases out of ten, respectively. All ten patients had T cell clonality in the spleen tissue, but in three cases it was absent in both blood and bone marrow. STAT3 mutations in the spleen tissue were detected in three of ten cases. In all eight cases studied, neither isochromosome 7q nor trisomy 8 was detected in the spleen tissue. Cases of RA-associated T-LGL leukemia with low LGL count in the peripheral blood, neutropenia, and marked splenomegaly present a diagnostic challenge and can be misdiagnosed as Felty's syndrome or hepatosplenic T cell lymphoma.

Characteristics of diffuse large B-cell lymphoma in patients with primary Sjögren's syndrome.

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.

Composite Epstein-Barr virus-positive mucosa-associated lymphoid tissue lymphoma and Epstein-Barr virus-negative diffuse large B-cell lymphoma in the parotid salivary gland of a patient with Sjögren's syndrome and rheumatoid arthritis: a case report.

BACKGROUND: Epstein-Barr virus is associated with many human hematopoietic neoplasms; however, Epstein-Barr virus-positive mucosa-associated lymphoid tissue lymphoma is extremely rare. In routine clinical practice, detection of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma in a tissue sample presumes a clonal relation between these neoplasms and that diffuse large B-cell lymphoma developed by transformation of the mucosa-associated lymphoid tissue lymphoma. However, evidence to support this presumption is sparse and controversial. Assessment of the clonal relationship of the lymphoid components of a composite lymphoma is important for understanding its pathogenesis and correct diagnosis. CASE PRESENTATION: We present an unusual case of composite lymphoma (Epstein-Barr virus-positive mucosa-associated lymphoid tissue lymphoma/Epstein-Barr virus-negative diffuse large B-cell lymphoma) in the parotid salivary gland of a 62-year-old Caucasian woman with Sjögren's syndrome and rheumatoid arthritis. Simultaneous occurrence of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma in the parotid salivary gland led us to initially assume a clonal relationship between diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma. Epstein-Barr virus was detected by in situ hybridization and polymerase chain reaction in the mucosa-associated lymphoid tissue lymphoma, but not in diffuse large B-cell lymphoma, suggesting that these lymphomas were not clonally related. Fragment analysis of frame region 3 polymerase chain reaction products from microdissected mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma components revealed different clonal pattern rearrangements of the immunoglobulin heavy chain gene. CONCLUSIONS: Our patient's case highlights the importance of assessing the clonal relationships of the lymphoid components of a composite lymphoma and Epstein-Barr virus screening in mucosa-associated lymphoid tissue lymphoma in patients with autoimmune disease.

Simultaneous Presentation of Leukemic Non-Nodal Mantle Cell Lymphoma and Gamma-Delta T-Large Granular Lymphocytic Leukemia in a Patient with Rheumatoid Arthritis.

The peculiar features of T-cell large granular lymphocytic leukemia (T-LGLL) are its association with autoimmune disorders (particularly with rheumatoid arthritis (RA)) and a broad spectrum of B-cell lymphoproliferative disorders. However, association of T-LGLL with mantle cell lymphoma (MCL) is extremely rare. Here, we describe a case of an 80-year-old man admitted with suspected Felty's syndrome. The blood count showed white blood cells at 2.2×109/L, with 3% neutrophils, 88% lymphocytes, and at 0.66×109/L LGLs. The spleen had been removed 43 months prior to the admission due to suspected B-cell splenic lymphoma. Re-examination of the spleen revealed cyclin D1+ and SOX11- lymphocytes in the inner part of the unexpanded mantle zones of the white pulp follicles, thus displaying a so-called in situ histologic pattern of MCL, and in small clusters in the red pulp. The splenic cords were moderately expanded by lymphocytes expressing CD3, TIA1, and granzyme B but not CD4 and CD8. Monoclonal rearrangements of the immunoglobulin heavy chain gene and the T-cell receptor (TCR) gamma and delta chain genes, polyclonal rearrangements of the TCR beta chain gene, mutation of the signal transducer and activator of transctiption 3  gene (c.1940A>T; p.N647I), and t(11;14)(q13;q32) translocation were identified in the spleen sample. Flow cytometry of bone marrow revealed a population of TCR γδ+, CD3+, CD4-, CD5-, CD7+, CD8-, CD16-, CD56-, and CD57- lymphocytes. Fragment analysis demonstrated identical TCR gene clonal rearrangement patterns in the spleen and bone marrow samples. In this study, we describe the first case of simultaneous presentation of γδ T-LGLL and leukemic non-nodal MCL (L-NN-MCL) in a patient with RA and present morphological findings of L-NN-MCL in the spleen.

High Incidence of Clonal CD8+ T-cell Proliferation in Non-malignant Conditions May Reduce the Significance of T-cell Clonality Assay for Differential Diagnosis in Oncohematology.

Polymerase chain reaction (PCR) analysis of rearranged T-cell receptor (TCR) genes is a valuable diagnostic tool for differential diagnosis of T-cell large granular lymphocytic (T-LGL) leukemia and reactive lymphocytosis. Age-related narrowing of T-cells repertoire and expansion of immune or autoimmune clones may lead to false-positive results. The objective of this study was to evaluate the specificity and positive predictive value of PCR-based clonality assessment for a differential diagnostics of T-LGL leukemia. Rearrangements of TCRG and TCRB genes using the BIOMED-2 protocol were assessed in healthy individuals including the elderly (n = 62) and patients with rheumatic diseases (n = 14), transitory reactive CD8+ lymphocytosis (n = 17), and T-LGL leukemia (n = 42). Monoclonal TCRG/TCRB rearrangements in blood were identified in 11.3%/4.8% (7/3 of 62) of healthy individuals; 21.4%/14.3% (3/2 of 14) of patients with rheumatic diseases, and 17.6%/11.8% (3/2 of 17) of patients with reactive lymphocytosis. Immunomagnetic selection of lymphocytes in healthy individuals (31 of 33) revealed that clonal T-cells belong to CD8+ and CD57+ population. No clonal Vß-Jß TCRB rearrangements were found in the control group, only Dß-Jß TCRB and TCRG. Given the high detectability (96.7%) of Vß-Jß TCRB monoclonal rearrangements in patients with αß-T-LGL leukemia, this marker had the greatest specificity and positive predictive value (100%; 99.2%). The presence of clonal CD8+CD57+ cells in blood is common for healthy individuals and patients with reactive conditions and may not associate with any malignancy. Different specificity of TCRG/ Dß-Jß TRB/ Vß-Jß TCRB PCR reactions should be taken into account for T-cell clonality data interpretation.

Increasing the Interval of Canakinumab Administration Effectively Supports the Remission of Schnitzler's Syndrome.

Schnitzler's syndrome (SchS) is a rare, disabling, autoinflammatory disorder characterized by recurrent urticarial rash and monoclonal IgM gammopathy. Interleukin-1 beta (IL-1ß) plays an important role in the pathophysiology of SchS. Only anecdotal reports demonstrate the efficiency and safety of human monoclonal anti-human IL-1ß antibody (canakinumab) use in SchS therapy. However, there are no generally accepted recommendations concerning the scheme (or frequency) of canakinumab use for this disease. Here, we report the effective long-term treatment of SchS in a 44-year-old male with a standard canakinumab dose (150 mg) but with an increased 4-month injection interval.

Simultaneous Occurrence of Rosai-Dorfman Disease and Nodal Marginal Zone Lymphoma in a Patient with Sjögren's Syndrome.

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.

Peripheral T-Cell Lymphoma of the Submandibular Salivary Gland as an Unusual Manifestation of Richter's Syndrome: A Case Report and Literature Review.

Richter's syndrome is the development of high-grade non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). In most patients with Richter's syndrome, the high-grade NHL is diffuse large B-cell lymphoma. Only a small minority of CLL/SLL patients develop T-cell malignancies. Herein, we describe a 40-year-old male patient presenting with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) in the submandibular salivary gland, two years after the diagnosis of CLL/SLL. The PTCL-NOS consisted of small lymphocytes, which complicated diagnosis. Immunohistochemical, cytological, and molecular studies allowed the correct diagnosis of composite lymphoma (SLL/PTCL-NOS) of the submandibular salivary gland. The PTCL-NOS had a cytotoxic phenotype and aberrant expression of CD79a. There was no evidence to suggest that the PTCL-NOS of the submandibular salivary gland developed from an intimately associated submandibular lymph node or by PTCL-NOS dissemination. A review of the literature and presented case suppose that the PTCLs developed following CLL/SLL have the cytotoxic phenotype and can clinically mimic typical Richter's syndrome.

Unusual course of generalized lymph node primary plasmacytoma in a patient with Sjögren's syndrome: a case report.

BACKGROUND: Primary lymph node plasmacytoma is a rare disease that typically involves lymph nodes of the neck. In only 15% of cases is the disease generalized. Here, we present a case of generalized lymph node plasmacytoma in a patient with Sjögren's syndrome with an unusual course. CASE PRESENTATION: A 48-year-old white woman presented to our hospital with enlargement of groups of lymph nodes, liver, and spleen. Her medical history was consistent with a 12-year course of Sjögren's syndrome. Blood and urine immunochemistry showed a massive (72 g/l) M-gradient formed from immunoglobulin Aκ in the serum and monoclonal free κ-type light chains in her urine. A skeletal X-ray revealed no bone destruction. Cytological and histological bone marrow assays showed no signs of plasma cell infiltration. The microarchitecture of her neck and inguinal lymph nodes was destroyed. Only small remnants of B cell follicles were found, while the interfollicular areas were expanded and infiltrated by CD138, MuM1, CD43, and IgAκ-positive plasma cells. After nine cycles of doxorubicin, cyclophosphamide, vincristine, and prednisolone chemotherapy, complete remission was achieved. However, the lymphoma relapsed 3 months later, with histological verification in her femoral lymph node. Despite the absence of subsequent adequate therapy, she gradually achieved complete remission of plasmacytoma with the disappearance of paraproteins. CONCLUSIONS: Currently, primary lymph node plasmacytoma is generally considered a nodal marginal zone lymphoma with an extensive plasmacytic differentiation. In our case, despite the critical histological and immunohistochemical evaluation of three lymph node biopsies from different anatomical areas at different times, no signs of nodal marginal zone lymphoma were found. An 18-year follow-up of our patient with primary lymph node plasmacytoma demonstrated an extremely unusual clinical course. Initially, primary lymph node plasmacytoma was refractory to chemotherapy. However, subsequently, she underwent a complete spontaneous remission of plasmacytoma.

Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome.

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.

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography evaluation of subcutaneous panniculitis-like T cell lymphoma and treatment response.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a very rare variant of non-Hodgkin's lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response. Here, we describe our use of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for staging and monitoring of treatment response in 3 cases of SPTCL. Primary staging by PET/CT showed that all 3 patients had multiple foci in the subcutaneous fat tissue, with SUVmax from 10.5 to 14.6. Involvement of intra-abdominal fat with high SUVmax was identified in 2 of the patients. Use of the triple drug regimen of gemcitabine, cisplatin and methylprednisolone (commonly known as "GEM-P") as first-line therapy or second-line therapy facilitated complete metabolic response for all 3 cases. FDG PET/CT provides valuable information for staging and monitoring of treatment response and can reveal occult involvement of the intra-abdominal visceral fat. High FDG uptake on pre-treatment PET can identify patients with aggressive disease and help in selection of first-line therapy.