Disseminated tumor cells (DTCs) are studied as a prognostic factor in many non-hematopoietic tumors. Melanoma is one of the most aggressive tumors. Forty percent of melanoma patients develop distant metastases at five or more years after curative surgery, and frequent manifestations of melanoma without an identified primary lesion may reflect the tendency of melanoma cells to spread from indolent sites such as bone marrow (BM). The purpose of this work was to evaluate the possibility of detecting melanoma DTCs in BM based on the expression of a cytoplasmatic premelanocytic glycoprotein HMB-45 using flow cytometry, to estimate the influence of DTCs’ persistence in BM on hematopoiesis, to identify the frequency of BM involvement in patients with melanoma, and to analyze DTC subset composition in melanoma. DTCs are found in 57.4% of skin melanoma cases and in as many as 28.6% of stage I cases, which confirms the aggressive course even of localized disease. Significant differences in the groups with the presence of disseminated tumor cells (DTCs+) and the lack thereof (DTC−) are noted for blast cells, the total content of granulocyte cells, and oxyphilic normoblasts of erythroid raw cells.
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.
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.
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 2.2×10 9 /L, with 3% neutrophils, 88% lymphocytes, and at 0.66×10 9 /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.
Цель исследования-установить основные типы лимфом, дебютирующие с поражения больших слюнных желез (БСЖ), с которыми приходится сталкиваться в ревматологической практике и оценить эффективность малоинвазивных инцизионных биопсий БСЖ/слезных желез в диагностике различных заболеваний, протекающих с поражением околоушных, поднижнечелюстных, подъязычных и слезных желез.
Background. The population of non-tumor plasma cells in healthy subjects’ bone marrow is known to be fairly heterogeneous. Among them, there may be a small number of CD19-, CD56+, CD45- plasma cells which differ from the main bulk of the normal plasmacytic cells by the lack of CD19 and CD45 expression and the presence of CD56 expression. It is the fact which makes the monitoring of minimal residual disease (MRD) especially challenging in multiple myeloma (MM) since normal and aberrant plasma cells should be compared. For this reason, a study of such complementary diagnostic markers as CD27, CD28, CD117, and CD81 is extremely important. Aim. To analyze the role of complementary diagnostic markers (CD27, CD28, CD117, and CD81) of MRD in MM patients at different disease stages. Materials & Methods. The present study enrolled 62 MM patients aged 31-76 years (median 58 years); 25 women and 37 men. The analysis focused on morphological and immunophenotypic properties of bone marrow plasma cells. MRD was detected by 8-color flow cytometry with the use of FACSCanto II Flow Cytometer (USA) based on EuroFlow standards. Results. At the stage of primary diagnosis of MM, the imunophenotype of plasma cells was analyzed in all 62 patients using two 8-color panels recommended by the EuroFlow Consortium (2012). In accordance with primary immunophenotyping data, MRD was evaluated on the basis of not only the main diagnostic markers of plasma cells (CD38, CD138, CD45, CD56, and CD19), but also the complementary ones, such as CD27, CD28, CD117, and CD81. The study was basically conducted after induction therapy and upon remission. With cut-off > 0.01 % of aberrant plasma cells, the MRD incidence was the following: 91.0 % with CD27, 90.6 % with CD28, 87.0 % with CD117, and 96.7 % with CD81 markers. Respectively, no MRD was detected in 9.0 % with CD27, 9.4 % with CD28, 13.0 % with CD117, and 3.3 % with CD81 markers.
EPOCH (infusional dose-adjusted etoposide, doxorubicin and cyclophosphamide with vincristine, prednisone and rituximab).Patients were classified into 3 risk groups (according to presence of pleural/pericardial effusion and IPI high/intermediate-risk or high-risk).Residual disease (RD) was evaluated by FDG-PET and defined as score 2 according to Deauville Criteria and partial response (PR) defined as score 4-5 with a reduction >50% in size of mass.Results: Median age at diagnosis was 29 (21-43) years, age <40 years in 86.7% (n = 13).Eleven patients (78.6%, n = 14) had a bulky disease (tumor mass-10 cm), and 6 (42.9%, n = 14) had superior vena cava syndrome at presentation. Presence of pleural/pericardial effusion in 7 patients (53.8%, n = 13) and pulmonary involvement in 5 (38.5%, n = 13).According to the prognostic score, two patients (15.4%) were classified as high risk (2 adverse factors), five (38.5%) in intermediate risk (1 factor) and six (42.2%) in low risk (0 factors).
Миеломная болезнь -онкологическое заболевание, при котором происходит бесконтрольное формирование плазматических клеток в костном мозге, ведущее к деструкции костной ткани и сопровождающееся анемией и почечной недостаточностью. На долю заболевания приходится 1-2 % в структуре заболеваемости злокачественными новообразованиями. Специфическая противоопухолевая терапия в совокупности с пересадкой костного мозга позволяет получить хорошие отдаленные результаты. Стоит отметить, что на фоне проводимой терапии нередко встречаются различные осложнения и обострение сопутствующей патологии, которая в любой момент может приобрести характер конкурирующего заболевания. Представлено клиническое наблюдение по лечению пациента с миеломной болезнью на фоне дивертикулярной болезни ободочной кишки, осложненной острым дивертикулитом с формированием параколического инфильтрата.
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