Malignant Lymphoproliferative Diseases Research Articles

Monitoring of Red Cell Donor Chimerism in Oncohematological Patients After Allogeneic Hematopoietic Stem Cell Transplantation

Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a definitive therapy for patients with different oncological and hematological diseases. The study of red cell chimerism is a crucial process for diagnosing transplant engraftment and functioning during the post-transplantation period.
 Aim. To assess the effect of immunohematological (АВО and HLA donor–recipient matching) and medical (conditioning regimens) parameters on the onset time of post-transplantation donor chimerism which is determined by RBC antigens.
 Materials & Methods. The study enrolled 54 patients at the Kirov Research Institute of Hematology and Transfusiology in Russia (25 female and 29 male patients) aged 3–60 years (median 32 years). All of them received allo-HSCT in 2013–2021. Acute leukemias were identified in 39 patients, 8 patients were reported to have malignant lymphoproliferative diseases, 3 patients had myeloproliferative neoplasms, and 4 patients were diagnosed with aplastic anemia. RBC antigens of donors and recipients were analyzed by gel hemagglutination using Bio-Rad (USA) reagents and equipment.
 Results. The onset time of donor chimerism depends neither on the degree of HLA donor–recipient matching, nor on conditioning regimen. Donor chimerism in recipients with major ABO-incompatibility occurs significantly later than in patients with minor АВО-incompatibility and ABO-identity.
 Conclusion. Monitoring of post-transplantation donor chimerism is an important diagnostic and prognostic tool to assess donor hematopoietic cell engraftment, hematologic recovery, graft rejection, and relapse of the disease. After allo-HSCT, first donor red cells occur in pairs with major АВО-incompatibility later than in pairs with minor АВО-incompatibility or ABO antigen compatibility. Other immunohematological and medical parameters do not affect the development rate of donor chimerism determined by RBC antigens.

Annular skin tumors and lymphoproliferative diseases

Determining the shape of a skin lesion may provide a diagnostic clue in dermatology practice, more commonly for inflammatory diseases but also for skin tumors. The annular formation may develop by diverse mechanisms in skin tumors. Annular lesions may occur from the onset of the tumor as sparing the central area or depression and/or ulceration in the center of the tumor or outward expansion of the primary lesion. Clustering of multiple papulonodular lesions sparing the central area or relatively independent processes acting on the central and peripheral components of the tumor may also result in an annular appearance. We have explored a wide variety of benign and malignant skin tumors and lymphoproliferative diseases forming an annular shape.

Endocrine disorders after combined chemoradiotherapy in Hodgkin Lymphoma survivors

Hodgkin's lymphoma (HL) is one of the most common malignant lymphoproliferative diseases. Chemotherapy and radiotherapy used in the treatment of LH induce a number of toxic effects leading to dysfunction of endocrine system. Hormonal disorders in HL and their relationships with the therapy used remain to be clarified. To assess disorders of the endocrine function of thyroid, parathyroid glands and gonads in HL survivors. Screening of endocrine dysfunction of the thyroid, parathyroid glands and gonads was performed in 160 adult patients with HL, 55 men and 105 women, at remission stage induced by chemotherapy or chemoradiotherapy. Forty healthy subjects, matched by age, were acted as control. The levels of TSH, T3, free T4, PTH, FSH, LH, free testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex-hormone binding globulin (SHBG) were measured in blood serum by ELISA. Bone mineral density (BMD) was assessed by DEXA. Hypothyroidism (25%), hyperparathyroidism (15.6%) and hypogonadism (29% of men and 25.3% of women) were the most prevalent endocrine disorders in LH survivors. Hypothyroidism was significantly more common in patients after chemoradiotherapy than in those who received only chemotherapy (χ2=9.4, р=0.002). In patients with hyperparathyroidism, there were negative correlations between PTH levels and BMD in the lumbar spine (r=-0.74, p=0.00002) and in the femoral neck (r=-0.66, p=0.0003). Men with HL demonstrated lower free testosterone concentrations when compared to control (p=0.04); LH and FSH levels were elevated (p=0.0004 and p=0.04, respectively). In men with HL the levels of DHEA-S were reduced (p=0.0009). The increased SHBG concentrations were revealed in 13 (23.6%) men. Women of reproductive age with HL had higher levels of LH in the luteal phase (p=0.05) and FSH in the follicular phase (p=0.02) than controls. The data indicate a high prevalence of the dysfunctions of thyroid, parathyroid glands, and gonads in HL survivors. Screening for endocrine disorders in these patients is highly recommended.

ANNULAR SKIN TUMORS AND LYMPHOPROLIFERATIVE DISEASES.

Determining the shape of the skin lesion may provide a diagnostic clue in dermatology practice, more commonly for inflammatory diseases but also for skin tumors. The annular formation may develop by diverse mechanisms in skin tumors. Annular lesions may occur from the onset of the tumor as sparing the central area or depression and/or ulceration in the center of the tumor or outward expansion of the primary lesion. Clustering of multiple papulonodular lesions sparing the central area, or relatively independent processes acting on the central and peripheral components of the tumor may also result in an annular appearance. We have explored a wide variety of benign or malignant skin tumors and lymphoproliferative diseases forming an annular shape.

Hodgkin lymphoma in patient with primary immunodeficiency: clinical features and treatment approaches

Primary immunodeficiencies (PID) are genetically determined irreversible disorders of structure and/or functions of the immune system's cellular and humoral components, accompanied by frequent infectious diseases and contributing to the development of malignant neoplasms. Lymphomas are the most frequent oncological disease in PID patients: non-Hodgkin's lymphomas occur in 60 % of malignant neoplasms cases, Hodgkin lymphoma - in 20 %, leukemias - in 10 %, solid tumors - in 10 %. The risk of malignant lymphoproliferative diseases in PID patients amounts to 4-25 %, with the overall incidence of cancer 100-200 times higher than in immunocompetent population. Results of malignant neoplasms treatment in children with PID remain unsatisfactory due to the high rate of relapsed, refractory disease and anticancer therapy complications.This paper presents a clinical case of Hodgkin lymphoma with atypical localization in a female PID patient. peculiarities of this case are eye socket soft tissue involvement, slow response to therapy, and a high rate of infectious complications.

Prognostic Value of the Degree of Tumor Tissue Infiltration by CD15-Positive Granulocytes in Nodular Sclerosis Classical Hodgkin’s Lymphoma

Nodular sclerosis classical Hodgkin’s lymphoma (NSCHL) is one of the most common malignant lymphoproliferative diseases among younger people. The tumor is considered to be potentially curable. However, despite successful application of standard treatment methods, primary resistance and relapses occur. At present, many researchers focus on studying the value of tumor microenvironment in the prognosis of the course and progression of classical Hodgkin’s lymphoma (cHL), aiming at identifying new therapeutic targets. The present paper shows that the relative count of CD15-positive granulocytes in patients with favorable course of the disease is significantly lower than in therapy-refractory patients. The threshold of tumor microenvironment cells expressing CD15 was 8 %. The data obtained provide the basis for determining prognostic value of CD15-positive granulocytes in NSCHL and presenting this cell pool as a potential therapeutic target.

P0498CLINICAL PRESENTATION AND RENAL HISTOPATHOLOGICAL FINDINGS IN PATIENTS WITH MONOCLONAL GAMMOPATHY

Abstract Background and Aims Monoclonal gammopathy is associated with renal lesions due to the toxic effect of M-protein. The aim of our study was to evaluate the prevalence and the clinical presentation of monoclonal gammopathy in patients who underwent kidney biopsy for renal impairment. Method We conducted a retrospective study at the Nephrology and Dialysis Unit of the University Hospital of Modena from 2005 to 2017. The diagnosis of renal disease was proved histologically. Results Monoclonal gammopathy was found in 179 out of 1334 patients (13.4%). Mean age was 66.1±13.4 years with a predominance of males (63.7%). There was no differences (P=0.16) between the age of patients with benign (64.9±14.3) and malignant lymphoproliferative diseases (67.6±12). The hematologic disorders involved in the production of M-protein were MGUS (51.9%), myeloma multiple (MM) (25.7%), amyloidosis (8.9%) smoldering MM (5 %), non-Hodgkin lymphoma (NHL) (6.7%) and HL (1.7%). The prevalence of MGUS was estimated to be 6.97% (93/1334). Mean serum creatinine was 2.68±2.12 mg/dl (eGFR of 35.24±29.32 ml/min) and urine protein/creatinine ratio of 5.1±6.5. None of the study subjects progressed to MM or other lymphoproliferative diseases. The most common kidney disease was membranoproliferative (GN) (19.3%). MGRS has been identified in five patients (5.4%). Mean age of MM was 66.84±13 years. Serum concentration M-protein was 1.47±0.98. Among patients with AKI (89.1%), 13 patients (28.2%) required urgent hemodialysis. Histological evaluation showed cast nephropathy (71.7%), MM-associated AL amyloidosis (15.2%), MM-associated-light chain deposition disease (4.3%) and interstitial nephritis (8.7%). Nine patients had a diagnosis of smoldering MM. Average age was 69.17±10.8 years old. At presentation, creatinine was 2.31±2.6 mg/dl (GFR of 41.35 ml/min). Evaluation of renal biopsies allowed us to identify different patterns of glomerular diseases, expression of an aspecific renal involvement of this hematological disease. AL amyloidosis was secondary to MGUS (75%) and smoldering MM (33%). Mean age was 66.04±11.7 years old. At presentation mean urine protein/creatinine ratio was 8.33±3.2 concomitant to a serum albumin level of 2.74±0.84 gr/dl. Mean creatinine was 1.4 mg/dl corresponding to eGFR= 56.5 ml/min. Average age of NHL patients was 72.6±9.6 years. Renal function was extremely variable at presentation; mean creatinine was 2.4±1.6 mg/dl (eGFR of 30.4±22.7 ml/min). Histological evaluation of biopsy specimen revealed amyloidosis (25%), cryoglobulinemic GN (25%), LCDD (16.6%), cast-nephropathy (8.3%), LCDD (8.3%) and other renal diseases (16.8%). Three patients (1.12%) had a diagnosis of HL at mean age of 69.04±5.3 years. At presentation, renal function was normal in all patients with a creatinine of 0.93±0.07mg/dl (eGFR of 62.7.3±7.4 ml/min). Urine protein/creatinine ratio was 0.3±0.2. Kidney biopsy revealed cryoglobulinemic GN (75%) and hypertensive nephrosclerosis (25%). ANOVA analysis did not found statistically significant differences in age (p=0.11) and serum concentration of M-protein (P=0.42) between groups. The differences in mean serum creatinine and mean urine protein/creatinine ratio were statistically significant between groups, (P<0.0001) and (P=0.003), respectively. A post hoc Tukey test showed that proteinuria was higher in AL amyloidosis compared to MM and HL, whereas renal function was worse in MM patients compared to the others. Conclusion MGUS was the most common monoclonal gammopathy. Surprisingly, it is frequently associated with membranoproliferative glomerulonephritis. MGRS is a rare histopathological entity (5.4%). MM manifests frequently with AKI whereas AL amyloidosis with nephrotic syndrome. Renal function was extremely variable in NHL patients; on the other hand, the limited number of HL patients with renal involvement in our cohort does not allow generalization of our findings.

Bendamustine–rituximab (BR) combined therapy for treatment of immuno-mediated neuropathies associated with hematologic malignancy

In chronic polyneuropathies associated with hematologic malignancy (HM) the optimal treatment management is primarily focused on the HM, but the parallel response of the neuropathy is still unclear. Rituximab is a recognized therapeutic choice in anti-MAG antibody polyneuropathy, that might be useful also in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with HM. The efficacy of immunochemotherapy, which is the standard approach to malignant lymphoproliferative diseases, has been poorly investigated in polyneuropathies.We describe a six-months combined bendamustine-rituximab (BR) treatment in nine patients affected by CIDP or paraproteinemic IgM neuropathies with antibodies to peripheral nerve antigens in course of malignant HM.All patients had a long-lasting response with an average relapse free-survival (RFS) time of 31.5 months. Clinical improvement was evident at 6 months from the beginning of therapy, even earlier in 6/9 patients (<2 months). Two patients dramatically improved the disabling attitudinal and intentional tremor and pathogenic autoantibodies significantly declined in 4/5 patients.Neurological relapses occurred in three patients after a mean of 38 months of sustained stability, even if HM remitted. In such cases rituximab was administered but was associated with a shorter RFS time (1 year) compared to the previous BR scheme (3 years).In our case series, the combined BR regimen was a valid option in immune-mediated neuropathies associated with HM. Moreover, in some patients BR scheme allowed an earlier response and a long-lasting improvement than rituximab alone.

Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma.

Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a group of heterogeneous malignant lymphoproliferative diseases ranging from indolent to highly aggressive forms. Although the survival after chemo-immunotherapy treatment of mature B-NHL has increased over the last years, many patients relapse or remain refractory due to drug resistance, presenting an unfavorable prognosis. Hence, there is an urgent need to identify new prognostic markers and therapeutic targets. Podocalyxin (PODXL), a sialomucin overexpressed in a variety of tumor cell types and associated with their aggressiveness, has been implicated in multiple aspects of cancer progression, although its participation in hematological malignancies remains unexplored. New evidence points to a role for PODXL in mature B-NHL cell proliferation, survival, migration, drug resistance, and metabolic reprogramming, as well as enhanced levels of PODXL in mature B-NHL. Here, we review the current knowledge on the contribution of PODXL to tumorigenesis, highlighting and discussing its role in mature B-NHL progression.

Treatment of patients with malignant lymphoproliferative diseases in the Russian Federation: analysis of the data from 75 regions

The aimis to analyze the medical records of patients with malignant lymphoproliferative diseases (LPD) in the Russian Federation in 2016- 2017.Materials and methods. Treating physicians in 75 regions of the Russian Federation were asked to fill the survey questionnaire containing 9 types of malignant LPDs (according to the ICD-10 classification). The questions covered the epidemiology of LPD (prevalence, resistant forms, relapses and mortality), the existence of specialized institutions and beds, the costs of medical care in patients with malignant LPD, and the financial support of pharmacotherapy in these patients during their hospital stay.Results. We found that the most common malignant LPD in 2016-2017 was Hodgkin’s lymphoma (73.5 and 73.4%, respectively). The prevalence of resistant forms and recurrences of malignant LPD over this period accounted for 6.8% of the total patient population. In 2017, the number of patients who died was 7.5% less than that in 2016. There are 815 and 1,763 specialized institutions of the oncology and hematology profiles that provide medical care to children and adult patients, respectively. Among the malignant LPDs, the highest costs of drug therapy in 2016 pertained to lymphosarcoma, and in 2017 – to Hodgkin’s lymphoma. In the system of compulsory health insurance (OMC), the largest spending for both adult and pediatric patients in 2016 and 2017 was accounted for Hodgkin’s lymphoma; a similar result was obtained for the cost of therapy based on high-tech medical care.Conclusion. In 2017, the total number of patients with malignant LPD in the Russian Federation increased by 2.65% as compared to 2016, while the proportion of primary LPD decreased by 1.2%. In 2017, the total costs of drug supply in patients with malignant LPD in the RF increased by 55.35% as compared with 2016.

Modern concepts of the mycosis fungoides pathogenesis

Mycosis fungoides – the most common form of cutaneous T-cell lymphoma. The pathogenesis of this disease is complex and remains unclear. The article contains a review of the literature devoted to the main mechanisms of T-lymphocytes malignant proliferation, known to date. Data on dysregulation of immune, genetic and epigenetic mechanisms, as well as the role of microenvironment cells in the proliferation of T lymphocytes, are given. Immunophenotypic characteristics and cellular composition of the infiltrate in patients with mycosis fungoides, are described depending on the stage of the disease. Prospective directions in studying molecular-biological predictors of malignant lymphoproliferative diseases development are highlighted.

INFECTIVE ENDOCARDITIS AND MALIGNANT NEOPLASMS: FACTS AND HYPOTHESES

The problem of the association of infective endocarditis (IE) and oncological diseases has been discussed for more than 60 years, and is now becoming increasingly relevant because of observed increasing of number IE in elderly patients. The review of the literature presents both data on the incidence of oncological diseases diagnosed with IE and in the long-term follow-up of patients after IE, as well as current estimates of IE incidence in cancer patients, obtained in large population-based studies. The highest risk of IE development was found in patients with tumors of the colon and rectum, and the predominant etiological role of Streptococcus bovis/gallolyticus was proved in such cases. The frequency of concomitant oncological diseases is higher in elderly patients with IE. On the other hand, it is obvious that IE can be considered as a marker of latent oncological pathology, especially gastrointestinal tumors, malignant blood diseases and lymphoproliferative diseases that are most often detected during the period of active IE and in the first 1–2 years later. Therefore, mandatory colonoscopy is recommended for patients with IE caused by Streptococcus bovis/gallolyticus during the period of IE and annually in subsequent years, even if initially the colonoscopy did not reveal pathology. In elderly IE patients we should also be aware of the high likelihood of concomitant oncological pathology and carry out appropriate oncological search. Antimicrobial prophylaxis of IE in patients with gastrointestinal cancer remains unresolved.

Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis

Background and aimsExtrahepatic manifestations of HCV are responsible for morbidity and mortality in many chronically infected patients. New, interferon-free antiviral treatment regimens, which present the opportunity to treat all HCV-infected...

Dacryocystitis provoked by recurrence of extramedullary plasmacytoma of the orbit: a case report

Extramedullary plasmacytoma (EMP) of the orbit is an extremely rare tumor, which frequently manifests with nonspecific symptoms. In the case reported, the symptoms of relapsing dacryocystitis appeared before the diagnosis of orbital EMP in a 60-year-old man. Moreover, EMP of the right submandibular gland that had been excised and treated by radiotherapy preceded the orbital lesion by seven years. The present report emphasizes the importance of an extensive medical workup to rule out multiple myeloma or other malignant lymphoproliferative diseases, because their treatment and prognosis are very different. Additionally, it is necessary to consider all tumors that can provoke relapsing dacryocystits.

Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT

Aim. To establish correlation between CD34+ autologous hematopoietic stem cell (HSC) count and colony-forming units (CFU) in the same peripheral blood apheresis product samples before and after cryopreservation in multiple myeloma and lymphoma patients, and to assess clinical value of these parameters. Materials &amp; Methods. Cell samples of peripheral blood cyta-pheresis product and cell cultures were studied before and after cryopreservation in 32 multiple myeloma and 25 lymphoma patients who underwent autologous HSC transplantation. The material was analyzed using culture technique and flow cytometry. Results. The paper provides information on the relationship between CD34+ HSC count obtained by flow cytometry, and CFU in cell culture obtained by cytapheresis of the same peripheral blood samples. A direct correlation was confirmed between CD34+ count and all the CFUs before and after cryopreservation in lymphoma patients. Correlation between CD34+ count and granulocyte-macrophage CFUs was revealed in multiple myeloma and lymphoma patients before cryopreservation. Conclusion. The parameter of colony-forming capacity used for the assessment of the functional HSC was shown to be equally reliable criterion for condition evaluation of autotransplant proliferative pool than CD34+ cells. Both methods should be applied for qualitative and quantitative evaluation of an autotransplant for multiple myeloma and lymphoma patients.

Notch4 and mhc class II polymorphisms are associated with hcv-related benign and malignant lymphoproliferative diseases.

Mixed cryoglobulinemia (MC), is a HCV-related, clinically benign, lymphoproliferative disorder (LPD) that may evolve into a non Hodgkin's lymphoma (NHL). Significant associations were found between two single nucleotide polymorphisms near NOTCH4 (rs2071286) and the HLA class II (rs9461776) genes and HCV-related MC syndrome (MCS). We analyzed NOTCH4 rs2071286 and HLA-II rs9461776 in 3 HCV-related LPD groups (asymptomatic MC, MCS, NHL) with HCV infection without lymphoproliferative disorders.We found a positive relationship between NOTCH4 rs207186 T minor allele frequency (MAF) and patients with HCV-related LPDs at risk of NHL (Chi-square test for trend = 14.84 p = 0.0001), in accordance with an over-dominant model in the NHL group (CT vs CC + TT, OR=1.88, 95% CI 1.24–2.83, p = 0.0026).Regarding HLA II rs9461776, G MAF increased in patients with HCV-related LPDs at risk of NHL (Chi-square test for trend = 8.40 p = 0.0038), in accordance with a recessive genotypic model in the NHL group (G/G vs A/A + A/G, OR = 11.07, 95% CI 2.37–51.64, p = 0.0022).Both NOTCH4 rs2071286 and HLA-II rs9461776 were present on chromosome 6 and showed D’ and r values of linkage disequilibrium (LD) of about 0.5 values, thereby suggesting there is no extensive LD in the HCV+ population.This data shows that the previously demonstrated association between NOTCH4 rs2071286 and HLA-II rs9461776 polymorphisms and HCV-related MCS could be extended to overall patients with HCV-related LPDs. The significant relationship between rs2071286 and rs9461776 MAF and the increased risk for NHL, suggests their use as non-invasive markers to categorize patients at risk of lymphoma.

Diagnostic and Prognostic Value of Biochemical Markers of Infectious Complications of High-Dose Therapy with Autologous Hematopoietic Stem Cell Transplantation in Malignant Lymphoproliferative Diseases

Aim. To evaluate diagnostic and prognostic value of C-reactive protein (CRP), procalcitonin (PCT) and presepsin (PSP) in patients with malignant lymphoproliferative disorders after a high-dose chemotherapy and auto-HSCT. Methods. 28 patients were included in the study (20 women and 8 men; 12 of them with Hodgkin’s lymphoma, 6 with non-Hodgkin’s lymphomas, and 10 with multiple myeloma). The median age was 40 years (23-66 years). The conditioning regimens were CBV, BEAM or melphalan 200 mg/m&lt;sup&gt;2&lt;/sup&gt;. PSP, PCT and CRP levels were evaluated on the day of admission (DA), D+1, D+3, D+7 and on the day of discharge (DD). Depending on the presence of infectious complications, the patients were divided into 2 groups: group 1 - patients without complications (n = 12), group 2 - patients with complications (n = 16). In group 2 there were 15 patients with febrile neutropenia (FN) and 1 with sepsis. Results. The median (range) of FN development was 5.5 days. Median CRP level on the DA and the DD in group 1 was 2.25 mg/l (0.6-20.4) and 14.85 mg/l (3.7-50), respectively (p = 0.001), while in group 2 it was 3.2 mg/l (0.2-53) and 19.7 mg/l (5.1-152.2), respectively (p = 0.025). However, CRP did not significantly differ between groups 1 and 2 at any point of analysis. The study also demonstrated a significant increase in the PCT levels in both groups after allo-HSCT. Median PCT level on the DA and the DD in group 1 was 0.023 ng/ ml (0.02-0.112) and 0.07 ng/mL (0.02-0.356), respectively (p = 0.04), and in group 2 - 0.039 ng/ml (0.02-0.158) and 0.106 ng/mL (0.045-3.67), respectively (p = 0.001). Comparison of PCT levels on study days demonstrated no significant difference between groups. On the DA the median PSP level in group 1 was 166.5 pg/ml (77.2-476), on the DD it was 199 pg/ml (90-298) (p = 0.78). Median PSP levels in group 2 on the DA (129 pg/ml, range 84.2-501) and also on the DD (288.5 pg/ml, range 83.4-1345) were significantly different (p = 0.03). In the comparative analysis of PSP in groups 1 and 2, there were no significant differences on the DA and on the D+1. Significant difference in PSP levels between the analyzed groups was on the D+3, D+7 and on the DA. Conclusion. The preliminary data showed that PSP is the most sensitive marker of infectious complications in patients with lymphoproliferative diseases after auto-HSCT.

Role of Superficial CD200 Marker in Differential Diagnosis of Malignant B-Cell Lymphoproliferative Diseases

Background &amp; Aims. Flow cytometry is successfully used for diagnosis of malignant lymphoproliferative disorders. However, there are atypical cases that are difficult to interpret; thus, new markers relevant for the differential diagnosis are to be searched for. The aim is to analyze CD200 expression in patients with B-cell lymphoproliferative disorders. Materials &amp; Methods. 187 patients with chronic lymphocytic leukemia (CLL), 14 patients with mantle cell lymphoma (MCL), 9 patients with marginal zone lymphoma (MZL), and 5 patients with hairy cell leukemia (HCL) were enrolled in the study. Neoplasm was not confirmed in 12 subjects. The patients underwent the following tests: CBC, immunophenotyping of peripheral blood or bone marrow lymphocytes, and a cytogenetic test. In some cases, an additional immunohistochemical test of bone marrow trepanobiopsy or lymph node biopsy samples was required. Results. In all cases of CLL and HCL, the CD200 expression was positive; mean fluorescence intensity was higher in these cases as compared to other groups. Negative expression of CD200 prevailed in MCL patients; however, at the same time 2 cases of intermediate and positive expression were reported, both showing moderate fluorescence intensity values. CD200 expression was heterogeneous in MZL patients. Conclusion. The CD200 negative expression excludes typical HCL and CLL. Additional cytogenetic and immunnohistoсhemical tests should be performed in such cases to verify the diagnosis, first of all, MCL or MZL.

Epigenetics in cutaneous T-cell lymphoma

Epigenetics means heritable changes in gene expressions without alterations in DNA sequence, and mainly involves DNA methylation, histone modification and non-coding RNA regulation. Cutaneous T-cell lymphoma is a class of malignant T-cell lymphoproliferative diseases originated from the skin. Mycosis fungoides and Sezary syndrome are the most common cutaneous T-cell lymphoma. Recent studies have shown that epigenetics not only plays an important role in the occurrence and development of cutaneous T-cell lymphoma, but also provides insights into the treatment of cutaneous T-cell lymphoma. Key words: Lymphoma, T-cell, cutaneous; Epigenesis, genetic; Mycosis fungoides; Sezary syndrome; DNA methylation

A difficult case of angioimmunoblastic T-cell lymphoma to diagnose.

Angioimmunoblastic T-cell lymphoma (AITL) is a malignancy of mature T-cells. It is characterized as a polymorphic lymphonodal lymphoid infiltrate accompanied by prominent proliferation of endothelial venules and follicular dendritic cells. AITL was first described in 1974 by Frizzera et al. as an angioimmunoblastic lymphadenopathy with dysproteinemia.1 A short time later, the name was changed to immunoblastic lymphadenopathy, and then to lymphogranulomatosis X in 1979.2 AITL comprises 15–20% of all peripheral T-cell lymphomas and 1–2% of all non-Hodgkin lymphomas (NHL). Most frequently, it occurs in aged patients, with equal prevalence between males and females. Typically, AITL displays an aggressive behavior, which makes the diagnosis difficult and it must be differentiated from other malignant lymphoproliferative diseases, drug reactions and viral infections. Patients with AITL frequently exhibit B-symptoms (e.g., fever and weight loss) and a generalized enlargement of the lymph nodes. Other