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Hodgkin’s lymphoma is a tumor characterized by predominant lesions in lymph nodes. Primary extranodal lesions are exceedingly rare. In the now available world literature, there are only single observations of classical Hodgkin’s lymphoma with ovary involvements. The present paper reports the diagnosis and treatment of a patient with classical Hodgkin’s lymphoma with ovary involvements confirmed by histological and immunohistochemical analyses.

The development of National clinical guidelines on diagnosis and treatment of Ph-negative myeloproliferative neoplasms comes in response to the need to standardize the approach to diagnosis and treatment. The availability of clinical guidelines can facilitate the choice of adequate treatment strategy, provides practicing physicians with exhaustive and up-to-date information on advantages and shortcomings of different treatment methods as well as lets health professionals better assess expected extents of treatment required by patients. In 2013 a working group was formed to develop and formulate clinical guidelines on the treatment of myeloproliferative neoplasms. These guidelines were first published in 2014, afterwards they were revised and republished. The dynamic development of current hematology presupposes constant updating of knowledge and implementation of new diagnosis and treatment methods in clinical practice. In this context clinical guidelines present a dynamic document to be continuously amended, expanded, and updated in accordance with scientific findings and new requirements of specialists who deal directly with this category of patients. The present edition is an upgraded version of clinical guidelines with updated information on the unification of constitutional symptoms assessment using MPN-SAF TSS questionnaire (MPN10), on applying prognostic scales in primary myelofibrosis, assessing therapy efficacy in myeloproliferative neoplasms, revising indications for prescription, on dose correction, and discontinuation of targeted drugs (ruxolitinib). The guidelines are intended for oncologists, hematologists, healthcare executives, and medical students.

The application of highly effective tumor treatment protocols in children and increasing number of patients healed resulted in a growing focus on long-term effects of chemotherapy. One of the most dangerous complications of a first malignant neoplasm (MN) is the development of second MNs. Cytostatic drugs of the epipodophyllotoxin group and alkylating agents contribute to secondary acute myeloid leukemias (AML), the rare and prognostically very unfavorable second MNs. The present article provides a review of literature on risks of secondary hematological MNs associated with the therapy of first tumors. It also contains a case report of successful treatment of AML which occurred after Burkitt’s lymphoma therapy.

Aim. Based on our own materials to characterize the clinical manifestations of hypereosinophilic states distinguishing between reactive eosinophilia (RE), clonal myeloproliferative neoplasms with eosinophilia (MPN-eo), and myeloproliferative variant of hypereosinophilic syndrome (MP-HES); to evaluate treatment results. Materials & Methods. The trial included 188 patients with primary HES (132 men and 56 women, aged 19-72 years) having been followed-up at the National Research Center for Hematology since 2001. The main entry criteria were blood eosinophilia > 1.5 x 109/L and clinical symptoms resulting sometimes from hypereosinophilia. All patients received complete physical examination, immunomorphological, standard cytogenetic, and molecular genetic testing. Treatment was provided to 73 patients (63 men and 10 women) including those with MPN-eo PDGFRA+ (п = 39), PDGFRB+ (п = 2), FGFR1+ (п = 1), chronic eosinophilic leukemia not otherwise specified (п = 8), systemic mastocytosis (п = 1), and MP-HES (п = 22). Complete hematological response (CHR) was the criterion for treatment efficacy. In the MPN-eo PDGFRA+ and PDGFRB+ groups molecular response (MR) rate was also estimated in cases of imatinib treatment. MR was considered as no expression of the FIP1L1-PDGFRA and ETV6-PDGFRB transcripts in RT-PCR. Results. The trial yielded the cause of eosinophilia in 117 (62.2 %) out of 188 patients. RE was diagnosed in 60 (32 %) out of 117 patients, various types of clonal MPNs were reported in 57 (30 %) patients. In 71 (38 %) out of 188 patients HES was still present at the first trial stages. Later within this group MP-HES was identified in 22 (30.9 %) out of 71 patients. Among imatinib recipients CHR was achieved in 37 (90 %) out of 41 patients within 1-3 months: in 36 patients with MPN-eo FIP1L1-PDGFRA+ and in 1 patient with MPN-eo ETV6-PDGFRB+. MR was achieved in 88 % of cases. In the absence of molecular markers characteristic of MPN-eo CHR was achieved in 26 % of cases. Among the recipients of treatments other than imatinib nobody achieved CHR. Conclusion. The diagnosis approach in patients with HES should be complex and individualized. Development and enhancement of molecular genetic diagnostic techniques are regarded as ones of the highest priority areas in modern hematology. The use of imatinib mesylate in MPN-eo therapy commonly results in long-term hematological and molecular remissions. On achieving CHR to imatinib treatment of patients without molecular markers characteristic of MPN-eo early use of this drug (or other tyrosine kinase inhibitors) can be recommended in acute forms of HES.

Aim. To compare NHL BFM-90 and CHOEP efficacy in adult patients with ALK-positive anaplastic large-cell lymphoma (ALK+ ALCL). Materials & Methods. Within the period from June 2014 to December 2019 the prospective randomized comparative study at the National Research Center for Hematology in Moscow included 23 ALK+ ALCL patients. In one study arm (n = 11) CHOEP was administered, whereas the other one (n = 12) received high-dose chemotherapy (CT) according to NHL BFM-90 protocol. The median age of patients in both arms was 33 and 40 years, respectively. Results. Overall survival (OS) and event-free survival (EFS) within 3 years were 91 % in the arm receiving CHOEP (this protocol was administered to all 11 patients), and 100 % in the arm receiving NHL BFM-90 (complete remission was achieved in all patients). Due to its toxicity NHL BFM-90 was fully implemented in 9 out of 12 patients. The 3-year OS and EFS in the CHOEP and NHL BFM-90 arms are comparable, and the difference between them is not significant. Conclusion. In ALK+ ALCL treatment high-dose CT according to NHL BFM-90 protocol has no advantage in terms of the 3-year OS and EFS compared to less toxic regimen CHOEP. A larger sample of patients is required to achieve significant results, which will further lead to a final judgement on feasibility of high-dose regimens in the treatment of adult patients with ALK+ ALCL.

Aim. To study the structure of Ph-negative myeloproliferative diseases (Ph- MPD) and to identify morphological markers for diagnosing masked polycythemia vera (PV). Materials & Methods. Bone marrow core biopsy samples from the database of pathology department of National Research Center for Hematology within the period from January 2014 to June 2017 provided the basis for analyzing the diagnosed Ph- MPD cases. The trial included the bone marrow core biopsy samples of the patients treated and fol-lowed-up not only at the National Research Center for Hematology but also at other medical centers in the Russian Federation in the context of clinical, laboratory and molecular data. Results. In 1611 Ph- MPD patients PV prevailed corresponding to 40.6 % of all cases. In the PV group the masked form was diagnosed in 29 % of patients. Primary myelofibrosis (PMF) was diagnosed in 26.6 % of all patients including 10 % of cases with pre-fibrosis/early stage. The 3d most frequent disorder was essential thrombocythemia (ET) which corresponded to 16 %. JAK2 driver mutation was identified in all 654 PV patients. In 4 cases out of them exon 12 mutation was detected. A similar mutation was found out in PMF (53 %) and ET (60 %). In 36 % of PMF patients and 27 % of ET patients CALR mutation was detected. MPL mutation was identified in 4 % of PMF cases and was not discovered in ET. Triple negative patients were identified in 7 % of PMF and 13 % of ET cases. The designation of “myeloproliferative disease unclassifiable” can be applied to 16.8 % of cases. The trial deals with morphological criteria for diagnosing masked PV during examination of bone marrow core biopsy samples. In 30 % of patients with masked PV (according to the 2017 WHO classification) and splenomegaly (> 14 cm) portal vein thrombosis was identified. Conclusion. In the Ph- MPD group PV diagnosis prevailed (40.6 %). The histological analysis of bone marrow core biopsy samples of the patients with the masked PV accounting for 29 % of all PV cases, revealed morphological features typical of overt PV. Histological analysis of bone marrow is a reliable method for diagnosing overt and masked PV. Among morphological characteristics of the bone marrow of patients with masked PV and portal vein thrombosis special attention should be paid to the MF-1 grade of reticulin fibrosis (29 % of cases) and loose clusters of megakaryocytes (71.4 %).

Aim. To study immunohistochemical parameters of tumor plasma cells in bone marrow and to assess how the expression of adhesion molecule CD56 impacts overall survival (OS) of multiple myeloma (MM) patients. Materials & Methods. The trial included 35 patients (19 men and 16 women) aged 23 to 73 years (with median age of 58 years) with newly diagnosed MM. At disease onset plasmacytoma was diagnosed in 21 patients. In all patients bone marrow core biopsy was performed followed by histologic and immunohistochemical (IHC) examinations. IHC examination was based on the panel of CD56, CD166, CXCR4, Ki-67, and c-MYC/CD138 antibodies. Kaplan-Meier survival curves and significance assessment by means of Cox's F-Test were used. Results. Expression mean values of most of studied markers (CD56, CXCR4, c-MYC, and Ki-67) in bone marrow of patients without plasmacytoma (n = 14) appeared to be higher than in patients with plasmacytoma at MM onset. Expression mean value is understood as percentage ratio of plasma cells expressing a studied marker to total cell count of tumor substrate. High expression of chemo-kine receptors (CXCR4), and adhesion molecules (CD56) probably inhibits plasma cell migration and impedes ex-tramedullary tumor progression. Comparison of protein expression by tumor plasma cells in bone marrow in the groups with bone extramedullary plasmacytoma shows a distinct regularity referring to CD56 adhesion molecule. For example, CD56 expression is significantly (р < 0.05) lower in terms of the count of tumor plasma cells with marker expression in bone marrow of MM patients with extramedullary plasmacytoma compared with patients with bone plasmacytoma (1 ± 1 % vs. 65.71 ± 12.12 %). Comparison of MM patients' OS depending on CD56 expression by tumor plasma cells in bone marrow showed that 4-year OS of patients with CD56 expression in bone marrow was significantly higher being 80 % vs. 38 % in the group with CD56 expression less than in 10 % of tumor cells. Conclusion. Expression of adhesion molecule CD56 in tumor plasma cells in bone marrow can be regarded as a prognostic factor in MM. Probably, when at disease onset CD56 expression is identified in less than 10 % of tumor cells in bone marrow, more detailed additional examination of patients should be carried out to rule out extramedullary lesions in different organs and tissues.

The paper focuses on Epstein-Barr virus (EBV)-associated inflammatory pseudotumor in the spleen, an extremely rare disease which so far remained undefined in the Russian literature. The morphology of it is not characterized by any specific features and is represented by a spindlecell component with pronounced inflammatory infiltration which complicates differential diagnosis. Previously this nosology was regarded within a group of the so-called inflammatory pseudotumors due to the similarity of the clinical course and radiological presentation with tumor processes. Today the term “inflammatory pseudotumor” is considered obsolete, since as pathogenesis was being studied within this disease group, the individual forms with similar morphology and different histogenesis were identified. Differential diagnosis in the context of additional diagnostic techniques is based in such cases on a wide range of reactive states, benign and malignant tumors.

Background. Primary bone lymphomas (PBL) are rare extranodal lymphomas. In more than 90 % of cases they are reported as diffuse large B-cell lymphomas (DLBCL). At local (IE) stage of PBL the standard R-CHOP immunotherapy demonstrates efficacy over 90 %. If, however, such poor prognostic factors (PPF) as multiple bone lesions (IVE stage), increased lactate dehydrogenase (LDH) activity, B-symptoms, and large tumor mass are identified, R-CHOP efficacy tends to decrease. There is currently no optimal regimen for treatment of PBL patients with PPF. We suggest intensified multiagent chemotherapy for this category of patients. Aim. To assess long-term results of prospective single-center trial on the use of high-dose mNHL-BFM-90 program in patients with primary bone DLBCL and PPF. Materials & Methods. The trial included 33 patients with primary bone DLBCL followed-up at the National Medical Hematology Research Center from 2006 to 2018. The median age of patients was 44 years (range 16-78 years). The spectrum of assessed data included main clinical, laboratory, X-ray and MRI tumor characteristics as well as survival rates and prognostic factors. Results. PPF were identified in 29 (88 %) patients, out of them 20 (61 %) patients had an advanced stage (> IE), 20 (59 %) patients showed an increased LDH activity, B-symptoms were identified in 15 (45 %) patients, and large tumor mass was reported in 23 (71 %) patients. High-dose antitumor treatment (mNHL-BFM-90) was administered in 27 out of 33 patients. Overall and progression-free survival within the period of 5 years was 92 %. None of PPF significantly influenced survival rates. Conclusion. The use of high-dose mNHL-BFM-90 program in PBL with poor prognosis achieves long-term remissions in 92 % patients. We recommend mNHL-BFM-90 as a therapy of choice for PBL patients with poor prognosis.

Background. Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a malignant tumor with large atypical lymphoid cells expressing post-germinal differentiation markers. Rearrangements of immunoglobulin genes in PMBCL are revealed in 30-65 % of cases. Immunoglobulin molecules, however, are expressed neither on the surface, nor in cytoplasm of tumor cells. Aim. To assess cell clonality rate on the basis of rearrangements of immunoglobulin heavy/light chain genes; to determine rearrangement stability at the time of relapse development; to study the range of rearrangements and clonal relationship with primary tumor in metachronous development of mediastinal gray zone lymphoma. Materials & Methods. The assessment of rearrangements of immunoglobulin heavy/light chain genes was based on molecular analysis of 29 primary tumor biopsies and 4 tissue samples with histologically and immunohistochemically verified relapses or metachronous lymphoma development. Results. In 16 (55.2 %) out of 29 cases a rearrangement of immunoglobulin heavy chain genes was reported, in 7 (24.1 %) cases a rearrangement of light chain genes was identified, in 6 (20.7 %) cases no rearrangements of immunoglobulin heavy/light chain genes were found. On the basis of immunoglobulin gene analysis in 2 patients with early relapse a tumor clone was detected that was identical with the one identified at the onset of the disease. In 2 patients with complete remission a metachronous development of mediastinal gray zone lymphoma was reported, whereas molecular genetic analysis revealed a change/disappearance of initial clonal rearrangements of immunoglobulin genes. Conclusion. Total detection rate of B-cell clonality in PMB-CL was 79.3 %. Molecular genetic analysis confirmed that initial clonal rearrangements of immunoglobulin genes were preserved in early relapses, and invalidated tumor clonal relationship in a metachronous development of mediastinal gray zone lymphoma.

Background. TP53 gene mutations impede cell apoptosis and lead to additional oncogenic events contributing to tumor progression. Aim. To assess TP53 gene mutation rate in patients with high-grade B-cell lymphoma double-hit (HGBCL DH) and not otherwise specified (HGBL NOS); to analyse its relationship with disease prognosis. Materials & Methods. Retrospective materials from medical data of 10 HGBL DH and 26 HGBL NOS patients were analyzed. Median follow-up was 26.5 months (range 0.6-160.9 months). Selection was based on the presence of available biological materials (paraffin blocks) for Sanger sequencing of TP53 gene from exon 5 to exon 8 (encoding DNA-binding domain of TP53 gene). FISH analysis of the tumor was performed in all patients to identify translocations involving c-MYC/8q24, BCL2/18q21, and BCL6/3q27 gene locus. To analyze differences between groups χ2 and Mann-Whitney tests were applied. Univariate event analysis (Kaplan-Meier and log-rank tests) and Cox regression analysis were used to assess the influence of molecular markers on the disease prognosis. Results. TP53 gene mutations in lymphoma cells were found in 13 (36 %) out of 36 patients, 10 (77 %) out of 13 mutations were pathogenic. In 8 out of 10 patients with TP53 mutations c-MYC/8q24 gene translocation was identified. Groups with wild (TP53-WT) and mutant (TP53-MUT) types of TP53 gene were similar in terms of main clinical characteristics. Patients with TP53-MUT in tumor cells showed worse 3-year overall survival (OS) compared with the group without TP53-MUT (30 % vs. 73 %; p = 0.026) as well as higher probability of disease progression in the period of 3 years (66 % vs. 15 %; p = 0.004). In multivariate analysis significant OS predictor was the presence of TP53 mutation (p = 0.006). Relapse/ progression probability was higher in combined cases of TP53 mutation and translocation involving c-MYC gene locus (p = 0.0003). Conclusion. Translocation involving c-MYC gene along with TP53 gene mutation in tumor cells can serve as a criterion for dividing HGBL DH and HGBL NOS patients into different lymphoma relapse/progression risk groups.

Background. Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) is a rare Hodgkin's lymphoma subtype with a variable growth pattern and immune tissue architecture of tumor. Clustering of patients into subgroups based on immunohistochemical (IHC) tumor subvariants is essential for prognosis assessment and development of new differentiated treatment approaches. Aim. To study clinical course of NLPHL in patients with different IHC-subvariants of the disease and identify a poor prognosis subgroup. Materials & Methods. From 2010 to 2017 the Department of Anatomic Pathology at the National Medical Hematology Research Center undertook morphological and IHC-analysis of lymph node and bone marrow core biopsies of 60 NLPHL patients: 47 men and 13 women (male/female ratio of 3.6:1) aged 17-68 years (median 37 years). IHC-analysis with expanded panel of antibodies was performed in all cases of determining IHC-subvariants in accordance with WHO-2017 classification. Results. The clinical and immunomorphological comparative study of NLPHL with variant immune tissue architecture allowed to divide the patient population into three subgroups with differently manifested areas similar to T-cell/ histiocyte-rich large B-cell lymphoma (THRLBCL) in lymph node sections or other site biopsies. These subgroups are characterized by different clinical course of the disease. The subgroup with ≥ 50 % THRLBCL-like areas was marked by the prevalence of clinical stage IV and significantly larger amount of extranodal lesions. Conclusion. In NLPHL the most unfavorable clinical course is typical of the patients whose biopsies contain ≥ 50 % THRLBCL-like areas. Semi-quantification of THRLBCL-like areas allowed to define a spectrum of NLPHL IHC-subvariants correlating with the clinical course of the disease. The true transformation into diffuse large B-cell lymphoma is a rare event, it occurred in 2 (3 %) out of 60 patients.

Background. MALT-lymphoma is usually characterized with an indolent course. The factors underlying the effectiveness of the standard chemotherapy in patients with MALT-lymphomas include MALT-IPI risk group and a high SUVmax according to the results of positron emission tomography (PET). All well-known MALT-lymphoma risk factors indirectly indicate a high risk of transformation to large cell lymphoma. The search for an effective chemotherapy continues. Aim. To evaluate the effectiveness of the R-EPOCH/R-BAC escalated immunochemotherapy for MALT-lymphoma patients with poor prognosis factors. Materials & Methods. In the period of 2016-2017 the study included 5 female MALT-lymphoma patients (the mean age of 41 years), of which 1 patient had an early relapse after surgery and 4 patients were newly diagnosed. Prior to therapy 4 patients were evaluated with PET. The mean SUVmax was 10.04. According to MALT-IPI 2 patients belonged to a high-risk group and 3 belonged to a middle-risk group. All the patients received R-EPOCH/R-BAC regimen therapy. A month after completing the treatment all the patients were again evaluated with PET. Results. In 4 patients with 10-24 months follow-up complete remission was reported, which was confirmed by the results of histology and PET. The treatment of 1 patient was not completed. The immunotherapy was well tolerated by the patients. Hematological toxicity grade 3-4 occurred only after completing R-BAC treatment regimens. No severe infectious complications were reported. Conclusion. MALT-lymphoma patients need to be evaluated in terms of all prognostic factors to identify the high-risk patients for whom escalated therapy is to be used already in the first line treatment. This pilot study of the use of R-EPOCH/R-BAC for treatment of MALT-lymphoma patients with poor prognosis factors yielded positive results and showed its acceptable tolerance.

Hydroxycarbamide is an antitumor agent mainly used for treatment of Ph-negative myeloproliferative disorders and sickle cell disease. The development of skin ulcers is a rare but serious adverse event in long-term antitumor therapy. Hydroxycarbamide-induced ulcers are often multiple and bilateral, and usually occur in the lower legs, although they can occur in other regions of the body. The ulcers are smallsized and shallow with sharp margins and yellow fibrine-covered base. They cause constant severe, difficult to treat pain which is a characteristic sign. The drug withdrawal usually leads to spontaneous healing of ulcers. Regular dermatologic screening must be obligatory for all the patients receiving hydroxycarbamide. The present paper provides a literature review on dermatological toxicity of hydroxycarbamide and a clinical case description.

Background. Grade 3 follicular lymphoma (FL) is a heterogenetic group of tumors. The selections of patients with similar characteristics of the tumor process is important for classification 3 grade forms of FL and risk stratification, as well as for the development of new therapeutic approaches. Different morphological, immunohistochemical and cytogenetical characteristics of the tumor result in different clinical forms of the disease. Aim. To describe the clinical, morphological, immunohistochemical and cytogenetical characteristics of grade 3 FL and evaluate their prognostic value for R-CHOP-21 chemotherapy. Materials & Methods. We performed retrospective and prospective analysis of morphological, immunohistochemical and genetical characteristics of 93 primary patients with grade 3 FL (21-78 years, median 53 years, women to men - 1:1.4) admitted to National Medical Hematology Research Center from years 2001 to 2016. Morphological and immunohistochemical assessment of the affected lymph nodes and bone marrow biopsy material was performed. Data obtained from the standard cytogenetic and FISH assessment were compared to identify the BCL2 rearrangement. Results. We proposed an algorithm for differential diagnosis of the 2 types of grade 3 FL: de novo FL (n = 22) and transformed FL (n = 21). De novo grade 3 FL had the immunophenotype of CD10- in 19 (86 %) cases, MUM1++ (monomorphically) in 19 (90 %), and BCL-2 in 5 (22 %). It was characterized by the absence of the BCL2 rearrangement (n = 22, 100 %) and bone marrow involvement (n = 14, 67 %) and/or bone marrow involvement (n = 7, 100 %). Third grade FL transformed from grades 1 or 2 had was CD10+ (n = 19, 90 %), MUM1+ (heterogeneously, n = 16, 76 %) or MUM1-(n = 4, 19 %), BCL-2+ (n = 20, 95 %) and had BCL2 rearrangement (n = 19, 90 %). Small cell bone marrow involvement was observed in 71 % of cases, whereas large cell involvement was seen predominantly in de novo FL (p = 0.06). The analysis showed that 5-year relapse-free survival in patients with grade 3 de novo FL after R-CHOP-21 therapy was 87 % compared to 16 % with transformed FL (p = 0.06) for the median 41 months of follow up. Conclusion. We described the morphological, immunohistochemical and cytogenetical characteristics of grade 3 de novo FL and grade 3 FL, transformed from grades 1 or 2. The described variants show different sensitivity to immunochemotherapy.

The diagnosis of myeloid tumors is based on a complex approach and causes significant difficulties especially in young children. Morphologic, immunologic, cytogenetic, molecular and biologic data on myeloid sarcoma are presented based on the literature data and own clinical case. Treatment results of myeloid sarcoma (especially in the high risk group) are unsatisfactory and should be improved.

Stevens-Johnson syndrome is a severe delayed type systemic allergic reaction which affects the skin and mucous membranes. In adults, Stevens-Johnson syndrome is usually caused by the administration of drugs or a malignant process. The paper presents a case of Stevens-Johnson syndrome after the treatment of a female patient with small lymphocytic B-cell lymphoma, autoimmune hemolytic anemia and antiphospholipid antibody syndrome with rituximab. A rare combination of Stevens-Johnson syndrome and small lymphocytic B-cell lymphoma of small lymphocytes, as well as the development of severe delayed type systemic allergic reaction to introduction of rituximab are of special interest. A detailed medical history and the clinical manifestations of the disease allowed to diagnose Stevens-Johnson syndrome at early stages and prescribe an adequate therapy. As a result of the treatment, the patient’s condition has improved considerably. Symptoms of general toxicity were arrested completely; there was a complete epithelization of erosive defects. Therefore, the presented clinical observation shows that timely diagnosis, complex drug therapy, and comprehensive care can cure the diseases as soon as possible and prevent complications.

Aim. Pathomorphological, immunophenotypical and clinical characteristics of a new clinico-morphological form of pediatric-type follicular lymphoma (FL) in young adults discovered in 2008 (WHO classification). Background. FL is a heterogeneous disease according to its morphological, immunophenotypical and molecular-genetic characteristics. FL de novo includes transformed FL, FL without t(14;18), FL with diffuse growth associated with del(1p.36) and TNFRSF14 mutation. Pediatric-type FL in young adults is poorly studied; and it is especially interesting because of its clinical diversity and molecular-genetic heterogeneity of FL, in general. Methods. Biopsy materials taken from 5 patients (aged 18-25 years; median age: 22 years; the female/male ratio 3:2) were included in the study; all patients were examined, diagnosed and treated in the Hematology Research Center over the period from 2012 to 2016. Clinical stage I with isolated involvement a palatine tonsil or an inguinal lymph node was diagnosed in 4/5 patients; clinical stage II with involvement of a palatine tonsil and cervical lymph node was diagnosed in 1/5 patients. Morphological, immunophenotypical and FISH tests were performed with paraffin blocks. Results. The morphological pattern was typical for FL 3B (n = 2) and FL 3 with blastoid nucleus morphology (n = 3). Immunophenotypical features demonstrated an intermediate position between FL 3 de novo and transformed FL 3. No BCL-2 rearrangement was detected in any observation. Conclusion. The comparison of our data on characteristics of pediatric-type FL with those published in the literature demonstrated that lack or weak expression (< 30 % of tumor substrate cells) of MUM1 was the key feature of the experimental group of young adults with pediatric-type FL. This, in turn, indicates the absence of IRF4 rearrangements and possible presence of other genetic abnormalities. The clinical, morphological, and immunophenotypical characteristics broaden the FL heterogeneity spectrum in young adults.

Background. The most common diseases among cutaneous T-cell lymphomas are mycosis fungoides (MF) and its leukemic variant Sezary Syndrome (SS). These malignant tumors have a progressive character course. To date, no therapy for these diseases has proven effective, especially in the late stages of the disease. Aim. We aimed to assess the effectiveness of treating resistant forms of MF/SS with prolonged gemcitabine regimen after initial treatment failure. Materials & Methods. The study included 14 patients with drug-resistant forms of MF/SS (10 patients with MF, 3 patients with SS, and 1 patient with the transformation of MF into large cell lymphoma). The median age was 62 years (range 34-78 years). The study population included 9 males and 7 females. Gemcitabine was administered at a dosage of 250 mg/m2 as a 6-8 hour IV infusion weekly, in a cycle of 21-28 days. Results. The overall response was 79 % (29 % of patients with complete remission, 50 % of patients with partial remission). In 21 % of patients, the treatment results met the criteria for tumor stabilization. The disease progression was observed in 2 (14 %) patients. This study demonstrates the potential of using prolonged gemcitabine regimen in patients of different age groups with advanced resistant MF/SS who received at least two courses of previous ineffective therapy. In order to evaluate long-term results, further research is needed. Conclusion. The administration of prolonged gemcitabine regimen may be a treatment of choice in resistant forms of MF/SS after initial treatment failure in different age groups including elderly patients.

Anaplastic large cell lymphoma (ALCL) includes different types of the disease that are heterogeneous according to clinical, morphological, immunological, cytogenetic and molecular biological features. The review demonstrates not only main clinical and morphoimmunological characteristics of ALCL, but also presents data about expression and prognostic significance of STAT3, pSTAT3tyr705 (transcription factor), and survivin (apoptosis inhibitor). It demonstrates the value of defining the minimal disseminated disease (the minimal disseminated disease is evaluated using the PCR test before initiation of the treatment, and the minimal residual disease is evaluated during the treatment and after its completion), and clinical and molecular biological prognostic factors are also identified. There is still no a standard therapeutic regimen for pediatric ALCL patients. However, the following therapeutic protocols are considered most effective: NHL-BFM 90/95, CCG5941, SFOP-LM 89/91, UKCCSG, ALCL99-Vinblastine, POG АРО 9315, AIEOP LNH-92/97. Treatment outcomes are presented in this paper. Particular attention is paid to different molecular biological markers that allow further improvement of patients’ stratification in risk groups and possible use of target medications (multikinase inhibitors and monoclonal antibodies) improving the therapy outcomes.

Background & Aims. Morphological, immunohistochemical, immunophenotypic, cytogenetic, molecular and genetic and other examinations of tissues affected by oncohematological diseases are obligatory. The aim of this paper is to evaluate findings of lung and pleura biopsies in different medical conditions using two basic techniques: thoracoscopy and diagnostic thoracotomy. Methods. Results of morphological examination of lung lesions in patients hospitalized in the Hematology Research Center under the Ministry of Health of the Russian Federation are presented. From 2004 till 2014, 76 biopsies of lung and/or parietal pleura were performed in 73 patients aged 19–77 years via thoracoscopic (48) and/or thoracotomic (28) approach. Results. No thoracoscopy- and thoracotomy-related complications were observed. Bioptate examinations proved to be informative in 66 (86.7%) patients. Lung lesions were most common in lymphoproliferative diseases. Lung involvement in cancer or metastases was twice as common as it has been expected before the biopsy. On the contrary, expected tuberculosis nature of lung lesions in 5 patients was confirmed only in 2 of them. In 18 cases (23.7 %), the cause of lung lesion was other than the expected one, and appropriate adjustments of the therapy were made. Conclusion. New less invasive methods of biopsy combined with complex laboratory diagnosing comply with current requirements and permit making a correct diagnosis of a pathological process located in lungs.

Background. Unclassifiable splenic B-cell lymphoma/leukemia is a rare and poorly studied disorder introduced in the WHO classification of hematopoietic and lymphoid tissue malignancies for the first time in 2008. This type of lymphoma requires differential diagnosing between hairy cell leukemia-variant (HCL-V) and splenic diffuse red pulp small B-cell lymphoma (SDRPL). Aim. To develop criteria for diagnosis of SDRPL by comparison of bone marrow biopsies (BMB) and surgical specimens of the spleen. Methods. In the Department of Morbid Anatomy of the Hematology Research Center, preoperative BMBs and surgical specimens of the spleen (2013-2015) were compared in 71 patients (men/women ratio 1:2.6, age range 44-81, median age 58 years) using morphological and extended immunohistochemical studies. Sanger sequencing and PCR assay were carried out to analyze the mutational status of IgHV and to identify mutations in MAP2K1, NOTCH, BRAF. Results. SDRPL was diagnosed in 5 (7 %) of 71 patients. In 2 groups of patients (with normal and high WBC count), the morphological features of spleen tissue were similar to those of a neoplastic substrate of HCL-V. The immunohistochemical assay demonstrates monomorphic expression of CD20 and DBA.44 and heterogeneous expression of CD11c, TRAP, CD103, CD123 in all cases. In none of the 5 cases, expression of CD25, CD27, Cyclin D1, Annexin-1 was found. In bone marrow (unlike HCL and HCL-V), predominantly interstitial and intravascular scant CD20+ lymphoid infiltration (4 of 5 cases) was found without detectable nucleoli in nuclei of small lymphoid cells. In 1 case, there was a combined lymphoid infiltration: CD20+ microfocalinterstitial infiltration with an intravascular component. No persistent molecular mutations in the spleen tissue specimens were found. Conclusion. SDRPL is diagnosed in 7 % of splenic B-cell lymphomas. It is a rare disorder, whose verification requires an integrated approach taking into account clini cal and laboratory data, results of flow cytometry, cytological, morphological, extended IHC and molecular biological studies.