[Diagnosis of latent polycythemia vera: A clinician's opinion]. / Diagnostika latentnoi istinnoi politsitemii (vzglyad klinitsista).

AIM: to identify the clinical features of latent polycythemia vera (PV) as an independent nosological entity. SUBJECTS AND METHODS: The investigation enrolled 81 patients (50 with extensive (manifest) PV and 31 with latent PV) who had visited the Outpatient Department, Hematology Research Center, Ministry of Health of Russia, in 2014 to October 2015. RESULTS: The gender distribution of the patients was statistically comparable in the analyzed groups. The patients with manifest PV were slightly older than those with latent PV: the median age in the compared groups was 56 and 44 years, respectively. Red blood cell counts, hemoglobin concentrations, and packed cell volume were higher in the patients with manifest PV. Blood platelet counts were higher in the latent PV group. There were no differences in the number of white blood cells in the compared groups. All the patients were JAK2 V617F mutation carriers. The JAK2 allele load was significantly higher in the manifest PV group than in the latent PV group. The compared patient groups differed in the rate of thromboses in the history or at diagnosis. In the patients with latent PV, thromboses were detected in 38% of cases versus 16% in those with manifest PV. In latent PV, there were mainly venous thromboses; abdominal vascular thromboses were diagnosed with a high frequency. Arterial thromboses were revealed in only 2 cases. CONCLUSION: Chronic myeloproliferative disease that is characterized by the JAK2 V617F mutation, borderline hemoglobin counts, and morphological features of a bone marrow trephine biopsy specimen, which are specific for PV, is an independent PV variant, namely: latent PV.

[Efficiency of interferon therapy in patients with essential thrombocythemia or polycythemia vera]. / Effektivnost' interferonoterapii u bol'nykh essentsial'noi trombotsitemiei i istinnoi politsitemiei.

AIM: To evaluate the efficiency of interferon (IFN) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). SUBJECTS AND METHODS: A total of 61 patients (41 with ET and 20 with PV) were examined. Prior to study enrolment, 44 (72%) patients with ET or PV received one or other therapy (aspirin was not taken into account). The mean Jak2V617F mutant allele at baseline was 23% (6-54%) in the patients with ET and 40% (11-88%) in those with PV. The median time from diagnosis to enrollment was 49 months. RESULTS: The paper presents the clinical and molecular findings of long-term INF-α therapy in patients with ET or PV. The median follow-up was 52 months. Recombinant IFN-α2 showed its ability to induce complete hematologic remission (ET (76%), PV (70%)) and a complete molecular response. 22 (69%) out of 32 patients were noted to have a smaller number of cells with the Jak2V617F mutation. In the patients with PV and in those with ET, the relative reduction in the proportion of cells with the Jak2V617F mutant gene averaged 85% and 56% of the baseline values, respectively. There was a reduction in the proportion of cells expressing the Jak2V617F mutation in both the ET (from 12 to 2.2%; p=0.001) and PV (from 32.7% to 3.2%) groups (р=0.001). Ten (31%) patients achieved a deep molecular remission (≤2% Jak2V617F allele); among them, 5 patients were not found to have Jak2V617F mutation. The obtained molecular response remained in 7 of the 10 patients untreated for 11 to 86 months. The long-term treatment with IFN-α led to normalization of the morphological pattern of bone marrow in 5 of the 7 PV or ET patients. CONCLUSION: Significant molecular remissions achieved by therapy with recombinant interferon-α2 confirm the appropriateness of this treatment option in in the majority of patients with ET or PV.

[Synchronous and metachronous myeloid and lymphoid tumors].

AIM: To determine the clinical features of multiple primary tumors (MPT) in patients with hemoblastoses, to develop treatment policy for synchronous and metachronous tumors, and to determine the impact of chemotherapy for one disease on the course and prognosis of another one. SUBJECTS AND METHODS: The investigation included 20 patients with multiple primary synchronous and metachronous myeloid and lymphoid tumors, who had been followed up at the Outpatient Department of the Hematology Research Center, Ministry of Health of the Russian Federation. The distribution of patients by nosological entities was as follows: 17 (85%) patients with myeloproliferative diseases (MPDs) concurrent with lymphoproliferative diseases (LPDs) and 3 (15%) with two types of MPD. A special group comprised 3 patients who successively developed 3 malignant diseases: cancer/B-cell chronic lymphocytic leukemia (B-CLL)/Ph-positive chronic myeloid leukemia (Ph+CML); cancer/polycythemia vera (PCV)/B-CLL; cancer/essential thrombocythemia (ETC)/multiple myeloma (MM). RESULTS: The Outpatient Department of the Hematology Research Center, Ministry of Health of the Russian Federation, followed up 20 patients with synchronous and metachronous tumors in 1996 to 2013. The patients' age was 42 to 82 years (64 years). The female/male ratio was 1:1.2. Metachronous tumors were 1.5-fold higher than synchronous ones. The time to detection of secondary hemoblastosis averaged 3.3 years; the longest interval was 14 years; the mean coexistence of 2 tumors was 4.8 years (1-11 years). The total length of the follow-up was 8 years (1-19 years). Among them, there were 17 (85%) patients with 2 chronic hematologic tumors with a myeloid or lymphoid phenotype; 3 (15%) of the 20 patients had 3 malignant diseases (cancer/ B-CLL)/Ph+CML, cancer/PCV/B-CLL, cancer/ETC/MM. In the group of 17 patients, 13 (76%) were diagnosed as having Ph-negative MPDs (PCV in 4 patients, primary myelofibrosis in 4, ETC in 4, undifferentiated MPD in1) and 4 (24%) patients had Ph+CML. This patient group was found to have the following LPDs: CLL in 5 (30%), hairy cell leukemia in 1 (5%), paraproteinemic hemoblastoses in 11 (65%). MPD preceded LPD in 8 (47%) patients; the development interval between two tumors averaged 6 years (1 to 14 years). LPD preceded MPD in 3 (18%) patients; the interval averaged 5 years (2 to 17 years). MPD and LPD appeared synchronously in 6 (35%) patients. CONCLUSION: The fact that 2 malignancies or more may occur in one patient determines the need for a careful follow-up of patients with blood system diseases. The activity of one hematologic disease or another is a leading criterion for choosing a therapeutic tactic.

[Chronic lymphocytic leukemia accompanied by renal failure].

AIM: To evaluate the efficiency and safety of monotherapy with bendamustine (B) and therapy with B in combination with rituximab (B + R) in patients with chronic lymphocytic leukemia (CLL) accompanied by renal failure (RF). SUBJECTS AND METHODS: The prospective pilot study included 8 patients (6 men, 2 women) with CLL concurrent with RF. The patients' median age was 63 years (51-77 years). The Binet classification stage of CLL corresponded to B in 2 cases and C in 6. The mean (± standard error) pretreatment concentration of creatinine was 218 ± 92 µmol/l and the glomerular filtration rate (GFR) was 33 ± 20 ml/min. The efficiency of monotherapy with B (n=5) and combination therapy with B + R (n=3) was evaluated. In progressive CLL, therapy was performed in specific treatment-naïve patients (n = 5) and in pretreated patients refractory to alkylating agents (cyclophosphan, chlorambucil) (n = 3). A total of cycles of B and B + R were carried out. RESULTS: After B monotherapy, one of the 5 cases achieved a complete remission, 3 a partial remission, and 1 a nodular partial remission. Three patients developed recurrence. In the B monotherapy group, the cumulative risk of recurrence was 70% at a median follow-up of 22 months and at a maximum follow-up of 27 months. In the B + R therapy group, all the 3 patients achieved a complete remission. The median follow-up was 7 months; the maximum follow-up was 1 year. There were no deaths or recurrences. During B monotherapy and B + R combination therapy, there was improved kidney function: the mean concentration of creatinine decreased from 218 ± 92 to 140 ± 57 µmol/l (p < 0.05); GFR increased from 33 ± 20.0 to 54 ± 25 ml/min; the mean increment was 20 ml/min (p < 0.01). Mild and moderate anemia and thrombocytopenia were most common during B and B + R therapies. Neutropenia with mild infection complications, as well as nonhematologic complications were detected in some cases. The drugs were observed to have no nephrotoxic effects. CONCLUSION: The performed pilot prospective indicated that the B + R combination therapy was effective in patients with RF-associated CLL. No toxic effect of B on kidney function was seen. During B therapy, there was better kidney function manifesting itself as a statistically and clinically important decrease in creatinine concentrations and a statistically and clinically important increase in GFR as compared to the baseline values.

[Mastocytosis. Review of the literature and description of clinical cases].

The term mastocytosis (MC) encompasses a group of rare diseases characterized by the tumorous proliferation of clonal mast cells and the infiltration of one or several organs. The clinical picture of MC is extremely diverse from skin lesions that can spontaneously regress to the aggressive disease forms associated with organ dysfunction and short survival. Nowadays, the 2008 WHO classification identifies 7 MC subtypes. The disease is diagnosed on the basis of its clinical manifestations and detection of tumorous mast cell infiltrations via morphological, immunohistochemical, immunophenotypic, genetic, and molecular examinations. Abnormal mast cells are characterized by the atypical morphology and pathological expression of CD25 and CD2 antigens. Enhanced serum tryptase activity is a common sign in all MC subtypes. More than 90% of the patients have D816V KIT mutations in the mast cells. This paper reviews the literature. Three cases are described as a clinical example in patients with different MC subtypes.

[Role of splenectomy in the treatment of myelofibrosis].

AIM: To evaluate the clinical and hematologic efficiency of splenectomy (SE) in patients with myelofibrosis (MF) resistant to conventional traditional treatment. SUBJECTS AND METHODS: Case histories were retrospectively analyzed in 52 MF patients who had been followed up at the Hematology Research Center, Ministry of Health of the Russian Federation, in 2004 to 2012 and undergone therapeutic SE (47 patients with primary myelofibrosis, 4 with postpolycythemia myelofibrosis, and 1 with postthrombocythemia myelofibrosis). The mean age was 47 years at diagnosis and 53 years before surgery. The patients younger than 50 years of age constituted 60%. Massive and giant splenomegaly was detected in 37 (71%) patients. The spleen weighing 0.9 to 2.9 and 3 to 7 kg was removed in 15 (29%) and 35 (67%) patients, respectively. In 2 cases, the weight of the removed spleen was as much as 10 and 11 kg. RESULTS: By the moment of SE, the disease duration averaged 76 (from 1 to 240) months. Twenty-one (40%) patients developed perioperative complications, including bleeding (15%), thrombosis (11.5%), and infectious complications (13.5%). There were no deaths from surgical interventions in the intra- and early postoperative periods. In more than 80% of the patients after SE, their general condition improved and the symptoms of intoxication disappeared; in the majority of patients, the therapeutic effect lasted about 2 years. In the follow-up period, 33 (63%) patients died; the time to death averaged 27 (1-84) months following SE. The causes of death were blast transformation in 27 (82%) patients and comorbidity in 6 (18%); 19 (37%) patients with an average post-SE follow-up of 37 (4-72) months continued hydroxyurea treatment. The median survival after SE was equal to 3 years; the median overall survival was 11 years. CONCLUSION: SE is effective palliative care with an acceptable level of occurring complications for individual patients with MF. Contraindications to SE as blast crisis and severe comorbidities should be strictly taken into account.

[Hereditary spherocytic hemolytic anemia in an adult with the formation of ectopic foci of extramedullary hemopoiesis in the chest].

The paper describes a rare case of formation of paravertebral extramedullary hemopoietic foci in microspherocytic anemia or Minkovsky-Shoffar disease in an adult. Therapeutic splenectomy has led to regression of extramedullary hemopoietic foci, which supports that there is a direct relationship of the above formations to the specific features of the etiology and pathogenesis of microspherocytic anemia.

[Tumor development from follicular dendritic cells in a hyaline-vascular variant of Castleman's disease].

Literature gives only few reports of hyaline-vascular variant of Castleman's disease associated with tumor from dendritic cells. A case of simultaneous detection of these diseases in the tumor located in the retroperitoneal space and successfully removed surgically is reported.

[Paraneoplastic lymphadenopathy].

AIM: To study a spectrum of histologic patterns in patients with paraneoplastic lymphadenopathies, to analyse repeating changes and the causes of diagnostic mistakes. MATERIAL AND METHODS: In a retrospective analysis of 457 patients observed in Hematology Research Center of the RF in 1994-2004, and diagnosed as having non-malignant lymphadenopathies, we identified 40 patients in whom the second or third biopsy showed lymphoma. Nineteen patients (47.5%) had Hodgkin's lymphomas, 11 (27.5%)--B-cell lymphomas and 10 (25%) T-cell lymphomas. RESULTS: In patients subsequently diagnosed with Hodgkin's lymphoma there were 4 repeating histologic patterns in paraneoplastic lymph nodes: sinus histiocytosis (7 patients, 37%), paracortical reaction with numerous plasma cells and macrophages (7 patients, 37%), marked fibrotic changes (4 patients, 21%) and necrotizing lesions (3 patients, 16%). In 15 patients the second biopsy was performed within 4 weeks, while in 4 patients intervals between biopsies were 2, 4, 10 and 24 months. Eight patients (42%) had paraneoplastic changes in lymph nodes located not in the adjacent zones (in 7 patients above the diaphragm, and in 1 patient in both sides of the diaphragm). Amongst patients with B-cell lymphomas 7 had follicular lymphomas, 3--diffuse large B-cell lymphomas and 1--mantle cell lymphoma. In paraneoplastic lymph nodes there were 3 cases of sinus histiocytosis, 1--necrosis. In 5 patients with follicular lymphoma initially diagnosed as having follicular hyperplasia, retrospective analysis and immunohistochemistry showed partial involvement of lymph nodes with lymphoma. In two of them the presence of malignancy was clinically evident at the moment of the first biopsy, while three had a long history of lymphadenopathy (time to diagnostic biopsies were 5, 13 and 34 months). Amongst patients with T-cell lymphomas 5 had undetermined peripheral T-cell lymphomas, 2--anaplastic large cell lymphomas, 1--angioimmunoblastic lymphoma, 1--hepatolienal lymphoma and 1--Lennert's lymphoma. Median of time to the second biopsy was 4 months, range 1-48 months. Five patients (50%) had in the first lymph node sinus histiocytosis, 3 (30%)--paracortical hyperplasia, and 2--granulomatous lesions. Clonal rearrangements of gamma-chain T-cell receptor genes were found in 2 patients from 3 tested. CONCLUSION: Histologic patterns in lymph nodes not involved by lymphomas in patients with lymphomas are not random. While sinus histiocytosis and necrosis are universal findings, some patterns are disease specific. Paracortical hyperplasia is typical for T-cell lymphomas, prominent fibrosis--for Hodgkin's lymphoma. We believe that paraneoplastic changes in lymph nodes are caused by partial tumor involvement, cytokine reaction, or antitumor immune response. From practical point of view, finding of necrosis, prominent sinus histiocytosis, or prominent fibrosis of a lymph node in the absence of a history of chronic lymphadenitis or inflammation in the draining area should be considered as possible indication to second biopsy. Interpretation of such paraneoplastic phenomena as paracortical hyperplasia and formation of epithelioid-cell granulemas is not easy and must consider context of a clinical picture.

[Bartonella infection in hematological practice].

AIM: To characterize the clinical and histological features of Bartonella infection in patients asking for hematological advice and to assess the significance of serological and molecular methods for the diagnosis of this infection. MATERIALS AND METHODS: The case histories of 747 patients asking for advice at the Hematology Research Cancer, Russian Academy of Medical Sciences, for lymphadenopaphy were retrospectively studied. The study included 10 patients in whom Bartonella infection could be suspected. For verification of the diagnosis, the authors conducted a serological study of the patients' sera and a molecular study of archival paraffined lymph node biopsy specimens. RESULTS: The study showed it possible to make a retrospective diagnosis of cat-scratch disease (CSD) by polymerase chain reaction (PCR) used in the study of archival lymph node biopsy specimens and stained preparations. CONCLUSION: CSD should be suspected when a patient has sustained lymphadenopathy and a respective epidemiological history (feline contact). Bartonella infection should be diagnosed on the basis of a dynamic serological study and, if possible, PCR of cells from biopsy specimens of lymph nodes or the lesion developed at the site of Bartonella penetration into the human body (primary affect).

[Ten-year outcomes of lymphogranulomatosis treatment according to the protocol MOPP-ABVD+radiotherapy].

AIM: To analyse overall recurrence-free survival of lymphogranulomatosis (LGM) patients given polychemotherapy (PCT) MOPP (mustargen-caryolisin, vincristine, natulan, prednisolone) - ABVD (adriamycin, bleomycin, vinblastin, dacarbasin) in combination with radiotherapy (RT) for 10 years. MATERIAL AND METHODS: The trial included 211 LGM patients admitted to Hematological Research Center in 1990-1996 from other hospitals without random selection. The patients were examined by the standard program including biopsy of the affected organ or lymph node, bilateral trephine biopsy. Splenectomy was performed in 17 patients, 83 patients received PCT in other hospitals, 128 untreated patients received MOPP-ABVD therapy (3 courses of MOPP and 3 courses of ABVD). Forty one patients had defects in PCT, 16 of them rejected PCT and RT. The latter was performed 4 weeks after the 6th course, contraceptives were not prescribed to women. At LGM stage II-III RT was performed by the subradical program (no radiation to ilioinguinal lymph nodes) in doses 40-44 Gy on the foci and 32-36 Gy preventively, on massive and residual foci after PCT - 5-10 Gy additionally. RESULTS: Ten-year overall and recurrence-free survival in the untreated group reached 83 and 80%, respectively, for pretreated patients - 46 and 36%, respectively. Causes of death of 26 patients were LGM progression, infection (tuberculosis, as a rule), secondary tumors and acute myeloblastic leukemia (AML). After remission 25 women gave birth to a healthy child and 12 healthy children were born to 9 males. CONCLUSION: MOPP-ABVD plus radiotherapy program according to subradical and radical variants was in the past effective but invalidating rescue therapy. Present-day programs consider the histological variant, stage and prognostic factors allowing an individual therapeutic approach with step-by-step reduction of RT in the treatment of LGM patients. Involvement of the bone marrow in primary patients had no influence on the treatment results. This refers this affection not to a generalized stage IV, but to stage III along with involvement of the lymph nodes and the spleen.

[Determination of T-cell clonicity by a T-cell receptor gamma-chain: final data].

AIM: To test diagnostic efficacy of T-cell clonicity determination by a gamma-chain of T-cell receptor (TCR). MATERIAL AND METHODS: The examination covered 426 patients (458 tests). T-cell tumors were detected in 132 patients. The samples from 294 patients in whom T-cell tumors were not found were referred to the laboratory for a differential diagnosis. Clonicity was determined by gamma-chain of TCR in the test for conformation polymorphism of one-chain DNA fragments. All the tests were made in one laboratory. RESULTS: Sensitivity of the method, found by analysis of different delusions of the cell line Jurkat in selected polyclonal CD3+ cells is 10%. The results were of 3 kinds: clonal, doubtful and polyclonal. In patients free of T-cell tumors there were 15 (5%), 34 (11%) and 258 (84%) false positive, doubtful and true negative results. False positive results were most frequent in an acute phase of infectious mononucleosis--in 8 (33%) of 24 patients. 127 (84%) true positive, 5 (3%) doubtful and 19 (13% 0 false negative results were documented in patients with T-cell lymphoma. The occurrence of false negative results was the highest in anaplastic CD30+ T-cell lymphomas--in 6 (46%) of 13 cases. CONCLUSION: Diagnostic efficacy of the method is 92%, but in 10% the result is doubtful. Main reason of false negative results is a small number of tumor cells in tissue samples. The main reason of false positive results is prevalence of one or some T-cell clones in the presence of immune response caused by viruses, autoimmune diseases and, possibly, depletion of bone marrow in aplastic syndromes.

[A case of cat scratch disease in a patient with diabetes mellitus and chronic renal failure].

The article describes a case of cat scratch disease in a female patient with severe chronic pathology. This relatively rare disease was manifested by regional (in the site of microbial intrusion) lymphadenopathy, and general infectious syndrome. The presence of oncohematological process was excluded without biopsy; serologic examination with bartonella antibodies confirmed the diagnosis. Combined treatment with two antibiotics, rifampicin and doxycycline, was successful. The article stresses that general practitioners should be aware of this disease; timely diagnosis and specific treatment are of utter importance.

[Castleman's disease].

AIM: To describe original experience in management of Castleman's disease (CD) and review literature data. MATERIAL AND METHODS: Twelve cases of HIV-free CD in patients aged 18-51 years (mean age 36 years) are reported. RESULTS: CD was plasmocell, mixed and hyalinovascular in 6, 2 and 4 patients, respectively. Histological and immunophenotypical characteristics of CD are detailed. Three patients with plasmocell CD died of severe autoimmune anemia. All the patients with hyalinovascular KD variant were treated surgically (enlarged lymph nodes were removed) and achieved remission. CONCLUSION: The diagnosis of plasmocell CD is made after exclusion of infections, collagenoses, autoimmune diseases and lymphomas. Therapy of plasmocell variant of CD has not been developed yet.

[The role of morphological characteristics of lymph nodes in differential diagnosis of reactive lymphadenopathies].

AIM: To analyse causes of reactive lymphadenitis regarding histological changes in the lymph node, of diagnostic errors; to determine frequency of establishment of nosological diagnosis. MATERIAL AND METHODS: A retrospective analysis of diagnostic examination of 375 patients with reactive lymphadenitis observed from 1992 to 2000 was made. RESULTS: For differential diagnosis 6 groups of reactive lymphadenopathies with different histological picture were identified: follicular hyperplasia, paracortical hyperplasia, granulomatous lymphadenitis, granulomatous pyonecrotic lymphadenitis, sinus histiocytosis as a leading sign and node necrosis as a leading sign. The analysis of making nosological diagnosis for each group and of diagnostic errors was conducted. CONCLUSION: Characteristics of lymph node changes in reactive lymphadenitis is of great importance. Better cooperation between histologists and clinicians must improve efficacy of reactive lymphadenitis diagnosis.

[Factors of an unfavorable prognosis in patients with B-cell chronic lymphoid leukemia: a retrospective analysis of 206 cases]. / Faktory neblagopriiatnogo prognoza u bol'nykh B-kletochnym khronicheskim limfoleikozom: retrospektivnyi analiz 206 sluchaev.

AIM: To assess factors of an unfavourable prognosis in a group of intermediate risk of B-cell chronic lymphoid leukemia (BCCLL). MATERIAL AND METHODS: 206 BCCLL patients (mean age 55.5 years, male/female = 1.66) entered the study conducted by Hematological Research Center in 1992-2000. RESULTS: Nine patients under 35 years of age did not survive 5 years except one female who achieved a complete remission on fludarabin. The type of bone marrow infiltration (diffuse vs interstitial and nodular), the time of lymphocyte count doubling (under or over 12 months) discriminate the patients by prognosis in the group of intermediate risk: medians of overall survival 65 months vs 148 months and 72 vs 133 months, respectively (p < 0.005 for both curves, log-rank criterion). Survival medians in groups with low (< 50% cells) and high (> 50% cells) expression of CD38+ cells in the group of intermediate BCCLL risk comprise 55 and 106 months (p = 0.005). The type of bone marrow infiltration and time of doubling of lymphocyte count overlap: > 70% patients with a diffuse type of bone marrow infiltration have the time of doubling under 12 months and vice versa while expression of CD38 do not overlap with these values. Combination of two signs (type of bone marrow infiltration and CD38 expression or time og lymphocyte count doubling and CD38 expression) allows more precise identification of prognostically unfavourable groups. Medians of survival for combination of the first two signs (two positive against two negative) comprise 51 months vs 169 months (p < 0.0001), for combination of the latter two signs 55 months vs 106 months was not reached (p < 0.001). Although most patients with a tumor form of BCCLL are referred to stage II, the prognosis in this form is much worse than in stage II, survival medians are 44 and 69 months, respectively (p < 0.05). A mutation status of the genes of a variable region of immunoglobulins enable identification of the group of patients with a relatively benign course of BCCLL (survival medians 61 and 289 months, p < 0.0001). CONCLUSION: In patients under 35 years of age BCCLL runs unfavourably and seems to require intensive polychemotherapy. Usage of a combination of the signs (CD38, time of doubling of lymphocyte count and type of bone marrow infiltration) is a simple and reliable method of identification of prognostically different categories of patients in the group of an intermediate BCCLL risk. Prognosis in patients with a tumor form of BCCLL is unfavourable: medians of survival in patients with a tumor form and stage III-IV are comparable. Mutational status of the genes of immunoglobulin variable region may serve a marker of a long-term prognosis.

[Use of polymerase chain reaction for determining T-cell clonality]. / Opyt ispol'zovaniia polimeraznoi tsepnoi reaktsii dlia opredeleniia T-kletochnoi klonal'nosti.

AIM: To distinguish T-cell lymphomas and reactive T-cell proliferation it is important to confirm the ability of T-cells to be cloned. Conventional histological and immunophenotypic methods fail to determine the ability of T-cells to be cloned. An experience in the use of detection of T-cell receptor gene gamma-chain (TCRy) rearrangement for determining T-cellular clonality is described. MATERIAL AND METHODS: Polymerase chain reaction (PCR) and single strand conformational polymorphism (SSCP) were used to determine T-cell clonality. Twenty healthy donors, 28 patients with T-lymphomas, and 26 patients with various non-T-cell lymphoproliferative disorders or reactive processes were studied. RESULTS: T-cell monoclonality was detected in 23/28 (82%) T-cell lymphoma cases, whereas in all the samples from normal subjects a polyclonal pattern of rearrangements TCRy was found. The sensitivity of the method was estimated as 2.5%, 7%, and 10% was demonstrated for bone marrow, spleen, and peripheral blood, respectively. CONCLUSION: PCR-SSCP for TCRy was found to be a useful supplement to routine histological and immunophenotypic methods in the diagnosis of T-cell lymphomas.

[Bone marrow alterations in sarcoidosis]. / Izmenenie kostnogo mozga pri sarkoidoze.

Trepanobiopsy of the bone marrow followed by a histological study was performed in 3 patients with sarcoidosis diagnosed in peripheral lymph node (LN) biopsies. Granulemas revealed in trepanobiopsies were identical to those found in LN. Trepanobiopsy is advisable in patients with sarcoidosis having some changes in hemogram.

[A comparison of the forms of chronic lympholeukemia in relation to the mutational status of the genes of the immunoglobulin variable region]. / Sravnenie form khronicheskogo limfoleikoza v zavisimosti ot mutatsionnogo statusa genov variabel'nogo regiona immunoglobulinov.

AIM: To compare forms of chronic lymphoid leukemia (CLL) regarding mutational status of immunoglobulin variable genes. MATERIAL AND METHODS: We have compared clinical, prognostic and immunophenotypic data obtained on 25 cases with different mutational status of IgV genes. There were 10 patients in the mutated group (median age 49.2 years, male to female ratio = 7:3), and 15 patients in unmutated group (median age 46.5, M:F = 13:2). RESULTS: Statistically significant differences were noted in overall survival and CD38 expression. 5-year overall survival in unmutated group was 35%, in mutated group 80% (p = 0.07). In unmutated group CD38 was expressed on more than 50% of cells in 7 out of 14 patients, while in the mutated group in 0 of 8 patients (p = 0.007). We noted high frequency of VH1-69 gene usage in unmutated group (7 of 15 patients), while in mutated group it was used in only 1 case of 10. CONCLUSION: We confirm the differences between groups of CLL with different mutational status of IgV genes. Highly restricted usage of VH-genes and CD38 expression possibly suggest that unmutated group also arises from antigen driven cells.

[A benign form of chronic lympholeukemia]. / Dobrokachestvennaia forma khronicheskogo limfoleikoza.

According to the classification of chronic lymphocytic leukemia (CLL) proposed by A. I. Vorob'ev and M. D. Brilliant in 1983, benign CLL is a distinct form of CLL which is characterized by low level of absolute lymphocytosis, absent or mild peripheral lymphadenopathy, slow progression. No specific therapy is needed. The paper presents clinical, morphological and immunological analysis of 34 cases of benign CLL (17 males and 17 females, mean age 58 years). Patients were included in the study if they had lymphocyte count less than 30,000 and no significant growth of lymphoid tissue for at least 3 years. They were followed up from 3 to 24 years (11 years, on the average). The main features of benign CLL are the following: no "B" symptoms, no essential enlargement of the lymphoid organs, a stable low level of absolute lymphocytosis, low prolymphocyte count in the blood smear (0.95% +/- 0.2), nodular or nodular-interstitial proliferation in the bone marrow. We failed to find any cases with paraprotein secretion. There was immunophenotype typical for CLL in 91% of cases (CD19+, CD20+, CD23+, CD5+, EM+, CR1-/CR2+, sIg+(-)). None was positive for CD38 activation marker. One trisomy 12 cases was detected by FISH method. 8 patients died so far, but not because of the tumor progression or transformation, median survival was 22 years.