[Multiple lymphomatous polyposis--rare case of gastrointestinal hemorrhage]. / Multiplex lymphomatosus polyposis--gastrointestinalis vérzés ritka esete.

The authors report a case of a 57 years old male patient, who was admitted to gastroenterology department with upper gastrointestinal haemorrhage. The urgent upper gastrointestinal endoscopy revealed an ulcerated polypoid tumor in the region of angulus of the stomach, and multiple polypoid lesions in the bulbar part of the duodenum. Upon this endoscopic appearance colonoscopy was performed, which revealed a polyposis syndrome in the colorectum. Computer tomography detected mesenterial, retroperitoneal and mediastinal lymph node involvement as well. In this case the primary or secondary origin of the gastrointestinal lymphoma was not verifiable. According to literature data this histological type of the gastrointestinal lymphoma has poor response to chemotherapy, the prognosis is unfavourable. In this particular case the administered chemotherapy resulted in total remission at the lymphoma patient clinically staging III Ae. In the proper follow-up examinations of the patient upper and lower endoscopy, histology samples, laboratory parameters, computer tomography, and physical examination in every 3 months are the methods.

[Molecular biology follow-up of interferon therapy in patients with chronic myeloid leukemia]. / Krónikus myeloid leukémiás betegek interferon-kezelésének követése molekuláris biológiai módszerekkel.

In a prospective survey clinical haematological and molecular biological data of 31 patients with chronic myelogenous leukaemia (chronic phase, CML) observed in their haematological outpatient department were analyzed. During 1996 and 1999 a regular follow-up of the Philadelphia chromosome level in treated patients was performed with molecular biological techniques, i.e. with reverse transcription polymerase chain reaction (RT-PCR) and with fluorescence in situ hybridization (FISH) methods. During the follow-up period of 33 months from the 31 patients with CML (16 males, 15 females) 25 ones were treated with human recombinant interferon-alpha (IFN), however, six others were getting only hydroxyurea (HU). During this period in three patients allogen bone marrow transplantation was performed and seven ones expired (six out of them of blastic crisis). The quality of therapeutic response at cytogenetical level was determined by decrease of the bcr-abl level due to the treatment (non-responders, major, minor and complete cytogenetic remission groups). In nine patients (five from the IFN-group, four from the HU-group) achieved no cytogenetic therapeutic response (non-responders, 29%). However, in 13 patients a minor (bcr-abl range of 60-30%), and in nine patients a maior/complete (bcr-abl of 30-10%) cytogenetic response (42% and 29%, respectively) were detected. Moreover, the quality of cytogenetic response correlated with the haematological remission. The maior/complete cytogenetic response was durable in eigth patients. The improvement of the overall survival of patients with CML, the postpone of the fatal accelerated-blastic phase could be expected only from the early introduced, in individually adjusted and given in maximally tolerated dosage of interferon (3-5 million UI/m2/day). The qualitative (RT-PCR) and quantitative (FISH) detections of the Philadelphia chromosome are reliably reproducible up-to-date molecular biological methods getting relevant results, which could be very helpful in the planning, monitoring, in setting of optimal dosage of the interferon therapy of patients with CML, in addition in the judgement of the effectiveness of the therapy, in the reduction of adverse effects, as well as in forecasting of the cytogenetic progression.

Phenotypic and genotypic analyses of blastic cell population suggest that pure B-lymphoblastic leukemia may arise from myelodysplastic syndrome.

The case history of a 70-year-old man with myelodysplastic syndrome terminated into acute leukemia in 22 months is presented. The leukemic cells exhibited multifocal acid phosphatase positivity and expressed TdT, CD45, CD34 and HLA-DR but not myeloid, monocytic or megakaryocytic differentiation antigenes. The genotypic analysis revealed clonal immunoglobulin heavy chain gene rearrangement. These phenotypic and genotypic analyses of the blastic cell population suggest that myelodysplastic syndrome may transform to pure acute lymphoblastic leukemia of B-cell origin.

[A case of myelodysplastic syndrome transforming into acute B-cell lymphoid leukemia]. / Tiszta B-sejtes akut lymphoid leukaemiába transzformálódó myelodysplasticus szindróma esete.

Case history of a seventy year old man with myelodysplastic syndrome is presented. The disease terminated into acute leukaemia in 22 months. The pure, B lymphoid stem cell nature of the leukaemic cells has been proved, beside morphology and cytochemistry, by detailed flow cytometric phenotyping and PCR amplification as well as sequencing of the immunoglobulin heavy chain gene CDR3 region.

[Anaplastic large cell lymphoma based on our clinicopathological cases]. / Az anaplasticus nagysejtes lymphomáról, eseteink klinikopatológiai elemzése kapcsán.

CD30(Ki-1) positive anaplastic large cell lymphoma (ALCL) is a distinct entity, in which the monoclonal antibody-positivity against the CD30(Ki-1) antigen of tumour cells has a diagnostic value. The histological subtypes of ALCL show also certain clinical differences. Except for some pediatric cases and cutaneous forms clinical outcome is very unfavourable despite of the various treatment methods. In this prospective study (follow-up of 11-60, median 16 months) clinicopathological data and treatment results of fifteen adult patients with ALCL were analysed, Mean age was 46 (16-69) ys with a bimodal tendency and a distinct female: male ratio (3:2) was observed. Early clinical stages (I-II/A-B, eight patients) dominated, and two main groups could be distinguished histologically (Hodgkin-related, ALCL-HR and common type, -CT in eight and seven patients), respectively. In all histological specimens CD30 antigen expression was detected. Additional immunophenotyping was performed in five cases (two 0-variant, two of B-cell and one of T-cell origin), respectively. A bulky disease, mainly in the mediastinum was observed in six cases, and a primary gastrointestinal localization in two other patients. In the treatment of these high grade malignant lymphomas a combination of cobalt irradiation and aggressive chemotherapy was applied (in elder the CHOP-regimen, in younger patients mainly the Pro-MACE-Cyta-BOM-protocol). In one relapsed younger patient autologous bone marrow transplantation was also performed. A complete or partial remission was achieved in thirteen patients (86.6%) but six patients expired after only a short response period to therapy. Overall survival was 19, whilst disease-free survival revealed to be 15 months. Eight of their living nine patients have a durable complete remission. Due to residual mediastinal mass after radiotherapy in three cases a permanent radiological follow-up is needed. Advanced age and clinical stages are considered to be unfavourable, whilst histological subtypes were indifferent prognostic factors, as well. Favourable results in therapy and durable complete remission in younger patients are probably caused by the their better tolerance of third-line aggressive chemotherapy.

Prognostic significance of bone marrow reticulin fibres in idiopathic myelofibrosis: evaluation of clinicopathological parameters in a scoring system.

A clinicopathological scoring system was performed for obtaining a better estimate of prognosis in 50 patients with idiopathic myelofibrosis (IMF). Laboratory parameters including Hb-level, leukocyte and platelet counts, percentage of blast cells in peripheral blood, spleen and liver size, and a semiquantitative histological grading of reticulin fibre content of bone marrow biopsies taken at the time of initial diagnosis were analysed. Based upon these haematological and histological parameters three prognostic groups could be categorized with a significantly different survival (low-risk group with 21 patients = 75 months; medium-risk group with 18 patients = 51 months, and 11 patients in a high-risk group = 18 months). In an univariate (log rank test) and in a multivariate regression analysis the Hb-concentration, mild splenomegaly (less than 5 cm) and a higher grade of bone marrow reticulin content proved to be important prognostic parameters, whilst leukopenia, thrombocytopenia and the presence of peripheral blast cells were only of prognostic significance within the first 6 months from initial diagnosis. It was concluded that the increase of reticulin fibre deposition in bone marrow together with anaemia and mild splenomegaly could be responsible for a progressively worse life-expectancy of high-risk patients with idiopathic myelofibrosis.

Megakaryocyte markers in myeloproliferative disorders.

Identification of megakaryocyte precursors with immunohistochemical methods in bone marrow trephine biopsy specimens (embedded in a plastic resin, Immuno-Bed) was performed from patients with blastic phase of chronic granulocytic leukaemia (five cases), from chronic megakaryocytic-granulocytic myelosis (four cases) and from acute megakaryoblastic leukaemia (11 cases). In megakaryoblasts of bone marrow biopsies immunohistochemical reactions using the ABC method and monoclonal antibodies against von Willebrand antigen and GpIIb/IIIa (CD41) were visible in various percentages depending on the maturation's degree of megakaryocyte precursors. The number of circulating blast cells determined by flow cytophotometry was nearly similar to those of observed in biopsies. The greatest bone marrow reticulin content could be detected in acute megakaryoblastic leukaemia cases. Despite the different clinicopathological entities, the presence of the same phenotype (megakaryoblasts) was associated with a short survival in these haematological malignancies (in CGL MKB phase 4.0, in CMGM MKB phase 4.2, and in AML M7 5.8 months, respectively).

Nucleolar organizer regions in acute and chronic leukaemias.

A silver staining technique for nucleolar organizer regions (NORs) has been applied to bone marrow biopsies of various types of acute and chronic leukaemias. This method could be easily evaluated on resin-embedded bone marrow obtained from acute lymphocytic leukaemia (n = 12), acute myelogenous (n = 16), chronic lymphocytic (n = 16) and chronic granulocytic (n = 20) leukaemia. A significant difference (p < or = 0.1) was only found between the AgNOR numbers in nuclei of lymphocytes from acute and chronic leukaemia (mean of 1.23 to 1.40 and 1.58) and those of cells from acute and chronic myelogenous leukaemia (from a mean of 5.00 to 9.17 per nucleus). However, no significant difference was observed among cells of various types of acute and chronic myelogenous leukaemias, despite of their markedly higher staining intensity and proliferative activity. The greatest mean of AgNOR numbers was counted in monoblasts of acute myelomonocytic leukaemia. It is suggested, that higher AgNOR counts in nuclei of more malignant leukaemic cells are in parallel with their mitotic activity and could be related to their elevated cell turn-over.

[The myelodysplastic syndrome]. / A myelodysplasiás szindrómáról.

Clinical data of 70 patients, treated and observed with myelodysplastic syndrome between 1977 and 1989 were analysed. Two-thirds of the patients belonged to the elder age-group and a mild female predominance was registered. With the application of complex cytochemical-histological and cytogenetical methods, correct diagnosis could be established. The clinical material included patients from different morphologic subtypes: 19 with refractory anaemia (with a longer course of the illness). 20 with sideroblastic anaemia, 26 with chronic myelomonocytic leukaemia and the remaining 5 with refractory anaemia with excess of blasts (a more progressive type of the myelodysplastic syndrome, with a short duration). The mean survival of all patients were 42 months. 45 (69%) died during this period and 12 (18.5%) among them in acute myelogenous leukaemia (mean survival: 16 month). Megakaryoblastic leukaemic transformation was observed in three patients with sideroblastic refractory anaemia. Haemorrhage and infection-sepsis, due to thrombocytopenia and/or granulocytopenia, was fatal in 30 cases. In the treatment of the myelodysplastic syndrome an appropriate supportive therapy (blood transfusion, antibiotics) has a decisive importance. A more aggressive treatment with cytostatic drugs is suggested in the progressive form of the disease of younger patients and in patients with overt acute leukaemia.

Histochemical observations on bone marrow biopsies embedded in glycol methacrylate (Technovit 7100).

Preparation of sections from undecalcified bone marrow biopsies embedded in glycol methacrylate (GMA, Technovit 7100) is reported. The beneficial effect of vacuum for a better penetration of resin into the hard tissue is assumed. Preserved details of 2- to 3-microns-thick sections of bone marrow specimens from various haematological malignancies yield a proper diagnosis and use of some histochemical methods on immature leukaemic cells is also possible. The use of embedding medium Technovit 7100 in the bone marrow histopathology is widely recommended for its simple, quick usage and non-toxic properties. An additional advantage is that blocks can be cut with ordinary steel knives (Histoknife H).

Experimental model of leukemic infiltrative pericarditis reflecting a human disease.

In human leukemias, pericarditis may be associated with leukemic pericardial infiltration. In order to obtain more information about the pathogenesis of the leukemic involvement of the pericardium, sterile talc-induced pericarditis was produced in acute lymphoid leukemic male hybrid mice. The animals invariable showed leukemic pericardial infiltration within 14 days. In leukemic mice without any treatment or with intrapericardial physiological NaCl injection (instead of talc), leukemic involvement of the pericardium did not occur.