Proliferative activity of myeloma cells determined by Ki-67 antibody: biological and clinical significance

In this study we analyzed proliferative activity of myeloma cells and a possible correlation with selected clinical data, histological features and survival in 59 patients with newly diagnosed multiple myeloma (27 females and 32 males, mean age 62 years). Imunohistochemical method was applied using Ki-67 antibody on B5-fixed and paraffin-embedded bone marrow specimens to evaluate growth fraction of myeloma cells. Clinical staging was done according to the Durie-Salmon classification (4 patients had stage I disease, 16 patients stage II and 39 patients stage III). The number of Ki-67+ myeloma cells ranged from 1% to 36% (mean value 7%). In 39 of 59 patients (66.1%) number of Ki-67+ cells was less than 10% (cases with low proliferative index). Ki-67 expression significantly correlated with the clinical stage, beta2-microglobulin level, plasma cell morphology, volume of myeloma infiltration and the extent of osteolytic lesions. Patients with increased proliferative index (Ki-67+ cells > or = 10%) showed a significantly shorter survival compared to those with low proliferative index (14 months vs. 36 months, p = 0.023). However, this difference was not shown in multivariate analysis, particularly due to the high correlation between proliferative activity and plasma cell morphology and the volume of myeloma infiltration.     

Megakaryocytopoiesis in experimentally induced chronic normobaric hypoxia

It was recently proposed that prolonged hypoxia produces hypomegakaryocytic thrombocytopenia by reducing the pool of committed megakaryocyte progenitor cells at the expense of a greatly expanded erythroid progenitor pool. In order to test this hypothesis we have studied the relationship between megakaryocytopoiesis, erythropoiesis, and granulopoiesis at the level of progenitor cells (megakaryocyte colony-forming unit, CFU-Mk; erythroid CFU, CFU-E; erythroid burst-forming units; BFU-E; and granulocyte-macrophage CFU, CFU-GM) in the marrow of rats exposed for 4 weeks to normobaric hypoxia. We have found that hypomegakaryocytic thrombocytopenia was accompanied by decreased CFU-Mk, increased CFU-E, and a normal number of BFU-E and CFU-GM. These results support the hypothesis that prolonged hypoxia reduces the precursor cell commitment to differentiate into the megakaryocyte series by enhancing demand for differentiation into the erythroid cell line. However, the underlying mechanism needs further investigation.     

Monocytoid B cell lymphoma associated with antibodies to myelin-associated glycoprotein and sulphated glucuronyl paragloboside.

Monocytoid B cell lymphoma (MBCL) is an immunologically and morphologically well-defined low-grade lymphoma with a predilection for lymph nodes of the parotid region. We describe an association of MBCL with anti-myelin-associated glycoprotein (MAG) polyneuropathy in a 53-year-old male. The diagnosis of stage IV MBCL with nodular bone marrow infiltration, Sj?gren's syndrome and sensorimotor polyneuropathy was made in October 1996. Serum immunoelectrophoresis demonstrated IgMkappa paraprotein. This was then cross-reacted with epitopes of MAG and sulphated glucuronyl paragloboside (SGPG) on myelin sheaths, and detected by thin layer chromatography and Western blot. Direct immunofluorescence of a sural nerve biopsy showed loss of myelin fibres, segmental demyelinization and IgM deposits on the myelin sheaths. The cerebrospinal fluid was normal. After six cycles of chemotherapy (ChlVPP protocol), all the patient's haematological parameters normalized accompanied by an improvement in neurological signs. The improvement of the polyneuropathy after chemotherapy indicates that the autoimmune anti-MAG and anti-SGPG antibodies resulted from the neoplastic lymphoid proliferation.     

Helicobacter pylori eradication can induce platelet recovery in chronic idiopathic thrombocytopenic purpura

We prospectively investigated the prevalence of Helicobacter pylori (H. pylori) infection in a cohort of 54 adult Serbian patients with chronic idiopathic thrombocytopenic purpura (ITP), and examined the effects of its eradication on their platelet counts. H. pylori infection was diagnosed in 39/54 (72.2%) patients, using the 14C-urea breath test; and was significantly higher than in the healthy Serbian population (55% P < 0.05). H. pylori-positive patients were significantly older than H. pylori-negative patients (P = 0.006), though there were no significant differences regarding gender, disease duration, mean platelet counts, previous therapies and spleen status between H. pylori-positive and H. pylori-negative patients. Successful eradication was confirmed in 23/30 (77%) treated patients. Stable platelet recovery was registered in 6/23 eradicated patients (26.1%) and maintained for 18 months. Complete and partial remissions were achieved in two and four patients, respectively, including one highly refractory patient. A significant mean platelet recovery was seen 6 months after successful H. pylori eradication in the group of 23 patients (P < 0.05). No platelet recovery was registered in either H. pylori-negative (n = 15), untreated H. pylori-positive patients (n = 9) or H. pylori-positive non-eradicated patients (n = 7). Even though the pathogenetic mechanisms of H. pylori-induced thrombocytopenia remain obscure, the results of this small prospective study support the use of H. pylori eradication as an effective non-immunosuppressive treatment for chronic ITP.     

Secondary myelofibrosis in visceral leishmaniasis--case report

A 39-year-old woman with a history of travel to the Montenegrin coast presented with a 9-month long history of fever and weakness, and on examination was found to be emaciated with hepatosplenomegaly and pancytopenia. Marrow aspiration showed poor cellularity with abundant Leishman Donovan (LD) bodies in the macrophages. Bone marrow trephine biopsy revealed a marked myelofibrosis (Manoharan classification: grade III) with osteosclerosis. The impression smears of a trephine biopsy stained with Güiemsa also showed LD bodies. The patient did not exhibit evidence of any risk factors for visceral leishmaniasis (VL). She was treated with meglumine antimoniate (Glucantime) without any adverse effect. The spleen returned to a normal volume after 4 months and bone marrow trephine biopsy performed 6 months after initiation of the therapy had returned to normal. A diagnosis was difficult to establish as VL is rarely encountered in the continental parts of Yugoslavia, and with the presence of associated myelofibrosis it could easily have been mistaken for chronic idiopathic myelofibrosis. The association of myelofibrosis with visceral leishmaniasis has been reported in the literature only three times; we thus feel that documentation of this case is merited.     

Thalassemia major. A report of two cases with severe skeletal involvement

Beta thalassemia major is rare in Serbia. Previously incurable, affected patients now live to adulthood with regular blood transfusions. The improvement in supportive treatment over recent decades has given rise to many more patients suffering from the associated metabolic complications of anaemia and iron overload, such as osteopenia and other skeletal changes. We present two patients with severe beta thalassemia major from early childhood, who encountered pathological long-bone fractures during the clinical course of their disease. One suffered a distal femoral diaphyseal fracture, and the second a distal tibia fracture. Both fractures occurred in osteopenic bone and were managed non-operatively due to the patients' general medical condition. Despite intense medical intervention, both patients died from disease progression within one year of their fractures, aged 23 and 24 years. As life expectancy rises it is anticipated that an increased number of beta thalassemia major patients will suffer pathological long-bone and other osteoporotic fractures. These fractures appear to both herald and contribute to a general clinical deterioration of this disease. Advances in stem-cell technology may hold the key for a definitive cure.     

Littoral-cell angioma as a rare cause of splenomegaly

We report the case of a littoral-cell angioma of the spleen, a recently described benign vascular tumour, whose imaging and pathological characteristics have been discussed only by a few authors. The diagnosis was made after elective splenectomy. The CT images, scintigraphy and histological specimens are presented, and differential diagnoses discussed.