RESUMO
In this study a large family group affectd with Tangier disease has been investigated. Besides two homozygous propositi, several heterozygous patients have been identified on the basis of quantitative measurements of high density lipoproteins and their constitutive polypeptides. By a variety of quantitative immunological methods, such as one-dimensional Laurell eletrophoresis, two-dimensional immunoelectrophoresis, and double-antibody radioimmunoassay, the total amount of apoprotein A-I and apoprotein A-I contained in the serum of heterozygous patients and the distribution of these A apoproteins among serum lipoproteins have been determined. The molar ration of apoprotein A-I and apoprotein A-II contained in high density lipoproteins of heterozygous patients did not significantly differ from that of control preparations, although the total mass of high density lipoproteins was reduced by approximately 50%. The elution profile of high density lipoproteins from agarose columns and their morphological appearance, as ascertained by electron microscopy, were similar to control preparations. In addition to the quantitative alterations of serum lipoproteins, lipid storage in histiocytes of the rectal mucosa obtained from heterozygous patients has been documented. It is concluded that patients heterozygous for Tangier disease have normal high density lipoproteins in circulation, the total mass of which is reduced by approximately 50%.
Assuntos
Hipolipoproteinemias/genética , Lipoproteínas HDL/genética , Doença de Tangier/genética , Apolipoproteínas/sangue , Colesterol/sangue , Cromatografia em Gel , Eletroforese em Gel de Ágar , Feminino , Heterozigoto , Humanos , Imunoeletroforese Bidimensional , Lipoproteínas HDL/sangue , Masculino , Linhagem , Radioimunoensaio , Doença de Tangier/sangueRESUMO
BACKGROUND: Endothelin-converting enzyme (ECE)-1 activates endothelin-1 (ET-1) and may thus contribute to the regulation of vascular tone and cell growth during atherosclerosis. METHODS AND RESULTS: To evaluate ECE-1 immunoreactivity concerning big ET-1/ET-1, we performed qualitative and quantitative immunohistochemistry in normal internal mammary arteries (n=10), in coronary arteries with adaptive intimal fibrosis (n=10), in aortic fatty streaks (n=10), and in distinct regions of advanced carotid plaques (n=15). Furthermore, we determined ECE-1 activity in the control specimens and in the inflammatory intimal regions of carotid plaques. Double immunolabeling showed that ECE-1 was present in endothelial cells, vascular smooth muscle cells, and macrophages. All ET-1(+) cells were simultaneously ECE-1(+). Most importantly, there were significantly more ET-1(+) cells in the intima and media when atherosclerosis was in an inflammatory stage than when it was in a noninflammatory stage. Moreover, ECE-1 activity was upregulated in the intima of carotid plaques, although immunohistochemically, there were no significant differences between the number of ECE(+) cells in the different compartments of the arterial wall. CONCLUSION: Together with ET-1, ECE-1 is abundantly present in human arteries and at different stages of atherosclerotic plaque evolution. The upregulation of the ECE-1/ET-1 system is closely linked to the presence of chronic inflammation and is present in very early stages of plaque evolution. Therefore, enhanced production of active ET-1 may substantially contribute to cell growth and the regulation of vascular tone in advanced atherosclerotic lesions and in the very early stages of plaque evolution, when a plaque is still imperceptible clinically.
Assuntos
Arteriosclerose/metabolismo , Arteriosclerose/patologia , Ácido Aspártico Endopeptidases/metabolismo , Endotelina-1/metabolismo , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/complicações , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Arteriosclerose/complicações , Ácido Aspártico Endopeptidases/análise , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Estenose das Carótidas/complicações , Estenose das Carótidas/metabolismo , Estenose das Carótidas/patologia , Doença Crônica , Doença das Coronárias/complicações , Doença das Coronárias/metabolismo , Doença das Coronárias/patologia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Progressão da Doença , Endotelina-1/análise , Enzimas Conversoras de Endotelina , Ativação Enzimática , Humanos , Imuno-Histoquímica , Inflamação/complicações , Inflamação/metabolismo , Inflamação/patologia , Artéria Torácica Interna/metabolismo , Artéria Torácica Interna/patologia , Metaloendopeptidases , Túnica Íntima/metabolismo , Túnica Íntima/patologia , Túnica Média/metabolismo , Túnica Média/patologiaRESUMO
PURPOSE: Multivariate risk classifications for chronic (stable)-phase Ph(1+) chronic myelogenous leukemia (CML) are generally focused on hematologic variables, and the putative prognostic property of bone morphology has been neglected or even contested so far. PATIENTS AND METHODS: A total of 510 consecutively recruited patients in first chronic phase Ph(1+) CML and pretreatment bone marrow biopsy specimens were entered onto this multicenter observational trial to evaluate the effect of bone marrow histopathology. According to generally accepted criteria, patients with any signs of accelerated disease were excluded. Treatment modalities included administration of interferon alfa-2b (IFN) and chemotherapy with hydroxyurea (HU) or busulfan. Immunohistochemical and morphometric techniques were applied to identify marrow cells and to quantify fiber density. Patients were separated into learning and validation samples, and classification and regression tree (CART) analysis was performed to establish a prognostic decision tree. RESULTS: CART analysis of the validation sample (123 patients with HU therapy) revealed the amount of erythroid precursors in the bone marrow, myelofibrosis, and splenomegaly as the most important prognostic features. Three risk profiles with significantly different survival patterns were established, with median survival times ranging from 33 to 108 months (two-sided log-rank test, P =.0001). The new score was confirmed by application to the learning sample with IFN therapy (two-sided log-rank test, P =.0002). Furthermore, risk status defined by the new score was significantly correlated with the occurrence of blast transformation. CONCLUSION: Our data strongly implicate that prognostic classification of chronic-phase Ph(1+) CML can be significantly improved by the inclusion of morphologic parameters. The variables of the presented scoring system may be easily assessed by routinely processed aspirates and bone marrow trephines.
Assuntos
Medula Óssea/patologia , Árvores de Decisões , Leucemia Mieloide de Fase Crônica/diagnóstico , Antineoplásicos/uso terapêutico , Feminino , Humanos , Hidroxiureia/uso terapêutico , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Leucemia Mieloide de Fase Crônica/classificação , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/mortalidade , Ativação Linfocitária , Macrófagos/patologia , Masculino , Megacariócitos/patologia , Pessoa de Meia-Idade , Análise Multivariada , Mielofibrose Primária/patologia , Prognóstico , Proteínas Recombinantes , Análise de Regressão , Reprodutibilidade dos Testes , Risco , Sensibilidade e Especificidade , Análise de SobrevidaRESUMO
A 32-year-old white woman was admitted with a diagnosis of T lymphoblastic lymphoma and a bone marrow and peripheral blood cytology that was suggestive of a myeloproliferative syndrome (MPS). In addition, islets of myeloid precursors were found in the lymph node where the lymphoma had been diagnosed. Cytogenetic examination was negative for the Philadelphia chromosome (Ph) as well as the RT-PCR for bcr/abl rearrangement, but surprisingly a t(8;13)(q10;p10) was detected. To our knowledge, this translocation has not been reported in such a clinical setting. The patient was treated for the lymphoblastic lymphoma and underwent autologous bone marrow transplantation. She has been in complete remission since induction chemotherapy with a Karnofsky score of 100%. The difficulty of classifying this case is discussed.
Assuntos
Cromossomos Humanos Par 13 , Cromossomos Humanos Par 8 , Linfonodos/patologia , Linfoma de Células T/genética , Transtornos Mieloproliferativos/genética , Translocação Genética , Adulto , Transplante de Medula Óssea , Mapeamento Cromossômico , Feminino , Seguimentos , Humanos , Cariotipagem , Linfoma de Células T/patologia , Linfoma de Células T/terapia , Transtornos Mieloproliferativos/patologia , Transtornos Mieloproliferativos/terapia , Reação em Cadeia da Polimerase , Síndrome , Transplante AutólogoRESUMO
Two middle-aged patients with T cell lymphoma, both natives of Bucharest, Romania, tested positive for HTLV-I antibodies. Malignant cells had the typical phenotype and morphology of adult T cell leukemia/lymphoma (ATL). Both cases presented with extranodal manifestation, hypercalcemia, early recurrence after initial responses to therapy, and subsequent resistance to conventional and intensified chemotherapy. Infection with HTLV-I was confirmed by PCR analyses of serial biopsies. Neither patient reported known risk factors for HTLV-I infection. This report points to the possibility that Romania may represent an endemic area for HTLV-I and should heighten the awareness towards HTLV-I infections in Romanian patients.
Assuntos
Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Adulto , Antígenos CD/análise , Sequência de Bases , Biópsia , Primers do DNA , DNA Viral/sangue , Feminino , Anticorpos Anti-HTLV-I/análise , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Imuno-Histoquímica , Imunofenotipagem , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/terapia , Leucemia-Linfoma de Células T do Adulto/virologia , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , RomêniaRESUMO
Atherosclerosis is a 'response-to-injury' process associated with chronic inflammation, tissue repair and a considerable cell turnover. These growth-related processes are controlled by the 'cell cycle clock' which is composed of cyclin-dependent kinases (Cdks), their activating subunits, the cyclins, and by inhibitors of Cdks (Ckis). P27 is a Cki which associates with cyclin A-Cdk2, cyclin D-Cdk4 and with cyclin E (CE)-Cdk2 complexes thereby abrogating their catalytic activity leading to potent inhibition of late G1 to S-phase transition. Furthermore, TGF-beta1 mRNA and immunoreactivity are locally increased in atherosclerotic lesions. Since TGF-beta1 growth suppressive function in the late G1 phase may be mediated by p27, blocking the catalytic activity of CE-Cdk2 complexes, via the stimulation of TGF-beta-RI and TGF-beta-RII, we investigated the topographical association between TGF-beta-RI, TGF-beta-RII, P27Kip1 and CE by immunohistochemistry in coronary artery segments without atherosclerosis and carotid atheromatous plaques of 11 patients undergoing carotid endarterectomy. P27-immunoreactivity was present in 11/11 atherosclerotic (92.7 +/- 3.3% of the cells) and 5/5 control (80.9 +/- 3.7% of the cells; P < 0.002 versus control) specimens and localized to nuclei of macrophages (CD68-positive), vascular smooth muscle cells (alpha-actin positive), T-lymphocytes (CD3-positive) as well as to the nuclei of endothelial cells. In the atherosclerotic tissue, TGF-beta-RI and TGF-beta-RII-immunoreactivity was present in 11/11 specimens and localized to inflammatory cells and to cells with VSMC-like-morphology. TGF-beta-RI-immunoreactivity was present in 87.4 +/- 5.3% (controls 75.3 +/- 7.48%; n.s.) and TGF-beta-RII-immunoreactivity was present in 83.7 +/- 6.8% (controls 39.5 +/- 7.3%; P < 0.002) of the cells. Double immunolabeling, and investigation of serial sections revealed co-expression of TGF-beta-RI and TGF-beta-RII in virtually all cells positive for P27. In the atherosclerotic specimens, CE-immunoreactivity was present in all specimens in macrophages (CD68-positive), vascular smooth muscle cells (alpha-actin positive) and in endothelial cells in 12.58 +/- 13.58% of the nuclei whereas in the controls CE staining was restricted to 0.19 +/- 0.43% of the cells (P < 0.001). Importantly, as shown by immunofluorescent double-labeling, we found cells expressing P27 that were simultaneously positive for CE. In summary, the present study provides evidence that TGF-beta1 present in human atherosclerotic tissue may mediate its growth suppressive activity also by p27, blocking the activity of CE-Cdk2 complexes. Quantitative analysis revealed that TGF-beta-RII, p27 and CE are concordantly upregulated in the atherosclerotic tissue with chronic inflammation, supporting the view that TGF-beta1, p27 and CE may play an important role in the processes associated with chronic inflammation and cell turnover in advanced human atherosclerotic plaques. Taken together, these results provide a possible link between the chronic inflammation associated with advanced atherosclerosis, the effects of extracellular growth factors and cell cycle control.
Assuntos
Arteriosclerose/metabolismo , Arteriosclerose/patologia , Proteínas de Ciclo Celular , Ciclina E/metabolismo , Quinases Ciclina-Dependentes/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas Supressoras de Tumor , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Divisão Celular/fisiologia , Técnicas de Cultura , Ciclina E/imunologia , Inibidor de Quinase Dependente de Ciclina p27 , Humanos , Imuno-Histoquímica , Valores de Referência , Sensibilidade e Especificidade , Fator de Crescimento Transformador beta/imunologia , Regulação para CimaRESUMO
A 46-year-old female presented with acute myeloid leukemia during complete remission of multiple myeloma after extensive treatment with alkylating agents. Leukemic blasts expressed CD34, platelet esterase and gp IIIa. RT-PCR analyses of peripheral blood cells detected a p190 type BCR-ABL rearrangement and high levels of MDR1. The patient expired during neutropenia shortly after induction chemotherapy. Autopsy revealed persistent blasts in the bone marrow, spleen and liver. 'Secondary' acute myeloid leukemia with megakaryoblastic features and p190-type BCR-ABL rearrangement has not previously been reported. The possibility that the combination of a BCR-ABL rearrangement with overexpression of MDR1 may have contributed to the treatment-refractory course is discussed.
Assuntos
Proteínas de Fusão bcr-abl/análise , Leucemia Megacarioblástica Aguda/genética , Mieloma Múltiplo/tratamento farmacológico , Segunda Neoplasia Primária , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Leucemia Megacarioblástica Aguda/tratamento farmacológico , Leucemia Megacarioblástica Aguda/etiologia , Leucemia Megacarioblástica Aguda/patologia , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The role of chronic inflammation in the pathogenesis of the acute coronary syndromes has received increasing attention since active plaques rich in macrophages (Mphi's) are more prone to rupture whereas plaques rich in myofibroblasts are considered to be stable. Functionally, active plaques show a locally enhanced vasoreactivity. Endothelin-1 (ET-1) a potent vasoconstrictor acts in a paracrine fashion to regulate vascular tone. ET-1 is also produced by inflammatory cells suggesting a role for ET-1 in inflammation. Additionally, ET-1 is a mitogen. Endothelin converting enzyme-1 (ECE-1) activates ET-1 and may thus contribute to the regulation of vascular tone and cell growth during atherosclerosis. We evaluated the presence of ECE-1 and big ET-1/ET-1 and the activity of ECE-1 in different plaque types. Together with ET-1, ECE-1 is present in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and Mphi's. ECE-1 activity and ET-1-immunoreactivity (IR) both are upregulated during the progression of atherosclerosis from a non-inflammatory to an inflammatory stage. Thus, enhanced production of active ET-1 may contribute to cell growth and regulation of vascular tone in advanced plaques and also in very early stages of atherosclerosis. Furthermore, we examined the presence of ET-1 in coronary plaque tissue obtained by directional coronary atherectomy. ET-1 IR localized to plaque components indicative of chronic inflammation. Semiquantitative analysis of ET-1 IR revealed significantly higher staining grades in active coronary lesions compared with nonactive lesions. The increased ET-1 content in active coronary lesions may be beneficial to the stabilization of the vessel wall after plaque rupture and disadvantageous because it may lead to vasospasm and to the progression of atherosclerosis.
Assuntos
Ácido Aspártico Endopeptidases/fisiologia , Aterosclerose/etiologia , Endotelina-1/fisiologia , Metaloendopeptidases/fisiologia , Ácido Aspártico Endopeptidases/análise , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Vasos Coronários/química , Antagonistas do Receptor de Endotelina A , Endotelina-1/análise , Enzimas Conversoras de Endotelina , Humanos , Imuno-Histoquímica , Artéria Torácica Interna/química , Metaloendopeptidases/análise , Metaloendopeptidases/antagonistas & inibidores , Microscopia Imunoeletrônica , Túnica Íntima/químicaRESUMO
After a single pulse dose of DMBA, rats develop bone-marrow hypoplasia, which is almost compensated for by regeneration after 16 weeks. Subsequently, dysplastic signs of hemopoiesis appear in all experimental animals as massive extrusion of normoblasts into the peripheral blood, red-cell aniso- and poikilocytosis, nuclear deformities, atypical mitoses, and PAS-positivity, as well as megaloblastoid maturation dissociation of erythroblasts and nuclear and granulation anomalies of neutrophilic granulocytes and monocytes, comparable to human "pseudo-Pelger cells" and "paraneutrophils". At the time of death (112-497 days after DMBA pulse) experimental animals showed hyperplastic bone marrow with increased granulopoietic/erythropoietic ratios and an augmented, mainly erythropoietic, hemopoiesis in the spleen, with splenomegaly in six rats. Splenic hemopoiesis is accompanied by white pulp atrophia. The cause of death was septicopyemia in three rats, anemia in three, and bleeding in one rat. None of the animals developed a leukemic blast phase. Myelodysplastic changes in this experiment are the same as have been shown to precede leukemia in rats treated with five DMBA pulses (Fohlmeister et al. 1981). Possible relations of myelodysplasia and leukemia are discussed.
Assuntos
Pré-Leucemia/patologia , 9,10-Dimetil-1,2-benzantraceno , Animais , Contagem de Células Sanguíneas , Exame de Medula Óssea , Contagem de Eritrócitos , Granulócitos , Hematopoese , Humanos , Injeções , Masculino , Neoplasias Experimentais/patologia , Pré-Leucemia/induzido quimicamente , Pré-Leucemia/etiologia , Ratos , Ratos Endogâmicos , Baço/citologiaRESUMO
Normal tissue as well as various benign and malignant lesions of the breast were histochemically examined for the presence of the Thomsen-Friedenreich (TF)-antigen. Fluorescein- or 3H-labelled peanut agglutinin was used for this purpose, a lectin that is known to have a high affinity for the TF-antigen. The occurrence of this TF-antigen seemed in all cases, even in the carcinoma lobulare in situ that is regarded as being derived from myoepithelial cells by some authors, to be associated with a secretory condition. Its presence (free and neuraminic acid covered) in normal, hyperplastic and malignant breast tissue, however, cannot be considered a specific tumour associated antigen as has been previously assumed. Furthermore the investigations have shown that the intensity of fluorescence for peanut agglutinin (PNA)-receptors was generally stronger in differentiated carcinomas than in undifferentiated carcinomas of the breast. The histochemical findings are discussed with regard to diagnostical and immunotherapeutical aspects.
Assuntos
Antígenos de Neoplasias , Neoplasias da Mama/imunologia , Mama/imunologia , Antígenos de Superfície , Mama/patologia , Doenças Mamárias/imunologia , Carcinoma in Situ/imunologia , Feminino , Humanos , Hiperplasia , Imunoquímica , Lectinas , NeuraminidaseRESUMO
We performed a retrospective clinicopathologic study on sequential biopsy specimens from 90 patients with Philadelphia chromosome-positive chronic myelogenous leukemia to study therapy-specific effects of busulfan (28 patients), hydroxyurea (32 patients), and interferon-alfa (IFN-alfa; 30 patients). Bone marrow specimens were evaluated by morphometry after silver impregnation and staining with monoclonal antibodies to identify reticulin fibers, nucleated erythroid precursors, megakaryocytes, and macrophages. To compute dynamics of histopathology implicating corresponding changes in time, relevant indices were calculated. Quantification of megakaryocytopoiesis and its precursor cell population showed a significant increase in the IFN-alfa and busulfan groups compared with the hydroxyurea group. These changes were associated with a development of myelofibrosis during therapy. Although a significant increase in fiber density was detectable in the busulfan group, the progression index proved to be twice as high after IFN-alfa therapy. In contrast, a considerable number of patients displayed a regression of myelofibrosis after hydroxyurea treatment. The general association of the megakaryocyte lineage with myelofibrosis was in line with experimental findings. The mature macrophage population and its activated subfraction revealed a marked proliferation (IFN-alfa group) during treatment. Growth and activation of macrophages may be compatible with their putative function during erythrocytopoietic regeneration and with stimulation of their phagocytic properties.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos/uso terapêutico , Bussulfano/uso terapêutico , Hidroxiureia/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Biópsia/métodos , Medula Óssea/patologia , Progressão da Doença , Feminino , Histocitoquímica , Humanos , Masculino , Megacariócitos/patologia , Pessoa de Meia-Idade , Mielofibrose Primária/patologia , Estudos Retrospectivos , TrepanaçãoRESUMO
BACKGROUND: Chronic neutrophilic leukaemia (CNL) is a distinct BCR/ABL negative myeloproliferative disorder of elderly patients characterised by sustained neutrophilia and splenomegaly. The bone marrow shows expansion of neutrophilic granulopoiesis, without excess of myeloblasts. To date, only 129 cases of CNL have been reported in the literature. AIMS: To report the findings from a large group of 14 new cases of CNL, consisting of eight women and six men (mean age, 64.7 years). METHODS: A review of the 14 new cases of CNL and the investigation of BCR/ABL translocations in these patients. RESULTS: Three quarters of the patients died within two years after diagnosis, mostly as a result of severe cerebral haemorrhage. Two younger patients were successfully treated with allogeneic bone marrow transplantation or interferon, which resulted in haematological remission for years. CONCLUSION: CNL is a rare myeloproliferative disease mostly taking a fatal clinical course, despite the presence of mature neutrophils as leukaemic cells in the blood. Thus, it is important to recognise CNL to develop appropriate therapeutic strategies for affected patients.
Assuntos
Leucemia Neutrofílica Crônica/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
In a retrospective study of 111 patients with aplastic anaemia iliac crest biopsies were evaluated for the presence of morphological features statistically related to the evolution of the disease. Prognostic variables for a transition to acute non-lymphatic leukaemia were: cellular atypias of the three haemopoietic lineages, as observed in the myelodysplastic syndrome, and especially "micromegakaryocytes"; high numbers or irregular distribution of megakaryocytes, or both; and (slight) marrow fibrosis. Clinical variables did not influence these prognostic correlations. Prognosis in relation to death from bone marrow failure without leukaemia might well have been influenced by a strong plasma cell reaction, but this correlation was weakened by clinical factors. On the basis of this study aplastic anaemia can thus be subdivided morphologically into two disease entities--namely, hypocellular myelodysplastic syndrome with a 23-82% risk of acute non-lymphatic leukaemia developing within three years, depending on how many variables associated with acute non-lymphatic leukaemia are present, and non-dysplastic myelohypoplasia.
Assuntos
Anemia Aplástica/patologia , Medula Óssea/patologia , Leucemia/etiologia , Adolescente , Adulto , Idoso , Contagem de Células , Transformação Celular Neoplásica , Criança , Células-Tronco Hematopoéticas/patologia , Humanos , Megacariócitos/patologia , Pessoa de Meia-Idade , Prognóstico , Reticulina , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Chronic neutrophilic leukaemia (CNL) is a rare myeloproliferative disorder of elderly patients characterised by sustained neutrophilia and splenomegaly. The diagnosis of CNL requires the exclusion of BCR/ABL positive chronic myelogenous leukaemia (CML) and of leukaemoid reactions (LRs). The differentiation between CNL and LR is problematic because both conditions share similar morphological features; it is also important because patients with CNL generally have a poor prognosis. AIMS: To determine whether CNL and LR could be distinguished on the basis of different clonality patterns. METHODS: Blood samples from 52 women were studied using the human androgen receptor gene assay (HUMARA). RESULTS: Monoclonality was found in the neutrophils in all 17 patients with different myeloproliferative syndromes (MPSs), including those with CNL. In four of the patients with CNL, autologous T cells were also monoclonal, suggesting that they belonged to the neoplastic clone. This finding was in contrast to other MPSs in which T cells were almost always polyclonal. Of nine patients with clinically suspected LR, the neutrophils of five were polyclonal, whereas three patients had monoclonal neutrophils, suggesting that they might be in the process of developing an MPS. Among 26 healthy blood donors, 20 had polyclonal neutrophils and five showed skewed clonality patterns. One case of LR and one normal blood donor were scored "not informative" at the HUMARA locus. CONCLUSIONS: Clonality studies of blood neutrophils using HUMARA aid in distinguishing female patients with monoclonal CNL from those with LR. For the diagnosis of CNL, monoclonality of the neutrophils should be demonstrated whenever possible.
Assuntos
Leucemia Neutrofílica Crônica/diagnóstico , Reação Leucemoide/diagnóstico , Células-Tronco Neoplásicas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Mecanismo Genético de Compensação de Dose , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Neutrofílica Crônica/genética , Reação Leucemoide/genética , Pessoa de Meia-Idade , Neutrófilos/patologia , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismoRESUMO
We report a case in which an adult form of Niemann-Pick disease (type B of NPD) was associated with a rapidly progressive generalized AL amyloidosis of kappa type. Both diagnosis were made by biopsy, the NPD by bone marrow biopsy and fibroblast culture, the amyloidosis by liver biopsy. Malignant non-Hodgkin lymphoma was not found. The patient, a 67-year-old woman, died from hepatic coma subsequent to a progressive liver failure. We discuss possible relations between the lysosomal storage disease and the development and rapid progression of amyloidosis.
Assuntos
Amiloidose/complicações , Falência Hepática/etiologia , Fígado/patologia , Doenças de Niemann-Pick/complicações , Idoso , Amiloidose/patologia , Feminino , Humanos , Falência Hepática/patologia , Microscopia Eletrônica , Doenças de Niemann-Pick/patologiaRESUMO
Polyneuropathy in Tangier disease can be divided into three clinical types. The most severe form (type III) with a syringomyelia-like syndrome has been described in three cases only. Here, a fourth case of this type is presented. Because of unusual trophic disturbances even leprosy was suspected. Electrodiagnostic findings, including evoked cerebral potentials in this case, were suggestive of a generalized neuropathy with some degree of primary or secondary demyelination and implied possible impairment of central structures. Sural nerve biopsy, including electron microscopy and quantitative analysis, revealed a predominant reduction of smaller myelinated and unmyelinated fibres. The main morphological feature was the abundance of abnormal non-membrane-bound vacuoles in Schwann cells, mostly of the unmyelinated type, and in some endoneurial fibroblasts, macrophages and perineurial cells. There was no inverse relationship between lipid vacuoles and axons in Schwann cell complexes as suspected by others. An excess of endoneurial collagen as well as an increased fascicular area were obvious. In five skin biopsy specimens of different regions typical vacuoles were noted in Schwann cells, histiocytes, nevus cells, and rarely in perineurial cells.
Assuntos
Hipolipoproteinemias/complicações , Hanseníase/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Siringomielia/diagnóstico , Doença de Tangier/complicações , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Microscopia Eletrônica , Músculos/patologia , Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/patologia , Doença de Tangier/diagnóstico , Doença de Tangier/patologiaRESUMO
Severe pancytopenia associated with moderate hepatosplenomegaly, increased serum lactic dehydrogenase (LDH) levels, and hypogammaglobulinemia were found in a young male patient. Bone marrow histology showed extensive fibrosis, hypoplasia of erythro- and granulocytopoiesis, and hyperplasia of megakaryocytopoiesis associated with histiocytic fat cell phagocytosis and infiltration of abnormal lymphocytes, compatible with lymphoid myelofibrosis. Striking chromosomal aberrations indicating karyotype evolution were also demonstrated by cytogenetic analyses (47, XY, +3 / 47, XY, +3, 1p+ / 46, XO, +3, 1p+, -Y). The clinical course was characterized by cyclic febrile episodes accompanied by excessive increase of serum LDH levels and leukocyte counts, and decrease of platelet counts, followed by spontaneous regression. Further diagnostic procedures, including two liver biopsies and computed tomography, did not detect any manifestation of lymphoma. Eventually, the patient developed rapidly progressive, lethal pulmonary aspergillosis. At autopsy, high grade B cell lymphoma of the liver was found. In this case, the lymphoid myelofibrosis seen on bone marrow biopsy may be considered as a manifestation of "discordant" bone marrow histology related to high grade lymphoma. With respect to the cyclic clinical course, a possible role of apoptotic mechanisms in the physiopathology of this disorder is reviewed.
Assuntos
Aberrações Cromossômicas , Neoplasias Hepáticas/genética , Linfoma não Hodgkin/genética , Mielofibrose Primária/genética , Adulto , Medula Óssea/patologia , Humanos , Cariotipagem , L-Lactato Desidrogenase/metabolismo , Contagem de Leucócitos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Linfoma não Hodgkin/enzimologia , Linfoma não Hodgkin/patologia , Masculino , Contagem de Plaquetas , Mielofibrose Primária/patologiaRESUMO
A multicenter, immunohistochemical and morphometric study was performed on diagnostic pretreatment bone marrow biopsies in 614 adult patients with Ph1+ chronic myeloid leukemia (CML) to compare histological features with clinical findings. For identification of megakaryopoiesis we used the monoclonal antibody CD61 and additionally the PAS reaction to determine the subfraction of atypical micromegakaryocytes and precursors. Labelling of erythroid precursors was carried out by a monoclonal antibody directed against glycophorin C. In order to selectively stain macrophages and their activated subset we applied CD68 and the GSA-I lectin. Density of argyrophilic fibers (reticulin plus collagen) was measured following Gomori's silver impregnation method. In accordance with laboratory data morphological variables revealed a comparable amount of congruence in the various groups of CML patients derived from different sources. In about 26% of patients early (reticulin) to advanced (collagen) fibrosis was detectable. Significant correlations were calculated between the extent of myelofibrosis with splenomegaly, anemia and increasing numbers of erythroblasts and myeloblasts in the peripheral blood count. These features were assumed to indicate more advanced stages of the disease process with ensuing transition into myeloid metaplasia and consequently were associated with an unfavorable prognosis. Significant relationships were revealed between the number of CD61+ megakaryocytes and more important, also their precursor fraction with the degree of fibrosis. This result extends previous experimental findings regarding the impact of immature elements of this cell lineage for the generation of myelofibrosis. The significant association of erythroid precursors with the number of mature (resident) macrophages including their activated GSA-I subset may shed some light on their functional involvement in iron turnover and hemoglobin synthesis. A modified histological classification of predominant bone marrow features is introduced. This simplified synthesis staging system (Cologne Classification) is not only associated with certain sets of laboratory data, but also with different survival patterns.
Assuntos
Medula Óssea/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Adulto , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Mielofibrose Primária/etiologia , Taxa de SobrevidaRESUMO
Normal kidney tissue as well as hypernephromas were examined histochemically for the occurrence of lectin receptors. FITC- and rhodamine-labeled peanut agglutinin (PNA) and Ricinus communis agglutinin (RCA) were used for labeling different carbohydrate residues which may be of interest in the evaluation of the histogenesis of hypernephromas and possibly for concepts regarding the immunotherapy of these tumors. By using fluorescence microscopy, the receptor for PNA was found on the epithelial cells of the thin limb, distal convoluted tubules, and the collecting ducts. These binding sites occurred in a free as well as in a sialic-acid-substituted form and were mainly exposed on the luminal surface of the epithelial cells. They were absent, however, in the proximal convoluted tubules. This finding contrasts with the demonstration of RCA receptors in the brush border of these tubules. Moreover, RCA reacted with the epithelial cells of all tubules. The hypernephromas showed a wide range in the distribution and the quality of the lectin receptors, which were localized within the cytoplasm as well as in the cell membrane of the tumor cells. As demonstrated by our histochemical investigations, these kidney neoplasms may originate from any part of the tubules, and not only from the epithelial cells of the proximal convoluted tubules, as was suggested by earlier findings that employed antibodies against the brush-border antigens. In addition, the demonstration of sialic-acid-substituted and, in particular, of free PNA-receptors, which represent the immunodominant group of the Thomsen-Friedenreich antigen, may supply useful information on an immunotherapy concept.
Assuntos
Adenocarcinoma/análise , Neoplasias Renais/análise , Rim/análise , Receptores Mitogênicos/análise , Sítios de Ligação , Humanos , Neoplasias Renais/terapia , Neuraminidase/farmacologiaRESUMO
Analysis of myelodysplastic syndromes (MDS) in 77 patients terminating in "overt" leukemia revealed sequential changes of marrow morphology with respect to cellularity and involvement of lineages, indicating that different "forms" of MDS represent in reality different phases. Three main phases were observed, which occurred in the following non-reversible sequence: (a) hypocellular dysplasia (H), (b) hypercellular dysplasia with predominance of erythropoiesis (E), and (c) with predominance of myelo(mono)poiesis (MM). Published studies suggest that these phases represent different manifestation stages of the stem cell lesion leading to MDS. Manifestation may probably be promoted by factors causing marrow aplasia. Transition to "overt" leukemia in several cases occurred locally, not throughout the whole marrow. In some patients a mature myelo(mono)-cytic cell population showed the capacity for widespread tissue infiltration, characteristic of leukemic cells. This argues against the theory that "overt" leukemia is the result of continuous dedifferentiation in MDS, but favours the concept of multiple initiating "events" leading to evolution of a leukemic subclone within a myelodysplastic clone. A connection between leukemia differentiation and MDS phase, from which leukemia developed, was also observed indicating that the risk of different stem cell subpopulations to become the target of the leukemia initiating "event" varies during the course of myelodysplasia.