Evaluation of stroma in human immunodeficiency virus/acquired immunodeficiency syndrome-affected bone marrows and correlation with CD4 counts

Division of Hematopathology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Archives of pathology & laboratory medicine (Impact Factor: 2.84). 10/2005; 129(9):1137-40. DOI: 10.1043/1543-2165(2005)129[1137:EOSIHI]2.0.CO;2
Source: PubMed


Little is known about cellular and extracellular composition of fibrosis in bone marrows in the context of human immunodeficiency virus/acquired immunodeficiency syndrome.
To evaluate the stromal composition of bone marrows affected by human immunodeficiency virus/ acquired immunodeficiency syndrome and to correlate this with laboratory parameters including CD4 lymphocyte counts.
We evaluated extracellular matrix and stromal cell composition in bone marrows and correlated these results with hematologic parameters. Extracellular matrix, stromal cells, and smooth muscle differentiation were evaluated by immunohistochemistry for collagen type IV expression and reticulin staining, an antibody directed against low-affinity nerve growth factor receptor (a marker of adventitial reticular cells), and actin staining, respectively. Concurrent laboratory information was collected, including white blood cell count, hemoglobin, platelet count, CD4 count, CD8 count, CD4/CD8 ratio, and absolute lymphocyte count.
Bone marrows of 35 patients with human immunodeficiency virus/acquired immunodeficiency syndrome were evaluated.
Correlation of reticulin, low-affinity nerve growth factor receptor, actin, and collagen IV staining with hematologic parameters.
More than half of the bone marrows showed moderate to severe reticulin fibrosis. The degree of reticulin fibrosis was correlated with the degree of low-affinity nerve growth factor receptor expression (P = .048). Actin expression was identified in only 3 of 35 cases and collagen IV in only 5 of 35 cases. No statistical relationship between degree of fibrosis and CD4 count was identified. Lower levels of low-affinity nerve growth factor receptor expression were associated with CD4 counts of >100 (P = .04). Marrow fibrosis was present in almost all cases studied (97%), and the staining of adventitial reticular cells correlated with the degree of reticulin fibrosis.
There does not appear to be a correlation between CD4 count and degree of fibrosis, suggesting that the mechanism of fibrosis is independent of disease status.

Download full-text


Available from: Dennis P O'Malley
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In bone marrow biopsies, stromal structural fibres are detected by reticulin and trichrome stains, routine stains performed on bone marrow biopsy specimens in diagnostic laboratories. Increased reticulin staining (reticulin fibrosis) is associated with many benign and malignant conditions while increased trichrome staining (collagen fibrosis) is particularly prominent in late stages of severe myeloproliferative diseases or following tumour metastasis to the bone marrow. Recent evidence has shown that the amount of bone marrow reticulin staining often exhibits no correlation to disease severity, while the presence of type 1 collagen, as detected by trichrome staining, is often associated with more severe disease and a poorer prognosis. It was originally thought that increases in bone marrow stromal fibres themselves contributed to the haematopoietic abnormalities seen in certain diseases, but recent studies suggest that these increases are a result of underlying cellular abnormalities rather than a cause. A growing body of evidence suggests that increased deposition of bone marrow stromal fibres is mediated by transforming growth factor-beta and other factors elaborated by megakaryocytes, but it is likely that other cells, cytokines and growth factors are also involved. This suggests new avenues for investigation into the pathogenesis of various disorders associated with increased bone marrow stromal fibres.
    Preview · Article · Dec 2007 · British Journal of Haematology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Systemic mastocytosis is a stem cell disorder characterized histologically by the presence of multifocal compact aggregates of mast cells in at least one extracutaneous organ with or without evidence of skin lesions. The mast cell aggregates are accompanied by fibrosis, which is often significant. However, in spite of its frequent occurrence and severity, little is known about its characteristics. In this study, we evaluated the composition of the fibrotic mast cell aggregates by studying eight bone marrow biopsies and two spleens involved by systemic mastocytosis, and compared the findings with those observed in other fibrotic bone marrow disorders such as primary myelofibrosis and metastatic malignancy. Histochemistry and immunohistochemistry were used to evaluate: (a) extracellular matrix (reticulin, trichrome, collagen IV, laminin); (b) stromal reticulum cells (low-affinity nerve growth factor receptor); (c) presence of myofibroblastic differentiation (smooth muscle actin) and (d) microvessel density (CD34). We found that all cases showed marked reticulin and collagen fibrosis. However, unlike primary myelofibrosis and metastatic malignancy, which are usually associated with increased low-affinity nerve growth factor receptor positivity, its expression was low in all cases of systemic mastocytosis. Myofibroblastic differentiation was only focally detected in two of eight bone marrow biopsies. In all cases, the systemic mastocytosis lesions were largely devoid of type IV collagen and laminin. The latter findings were in contrast with those seen in cases of primary myelofibrosis and metastatic malignancy where smooth muscle actin, collagen IV and laminin were expressed in most cases. Also in contrast with the other two conditions, only minimal vascularity was detectable within the fibrotic mast cell lesions. These findings indicate that systemic mastocytosis exhibits a distinct pattern of stromal change, and suggest that the fibrogenetic mechanism in systemic mastocytosis is most likely different from that of other bone marrow neoplasms which are also associated with fibrosis.
    Full-text · Article · May 2009 · Modern Pathology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Session 4 of the 2007 Workshop of the Society for Hematopathology/European Association for Haematopathology was devoted to myelodysplastic syndromes (MDSs). Submitted cases highlighted important issues and difficulties in relation to the diagnosis and classification of MDS. Much of the discussion focused on the correlation, or lack of it, between morphologic examination and other diagnostic techniques, cytogenetics in particular. The cases included examples of isolated del(5q) chromosomal abnormality, including the "classical" 5q- syndrome and other myeloid neoplasms. Other cytogenetic abnormalities in MDSs and the role of cytogenetics in diagnosing MDSs were addressed. Particularly challenging is the correct identification of fibrotic subtypes of MDSs and their separation from subsets of acute myeloid leukemia with myelofibrosis such as acute panmyelosis with myelofibrosis. The association and eventual relation of MDSs (hypoplastic in particular) with aplastic anemia, paroxysmal nocturnal hemoglobinuria, and other nonneoplastic disorders were illustrated. Novel cytogenetic and molecular genetic approaches are likely to revolutionize the classification of MDSs. However, it is unlikely that these new techniques will be capable, on their own, of adequately stratifying patients for treatment purposes. At least for the foreseeable future, the diagnosis of MDS requires integration of morphologic, immunophenotypic, and genetic features in the light of patient history and clinical manifestations.
    Preview · Article · Sep 2009 · American Journal of Clinical Pathology
Show more