Chronic myelomonocytic leukemia: The role of bone marrow biopsy immunohistology

Clarian Pathology Laboratory, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202-5200, USA.
Modern Pathology (Impact Factor: 6.19). 01/2007; 19(12):1536-45. DOI: 10.1038/modpathol.3800707
Source: PubMed


The World Health Organization criteria for diagnosing chronic myelomonocytic leukemia (CMML) are largely based on findings observed in the peripheral blood and bone marrow aspirate. A specific diagnostic role for the bone marrow biopsy has not been adequately explored. We examined whether bone marrow biopsy supplemented by immunohistochemistry may be helpful in distinguishing CMML from cases of chronic myelogenous leukemia and atypical chronic myeloid leukemia (aCML). We immunostained 25 cases of CMML with paraffin reactive antibodies which included CD68 (KP1), CD68R (PG-M1), and CD163, and compared the results with those observed in six cases of chronic myelogenous leukemia and in three cases of atypical CML. In addition, we examined whether CD34 immunohistochemistry could be useful in separating cases of CMML with less than 10% blasts (type-1) from cases of CMML with blasts accounting for 10-19% (type-2), and cases of CMML in acute transformation to acute myeloid leukemia (blasts > or = 20%). The presence of nodules of plasmacytoid monocytes was investigated by CD123 staining. CD42b was used to highlight abnormal megakaryocytes. Our results demonstrate significant differences between the groups. CD34 analysis allowed separating CMML type-1 from type-2 and the former from CMML in acute transformation. CD123-positive plasmacytoid monocyte nodules were found only in CMML and not in the other two disease groups. Overlap between CMML and the other two groups were observed with CD68 immunostaining. CD68R was more restricted to bone marrow macrophages and monocytes than CD68, but the differences between CMML and chronic myelogenous leukemia or atypical CML were still not significant. Although CD42b immunostaining facilitated the detection of dwarf megakaryocytes often present in CMML, the distinction between those and the small forms seen in chronic myelogenous leukemia was still problematic.

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    • "monocytosis is accompanied by a neutrophilia without a significant left shift (i.e., neutrophilic precursors comprise <10% of WBCs). (Orazi et al., 2006; Wang et al., 2006a; Beran et al., 2007; Germing et al., 2007) Alternatively, some patients present with normal or even decreased WBCs ± neutropenia. Mild to moderate anemia and thrombocytopenia are also common findings. "
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    • "The WHO classification discriminates CMML-1 (less than 10% blasts in BM) from CMML-2 (10-19% blasts). The faculty agreed that a thorough histomorphological and immunohistochemical (or flow cytometric) investigation of BM cells is essential for the diagnosis of CMML (recommended marker: CD14)[43] and delineation between CMML-1 and CMML-2 (recommended marker: CD34), which may be difficult as monoblasts or promonocytes often lack CD34 [41,42]. Because of their frequent CD34-negativity and the difficult histologic identification of promonocytes, the separation of CMML-2 from acute myelomonocytic or acute monocytic leukemia may sometimes be difficult, particularly in the absence of flow cytometry and/or cytogenetics. "
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    • "The scoring system underlines the prognostic significance of myeloblast percentage, presence of myelofibrosis and abnormal localisation of immature precursors (ALIP) (Tricot, 1992; Maschek et al, 1994). Recently, following publication of the WHO classification, Orazi et al (2006) addressed the role of BMTB as a diagnostic tool in distinguishing CMML from chronic myeloid leukaemia (CML) and atypical chronic myeloid leukaemia (aCML). In addition, they examined the use of CD34 antibody as a tool to separate CMML-1, CMML-2 and CMML in acute transformation to acute myeloid leukaemia. "
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