The detection of CD14 and CD16 in paraffin-embedded bone marrow biopsies is useful for the diagnosis of chronic myelomonocytic leukemia

Abstract

Histopathological study of bone marrow biopsy (BMB) in chronic myelomonocytic leukemia (CMML) is often difficult and might benefit from an immunohistochemical approach. We immunostained 15 cases of CMML, focusing at two new antibodies staining for CD14 and CD16 on paraffin-embedded tissues. CD68 (KP1), CD68 (PG-M1), and CD163 were not differentially expressed between CMML and chronic myelogenous leukemia (CML). In CMML BMB, we found a significant increase in the number of CD14+ monocytes. This increase was made of dispersed cells in the interstitium, often exhibiting bilobated nuclei, and being difficult to differentiate from neutrophils. There was no expansion of CD16+ monocyte-like cells. However, we found a significant decrease in the number of granulocytes expressing CD16, MPO, and CD15 in CMML compared to CML and control BMB, probably related to dysgranulopoiesis. Indeed, BMB immunohistochemistry can be helpful in CMML by identifying both the monocyte expansion with CD14 and the dysgranulopoiesis with CD16.

Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease

“…In two of these patients, however, an increased number of marrow monocytes was identified by immunostaining with CD14, a finding which is typically seen in chronic myelomonocytic leukemia and in a proportion of cases of acute myeloid leukemia but not in myeloproliferative neoplasms. [18][19][20] The variable marrow characteristics seen in cases of primary myelofibrosis associated with monocytosis would suggest that different pathogenetic mechanisms are involved in this phenomenon and that it may be genetically heterogeneous.…”

Recent advances in bone marrow biopsy pathology

“…According to definition, the presence of peripheral blood monocytosis is essential for the diagnosis of CMML. Human peripheral blood monocytes are distributed between a major CD14+ CD16− population representing 90–95% of total blood monocytes and a minor CD14 low CD16+ population [5]. CD14 is considered to be a good marker of the major monocyte population and can be now evaluated on paraffin-embedded tissue [5].…”

“…Human peripheral blood monocytes are distributed between a major CD14+ CD16− population representing 90–95% of total blood monocytes and a minor CD14 low CD16+ population [5]. CD14 is considered to be a good marker of the major monocyte population and can be now evaluated on paraffin-embedded tissue [5]. Although flow cytometry has demonstrated a moderate increase of CD14+ cells in CMML, the level and pattern of monocytic proliferation in the BMB of patients have not been clearly established.…”

Standards and Impact of Hematopathology in Myelodysplastic Syndromes (MDS)

“…Traditionally, CMML is defined by absolute monocytosis (>1000/µL), myeloid dysplasia, and exclusion of AML [25,[40][41][42][43]. The faculty agreed that an absolute monocytosis is a robust criterion of CMML.…”

“…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.…”