Chronic myelomonocytic leukemia with abormal bone marrow eosinophils

Archives of Pathology & Laboratory Medicine, Sep 2003 by Hyde, Jason, Sun, Tsieh

* Chronic myelomonocytic leukemia with eosinophilia is a recently defined rare entity frequently associated with t(5;12)(q33;p13) translocation. It usually shows a peripheral eosinophil count greater than 1500/[mu]L. However, the literature contains a small subset of cases in which the major manifestation is bone marrow eosinophilia. We report a case similar to that subset and discuss our finding that the immature eosinophils are identical to those seen in acute myelomonocytic leukemia with abnormal bone marrow eosinoohils.

The World Health Organization currently classifies chronic myelomonocytic leukemia (CMML) under myelodysplastic/chronic myeloproliferative disorders.1 This new classification is based on the fact that CMML may have features of myelodysplastic syndrome, chronic myeloproliferative disorder, or both. Because of this great variation in presentation and also because the monocytic component in the bone marrow is difficult to recognize, this entity is probably underdiagnosed.1 Eosinophilia is a rare manifestation in CMML.2 However, Keene et al first reported t(5;12)(q33;p13) in association with eosinophilia in chronic myeloproliferative disorders in 1987.3 Subsequent studies found that this anomaly is most frequently seen in CMML with eosinophilia.3-7 Nevertheless, this karyotype is seen in less than 1% to 2% of patients with CMML,1 and only about 40 cases have been reported to date.6 Chronic myelomonocytic leukemia with eosinophilia is frequently defined by the presence of peripheral eosinophilia at a level above 1500/[mu]L, but Wlodarska et al4 described 3 patients who had mainly bone marrow eosinophilia. The current case is similar to those reported by Wlodarska et al with the presence of eosinophils in various developmental stages, mimicking acute myelomonocytic leukemia with abnormal bone marrow eosinophils (World Health Organization classification).

REPORT OF A CASE

A 63-year-old man presented with a 2-year history of elevated leukocyte count and a 9-kg weight loss during the preceding 4 months. Significant past medical history included coronary artery disease, status post coronary artery bypass graft, obesity, and hypertension. The patient denied any fevers, chills, or night sweats. There were no localizing symptoms or somatic complaints. The results of physical examination were unremarkable, and he was afebrile and normotensive.

The patient's hematocrit was 44% (down from 48%, 4 months previously), the leukocyte count was 15400/[mu]L (63.6% neutrophils, 21.9% lymphocytes, 8.1% monocytes, 6.0% eosinophils, and 0.4% basophils), and the platelet count was 338000/[mu]L. Given the patient's chronic leukocytosis and recent weight loss, a bone marrow aspirate and biopsy were performed. Following diagnosis, the patient was treated conservatively with observation and is scheduled for regular follow-up hematologic review.

MATERIALS AND METHODS

The bone marrow core biopsy specimen was fixed and processed routinely, after touch preparations, aspirates, and samples were taken for flow cytometry and cytogenetics. The samples were then stained with hematoxylin-eosin, periodic acid-Schiff, Giemsa, and iron.

PATHOLOGIC FINDINGS

Microscopic examination of the peripheral blood smear showed leukocytosis, including mainly segmented neutrophils. However, the absolute counts of monocytes (1200/[mu]L) and eosinophils (900/[mu]L) were also increased. No immature forms of myeloid cells or monocytes were noted in the peripheral blood.

The bone marrow aspirate revealed complete differentiation and full maturation of the 3 cell lines. The myeloiderythroid ratio was 5.4:1 with predominance of myelomonocytic cells. The monocytic series was increased (10.25%) in various developmental stages, from mature monocytes to monoblasts. The sum of myeloblasts, monoblasts, and promonocytes was 3.8%. A striking eosinophilia was present, comprising 7.2% of the cellular aspirate. The eosinophils were present at various developmental stages, up to myelocytes. Dysplastic changes were present within the granulocytic population, such as hypolobation, pseudo-Pulger-Huet cells, and a decrease in granule production (Figure, A). Megaloblastoid changes were seen frequently in the normoblast populations.

The core biopsy showed an overall cellularity of approximately 50%. Although normal differentiation and maturation were still visible, the marrow was dominated by myelomonocytic cells. Many immature forms were seen throughout the marrow, but few appeared to be blasts. Clusters of immature precursors could be seen within the intertrabecular areas. Eosinophilia was conspicuous throughout the core biopsy, showing varying developmental stages (Figure, B). An immunohistochemical stain for CD68 (all antibodies from Becton Dickinson, San Jose, Calif), with appropriate controls, demonstrated positive reaction in most nonerythroid marrow cells (Figure, C). An [alpha]-naphthyl butyrate esterase stain showed widespread positive staining of the monocytoid cell line (Figure, D). Megakaryocytes were present in adequate numbers, but many hypolobate cells, micromegakaryocytes, and naked nuclei of megakaryocytes were observed. The bony trabeculae were unremarkable. Periodic acid-Schiff and Giemsa stains were confirmatory. The iron stain showed normal iron stores. Flow cytometric findings showed CD13/CD33, 82%; CD14, 34%; CD34, 12%; and CD45, 100%; indicating the presence of a large monocyte population. Genetic studies produced a 46,XY karyotype, and fluorescence in situ hybridization studies demonstrated no rearrangement of the TEL (ETV6) locus associated with a translocation 5;12.