Diagnostic Approach To Oligomonocytic Chronic Myelomonocytic Leukemia

Abstract

Casestudy: Pathologic diagnosis of chronic myelomonocytic leukemia (CMML) is typically straightforward with the majority of patients presenting with persistent monocytosis (>1x109/L, >=10%) and bone marrow dysplasia. The diagnosis may be challenging in patients with unusual features such as lack pf peripheral blood monocytosis and non-diagnostic bone marrow morphology. In this abstract, we present a 67-year-old female with a 5-year history of anemia of unclear etiology. At the time of initial presentation, the laboratory work-up of normocytic anemia was non- contributory, the bone marrow was reported as normocellular with maturing trilineage hematopoiesis and no significant dysplasia. Over the course of the disease, the peripheral blood monocyte count fluctuated from 11% to 18% with absolute monocyte count ranging from 0.4 to 0.7x109/L. The most recent bone marrow was markedly hypercellular with increased trilineage hematopoiesis with left shift, dysgranulopoiesis and dysmegakaryopoiesis. Blasts (including promonocytes) constituted 10% of the differential count and were immunophenotypically abnormal with uniform expression of CD117, dim to negative CD13, and partial CD15. Monocytes were elevated at 12% and were strongly positive for CD64 and partially for CD14. They were negative for CD16 consistent with classical monocytes, and showed partial loss of CD13. The karyotype was normal. Molecular testing revealed TET2, RELN and SRSF2 mutations at high allelic frequencies. This case illustrates a value of flow cytometric immunophenotyping and molecular genetic studies in diagnosing challenging cases of CMML. While the patient’s absolute monocyte count remained below the diagnostic threshold of 1x109/L throughout the course of the disease, peripheral blood and bone marrow monocytes showed skewed classical immunophenotype, immunophenotypic abnormalities of myeloid series and high allelic frequency mutations. These findings should raise a differential diagnosis of oligomonocytic CMML, even when morphologic abnormalities and monocyte count threshold are not diagnostic.