The association of chronic myelomonocytic leukemia, with bone marrow infiltration by chronic lymphoproliferative diseases has been reported in the literature mainly by case reports, and documented through bone marrow biopsies. More recently, as the diagnosis of CMML can be made by peripheral blood immunophentyping, this association could be detected more frequently. This association has been included in the ICC classification of subtypes of CMML.1

Male patient, 72 years old, was hospitalized due to pneumonia. At that time, the peripheral blood (PB) count showed leukocytosis with monocytosis and thrombocytopenia, which did not resolve after the pneumonia was cured. Reviewing former PB counts, monocyte counts >10% could be detected. In 2024, no lymphadenopathy could be observed, but the spleen was 2 cm below the costal margin. Tests during most recent hospitalization: Creatinine: 0.9 mg/dL, Ferritin: 46 ng/mL, Serum iron: 67.7 µg/dL, ALT: 34 U/L, Vitamin B12: 794 pg/mL, Folic acid: 6.01 ng/mL, Beta-2 microglobulin: 2244 ng/mL (normal <2164), LDH: 320 U/L (normal), Protein electrophoresis: monoclonal peak of 1.46 g/dL; Serum immunofixation: IgM/Kappa.

Bone marrow aspirate: Hemodiluted. M:E ratio: 4.28. Lymphocytes: 15%. Bone marrow biopsy: markedly hypercellular marrow tissue, granulocytic hyperplasia with maturation arrest. Scattered CD34+ cells. Interstitial infiltration by low-grade lymphoma (lymphocytes and plasma cells) with IgM Kappa on immunohistochemistry. Likely Waldenström macroglobulinemia, with marginal zone lymphoma as differential diagnosis. Immunophenotyping suggested. Bone marrow immunophenotyping (October 2024): Monocytosis of 9.1% composed of mature elements. Classical monocytes: 86.1%, Intermediate: 10.8%, Non-classical: 3.1%. Polyclonal plasma cells: 0.15%. Monoclonal B lymphocytes with the following phenotype: CD45+++, CD19++, CD20++, CD43+, CD79b++, CD200++, partial IgM (41%), and predominance of kappa light chain. Peripheral blood immunophenotyping (November 2024): Monocytosis of 22.3% composed of mature elements. Classical monocytes: 97.2%, Intermediate: 2.0%, Non-classical: 0.4%. 3.2% monoclonal B lymphocytes with phenotype: CD45+++, CD19++, CD20+++, CD79b++, CD200++, IgM+++, partial CD23 (30%), kappa light chain.

In the last years, new strategies for the study of subtypes of monocytes using flow cytometry have been developed. This permitted to better understand the role of these cells in non-neoplastic inflammatory diseases as well as the detection of neoplastic clones. In the present case, the diagnostic work-up in a case with CMML using PB immunophenotyping by multiparametric flow cytometry permitted also the detection of a small lymphoid clone of Waldenström macroglobulinemia. The examination of bone marrow biopsy permitted to diagnose an extensive infiltration of this lymphoproliferative disorder. The patient was treated for macroglobulinemia, and is well and in observation.

In this case, peripheral monocytosis detected during infections was known since 2015 but had never been thoroughly investigated. Only during the last infectious episode was the patient referred to a hematologist. After bone marrow immunophenotyping—of which the sample was very diluted—CMML was suspected, and peripheral blood testing confirmed the diagnosis. The monoclonal peak was an incidental finding, but immunophenotyping allowed the diagnosis of chronic lymphoproliferative disease. However, the true extent of this disease in the bone marrow was only assessable through biopsy. The co-existence of myeloproliferative neoplasms or CMML with chronic lymphoproliferative diseases is a rare event (1–2% of chronic myeloproliferative neoplasms). According to limited literature, these appear to be independent neoplasms, not derived from the same stem cell. Immunophenotyping (blood or bone marrow) is the most sensitive technique for detection.