An 86-year-old man was investigated for persistent thrombocytosis, leukocytosis, and monocytosis (>1 × 109/L). He had no reactive causes, constitutional symptoms, or splenomegaly. JAK2 was wild type. C-reactive protein was normal. Blood work showed: leukocytes, 16 × 109/L; monocytes, 1.413 × 109/L; hemoglobin, 124 g/L; mean corpuscular volume, 90.2 fL; and platelets, 556 × 109/L. Peripheral blood (PB) film illustrated leukoerythroblastosis and thrombocytosis; no blasts, dysplastic granulocytes, or promonocytes were found. Marrow aspirate was hypercellular, with megakaryocytic proliferation and atypia, granulocytic proliferation, and decreased erythropoiesis (panel A; May-Grunwald Giemsa stain; original magnification ×20). Blasts were <5%. Interestingly, dysplastic megakaryocytes (>10%) were observed (panels B-C; May-Grunwald Giemsa stain; original magnification ×40). Iron and ring sideroblasts were absent. Biopsy was consistent with myeloproliferative neoplasm (MPN) features, with megakaryocytic hyperplasia and atypia/granulocytic hyperplasia (panel D; hematoxylin and eosin stain; original magnification ×20). CD34, CD117, myeloperoxidase, factor 8, E-cadherin, hemoglobin A, CD3, and CD20 confirmed the biopsy findings. Reticulin stain was 0 of 4. Cytogenetics showed 46,XY,del(20)(q11.2)[6]/46,XY[14]. Despite persistent monocytosis (>1 × 109/L), dysmegakaryopoiesis, and del(20q), chronic myelomonocytic leukemia (CMML) was excluded based on the monocytes accounting for <10% of leukocytes and PB/marrow lacking promonocytes and monoblasts. Myeloid panel demonstrated CALR mutation. A diagnosis of myelodysplastic (MDS)/MPN unclassifiable (MPN-U) was rendered.

The 2017 World Health Organization classification updates CMML diagnostic criteria, specifically including monocytes accounting for ≥10% of leukocytes. Cases with MDS/MPN features and/or CALR mutation may constitute MPN progression, but a lack of the chronic phase and prior documentation justifies the diagnosis of MDS/MPN-U, the great masquerader.

An 86-year-old man was investigated for persistent thrombocytosis, leukocytosis, and monocytosis (>1 × 109/L). He had no reactive causes, constitutional symptoms, or splenomegaly. JAK2 was wild type. C-reactive protein was normal. Blood work showed: leukocytes, 16 × 109/L; monocytes, 1.413 × 109/L; hemoglobin, 124 g/L; mean corpuscular volume, 90.2 fL; and platelets, 556 × 109/L. Peripheral blood (PB) film illustrated leukoerythroblastosis and thrombocytosis; no blasts, dysplastic granulocytes, or promonocytes were found. Marrow aspirate was hypercellular, with megakaryocytic proliferation and atypia, granulocytic proliferation, and decreased erythropoiesis (panel A; May-Grunwald Giemsa stain; original magnification ×20). Blasts were <5%. Interestingly, dysplastic megakaryocytes (>10%) were observed (panels B-C; May-Grunwald Giemsa stain; original magnification ×40). Iron and ring sideroblasts were absent. Biopsy was consistent with myeloproliferative neoplasm (MPN) features, with megakaryocytic hyperplasia and atypia/granulocytic hyperplasia (panel D; hematoxylin and eosin stain; original magnification ×20). CD34, CD117, myeloperoxidase, factor 8, E-cadherin, hemoglobin A, CD3, and CD20 confirmed the biopsy findings. Reticulin stain was 0 of 4. Cytogenetics showed 46,XY,del(20)(q11.2)[6]/46,XY[14]. Despite persistent monocytosis (>1 × 109/L), dysmegakaryopoiesis, and del(20q), chronic myelomonocytic leukemia (CMML) was excluded based on the monocytes accounting for <10% of leukocytes and PB/marrow lacking promonocytes and monoblasts. Myeloid panel demonstrated CALR mutation. A diagnosis of myelodysplastic (MDS)/MPN unclassifiable (MPN-U) was rendered.

The 2017 World Health Organization classification updates CMML diagnostic criteria, specifically including monocytes accounting for ≥10% of leukocytes. Cases with MDS/MPN features and/or CALR mutation may constitute MPN progression, but a lack of the chronic phase and prior documentation justifies the diagnosis of MDS/MPN-U, the great masquerader.

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