Polycythaemic panmyelosis in chronic myeloid leukaemia

A 71-year-old man had been on long-term testosterone undecanoate for complex hypogonadal osteoporosis and the sodium-glucose co-transporter-2 inhibitor (SGLT2i) for metabolic syndrome. He presented with subclinical cytoses: haemoglobin 169 g/L, haematocrit 0.55, platelet count 439 × 109/L, neutrophil count 12.44 × 109/L, myelocyte count 0.78 × 109/L. Bone marrow trephine demonstrated marked trilineage hyperplasia with left-shifted granulopoiesis. Marrow topology was preserved; there were 8–10 layers of paratrabecular myeloid progenitors and increased numbers of interstitial erythroid islands (composite image; top left, objective ×4, Hematoxylin and eosin (H&E), top right objective ×20, H&E). Dwarf megakaryocytes were present. The Myeloid:Erythroid (M:E) ratio was 3-to-1 (composite image; bottom left, objective 4×, myeloperoxidase immunohistochemistry, bottom right, objective 4×, glycophorin A immunohistochemistry). Iron stores were absent. G-banded karyotype demonstrated a Philadelphia translocation (see karyogram) and fluorescent in situ hybridisation demonstrated a BCR::ABL1 fusion product, confirming the diagnosis of chronic myeloid leukaemia in chronic phase. Myeloid next generation sequencing excluded a superimposed variant driving polycythaemia. Cautious decreases in hormone replacement therapy were undertaken. A major haematological response was induced with dasatinib. Chronic myeloid leukaemia (CML) classically presents with granulocytic and megakaryocytic hyperplasia with a heavily skewed M:E ratio, but polycythaemia is not a typical feature.1 In this case of CML, the degree of accompanying erythroid hyperplasia was sufficient to produce a normal M:E ratio. SGLT2 inhibitors are increasingly prescribed and have been associated with an unmasking of previously subclinical myeloproliferative neoplasms2 due to iron mobilisation and inducing endogenous and ectopic secretion of renal and hepatic erythropoietin respectively.3 Polycythaemia emerges in up to 17% of patients commenced on SGLT2 inhibitor therapy for metabolic syndrome and its sequelae.4 The incidence of polycythaemia rises in the context of therapeutic hormone replacement therapy.5 In this era of multiple SGLT2i indications, CML may now present as a polycythaemic panmyelosis with both myeloid and erythroid hyperplasia. Thorough molecular assessment may be required to appropriately classify such cases. Open access publishing facilitated by The University of Sydney, as part of the Wiley - The University of Sydney agreement via the Council of Australasian University Librarians. Funding was not provided.