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A 66-year-old man presented to the hospital with a 2-week history of generalized weakness, progressive fatigue, and shortness of breath. His medical history was significant for anemia of chronic disease, hypertension, hyperlipidemia, diabetes, gastroesophageal reflux, and Roux-en-Y gastric bypass surgery 30 years earlier. He denied having fever, chills, night sweats, weight change, cough, chest discomfort, hematochezia, melena, hematemesis, or bruising. On physical examination the patient was obese and pale. The rest of the examination was unremarkable. His complete blood count with differential showed white blood cell count of 2.4 x103/μL, (38% neutrophils, 41% lymphocytes, 17% monocytes, 3.5% eosinophils, 0.5% basophils), absolute neutrophil count of 700 /μL, hemoglobin of 7. 9 g/dL, mean corpuscular volume of 106.1 fL, and platelet count of 138 x103/μL. The other blood tests revealed: reticulocyte count 1.2%, total bilirubin 1 mg/dL, vitamin B12 592 pg/mL, red blood cell (RBC) folate 1500 ng/mL, lactate dehydrogenase 170 U/L, haptoglobin 213 mg/dL, ferritin 183.4 ng/mL, total iron-binding capacity 297, and iron saturation 13%. Serum electrolytes and liver function tests were unremarkable. Peripheral smear (Figure 1) showed moderate anemia with anisocytosis and macrocytosis, as well as mild leukopenia and mild thrombocytopenia; the peripheral smear was negative for myelocytes or myeloblasts. The patient’s baseline complete blood count 5 months before his admission showed white blood cell count of 5.8 x103/μL, absolute neutrophil count of 4000/ μL, hemoglobin of 10.2 g/dL, mean corpuscular volume of 91 fL, and platelet count of 193 x103/μL. Because of his age we proceeded with bone marrow biopsy examination to rule out myelodysplastic syndrome. The bone marrow aspirate and biopsy showed 60% cellularity, with abnormal erythropoiesis including megaloblastic pronormoblasts with prominent nucleoli and multiple cytoplasmic vacuoles (Figure 2). Some nuclear/cytoplasmic dyssynchrony was noted, but no nuclear budding or bridging was seen in maturing erythroid cells. Myelopoiesis was shifted toward intermediate forms but was not obviously dysplastic. The myeloid:erythroid ratio was within normal limits. There were less than 3% myeloblasts. Megakaryocytes were increased in number without dysplastic features. Cytogenetic analysis showed the normal male karyotype (46, XY). Fluorescent in situ hybridization study of the most common myelodysplastic syndrome-related chromosomal abnormalities, which include +8, -5q, -7q, and -20q, was normal. The bone marrow biopsy results of megaloblastic pronormoblasts with cytoplasmic vacuolization suggested exposure to toxic substances or copper deficiency secondary to zinc toxicity. On further interview, the patient denied known toxin exposure but admitted taking daily zinc gluconate 200 mg in addition to other over-the-counter zinc supplements. Subsequent testing revealed an elevated plasma zinc level of 137 μg/dL (normal range 56-134 μg/dL) and a markedly low plasma copper level of 7 μg/dL (normal 72-166 μg/dL), and ceruloplasmin of 2.1 mg/dL (normal 20-60 mg/dL). The patient was diagnosed with pancytopenia secondary to hypocupremia from zinc toxicity, possibly exacerbated by his gastric bypass surgery 30 years before. He was started on copper gluconate 8 mg by mouth daily for 1 week, followed by 6 mg daily for 1 week, followed by 4 mg daily for 1 week, and then continued on 2 mg

Image Diagnosis: Zinc-Induced Copper Deficiency Causing Pancytopenia Recognized on Bone Marrow Examination