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We report the case of a 73-year-old woman hospitalized for fatigue, normochromic and normocytic anemia. During hospitalization, physical examination showed no hepatosplenomegaly and/or lymphadenopathy, but a breast lump was present. Laboratory tests showed anemia (Hb = 7.6 g/dL), relative reticulocytosis, thrombocytopenia (PLT = 27 × 109/L), erythropoietin was clearly increased (Epo = 205 mUI/mL; r. v. = 2.5–18.5 mUI/mL). Peripheral blood smear showed red blood cell anisocytosis, teardrop, basophilic stippling, many erythroblasts, myelocytes and metamyelocytes, moreover immature mononuclear cells related to blasts were observed (Fig. 1). Bone marrow aspiration and bone marrow trephine were performed. The bone marrow aspiration not allowed the cytomorphologic diagnosis because of “dray tap.” Conversely, bone marrow biopsy showed the strong and widespread bone marrow infiltration by epithelial breast cancer (Fig. 2), confirmed by breast lump biopsy.

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Figure 1. Peripheral blood smear. A. Granulocyte precursor and teardrop; B. Erythroblast with nuclear alterations; C. Agranular blast with a high ratio nucleus/cytoplasm and two clear nucleoli.

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Figure 2. Bone marrow biopsy. A. Infiltration of epithelial breast cancer (H&E stain); B. Cytokeratin AE1/AE3 positivity; C. Estrogen receptor positivity.

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Myelophthisis [1] occurs in less than 10% of patients with metastatic cancer and it is present in advanced stage of disease. The bone marrow infiltration of non hematopoietic cells may cause cytopenia such as anemia, thrombocytopenia, neutropenia, and different degrees of pancytopenia. The bone marrow failure is the result of inadequate hematopoiesis and in peripheral blood smear teardrop, leukoerythroblastosis, myeloid precursors (myelocytes and metamyelocytes, promyelocytes and myeloblasts occasionally) are observed. As in chronic myeloproliferative neoplasms, e.g., agnogenic myeloid metaplasia, even in secondary myelofibrosis due to implantation or widespread bone marrow infiltration by malignant cancer cells, the pathological morphology of the peripheral blood smear is the same. The tumors of the lung, breast [2], prostate, and sarcomas are the most common neoplastic diseases that cause bone marrow infiltration. Instead, inflammatory cells, miliary tuberculosis, fungal infections and sarcoidosis, macrophage proliferation due to storage diseases like Gaucher disease, necrosis sickle cell anemia and septicemia, and congenital bone disease osteoporosis are the most frequent non-neoplastic disease that cause myelophthisis.

Bone marrow fibrosis, due to both neoplastic or non-neoplastic myelophthisis, often can not make eligible bone marrow aspirate, “dray tap.” The bone marrow infiltration by non-hematologic neoplastic cells can have a major impact on bone marrow function. Bone marrow biopsy generally shows the cancer cells infiltration and infiltrating cells are often the same as the primary tumor. In these patients, anemia and cytopenia is often multifactorial, and to make a specific diagnosis can be difficult. The careful peripheral blood smear evaluation as well as bone marrow aspirate and/or immunohistochemistry on bone marrow biopsy provide important diagnostic clues that can have a significant impact on prognosis and therapy.

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