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Bone marrow erythrocyte and neutrophil phagocytosis and cannibalism by neuroendocrine carcinoma

A 61-year-old non-smoking woman, who previously worked at a tobacco company for 36 years, had been diagnosed with stage IV lung adenocarcinoma 4 years earlier. After several lines of treatment, she had achieved a partial response. On this presentation, a full blood count showed pancytopenia (Hb 70 g/l, neutrophil count 0 7 9 10/l, platelet count 4 9 10/l), with a leucoerythroblastic picture. The bone marrow (BM) aspirate showed an infiltration by 86% of non-haematological neoplastic cells, of which 12% showed cell internalisation phenomena: approximately 2/3 were neutrophil (top) or erythrocyte (bottom left) haemophagocytosis and 1/3 were cellular cannibalism. Cellular cannibalism and haemophagocytosis by the same cells, and even phagocytosis of cells that had already phagocytosed other cells (bottom centre), were occasionally seen. BM histological examination showed diffuse neoplastic infiltration by medium-sized to large cells with sporadic haemophagocytosis (bottom right). Immunohistochemistry showed strong diffuse positivity for synaptophysin, and weaker staining for chromogranin A and CD56. Further images are shown in the Supplementary information. BM involvement by neuroendocrine carcinoma with a high proliferation index (Ki67: 80%) was diagnosed. Palliative care was chosen and, 3 weeks later, the patient died of septic shock and multiple organ failure. Neuroendocrine carcinomas rarely involve the BM, while haemophagocytosis by tumour cells, especially of neutrophils, is unusual. Cellular cannibalism has been related to tumour aggression while haemophagocytosis by tumour cells is of uncertain significance.