Phagocytized Neutrophil Fragments in the Bone Marrow: A Phenomenon Most Commonly Associated with Hodgkin Lymphoma

Bone marrow macrophages containing other cells, or large pieces of other cells, represent a distinctive feature of diseases such as Hemophagocytic Lymphohistiocytosis (HLH) and Rosai-Dorfman disease. We describe a distinct variation of phagocytic histiocyte morphology, featuring histiocytes containing predominantly fragments of neutrophil nuclei. We retrospectively reviewed initial bone marrow samples for Hodgkin lymphoma, Burkitt lymphoma, Ewing sarcoma, or evaluation for nonneoplastic conditions, scoring the presence or absence of the above-described histiocytes. We find that these histiocytes, which we term “fragmentophages,” are associated with staging marrow sampling for malignancy, especially Hodgkin lymphoma (Hodgkin lymphoma: 28/34 or 82.4%, Ewing sarcoma: 11/26 or 42.3%, Burkitt lymphoma: 4/13 or 30.8%). These cells are significantly less common in marrow samples for nonneoplastic conditions (4/21 or 19.0%). Fragmentophages are significantly associated with malignancy, especially Hodgkin lymphoma, and their recognition has the potential to provide a clue to an underlying malignancy. 1. Introduction The histologic patterns of Hemophagocytic Lymphohistiocytosis (HLH) and Rosai-Dorfman disease are distinctive, each characterized by macrophages containing large parts of other cells. HLH is characterized by increased macrophage uptake and destruction of red blood cells, red blood cell precursors, and platelets, resulting in potentially lethal peripheral cytopenias. Rosai-Dorfman disease features the proliferation of distinctive, large histiocytic cells which accumulate usually in the sinuses of lymph nodes and contain predominantly intact lymphocytes. Both of these diseases can involve the bone marrow. Thus, the identification of bone marrow macrophages containing other cells in their cytoplasm evokes consideration of these diagnoses [1, 2]. We have observed a morphologically distinct pattern of macrophages containing mainly neutrophil nuclear fragments in bone marrow samples of children in association with malignancy. This pattern is important to distinguish from HLH and Rosai-Dorfman disease and has the potential to be a first clue to an associated malignancy. 2. Methods and Materials A retrospective review of initial bone marrow samples and patient chart material over a 5-year period was performed in accordance with an Institutional Review Board approved protocol. Staging marrow samples represented patients treated at our pediatric center for Hodgkin lymphoma, Ewing Sarcoma, and Burkitt lymphoma or were initial bone marrow biopsies for