A 43-year-old man with a known history of WHIM syndrome (warts, hypogammaglobulinemia [IgG 271 mg/dL, IgM 39 mg/dL], infecions with chronic neutropenia [0.72 X 109/L], and myelokathexis, with a documented CXCR4 mutation) had previously been treated for B-cell lymphoma and maxillary sinus squamous cell carcinoma. He was hospitalized for a surgical excision of a portion of necrotic mandible secondary to chronic bacterial infections. When anemia and mild thrombocytopenia developed, he was evaluated for a possible treatment-related (chemo-radiotherapy) bone marrow disorder. The blood smear confirmed neutropenia and showed granulocytes with widely spaced lobules (panel A). The bone marrow biopsy was markedly hypercellular with a granulocytic hyperplasia (panel B). The neutrophils had cytoplasmic vacuoles and abnormally clumped chromatin with excessively long intersegmental filaments (panel C). These 3 features are consistent with myelokathexis found in patients with WHIM syndrome. No dysplasia was noted. WHIM syndrome is a rare autosomal dominant disorder resulting from a gain-of-function mutation in the CXCR4 receptor encoded by the CXCR4 gene on chromosome 2q21. This results in increased responsiveness to the ligand CXCL12 produced by bone marrow stromal cells, resulting in retention and apoptosis of aging granulocytes in the bone marrow and peripheral neutropenia.
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