A 46-year-old woman with metastatic invasive ductal breast carcinoma developed a progressive leukocytosis and bicytopenia. Her blood count showed: white cell count 146.4 × 109/L, neutrophils 143.8 × 109/L, monocytes 0.9 × 109/L, eosinophils 0.0 × 109/L, basophils 0.1 × 109/L, hemoglobin concentration 98 g/L, mean cell volume 92 fL, and platelet count 96 × 109/L . C-reactive protein was 349 mg/L (normal <5). Her blood film showed marked neutrophilia with toxic granulation and vacuolation (top left). Dohle bodies and macropolycytes (top right) were also observed. There was mild dysplasia including detached nuclear fragments in some neutrophils (bottom left). There was no basophilia or eosinophilia and no circulating granulocyte precursors. A bone marrow aspirate and molecular analysis were done to exclude chronic neutrophilic leukemia, since cytological features similar to those observed are seen in this condition. The aspirate was markedly hypercellular due to granulocytic hyperplasia; tumor cells were present in large and small clumps (bottom right). The neutrophils showed the same cytological features as those in the blood. Plasma cells were cytologically normal and not increased in number. The tumor cells were large cells with large ovoid nuclei, fine chromatin, multiple nucleoli, and cytoplasmic vacuoles. Eosinophils, basophils, and blasts were not increased. Megakaryopoiesis was normal. Fluorescence in situ hybridization for PDGFRA, PDGFRB, and FGFR1 rearrangements was negative. No mutations were detected using a 26-gene myeloid-targeted amplicon next generation sequencing panel (including CSFR3, JAK2, CALR, and MPL). The bone marrow karyotype was highly complex with an evolving karyotype, more characteristic of an advanced solid tumor than a hematopoietic malignancy, supporting marrow infiltration by breast carcinoma. No paraprotein was detected and she had not received granulocyte colony-stimulating factor (G-CSF) therapy. Clinically there was no cause for a reactive neutrophilia (apart from metastatic breast carcinoma).
Leukemoid reactions can be a paraneoplastic phenomenon associated with plasma cell neoplasms and, less often, carcinoma or sarcoma. Small numbers of cases have been associated with breast cancer with the leukemoid reaction sometimes acting as a tumor marker, preceding other evidence of recurrent disease. In this case, there was no leukemoid reaction at diagnosis or when metastases were initially identified. The leukemoid reaction progressed over a 4-month period, with worsening cytopenias, prior to the patient succumbing, supporting previous reports of a leukemoid reaction portending a poor prognosis.
The marked granulocytic hyperplasia in this case resembles features observed in the marrow due to G-CSF therapy and is consistent with the hypothesis that the tumor cells secrete G-CSF. This mechanism has been reported in breast cancer.1
CONFLICT OF INTEREST
Nothing to report.
REFERENCE
1Suzuki K, Ota D, Nishi T, Mori M, et al. A case of granulocyte-colony stimulating factor-producing spindle cell carcinoma of the breast. Clin Breast Cancer.2015; 15(4): e213–e217.
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