A 76-year-old woman presented with epistaxis and was found to have an abnormal complete blood count (white blood cells, 13 × 10³/μL; hemoglobin, 7.2 g/dL; platelets, 77 × 10³/μL) and new renal dysfunction. Physical examination was unremarkable. Imaging showed a single sclerotic bone lesion but no chest or abdominal abnormalities. Peripheral smear showed 22% large abnormal cells with eccentric nuclei, cup-shaped nuclear invaginations and variable blue-gray cytoplasm, and background leukoerythroblastic picture (panels A-B; Wright-Giemsa stain; original magnification ×1000). By flow cytometry, the neoplastic cells were CD138⁺, with dim CD81, initially suggesting plasma cell origin, but CD38, cytoplasmic κ and λ were negative. T, B, and myeloid antigens, including CD117, CD33, and CD56, were also negative (panels C-E). Bone marrow biopsy showed marrow replacement by tumor cells infiltrating in single file (panels F-G; hematoxylin and eosin stain [F], CAM 5.2 immunohistochemical [IHC] stain [G], CD138 IHC stain [H]; original magnification ×200). The tumor was keratin, CD138, GATA-3, and estrogen receptor positive, with loss of E-cadherin, consistent with lobular breast cancer.

Approximately 30 cases of carcinocythemia have been identified, most often breast carcinomas. The proportion of peripheralizing malignant cells can vary from rare cells to 80% of circulating nucleated cells resembling hematolymphoid neoplasms. CD138 is expressed on some carcinomas; identification of CD138⁺ cells without other lineage markers should raise the possibility of peripheralizing carcinoma. Carcinocythemia indicates widely systemic disease, and autopsy often shows identifiable intravascular tumor.