Carcinocythemia detection in peripheral blood smears: a literature review

Carcinocythemia, or carcinoma cell leukemia, is a rare but striking manifestation of advanced malignancy in which circulating tumor cells (CTCs) are visible in peripheral blood (PB) smears using conventional staining. It is typically associated with advanced stage disease and poor prognosis. This review updates current knowledge on the pathophysiology, cytological features, detection methods, and clinical relevance of carcinocythemia. It explores mechanisms such as bone marrow infiltration, splenic dysfunction, and immune evasion that may facilitate tumor cell release into circulation. Morphologically, CTCs are large atypical cells often mistaken for hematologic blasts, with features that vary by tumor type. Immunocytochemistry using cytokeratins and epithelial markers (e.g. AE1/AE3, EpCAM) is crucial for confirmation. While most cases involve breast or lung cancer, other malignancies, ranging from melanoma to rhabdomyosarcoma, have also been implicated. Carcinocythemia often mimics acute leukemia and coexists with disseminated intravascular coagulation or thrombosis. To date, 95 cases have been reported, but its true prevalence may be underestimated. Recognition of this phenomenon in PB smear reviews is critical for accurate diagnosis and prognostication, especially in acutely ill or cytopenic patients. Further research is needed to elucidate its biology and clinical implications.