positive pancitokeratin cells in bone marrow

The clinical significance of detecting positive cytokeratin (CK) cells in the bone marrow lies primarily in their identification as disseminated tumor cells (DTCs), which are indicative of tumor cell dissemination and potential early metastatic spread. CK positivity marks epithelial tumor cells that have migrated from the primary tumor to the bone marrow, where they can remain dormant or contribute to relapse and metastasis. The presence of these CK+ DTCs in bone marrow has been established as an independent prognostic factor associated with an increased risk of disease recurrence and poorer survival outcomes in breast cancer patients, particularly in aggressive subtypes such as triple-negative breast cancer (TNBC) NICE CG104,Eckardt et al. 2025.

More specifically, CK+ DTC detection identifies epithelial tumor cells among bone marrow cells, often using immunocytochemical staining. These CK+ cells exhibit high nucleus-to-cytoplasm ratios and lack normal hematopoietic markers like CD45, confirming their malignant epithelial lineage. Their detection supports the concept that hematogenous spread can occur early in breast cancer and that these cells can persist in a latent state, potentially evading initial therapies and causing future relapse Eckardt et al. 2025.

Importantly, research shows heterogeneity within DTC populations. While CK+ DTCs represent epithelial phenotypes, subpopulations also exist with mesenchymal or epithelial-mesenchymal transition (EMT)-like characteristics, including CK negativity with vimentin positivity. CK+ DTCs are often negative for markers of proliferation (Ki67), immune evasion (PD-L1), and HER2, whereas CK- DTCs (mesenchymal-type) more frequently express these markers and are associated with poor prognosis and chemotherapy resistance Eckardt et al. 2025.

In patients achieving pathologic complete remission (pCR) after neoadjuvant chemotherapy, CK+ DTCs tend to be the predominant phenotype detected, indicating a better prognosis, while persistence or emergence of CK- DTCs correlates with non-pCR status and worse outcomes. Therefore, detection of CK+ DTCs, especially if accompanied by proliferative and therapeutic target markers, can inform prognosis and potentially guide therapy Eckardt et al. 2025.

Furthermore, the detection of CK+ DTCs expressing molecules such as PD-L1 or prostate-specific membrane antigen (PSMA) has been associated with poor progression-free and overall survival in TNBC patients, highlighting their role as prognostic biomarkers and potential therapeutic targets. PSMA+ and PD-L1+ DTCs are frequently identified before and early after treatment, suggesting their persistence contributes to relapse risk. Monitoring these CK+ DTC subpopulations can therefore stratify patients for therapies including immune checkpoint inhibitors or targeted treatments Tolios et al. 2025.

From a clinical perspective, detection of CK+ DTCs in bone marrow is not yet standard of care but is emerging as a valuable biomarker reflecting minimal residual disease and metastatic potential. It complements tumor tissue analysis, acknowledging tumor heterogeneity and possible discordance between primary tumor receptor status and DTC profiles, which may influence prognosis and treatment choices NICE CG104,Eckardt et al. 2025.