Artifactual distortion of cells simulating metastatic small cell carcinoma in the bone marrow

Artifactual distortion of hematopoietic elements in histologic preparations and smears of bone marrow aspirates simulating metastatic small cell carcinoma has been recently described. The clinical, pathologic, and immunohistochemical features in 12 such cases have been studied by us. In all these cases, bone marrow smears and histologic sections showed multiple small clusters of atypical, hyperchromatic cells suspicious for metastatic small cell carcinoma. Immunohistochemical stains showed focal positivity of the suspicious cells for leukocyte common antigen (LCA), anti-hemoglobin A (Hem A) and anti-erythrocyte membrane antigen (ERM), and negative staining for epithelial membrane antigen (EMA) and neuron specific enolase (NSE). Clinical follow-up of two years did not demonstrate any evidence of a primary small cell carcinoma in the lung or elsewhere. Comparison of these 12 cases with four cases of transbronchial biopsy-proven metastatic small cell carcinoma to the bone marrow showed that this artifact had a tendency to be located at the periphery of the marrow particles, unlike the true metastatic carcinoma cells which were predominantly found within the marrow particles and replacing the hematopoietic elements. The results of our immunohistochemical studies appear to indicate that these cells correspond to aggregated nuclei and cytoplasmic remnants from erythroid as well as myeloid and lymphoid cells. The main importance of identifying this artifact lies in avoiding confusion with metastatic small cell carcinoma, a distinction that may be very difficult to establish on morphologic grounds alone. Immunohistochemical stains and a thorough clinical follow-up are necessary for arriving at the correct diagnosis.