Ultrastructural features associated with the dot-like cytokeratin pattern in Merkel cell carcinoma: a spectrum of intermediate filament organization

Background The characteristic paranuclear “dot-like” immunohistochemical staining pattern is a hallmark of Merkel cell carcinoma (MCC), yet its ultrastructural correlates and potential biological significance remain incompletely defined. Methods We analyzed four MCC cases. Three tumors showed a classic paranuclear dot-like staining pattern with cytokeratins (CKAE1/AE3, CK20), while one tumor lacking this pattern served as a control. Ultrastructural evaluation was performed using transmission electron microscopy on FFPE tissue reprocessed for ultrastructural analysis. Results In all three tumors exhibiting a dot-like cytokeratin pattern, cytokeratin immunoreactivity displayed a morphological spectrum. In some areas, submembranous or linear perinuclear staining predominated and corresponded ultrastructurally to thick bundles of intermediate filaments arranged along the nuclear envelope. Elsewhere, these bundles appeared condensed into compact, dense fibrillar bodies composed of tightly packed, coiled cytokeratin filaments. In additional areas, less dense fibrillar bodies with reduced filament packing were observed. The relative proportion of tumor cells exhibiting each pattern varied among cases. Nuclear envelope invaginations (nuclear pockets) were also identified as an additional ultrastructural feature with variable frequency, forming pseudo-inclusion–like profiles; however, they did not constitute the structural substrate of the dot-like cytokeratin pattern. The control tumor lacked both dot-like cytokeratin expression and fibrillar bodies. Conclusions Our findings support fibrillar bodies as the primary ultrastructural correlate of the classical dot-like cytokeratin pattern in MCC. The coexistence of thick filament bundles, dense fibrillar bodies, and less dense fibrillar bodies suggests a continuum of intermediate filament reorganization rather than discrete categories. These changes may reflect progressive cytoskeletal remodeling and spatial reorganization with potential links to cellular polarization, motility, and cell division. In contrast, nuclear pockets represent a distinct and unrelated ultrastructural phenomenon. Further functional studies are warranted to clarify the biological significance of these observations.