Ultrastructural features associated with the dot-like cytokeratin pattern in Merkel cell carcinoma: a spectrum of intermediate filament organization
Abstract
BackgroundThe 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.MethodsWe 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.ResultsIn 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.ConclusionsOur 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.
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BibTeX
@article{krotofil2026ultrastructural,
title = {{Ultrastructural features associated with the dot-like cytokeratin pattern in Merkel cell carcinoma: a spectrum of intermediate filament organization}},
author = {Mateusz Krotofil and Maria Maksymowicz and Daria Owczarek and Jakub Siednienko and Wojciech Wawręty and Piotr Rutkowski and Anna Szumera-Ciećkiewicz and Piotr Donizy},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.1852807},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1852807},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Ultrastructural features associated with the dot-like cytokeratin pattern in Merkel cell carcinoma: a spectrum of intermediate filament organization
AU - Mateusz Krotofil
AU - Maria Maksymowicz
AU - Daria Owczarek
AU - Jakub Siednienko
AU - Wojciech Wawręty
AU - Piotr Rutkowski
AU - Anna Szumera-Ciećkiewicz
AU - Piotr Donizy
PY - 2026
DA - 2026/11/09
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1852807
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1852807
AB - BackgroundThe 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.MethodsWe 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.ResultsIn 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.ConclusionsOur 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.
SN - 2234-943X
ER -