Histopathologic study of 108 keratoacanthomas and 14 squamous cell carcinomas failed to reveal any consistent, single feature allowing for their distinction. Variation in clinical features of keratoacanthoma minimizes their value in this regard. On the other hand, crater, flask‐like configuration, lipping of edges, collarette and cytoplasmic eosinophilia were statistically more frequent in lesions regarded as keratoacanthoma whereas atypical cytologic alterations including greater numbers of typical and atypical mitoses and a desmoplastic tumor stroma were most frequent in squamous cell carcinoma. Electron microscopy of examples of each lesion revealed the well‐differentiated appearance of cells comprising keratoacanthoma. In addition, intracytoplasmic aggregates of desmosomes were unique but not consistently observed in keratoacanthoma. Cells comprising squamous cell carcinoma exhibited decreased numbers of tonofilaments and intercellular desmosomes. The subjective nature of these distinguishing ultrastructural features minimizes the value of electron microscopy for the differentiation of these two lesions. Intranuclear bodies noted in some cells of keratoacanthoma resemble similar non‐viral particles observed in a variety of pathologic and even some normal cells. Interpretation of these findings as well as follow‐up observations have provided practical guidelines for therapy.
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