Merkel cell carcinoma in situ associated with actinic keratosis: fortuitous or serendipitous?

To the Editor, Merkel cell carcinoma (MCC) commonly presents as a malignancy confined to the dermis. Fewer than 10% of cases show varying degrees of epidermal involvement.1 Only a small number of cases of entirely intraepidermal ‘in situ’ MCC (MCCIS) have been reported.2– 8 All but one7 of these cases were encountered as an incidental histopathological finding in the presence of an otherwise common cutaneous lesion, such as squamous cell carcinoma in situ,2– 5 trichilemmal cyst6 or seborrheic keratosis.8 Figure 1A illustrates a gritty, indurated plaque above the upper lip in a 68-year-old woman, skin-type I, who was followed regularly because of a history of multiple actinic keratoses and basal cell carcinomas. The clinical differential diagnosis included actinic keratosis and squamous cell carcinoma. A shave biopsy specimen disclosed rare intraepidermal nests of hyperchromatic basaloid cells with nuclear moulding set in a background of a characteristic actinic keratosis (Fig. 1B and C). Immunohistochemically, the basaloid cells expressed cytokeratin-20 (CK20) in a paranuclear dot-like pattern (Fig. 1D) and neuron-specific enolase and lacked expression of S100 protein. A diagnosis of MCCIS in association with actinic keratosis was thus made. The patient underwent subsequent excision by micrographic surgery, which disclosed residual squamous cell carcinoma but not MCCIS. Table 1 summarizes the clinicopathological features of the present case compared with those from previous reports of MCCIS. This highly uncommon malignancy seems to favor sun-exposed areas, as with conventional MCC, and is associated with more common sun-induced lesions, such as actinic keratosis and squamous cell carcinoma. In the present case, the keratinocytic component of this association defined the clinical picture, but we can speculate that the latter could vary case by case depending on the quantitative representation of each component. Cases associated with a scant MCCIS component are incidental, and are thus due to a fortuitous histopathological discovery. Serendipity refers to a fortuitous and fortunate finding during the search for something unrelated.9 Therefore, most, if not all of the cases of MCCIS reported to date could be considered serendipitous. There is, however, one major aspect of Horace Walpole’s original definition of serendipity,9 which does not apply here, namely, the ability of linking findings to reach a valuable conclusion. How can we link actinic keratosis and squamous cell carcinoma with MCCIS? We can speculate that this association simply represents a chance collision between two ultraviolet-induced neoplasms. Curiously, the present case is the first example of MCCIS associated with actinic keratosis located on