Clinical Reference / Clinical Atlas / Squamous Cell Carcinoma

Squamous Cell Carcinoma

Integration: Unifying Concept

The most common type of cutaneous squamous cell carcinoma is solar keratosis, analogues of which are radiation keratosis, arsenical keratosis, and actinic “cheilitis.” Another type of squamous cell carcinoma in skin is Bowen’s disease, and its analogue is bowenoid papulosis. Erythroplasia of Queyrat is merely Bowen’s disease on a mucous membrane or a mucocutaneous surface. Each of the conditions just mentioned is an authentic squamous cell carcinoma, akin to superficial basal-cell carcinoma. All clinicians and histopathologists acknowledge that superficial basal-cell carcinoma is a true basal-cell carcinoma (the name tells that!), but few clinicians and histopathologists are prepared to accept the fact that solar keratosis is just as much a squamous cell carcinoma as Bowen’s disease is. The latter neoplasm is understood to be a squamous cell carcinoma because the synonym for it is “squamous cell carcinoma in situ.”

The term “solar keratosis” neither connotes nor denotes squamous cell carcinoma, but that neoplasm, nonetheless, is a squamous cell carcinoma, albeit a superficial one. Solar keratosis is not a premalignancy and does not “convert” or “transform” into squamous cell carcinoma; it is a squamous cell carcinoma from the outset. If left to its own devices, solar keratosis may extend progressively deeper into the dermis and when that happens, all pathologists, universally, then designate it squamous cell carcinoma. No boundary exists between solar keratosis and squamous cell carcinoma because solar keratosis is a squamous cell carcinoma.

What has just been written for solar keratosis applies equally to radiation keratosis, arsenical keratosis, Bowen’s disease, and bowenoid papulosis. The last enumerated is simply a condyloma acuminatum in which the hyperplasia induced by papillomavirus has progressed to malignant neoplasia, to wit, squamous cell carcinoma in situ. Bowenoid papulosis has the silhouette of a condyloma and the cytologic features of squamous cell carcinoma.

The cytologic attributes of squamous cell carcinoma are nuclei of keratinocytes that are crowded, large, and pleomorphic, individual keratinocytes that are cornified abnormally (dyskeratotic), and groups of keratinocytes that mature abnormally in the form of either parakeratosis in foci in the stratum corneum or as “horn pearls” within dermal aggregations of the neoplasm. Using these criteria, solar keratosis, radiation keratosis, arsenical keratosis, actinic “cheilitis,” Bowen’s disease, and bowenoid papulosis fulfill requirements for diagnosis of squamous cell carcinoma.

In addition to the types of squamous cell carcinoma already mentioned, there are other cutaneous expressions of squamous cell carcinoma, to wit, verrucous carcinomas, keratoacanthomas, and proliferating tricholemmal cystic squamous cell carcinomas. The clinical expressions of verrucous carcinoma are giant condyloma of Buschke and Löwenstein in the anogenital region, carcinoma cuniculatum on the sole or palm, and florid oral papillomatosis in the oral cavity or on other mucous membranes. They are merely different names for the same process on different sites. Each of those neoplasms is exo-endophytic, and the endophytic component is bulbous. The cytologic features at the periphery of bulbous aggregations are typical of squamous cell carcinoma.

Keratoacanthomas are a special type of squamous cell carcinoma. The type called “solitary” (but which may be multiple) occurs on skin injured by the effects of sunlight and is characterized by rapid growth and often by involution in months in the absence of therapy. It has a characteristic crateriform appearance as a consequence of dilation of contiguous infundibula that are filled with corneocytes. The squamous cell carcinoma seems to derive from infundibular keratinocytes. The “solitary” kind of keratoacanthoma is a squamous cell carcinoma, not only for reasons that pertain to architectural and cytologic characteristics, but because, rarely, the neoplasm metastasizes (especially in persons who are immunosuppressed).

Subungual keratoacanthoma is wholly unrelated to “solitary” keratoacanthoma, being unassociated as it is with follicles. It also has a crateriform appearance and it burrows, slowly but surely, through the subungual soft tissues and often into bone of the distal phalanx. Other types of keratoacanthoma are the eruptive, the familial, and the gigantic.

What for decades has been called proliferating tricholemmal cyst is not a cyst or a benign neoplasm, but a carcinoma with tricholemmal differentiation toward the isthmus and toward the base of the tricholemmal sheath well advanced in catagen. Because of the domination of corneocytes, we thought, mistakenly, that it was a type of squamous cell carcinoma. In fact, unlike squamous cell carcinoma, which differentiates in a single direction only, that is, toward cornification, proliferating tricholemmal cystic carcinoma does not just cornify; it displays features of the tricholemmal sheath similar to that of an isthmic-catagen (tricholemmal) cyst, from whence it likely originates.

In sum, there are several different types of cutaneous squamous cell carcinoma, and each has its own diagnostic features, clinically and histopathologically, and biologic characteristics. Each can be identified for what it is by those particular features. When squamous cell carcinoma no longer is superficial, it often loses its peculiar character and then may be designated “squamous cell carcinoma,” unmodified. Had such a squamous cell carcinoma been examined histopathologically at an earlier stage, its specificity could have been recognized, for example, solar keratotic type, Bowen’s type, or verrucous type. The overwhelming majority of squamous cell carcinomas are solar keratotic type, that is, they begin as what is trivialized as solar keratosis.