Histologic Variants of Squamous Cell Carcinoma of the Skin

Margaret H. Rinker, MD; Neil A. Fenske, MD; Leigh Ann Scalf, MD, and L. Frank Glass, MD, Division of Dermatology and Cutaneous Surgery, Department of Internal Medicine at the University of South Florida, Tampa, Fla.

Cancer Control. 2001;8(4) 

In This Article


Keratoacanthomas (KAs) were first described in 1889 by Jonathan Hutchinson as crateriform ulcers of the face. They have also been referred to by other terms such as molluscum sebaceum, molluscum pseudocarcinomatosum,self-healing primary squamous carcinoma, and keratocarcinoma.[5] They are clinically distinctive, rapidly growing, cutaneous tumors that generally present as crateriform nodules in elderly,fair-skinned individuals (Fig 2). The tumor most commonly appears on sun-exposed skin but may occur anywhere on the body. In addition to ultraviolet exposure, KAs have also been associated with chronic skin conditions that produce scarring such as stasis dermatitis, lichen planus, discoid lupus erythematosus,and thermal burns.[6]

Keratoacanthoma. This cutaneous tumor is a clinically distinctive, rapidly growing, cutaneous tumor that generally presents as a crateriform nodule in elderly, fair-skinned individuals.

The three clinical stages of KAs are proliferative, maturation, and involution. The proliferative stage is noted for the sudden appearance of an erythematous to flesh-colored papule with fine telangiectasias.The lesion enlarges rapidly, achieving a diameter of up to 2 cm or more. As the KA progresses through the maturation stage, it becomes dome-shaped with a central keratinous core. It typically lacks induration or fixation to underlying tissue. Within a few months, involution may take place,eventually resulting in a depressed hypopigmented scar.[5]

Histologically, in the proliferative stage, the lesion appears as a well-circumscribed, keratin-filled invagination of the epidermis with hyperkeratosis and acanthosis.Epidermal lobules and strands composed of atypical squamous cells extend into the dermis. There usually is a surrounding mixed inflammatory infiltrate. Atypical mitotic figures, perineural invasion,and intravascular extension may be present. As the tumor progresses into the maturation stage,the atypia becomes less prominent.The fully developed lesion is volcano-shaped with buttresses of normal epidermis. Within the volcano is abundant hyaline keratin,which has a "glassy" appearance.Atypical squamous proliferations may be seen at the base of the crater and extending into the crater (Fig 3). During the involution stage, the lesion has a dense lichenoid infiltrate with multinucleated histiocytes, granulation tissue,and fibrosis, and it may eventually result in an atrophic scar.[5]

Atypical squamous proliferations of keratoacanthoma. Atypical squamous proliferations may be seen at the base of the crater and extending into the crater.

KAs can be difficult to distinguish histologically from conventional SCCs. This has prompted some to consider KAs and SCCs to be the same. Clinically, they are differentiated by their history of rapid growth and their volcano shape,yet histologically, there are too many features that overlap with SCC to allow reliable separation.

Although KAs were once considered benign based on behavior,it is now believed that they should be regarded as well-differentiated variants of SCC that are capable of spontaneous regression. Some KAs have displayed aggressive biologic behavior that has led to metastases and even death.[7,8] Because of this potential for local recurrence and metastasis, treatment by excision or destruction is recommended.


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