The keratoacanthoma is a rapidly growing malignant tumor of the skin that is derived from the keratinocyte. The tumor is believed by many to be a subset of squamous cell carcinoma of the skin, but its natural history and morphology are distinct enough to merit a separate discussion. Most keratoacanthomas are solitary, but many rare variants have been well documented. These variants include the Ferguson-Smith, Witten-Zak, and Grzybowski syndromes.
Clinical Findings: The classic solitary keratoacanthoma starts as a small, flesh-colored papule that rapidly enlarges to form a crateriform nodule with a central keratin plug. The tumor is unique in that, if left alone, the keratoacanthoma will spontaneously resolve after a few weeks to months. The nonclassic form of keratoacanthoma does not spontaneously resolve, and it is inadvisable to leave these tumors alone, because a high percentage will continue to enlarge. If left alone, these tumors can behave aggressively, with local invasion as well as distant metastasis. The most common area of metastasis is the regional lymph nodes. The most common variant of keratoacanthoma is the solitary variant. This almost exclusively occurs in sun-exposed regions of the body. The peak age at onset is in the fifth to sixth decades of life. These tumors are more common in the Caucasian population, and there is slight male preponderance.
Many unique variants of keratoacanthomas exist. Keratoacanthoma centrifugum marginatum is one such variant that manifests with an ever-expanding ridge of neoplastic tissue. As the tumor enlarges, it becomes an enormous-sized plaque with a peculiar raised border. These tumors can be massive and can encompass a large portion of a limb. This subtype presents a therapeutic challenge.
Multiple keratoacanthomas occur rarely and have been divided into three distinct subtypes. The Gryzbowski syndrome consists of multiple keratoacanthomas erupting in a generalized distribution, almost always in an adult. The Ferguson-Smith form consists of multiple keratoacanthomas occurring in an autosomal dominant fashion. The keratoacanthomas are uniform in appearance and also form in a generalized pattern. The onset is in childhood, and the tumors have a higher chance of spontaneously resolving. The Witten-Zak syndrome also has an autosomal dominant inheritance pattern. The tumors are more variable in size and configuration than in the Ferguson-Smith subtype. The onset of this type is also in childhood.
Pathogenesis: The exact pathogenesis is unknown; however, the tumor has a keratinocyte cell origin. There is more evidence for the keratinocytes derived from hair follicle epithelium as the primary cell responsible for the formation of this tumor. Keratoacanthomas have an increased incidence in patients with chronic ultraviolet exposure and in the chronically immunosuppressed. The classic keratoacanthoma is described as a self-resolving tumor. The reason that some of these tumors undergo autoinvolution is unknown. There is evidence to suggest that the tumors, like hair follicles, are under a preset growth and involution control system. The hair follicle grows to a certain point, after which a signal stops the growth of the hair, the follicle is shed, and a new hair shaft is formed. Perhaps the growth and involution of keratoacanthomas is analogous to the turnover of hair follicles. Keratoacanthomas are also seen with an increased incidence in Muir-Torre syndrome. It is possible that the genetic defect in these patients may play a role in the pathogenesis of keratoacanthomas.
Histology: The tumor is typically a cup-shaped exophytic nodule that has a prominent keratin-filled plug. The borders of the tumor are well circumscribed. The tumor is symmetric. Neutrophilic abscesses within the outer layers of the involved epidermis are a characteristic finding in keratoacanthomas. The keratinocytes that make up the bulk of the tumor have a glassy cytoplasm with large amounts of glycogen. Other unique findings in this tumor are the presence of plasma cells and eosinophils and the elimination of elastic fibers through the overlying epidermis.
Treatment: After a keratoacanthoma has been biopsied, the treatment of choice is surgical removal. This can be done with a standard elliptical excision or with Mohs micrographic surgery. Intralesional methotrexate and oral retinoids have been used in refractory cases and in individuals who cannot tolerate surgery. The familial forms of keratoacanthoma often require longterm retinoid therapy to keep the tumors at bay.