Keratoacanthoma
Definition
Keratoacanthoma is a common, rapidly growing squamoproliferative tumour that may spontaneously regress. It is histologically indistinguishable from (and likely a variant of) well-differentiated cutaneous invasive squamous cell carcinoma, with distinct clinical behavior.
Synonyms
Welt-differentiated squamous cell carcinoma, keratoacanthoma type; keratoacanthoma-like squamous cell carcinoma
Epidemiology
Keratoacanthomas typically arise in the sun-exposed skin of older, fair-skinned individuals between the sixth and seventh decades of life and have a slight predilection for men. Rare cases occur in childhood and adolescence in association with organoid naevus or xeroderma pigmentosum.
Etiology
Ultraviolet (UV) radiation, photon radiation, trauma (e.g. at sites of a skin graft or vaccination), infections, and chemical carcinogens have been linked to the development of keratoacanthoma lesions, with solar damage being the predominant risk factor. Other factors include immunosuppression/immunodeficiency, tattoos, and BRAF inhibitors. Human polyomavirus 6 (HPyV6) DNA was recently detected in keratoacanthomas, and other serotypes (HPyV19 and HPyV48) have been isolated in giant keratoacanthomas and keratoacanthomas in HIV-infected patients.
Localization
Keratoacanthomas most commonly occur in facial skin (in as many as 70% of cases in temperate climates); they also commonly occur on the dorsum of the hands and forearms among men and on the legs among women.
Clinical features
Solitary keratoacanthoma
This is the most common variant. It presents as a symmetrical, dome-shaped tumour, capped with keratin. It evolves rapidly and may involute over the course of several months. The size ranges from a few millimeters to 20 cm. Giant keratoacanthomas (>5 cm) have a predilection for the nose and the dorsum of the hands; they can reach up to 15 cm, with destruction of underlying tissues. Three clinical stages have been observed: a proliferative stage (a rapidly enlarging erythematous papule or nodule with a smooth surface), a mature stage (a central whitish-yellow nodule with a crateriform keratotic core), and a regressing stage (a keratotic nodule that progressively flattens in association with elimination of the central keratotic plug, sometimes followed by the formation of a hypopigmented scar).
Multiple keratoacanthomas
These rare tumours can be sporadic or familial. Sporadic multiple keratoacanthomas may be associated with prurigo nodularis, usually on the sun-damaged lower legs of elderly women.
Multiple familial keratoacanthomas of Ferguson-Smith type
These keratoacanthomas, also known as multiple self-healing squamous epithelioma, were first described in Scottish families with an autosomal dominant inheritance pattern with variable penetrance. Patients may have hundreds of keratoacanthomas, each with characteristics similar to those seen in solitary keratoacanthoma.
Multiple keratoacanthoma centrifugum marginatum
Theses rare skin tumours show persistent growth with an annular, coral reef— like appearance. The lesions involve the back of the hands and can become very large, approaching 20 cm.
Generalized eruptive keratoacanthomas of Grzybowski
Affected patients have a generalized eruption of hundreds to thousands of small, well-demarcated papules (some with keratotic centres), predominantly in unexposed skin. The condition is exceedingly rare, and familial clustering has been described.
Subungual keratoacanthoma
This rapidly growing and locally destructive tumour originates in the distal nail bed, separating it from the nail plate. The thumb, middle finger, and big toe are most commonly involved.
Histogenesis
Most examples of keratoacanthoma affect hair-bearing skin, and are most likely to be derived from follicular infundibular/isthmus keratinocytes. Rare tumours located on glabrous skin and mucous membranes are probably derived from epithelial keratinocytes.
Genetic profile
The MAP3K8 (TPL2) oncogene may be a driver common to the development of both keratoacanthoma and squamous cell carcinoma. Patients with multiple familial keratoacanthomas of Ferguson-Smith type have DNA repair failures associated with Muir—Torre syndrome and xeroderma pigmentosum. Disease-specific mutations in TGFBRI have also been identified in patients with multiple familial keratoacanthomas of Ferguson-Smith type. There is a possible role of TP53in the development of some keratoacanthomas; mutant p53 oncoproteins are found in about 10% of tested lesions.
Genetic susceptibility
Rarely, there is a genetic predisposition to developing keratoacanthomas, in particular multiple familial keratoacanthomas of Ferguson-Smith type. Muir—Torre syndrome is commonly associated with keratoacanthoma lesions, suggesting that the genetic defect (or defects) that causes the syndrome also plays an etiological role in keratoacanthoma.
Prognosis and predictive factors
Many (if not most) keratoacanthomas eventually undergo resolution, but central facial giant keratoacanthoma and subungual keratoacanthoma may be locally aggressive. It is impossible to predict with certainty the behaviour of a well differentiated squamoproliferative lesion on the basis of a partial biopsy, or when margins are involved.
Reference:
WHO classification of skin tumours, 4th edition (2018): 36-38.