Keratoakanthoma (overview)D23.-

Initially fast-growing (according to typical history usually lasting a few weeks), solitary, more rarely in plural, then also in the context of syndromes (see classification below; see Leblebici C et al. 2017) or under immunotherapy (e.g. with pembrolizumab/Freites-Martinez et al.2017), 1.0 to a maximum of 3.0 cm in size, solid, epithelial tumor that develops from the hair follicle or the surface epithelium of the skin (rarely the mucosa), initially grows infiltratively, and may have a spontaneous regression tendency after weeks to months with the expulsion of a central horny plug (the growth behavior is interpreted as analogous to the hair cycle).

In addition to the classic type of keratoacanthoma, different clinical variants have been described. All variants show an identical histological picture and differ only in their macro-morphological pattern, their localization (e.g. in subungual KA) and their growth behavior (destructive variants).

Clinical variants of keratoacanthoma (KA)

• KA, solitary
  • KA, classic type (description see here)
  • KA, squamous type.
• KA, multiple
  • KA,multiple, eruptive multiple ( Grzybowski type)
  • KA, multiple,self-healing (type Ferguson-Smith mutation in TGFBR1)
  • KA , multiple, self-healing (multiple self-healing palmoplantar carcinoma/MSPC/mutation in NLRP1)
  • KA, multiple with pruritus (Witten Zak type)
  • KA, multiple under immunotherapy (Freites-Martinez et al.2017)
• KA, multiple with other genetic syndromes
  • Muir-Torre syndrome
  • Xeroderma pigmentosum.
• KA, destructive:
  • KA, destructive, subungual
  • KA, destructive, aggregated
  • KA, multiple, destructive
  • Keratoacanthoma marginatum centrifugum (Miedzinski-Kozakiewicz type).
  • KA, destructive, giant keratoacanthoma.

Unexplained. Mostly after chronic actinic noxae (predominant occurrence in light-exposed areas), also after mechanical trauma, after contact with chemical carcinogens, in immunosuppression as well as paraneoplastic in neoplasms of internal organs (especially of the intestinal tract).

Genetic factor: occurrence of multiple KA in genetic syndromes (see classification).

The pathogenetic significance of HPV (HPV 25), especially in multiple CA, is still unclear.

Manifestation rarely before the 20th LJ, more frequent in men from the age of 55 (frequency peaks between 50th-79th LJ). More frequent occurrence is observed in immunocompromised persons. Men are affected about twice as often as women.

Light-exposed areas of fair-skinned persons, especially face, also back of the hand. Palms of hands and soles of feet remain free, as do mucous membranes.

The classic keratoacanthoma described here appears as a solitary, 0.5 cm to a maximum of 3.0 cm (literature: in individual cases up to 9.0 cm!) large, spherically bulging, hard, red or red-brown, centrally dented, painless nodule (or nodule), the surface of which is permeated by telangiectasias.

Typically, there is a mound-like raised rim lip-like surrounding the central grayish-yellow keratotic plug.

The keratoacanthoma is easily displaced on its base.

Typically, a three-phase clinical course is observed:

1. Stage of proliferation (duration about 2-6 weeks) with rapid growth (period of clinical presentation).
2. stage of maturation (static phase; duration undetermined)
3. Stage of regression (this phase is controversial and should not be waited for).

Multiple eruptive keratoacanthomas are described as 0.1-1.2 cm solid, skin-colored to reddish papules and nodules. They occur under immunosuppression. Sporadically, they also occur after tattoos.

Giant keratoacanthoma (also called keroacanthoma giganteum) shows unusual oversized (up to 10 cm) growth in size with typical clinical and histologic morphology.

Keratoacanthoma marginatum centrifugum, is an unusual variant of giant keratoacanthoma and is characterized by a plate-like appearance with a lack of regression tendency in the marginal area of the tumor.

Histological differentiation from squamous cell carcinoma in punch biopsies or partial excisional data is not possible. In this respect, the histological diagnosis of KA can only be made if it presents in its typical histomorphological shape.

In this case, a central horny plug is seen, which is lipped by broad epidermal tumor proliferates. The tumor proliferates show infiltrative and destructive growth. The surrounding connective tissue is markedly fibrosed as well as vigorously round cell infiltrated. The basal keratinocytes are markedly enlarged and show a vigorous eosinophilic cytoplasm. Especially in the proliferation stage the basal tumor parts are clearly cell and nucleus polymorphic with single cell dyskeratosis and numerous pathological mitoses. In addition, small horny beads with concentrically stratified keratinocytes. The number of mitoses varies and is markedly increased in young KA and only moderately increased in older KA. In older KA, there is an increasing inflammatory component in the tumor parenchyma with microabscesses of eosinophilic and neutrophilic leukocytes as well as isolated giant cells of the foreign body type.

Excision is the 1st choice therapy. Safety distance to the side and to the depth of 2-3 mm.

Alternative: curettage followed by immediate application of a 5-fluorouracil cream(e.g. Efudix). Repeat Efudix treatment 3-4 times at 2-day intervals.

Alternative: curettage followed by immediate application of cryosurgery (2 times cycle, closed procedure) or curettage and cauterization of the base.

Keratoacanthoma is neither clinically nor histologically clearly distinguishable from spinocellular squamous cell carcinoma. Significant is the short duration of existence of a few weeks!

In this respect, it is not advisable to wait for the tumor to "heal itself".

1. Boateng B et al (1995) Multiple keratoacanthomas (Witten-Zak type) in prurigo simplex subacuta. Dermatologist 46: 114-117
2. Chu DH et al (2003) Generalized eruptive keratoacanthoma of Grzybowski. J Drugs Dermatol 2: 318-319
3. Consigli JE et al (2000) Generalized eruptive keratoacanthoma (Grzybowski variant). Br J Dermatol 142: 800-803
4. Freites-Martinez et al.(2017) Eruptive Keratoacanthomas Associated With Pembrolizumab Therapy. JAMA Dermatol 153: 694-697.
5. Hsu S et al (2003) Reactive multiple keratoacanthoma in a patient with chronic renal insufficiency. Br J Dermatol 148: 1270-1271.
6. Hutchinson J (1889) The crateriform ulcer of the face, a form of acute epithelial cancer. Trans Pathol Soc London 40: 275-281.
7. Jasnoch V et al (1995) The rare variants of keratoacanthomas. Dermatologist 46: 244-9
8. Kato N et al (2003) Ferguson Smith type multiple keratoacanthomas and a keratoacanthoma centrifugum marginatum in a woman from Japan. J Am Acad Dermatol 49: 741-746.
9. Laaff H et al (1992) Eruptive keratoacathomas of the Grzybowski type and ectropion. A therapeutic problem. Dermatologist 43: 143-147
10. Leblebici C et al (2017) Cytokeratin 17 and Ki-67: Immunohistochemical markers for the differential diagnosis of keratoacanthoma and squamous cell carcinoma. Oncol Lett 13: 2539-2548.
11. Norgauer J et al (2003) Human papillomavirus and Grzybowski's generalized eruptive keratoacanthoma. J Am Acad Dermatol 49: 771-772.
12. Peris K et al (2003) Successful treatment of keratoacanthoma and actinic keratoses with imiquimod 5% cream. Eur J Dermatol 13: 413-414.
13. Remling R et al (2000) Intralesional methotrexate injection: an effective time and cost saving therapy alternative in keratoacanthomas that are difficult to treat surgically. Dermatologist 51: 612-614
14. Rinker MH et al (2001) Histologic variants of squamous cell carcinoma of the skin. Cancer Control 8: 354-363
15. Schwartz RA et al (2002) Generalized eruptive keratoacanthoma of Grzybowski: follow-up of the original description and 50-year retrospect. Dermatology 205: 348-352
16. Sanchez Yus E et al (2000) Solitary keratoacanthoma: a self-healing proliferation that frequently becomes malignant. Am J Dermatopathol 22: 305-310.