3.2.2 Keratoacanthoma

2F2Y / 2F2Z

Epidermoid carcinoma.

Pseudocarcinoma.

Estimated incidence of KA ranges between 100 and 150 cases per 100,000 individuals. Quite common tumor mostly affecting those older than 60 years. Males are more affected than females (3:1). Smoking and solar damage are risk factors.

Keratoacanthoma (KA) is by histology a well-differentiated cutaneous squamous cell carcinoma. It growths very fast and it typically presents as a dome-shaped nodule with a central keratin-filled crater. It is a low malignancy tumour with uncertain biologic behaviour that might present spontaneous regression. This regression is thought to be due to immune mediated destruction of squamous cells.

Keratoacanthomas are derived from follicular infundibular areas out of the epidermal hair follicle stem cell pool. About 25% are human papilloma virus type 21-related, particularly β-genus types. Transforming growth factor beta receptor 1 (TGFBR1) can cause multiple self-healing squamous cell carcinomas (MMSE, type Ferguson- Smith), which is the most common cause of multiple KA’s. There is evidence for germline mutations of hMSH2 and hMLH1 mismatch repair genes causing Muir-Torre syndrome in solitary and multiple KA’s.

Major risk factors include excessive UV exposure, radiation, immunosuppression, chronic non-healing wounds, and HPV infection. It has also been reported to occur in sites of iatrogenic or accidental trauma.

There is now strong evidence that Mitochondrial Microsatellite Instability (MtMSI) help to differentiate between KA's and SCC's. MtMSI was detected at mitochondrial D514 D-loop and presented with (CA) n repeats. In contrast, all of the SCC patient experienced mtMSI with (C)n repeats at the D-loop region D310. These differences in location are highly significant, which further supports the hypothesis that KA and SCC have different pathogenetic pathways.

KA, in contrast to SCC, shows three clinical stages:

a. proliferative,

b. mature, and,

c. involutional / regressing.

Regression is thought to be due to immune mediated destruction of squamous cells. In particular, it is of note that in the proliferative stage, strong infiltration of the epithelial strands with eosinophils can be seen, and they are known to have potent anti-cancer properties. Spontaneous tumour regression in keratoacanthomas is driven by Wnt/retinoic acid signalling cross-talk.

In patients with metastazing malignant melanoma under treatment with BRAF inhibitors, KA`S can occur as multiple eruptive variants.

Typically, KA appears solitary but KA may present with multiple tumors or may be of a giant type. Lesions are hyperkeratotic, irregular papules or nodules, sometimes crusted and ulcerated. As a highlight one can see a crater filled with keratotic and necrotic material. A large and centrifugal growing subtype of KA with elevated margins without the central keratotic plug or crater can be seen at the dorsum of hands and feets.

For a reliable and clear dermatopathological diagnosis of a KA, one needs a representative elliptoid biopsy (a punch biopsy is usually less helpful). By low power magnification one can see a proliferating well-differentiated squamous tumour with a central keratin-filled crater. Typically, the surrounding epidermis forms a lip around the invaginating crateriform tumour composed of rather normal cells. The proliferating tumour itself is composed of squamous cells with abundant eosinophilic or milky-glassy cytoplasm and enlarged hyperchromatic to vesicular-appearing nuclei. In the proliferative stage, one finds in the epithelial strands eosinophilic and neutrophilic microabscesses and also eosinophils in large numbers invading the tumour or free in the inflammatory infiltrate. Huge keratin horn pearls are seen within the tumour.

Regressing tumours ultimately show epidermal atrophy, bland cytologic features, dermal inflammation and fibrosis at the periphery of tumour. Scarring occurs to a variable degree.

KA is typically a non-fatal tumor. It can regress; however, final size prior to regression is difficult to predict. Recurrence is uncommon with surgical removal. The scar is permanent.

Scarring.

In cases of ambiguous dermatopathological findings, an unusual fast proliferating SCC or other types of benign or malignant mostly skin appendage-related tumors may have been overlooked.

Diagnosis relies on clinical features and histology. Dermoscopy is extremely helpful and the main features are: white circles (white ring-like structures within the hair follicle; a centrally located keratin mass, and white structureless areas. Vessels can be hairpin-like linear-irregular or glomerular. Skin ultrasound can help determine tumour depth and volume.

Treatment depends on size and localization. Monitoring for spontaneous regression is common in clinical practice. In particular, in the situation of tumors in the face and at functional areas over joints and close to orifice, two weeks will often be enough to assess if the tumour will regress or not.

Typically, if not regressing, it is treated with complete surgical excision. Mohs’ surgery or 24 hrs. dermatopathological finding is performed dependent on anatomic location.

Electrosurgery, cryosurgery, laser surgery, systemic or topical chemotherapy are occasionally performed. Low dose radiotherapy can be used if the lesion recurs or if there would be significant cosmetic disfigurement with other surgical options.

None.