A case of sporadic solitary keratoacanthoma

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A male in his sixties presented with the chief complaint of a raised, asymptomatic lesion on his right cheek for a 1-month duration, which had gradually increased in size and developed spontaneous central ulceration. Cutaneous examination revealed a single, dome-shaped nodule measuring approximately 1 cm in diameter with central crateriform ulceration with hemorrhagic crusting and surrounding erythema over the right cheek [Figure 1]. Dermoscopy of the lesion showed a central crater with yellowish crust and blackish areas, suggesting hemorrhage, and was surrounded by a thick margin. On the margin of the lesion, ivory white areas with a few vessels and minimal scaling were present [Figure 2]. Differential diagnoses of solitary keratoacanthoma (KA) and squamous cell carcinoma (SCC) were considered. A thorough excisional biopsy was performed, and the specimen was sent for histopathology to rule out malignancy in view of the short duration of the lesion. Histopathology revealed a well-circumscribed squamous epithelial tumor with a central keratin-filled crater. The surrounding epidermis formed a raised lip at the periphery of the tumor. The tumor showed exophytic and endophytic cyst-like epidermal invaginations. The tumor cells had eosinophilic cytoplasm with no cytological atypia [Figure 3]. Staining for immunohistochemistry (IHC) markers revealed p16 with a ragged, discontinued mosaic pattern expression [Figure 4a], retained expression of E-cadherin, [Figure 4b], CD10 positivity (localized predominantly at stratum basale [Figure 4c]), and a low proliferation index of Ki-67 (localized to stratum basale; [Figure 4d]). Based on the clinical, histopathological, and IHC features, a final diagnosis of solitary KA was made.

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Figure 1:

Nodular lesion on the right cheek with central crater covered by hemorrhagic crusting.

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Figure 2:

Dermoscopy showing central crater with yellow crust (red arrow) and blackish areas suggesting hemorrhage (black arrow) and ivory white areas (blue arrows) (DermLite DL4 dermoscopy ×10).

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Figure 3:

Haematoxylin and eosin (H&E) stained section shows a tumour with both exophytic (red arrow) and endophytic growth (green arrow) from the skin’s surface (exophytic or endophytic cyst-like epidermal invagination). The downward growth is bowl-shaped and smooth while the surrounding epidermis forms a lip around the invaginating crateriform tumour with central keratin filled crater (yellow circle) (x40).

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Figure 4:

(a) Immunohistochemistry (IHC) for p16 shows patchy/ragged, discontinued expression (mosaic pattern) (x100); (b) IHC for E-cadherin is positive (retained expression) (x200); (c) CD10 shows positivity mainly localized to the stratum basale (red arrow) (x200); (d) Ki-67 shows low proliferation index (localized to the stratum basale) (green arrow) (x200).

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KA is a common, rapidly growing, locally destructive skin lesion. KAs may rarely regress spontaneously, but clinically, they may be indistinguishable from well-differentiated SCC. As the clinical course may be unpredictable, many clinicians prefer the term “SCC, KA-type.”^[1,2] KA is most common in fair-skinned older males, often with a history of chronic sun exposure. It is twice as common in males as in females, and most patients are over 60 years of age. Increased incidence of KA is seen in immunocompromised patients, patients with genetic cancer syndromes, such as xeroderma pigmentosum, Muir-Torre syndrome, and incontinentia pigmenti. Medications, e.g., B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitors such as vemurafenib and dabrafenib (for metastatic melanoma) and hedgehog pathway inhibitors for basal cell carcinoma, such as vismodegib, also predispose to KAs.^[3]

KA originates from the infundibulum of a hair follicle. Presize pathogenetic mechanisms probably include aberrant regulation of the Wingless-related integration site signal transduction (WNT) signal transduction pathways and mutations in the tumor suppression gene TP53. The risk factors for KA are similar to SCC, include exposure to ultraviolet light, chemical carcinogens (e.g., smoking, industrial workers exposed to pitch, tar, and mineral oils), and probably human papillomavirus infection.

Morphologically, sporadic solitary KA (the most common variant) presents as a solitary, rapidly growing nodule on sun-exposed skin of the face and upper limbs. The lesions are sharply demarcated, firm, erythematous, or skin-colored, with a classic central hyperkeratotic plug. Removal of the keratotic core will leave a “crater”-like appearance to the lesion, as was seen in our patient.^[1] There are several rarer variants of KA including KA centrifugum marginatum (often with no tendency to regression), giant KA (size usually more than 2 cm), multiple familial KA of Witten and Zak (rare variant of KA that presents in childhood with overlapping features of the Ferguson-Smith and Grzybowski subtypes), generalized eruptive KAs of Grzybowski, and multiple self-healing squamous epithelioma of Ferguson-Smith disease.^[4]

Typical dermoscopic features of KA and SCC include concentric circles of a central crater, surrounded by ivory white circles with few peripheral vessels and scaling. These dermoscopic features usually cannot reliably discriminate KA from SCC. However, these features would help in excluding other non-pigmented lesions.^[5] Histopathology and IHC markers help differentiate a solitary KA from SCC.^[6,7] However, the specimen should be sufficiently representative, performed by total or partial excision or a fusiform partial excision through the entire KA, including its center and both sides. This approach allows for a comprehensive analysis of its whole architecture.^[1]

Surgical treatment is considered the first line unless there is clear evidence of spontaneous regression. However, most clinicians consider it best to assume a KA-like lesion as an SCC and send the specimen for appropriate histopathological examination.^[6,1] In selected cases, cryotherapy, curettage, and electrodessication, or topical or intralesional chemotherapy with 5-fluorouracil, imiquimod, bleomycin, or methotrexate may be helpful.

To conclude, we describe a case of solitary KA. A complete surgical excision with a histopathological examination to rule out SCC is essential for managing these patients.