BACKGROUND: Solitary large keratoacanthomas (KAs) of the head and neck present a management dilemma, as no reliable means to predict the clinical course is available. Although typically considered a low-grade tumor, KAs are reported to invade/metastasize, prompting more aggressive treatment. There is little published regarding factors that predict when a KA behaves more like an aggressive squamous cell carcinoma (SCC). OBJECTIVE: To study the clinical and pathologic features of large solitary head and neck KAs and assess response to intralesional methotrexate (IL-MTX) as well as predictors of clinical course. MATERIALS AND METHODS: An observation study of 14 patients with large solitary head and neck KAs were treated with IL-MTX and then excised by Mohs micrographic surgery (MMS) at a later time point. Clinical presentation, treatment, response, and pathology were recorded. Features of classic KAs were compared with those with an aggressive SCC course. RESULTS: Ten of fourteen lesions responded with necrosis, a decrease in size and/or pain, and histological clearance on MMS. However, 4/14 lesions continued to have progression despite IL-MTX therapy. These showed persistent pain, perineural invasion, moderate/poor differentiation, and an infiltrative growth. LIMITATIONS: Small sample size. CONCLUSION: Significant pain, or continued growth may suggest an underlying aggressive SCC in clinically classic large KAs. In these cases, surgical management with assessment for high-risk tumor features is recommended.
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