Keratoacanthoma (KA) and cutaneous Squamous Cell Carcinoma (SCC) are both growths on the skin that originate from keratinocytes, the cells that make up the majority of the skin’s surface. These two entities frequently present a challenge for medical professionals because they can appear nearly identical. While KA is often considered a benign, self-limiting tumor, SCC is an established form of skin cancer that can spread if not treated. Because of their shared cellular origin and overlapping characteristics, a definitive diagnosis requires careful analysis, as the distinction carries vastly different implications for treatment. The controversy surrounding whether KA is a true cancer or a separate, benign entity further complicates identification and management.
Clinical Presentation and Growth Rate
The most striking initial difference between Keratoacanthoma and Squamous Cell Carcinoma is often the speed at which the lesion develops. Keratoacanthoma is characterized by a rapid growth phase, often reaching its maximum size of one to two centimeters within weeks. This fast, proliferative phase helps distinguish it from most standard SCCs, which typically grow much slower over many months or years.
Keratoacanthoma typically appears as a dome-shaped nodule with a central crater filled with a core of keratin, giving it a characteristic plug-like appearance. Conversely, while SCC can also be nodular, it often presents as a persistent, scaly patch, an ulcerated lesion, or a firm plaque that lacks the symmetrical, volcano-like structure of KA. Both lesions primarily occur on sun-exposed skin (face, neck, and extremities), reflecting the shared influence of ultraviolet light exposure. Since clinical presentation alone is not reliable, a rapid growth history in a dome-shaped lesion strongly suggests KA, but aggressive SCC cannot be ruled out without further testing.
Definitive Identification Through Biopsy
Because clinical features are ambiguous, a definitive diagnosis relies on a biopsy, where a tissue sample is examined by a pathologist. Under the microscope, KA often exhibits symmetry and well-defined borders, with the epithelial tissue appearing to “lip” over the central crater. Keratoacanthoma cells are typically well-differentiated, with abundant, glassy cytoplasm, and the cellular atypia is often confined to the basal layer at the periphery of the lesion.
In contrast, SCC tends to show more aggressive features, including significant cellular atypia, meaning the cells appear haphazard, disorganized, and pleomorphic. SCC frequently demonstrates invasive growth, pushing irregularly into the dermis beyond the level of the sweat glands, a feature less common in KA. SCC is classified under the ICD-10 code C44, designating a malignant neoplasm of the skin and reflecting its capacity for destructive and metastatic behavior. KA is often classified separately (sometimes under ICD-10 code L85.8 or D23), reflecting its non-malignant or uncertain behavior, though many pathologists treat it as a variant of SCC due to histological similarity. To ensure accurate subtyping, a deep or excisional biopsy is often necessary, as a superficial shave biopsy may miss the architectural features that differentiate KA from truly invasive SCC.
Treatment Strategies
The difference in diagnostic classification immediately affects the treatment strategy, though the initial approach is often conservative. For confirmed KA, treatment options vary widely, sometimes including observation if the lesion is small and regression is anticipated. Alternative, non-surgical approaches involve intralesional injections of chemotherapy agents (like 5-fluorouracil or methotrexate) delivered directly into the lesion to induce breakdown. Simple excision or destructive techniques like cryotherapy or curettage are also common for KA, especially for cosmetic reasons or to eliminate the risk of misdiagnosis.
Confirmed SCC, even if it mimics KA clinically, demands a more aggressive, margin-controlled approach to ensure complete removal. The standard of care for most SCCs is surgical excision with clear margins, or Mohs micrographic surgery for high-risk or cosmetically sensitive areas. Mohs surgery involves removing the tumor layer by layer and immediately examining the margins under a microscope until no cancer cells remain, maximizing tissue preservation. Radiation therapy may also be used for SCC, particularly when surgery is not feasible due to the lesion’s size or location, or if the patient has significant comorbidities.
Long-Term Prognosis
The long-term outlook for KA is excellent, primarily due to its propensity for spontaneous resolution or successful removal, and its minimal risk of spreading. While some aggressive sub-types or misdiagnosed lesions have been reported to metastasize, the overall risk is very low, estimated to be less than two percent. The self-limiting nature of KA means that post-treatment surveillance is generally aimed at monitoring for the development of other sun-related skin cancers, but not for metastasis from the original lesion.
Conversely, SCC carries a risk of local recurrence and distant metastasis, especially if it is large, deeply invasive, or located on high-risk sites (like the lip or ear). Untreated SCC can lead to morbidity and even death, necessitating rigorous post-treatment surveillance, which is often more frequent than for KA. For SCC, the metastasis-free survival rate is distinctly lower than for KA, reinforcing the need for complete removal and long-term follow-up to detect any signs of local relapse or distant spread.