Keratoacanthoma vs Squamous Cell Carcinoma: Distinguishing Traits

Skin lesions that appear similar can have vastly different prognoses and treatments. Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are often mistaken for one another due to overlapping features, but distinguishing them is crucial. SCC poses a higher risk of aggressive behavior and metastasis, while KA typically follows a benign course.

Understanding their differences requires examining their visual traits, clinical behaviors, histological characteristics, and diagnostic methods.

Visual Characteristics

KA and SCC share visual similarities, making differentiation based on appearance alone difficult. Both present as rapidly growing nodules on sun-exposed areas such as the face, forearms, and hands, particularly in older adults with a history of ultraviolet (UV) exposure. However, distinct morphological traits help distinguish them.

KA appears as a dome-shaped, symmetrical nodule with a well-defined border and a central keratin-filled crater, creating a volcano-like appearance. The lesion develops rapidly over weeks, reaching 1–2 cm before stabilizing. A keratin plug is a distinguishing feature, as well as a well-demarcated margin, contrasting with SCC’s more infiltrative nature.

SCC, by contrast, lacks a symmetrical, crateriform structure and often presents as an irregular, scaly, or ulcerated plaque or nodule. The surface may be rough with hyperkeratosis and signs of bleeding, crusting, or erosion. Unlike KA, SCC has an ill-defined border, reflecting its invasive potential. Its coloration varies from pink to reddish-brown, and it may develop satellite nodules or surrounding induration, indicating deeper tissue involvement.

Clinical Presentations

KA and SCC differ significantly in clinical behavior despite similar appearances. KA has a rapid onset and self-limiting nature, emerging within weeks and progressing through distinct phases. Patients report a sudden firm, dome-shaped lesion that expands quickly before stabilizing. This is followed by a plateau stage and eventual regression, often leaving a depressed scar. The entire process can take months, though not all KA lesions resolve on their own.

SCC, in contrast, follows a persistent course, gradually increasing in size over weeks to months without a regression phase. Unlike KA, which is typically solitary, SCC may present as multiple lesions in patients with extensive sun damage or immunosuppression. SCC lesions often cause tenderness, bleeding, or pruritus, particularly when ulcerated. Progressive thickening with a firm, indurated base suggests deeper invasion, and perineural involvement can manifest as pain, numbness, or paresthesia, signaling a more aggressive course.

Location-specific symptoms also provide insight. SCC is more likely than KA to develop in sites of chronic irritation, such as scars, burns, or previously irradiated areas. Lesions on the lower lip pose a higher metastatic risk. In immunocompromised individuals, SCC tends to be more aggressive, with a greater likelihood of recurrence and regional spread. KA, while less frequently systemic, may warrant closer observation in atypical cases.

Histopathological Features

Microscopic examination reveals key differences between KA and SCC. KA has a well-circumscribed, lobular proliferation of keratinocytes with a central keratin-filled crater. The lesion’s edges form epidermal lips extending downward, creating a cup-shaped structure. Keratinocytes in KA are relatively uniform, with eosinophilic cytoplasm and minimal nuclear atypia. Mitoses are present but not excessive, and inflammatory infiltrates, particularly lymphocytes and histiocytes, suggest a host response consistent with spontaneous regression.

SCC, by contrast, lacks KA’s well-demarcated growth pattern and instead shows an infiltrative architecture with irregular nests of atypical keratinocytes extending into the dermis. Cells exhibit significant pleomorphism, hyperchromatic nuclei, and increased mitotic activity, including atypical mitoses. Well-differentiated SCCs often form keratin pearls, while poorly differentiated cases show more cellular disorganization and loss of normal maturation. Tumor-stroma interactions are more pronounced in SCC, with desmoplastic reactions indicating deeper invasion and potential perineural involvement.

The pattern of keratinization further differentiates these lesions. KA has an abrupt transition from normal epidermis to proliferative keratinocytes, while SCC exhibits more gradual dysplastic changes. Additionally, KA typically has a pushing rather than infiltrative border, distinguishing it from SCC’s more destructive growth. Immunohistochemical markers such as p53 and Ki-67 can help differentiate the two, with SCC showing higher proliferative indices.

Growth Patterns

KA and SCC differ in progression, particularly in speed, structural expansion, and long-term behavior. KA is known for its rapid onset, often reaching full size within weeks. This explosive growth phase can initially raise suspicion of malignancy. Unlike SCC, which steadily enlarges over time, KA stabilizes at 1–2 cm before regressing, often leaving an atrophic or hypopigmented scar. Spontaneous involution, though not universal, supports its classification as a self-limiting tumor.

SCC, on the other hand, follows a relentless trajectory, continuously expanding without a regression phase. Growth rate varies based on differentiation, location, and host factors such as immunosuppression. Unlike KA’s well-demarcated borders, SCC exhibits an infiltrative pattern, extending into surrounding tissues with irregular margins. This invasive growth increases the risk of local destruction, particularly in high-risk areas like the lips, ears, and genitals. SCC may also penetrate deeper skin layers and, in aggressive cases, invade underlying structures such as muscle or bone.

Diagnostic Approaches

Distinguishing KA from SCC requires a thorough diagnostic evaluation. A combination of physical assessment, histopathological analysis, and imaging techniques provides a definitive classification, guiding appropriate management.

Physical Evaluation

A detailed clinical examination offers initial clues for differentiation. Dermatologists assess lesion morphology, growth history, and surface characteristics, focusing on features such as symmetry, border definition, and central keratinization. KA’s rapid growth followed by stabilization is a distinguishing trait, whereas SCC grows progressively without a plateau.

Dermoscopy aids in assessment, revealing KA’s central keratin plug with a surrounding vascular pattern, while SCC often displays irregular blood vessels, scaling, and ulceration. Palpation is also critical, as SCC may exhibit a firmer, more indurated consistency, suggesting deeper invasion.

Biopsy Methods

Histopathological examination remains the definitive diagnostic tool. A deep shave, punch, or excisional biopsy is chosen based on lesion size and location. A deep shave biopsy captures KA’s epidermal lips and crateriform architecture, while a punch biopsy provides insights into cellular atypia and invasion depth, crucial for SCC diagnosis.

In challenging cases, immunohistochemical staining for markers such as p53 and Ki-67 highlights proliferative differences, with SCC demonstrating higher expression. Given KA’s potential for spontaneous regression, some clinicians opt for complete excision when uncertainty exists, ensuring both diagnosis and treatment in a single procedure.

Imaging Considerations

While imaging is not routinely needed for superficial lesions, advanced cases may require further evaluation. High-frequency ultrasound helps assess lesion depth and detect subclinical spread, particularly in SCC with suspected dermal invasion. MRI is occasionally used in high-risk areas, such as the periocular region or mucosal surfaces, to evaluate potential soft tissue involvement.

For SCC with aggressive features, such as perineural invasion or regional lymphadenopathy, CT or PET scans may be warranted to assess metastatic spread.

Prognostic Factors

KA and SCC have distinct prognoses, making accurate classification essential for treatment and follow-up. KA generally has a favorable prognosis, with most lesions resolving spontaneously or responding well to surgical excision. Recurrence is rare, though atypical cases may require further intervention. In immunosuppressed individuals, multiple or recurrent lesions can complicate management, but metastatic potential remains extremely low.

SCC, in contrast, varies widely in prognosis. Tumor differentiation, depth of invasion, and location influence its behavior. Well-differentiated SCCs confined to the epidermis or superficial dermis have lower recurrence rates, while poorly differentiated or deeply invasive lesions pose higher risks for local destruction and metastasis. High-risk sites, such as the lips, ears, and genitals, are associated with increased lymphatic spread, necessitating close surveillance. Immunosuppressed individuals, particularly organ transplant recipients, face a significantly elevated risk of aggressive SCC, requiring more extensive treatment and monitoring.