Background

• Keratoacanthoma (KA) is a common benign skin tumor that arises from hair follicles. KA typically appears as a rapidly growing dome-shaped nodule with a central keratin-filled crater, giving it a volcano-like appearance. The lesion is usually flesh-colored, pink, or reddish, and it can vary in size from millimeters to centimeters in diameter. 
• The exact cause of Keratoacanthoma is unknown, but it is related to factors such as sun exposure, trauma to the skin, and a weakened immune system. UV radiation from the sun plays a role in the development of some KA lesions, especially in sun-exposed areas like the face, neck, and hands. Additionally, individuals with suppressed immune systems, either due to medications or underlying medical conditions, may have an increased risk of developing Keratoacanthoma. 
• Keratoacanthoma commonly occurs in older adults, but it can also affect younger individuals. It is more prevalent in fair-skinned individuals, and there is a slightly higher incidence in men compared to women. It is essential to distinguish KA from other skin lesions, especially from SCC, as their treatments and potential for aggressive behavior can differ. 

Epidemiology

Incidence and Prevalence: 

• Keratoacanthoma is a common benign skin tumor, but its exact incidence and prevalence are not well-defined due to its often-self-limiting nature and lack of comprehensive reporting. 

Age and Gender: 

• Keratoacanthoma can occur at any age, but it is more commonly seen in older adults, usually over the age of 50 or 69. However, it can also affect younger individuals, including children. 
• In general, KA has a slight male predominance, with a slightly higher incidence in men than women. 

Ethnicity and Skin Type: 

• Keratoacanthoma is more prevalent in fair-skinned individuals, especially those with a history of sun exposure. People with lighter skin types, such as those of European descent, are more commonly affected. 
• The incidence of Keratoacanthoma in individuals with darker skin tones, including people of African, Asian, or Hispanic descent, is lower. 

Geographic Distribution: 

• The prevalence of Keratoacanthoma may vary based on geographic location and climate. Regions with a higher ultraviolet (UV) radiation exposure from the sun tend to have a higher incidence of KA. 

Occupational Exposure: 

• Occupational exposure to certain carcinogens or ultraviolet radiation may contribute to the development of Keratoacanthoma, particularly in outdoor workers or those in jobs with high sun exposure. 

Anatomy

Pathophysiology

Genetic Alterations: 

• Genetic mutations in the cells of the hair follicles are thought to play a significant role in the pathophysiology of Keratoacanthoma. These mutations may lead to uncontrolled cell growth and proliferation, resulting in the formation of the characteristic dome-shaped tumor. 

Sun Exposure: 

• Ultraviolet radiation from the sun is an environmental factor in the development of Keratoacanthoma, especially in sun-exposed areas of the body. UV radiation can cause DNA damage and promote abnormal cell growth, contributing to the initiation and progression of the tumor. 

Immune Dysfunction: 

• The immune system plays an important role in recognizing and eliminating abnormal or cancerous cells. In individuals with weakened immune systems or immunosuppression, such as organ transplant recipients, the body’s ability to control the growth of abnormal cells may be compromised. This can increase the risk of developing Keratoacanthoma. 

Inflammatory Response: 

• Inflammation is an essential component of the body’s response to injury or stress. Chronic inflammation can lead to uncontrolled cell growth and tissue damage.  

Proliferation of Keratinocytes: 

• Keratoacanthoma is characterized by the rapid growth and proliferation of keratinocytes, the main cell type found in the epidermis. 

Etiology

Genetic Factors: 

• Genetic mutations in the cells of hair follicles are thought to be a significant factor in the etiology of Keratoacanthoma. These mutations lead to abnormal proliferation and growth of keratinocytes, which are the main cell type in the epidermis. 

Ultraviolet (UV) Radiation: 

• Exposure to UV radiation from sun is considered a crucial environmental factor in the etiology of Keratoacanthoma, particularly in sun-exposed areas of the body. UV radiation can cause DNA damage in skin cells and trigger abnormal cell growth. 

Trauma and Irritation: 

• Some cases of Keratoacanthoma may arise at sites of previous skin trauma or irritation. Physical trauma or chronic irritation to the skin can lead to cellular changes that contribute to the development of the tumor. 

Immune System Dysfunction: 

• Immune system dysfunction or immunosuppression can play a role in the etiology of Keratoacanthoma. Individuals with weakened immune systems like organ transplant recipients or those with certain autoimmune diseases, have an increased risk of developing Keratoacanthoma. 

Chronic Inflammation: 

• Chronic inflammation in the skin may be associated with the development of Keratoacanthoma. Inflammatory processes can lead to tissue damage and uncontrolled cell growth. 

Hormonal Factors: 

• Hormonal changes or imbalances have been proposed as potential contributors to the development of Keratoacanthoma. Some cases have been reported to arise during pregnancy or with the use of certain hormonal medications. 

Genetics

Prognostic Factors

Size and Location: 

• Larger lesions or those located in areas where functional or cosmetic concerns are prominent (e.g., face, hands) may require more aggressive treatment or closer monitoring. 

Rapid Growth and Duration: 

• Lesions that grow rapidly or have been present for an extended period may raise suspicion for other skin conditions, including squamous cell carcinoma (SCC). Early diagnosis & treatment are essential to ensure appropriate management. 

Histopathological Features: 

• Accurate histopathological evaluation of a skin biopsy is crucial to distinguish Keratoacanthoma from other skin tumors, particularly SCC. The presence of well-defined keratin-filled crater, absence of invasion into deeper tissues, and characteristic histological features help confirm the diagnosis of KA and guide treatment decisions. 

Immune Status: 

• The immune status of the individual may influence the behaviour of Keratoacanthoma. In individuals with compromised immune systems like organ transplant recipients, the lesion may be more persistent and require specialized management. 

Recurrence: 

• Although KA is a self-limiting condition, in some cases, it may recur after regression or be associated with multiple lesions. Recurrence may be influenced by the completeness of initial treatment or underlying risk factors. 

Clinical History

Age Group: 

• Younger Age Group: Keratoacanthoma can occur in younger individuals, including children and adolescents. Lesions in this age group may be less common but are not unheard of. 
• Older Age Group: Keratoacanthoma is more commonly seen in older adults, usually over the age of 40 or 50. Lesions may appear more frequently in this age group due to cumulative sun exposure over time. 

Physical Examination

Visual Inspection: 

• The dermatologist will visually examine the skin lesion to observe its size, shape, color, and surface characteristics. Keratoacanthoma commonly presents as a dome-shaped nodule with a central keratin-filled crater, resembling a volcano. 

Location: 

• The location of the lesion will be noted, as Keratoacanthoma frequently occurs in sun-exposed areas of the body, such as the face, neck, hands, and forearms. 

Size and Growth Pattern: 

• The size of the lesion will be measured and documented. Keratoacanthomas can vary in size from a few millimeters to a few centimeters in diameter. 
• The dermatologist will inquire about the lesion’s growth pattern, noting whether it has rapidly increased in size or developed more slowly. 

Color and Texture: 

• The color of the lesion will be evaluated. Keratoacanthomas may appear flesh-colored, pink, or reddish. 
• The texture of the lesion will be assessed, particularly noting the presence of a central keratin-filled crater. 

Margins and Borders: 

• The dermatologist will examine the edges of the lesion to assess their appearance and whether they are well-defined or irregular. 

Tenderness and Sensation: 

• The patient may be asked about any tenderness or pain associated with the lesion, as Keratoacanthomas can be sensitive to touch in some cases. 

Palpation: 

• The dermatologist may gently palpate the lesion to feel its consistency, firmness, and whether it is freely movable or fixed to deeper tissues. 

Assessment of Surrounding Skin: 

• The skin around the lesion will also be examined for signs of inflammation, scaling, or other abnormalities. 

Age group

Associated comorbidity

• Immunosuppression: In individuals with compromised immune systems, such as organ transplant recipients or those with immunosuppressive conditions, Keratoacanthoma may exhibit more aggressive behaviour and be more persistent. 
• Occupational Exposure: Individuals with occupational exposure to carcinogens or chemicals may have an increased risk of developing Keratoacanthoma on exposed areas of the skin.

Associated activity

Acuity of presentation

• Rapid Onset: Keratoacanthomas often display a rapid growth phase, and the lesion may enlarge over a few weeks to a few months. 
• Chronic Presentation: Some Keratoacanthomas may have a slower and more chronic course, with gradual enlargement over a longer period. 

Differential Diagnoses

• Squamous Cell Carcinoma (SCC): SCC is a type of skin cancer that can resemble Keratoacanthoma in appearance, especially in its early stages. Both may present as dome-shaped nodules with a central keratin-filled crater. 
• Actinic Keratosis (AK): AK is a precancerous skin condition caused by chronic sun exposure. It appears as dry, scaly patches or small, rough, pink, or reddish papules on sun-exposed skin. 
• Seborrheic Keratosis (SK): SK is a benign skin growth that is often brown or black and has a waxy, stuck-on appearance. It can vary in size and texture. 
• Basal Cell Carcinoma (BCC): BCC is another common form of skin cancer that typically presents as a shiny, pearly bump with visible blood vessels on the surface. 
• Hypertrophic Actinic Keratosis: Hypertrophic actinic keratosis is a variant of AK that appears as a thicker, more hyperkeratotic lesion. 
• Cutaneous Horn: Cutaneous horns are keratinized skin growths that appear as horn-like projections. They can arise from various underlying conditions, including KA. 
• Inflammatory Conditions: Various inflammatory skin conditions, such as pyogenic granuloma, granuloma annulare, and sarcoidosis, may present with dome-shaped nodules that can mimic Keratoacanthoma. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Clinical Evaluation and Diagnosis: 

• A dermatologist examines the skin lesion to determine if it is consistent with Keratoacanthoma. The clinical appearance and history of rapid growth help in the initial diagnosis. However, a definitive diagnosis is confirmed through a skin biopsy. 

Biopsy and Histopathological Examination: 

• A skin biopsy is performed to obtain a small sample of the lesion. The sample is sent to histopathological examination to confirm the diagnosis of Keratoacanthoma and to rule out other skin conditions, especially squamous cell carcinoma (SCC). 

Observation and Expectant Management: 

• Some smaller Keratoacanthomas may undergo spontaneous regression without any treatment. In cases where the lesion is small, stable, and not causing symptoms or functional impairment, a “wait and watch” approach may be adopted. 

Surgical Excision: 

• Surgical excision is the first line treatment for most Keratoacanthomas. During the procedure, the dermatologist removes the lesion along with margins of healthy surrounding tissue to ensure complete removal. 

Cryotherapy: 

• Cryotherapy using liquid nitrogen may be considered for smaller, solitary lesions that are not amenable to surgical excision. Freezing the lesion with cryotherapy destroys the abnormal cells. 

Curettage and Electrodesiccation: 

• Curettage involves scraping off the lesion using a sharp instrument (curette). Afterward, electrodesiccation is performed to destroy any remaining abnormal cells using an electrical current. 

Topical Medications: 

• In some cases, topical medications may be applied directly to the lesion to promote regression. Medications such as 5-fluorouracil (5-FU) or imiquimod may be used. 

Laser Therapy: 

• Laser treatment may be considered for select cases of Keratoacanthoma, especially for lesions on the face or in cosmetically sensitive areas. 

Follow-up and Monitoring: 

• After treatment, regular follow-up visits with the dermatologist are important to monitor the treated area for recurrence and detect any new skin changes. 
• Long-term follow-up is necessary to ensure there is no recurrence or development of new lesions. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

non-pharmacological-treatment-of-keratoacanthoma

Lifestyle modifications: 

• Sun Protection: Limiting sun exposure and using sun-protective measures like wearing sunscreen, protective clothing, and sunglasses, can help reduce the risk of sun-related skin damage and skin cancers. 
• Avoiding Tanning Beds: Tanning beds emit harmful UV radiation therby damaging the skin and increases the risk of skin cancer. Avoiding tanning beds altogether is recommended. 
• Healthy Diet: The balanced diet rich in fruits, vegetables, and antioxidants can support overall skin health. Proper nutrition helps the body’s natural defense mechanisms and promotes skin repair and regeneration. 
• Hydration: Staying adequately hydrated by drinking plenty of water helps maintain skin hydration and overall well-being. 
• Stress Management: Stress can exacerbate certain skin conditions and impact overall health. Practicing stress-reducing techniques like mindfulness, meditation, or exercise, may be helpful. 
• Regular Skin Self-Examination: Being familiar with one’s skin and performing regular skin self-examinations can help detect any changes or new skin lesions, including Keratoacanthomas, at an early stage. 

use of Intralesional and Topical therapies in the treatment of Solitary Keratoacanthoma

Intralesional Therapy: 

• Intralesional therapy involves injecting a medication directly into the Keratoacanthoma to promote regression or destruction of the lesion. Two commonly used intralesional agents are: 
• Topical Fluorouracil (5-FU): Injecting 5-FU directly into the lesion can help induce cell death and shrink the Keratoacanthoma. 
• Methotrexate: Intralesional methotrexate may be used in select cases to treat larger or more aggressive Keratoacanthomas. 

Radiation Therapy: 

• It involves high-energy radiation to target and destroy cancer cells, including those of Keratoacanthoma. 
• It is typically reserved for cases where surgical options are limited due to the lesion’s location or if the patient cannot undergo surgery. 

Topical Therapy: 

• Topical treatments are applied directly to the surface of the Keratoacanthoma and can be considered for smaller lesions or in patients who cannot undergo surgery. Two commonly used topical agents are: 
• Topical Fluorouracil (5-FU): Applied directly to the lesion, 5-FU can cause cell death and promote the regression of the Keratoacanthoma. 
• Imiquimod: This immune response modifier is applied topically and can stimulate the body’s immune system to attack the lesion. 

Use of other therapies in the treatment of Keratoacanthoma

Curettage Alone: 

• Curettage alone, without electrodesiccation, involves scraping off the Keratoacanthoma using a curette. This technique may be suitable for smaller, less aggressive lesions. 

Cryotherapy: 

• Cryotherapy involves freezing the Keratoacanthoma using liquid nitrogen. The freezing temperature causes cell death and leads to the sloughing off the lesion. 

Argon Laser: 

• Argon laser is a type of laser therapy that can be used to vaporize and remove Keratoacanthoma. The laser energy precisely targets the lesion, minimizing damage to surrounding tissues. 

Erbium:Yttrium Aluminum Garnet (Er:YAG) Laser in Combination with Topical Fluorouracil: 

• This combination therapy involves using the Er:YAG laser to ablate the lesion, followed by the application of topical fluorouracil to enhance the treatment’s effectiveness. 

Photodynamic Therapy (PDT): 

• PDT utilizes a photosensitizing agent, applied topically, or injected, which is then activated with light of a specific wavelength to destroy the Keratoacanthoma cells. 

Use of systemic therapies due to the presence of multiple or large lesions

Systemic Retinoids (Acitretin or Isotretinoin): 

• Acitretin (25 to 60 mg per day) or isotretinoin (20 mg per day up to 1.5 mg/kg per day) can be prescribed for several months to achieve a satisfactory response in cases with multiple or large Keratoacanthomas or when other treatments have not been effective. 
• These retinoids have an anti-proliferative effect on the skin cells and can help control the growth of the lesions. 

Methotrexate plus Prednisone: 

• Methotrexate, an immunosuppressive drug, may be combined with prednisone (a corticosteroid) to manage severe or rapidly growing Keratoacanthomas. 
• This combination therapy helps control inflammation and suppresses the immune response that contributes to the lesion’s development. 

Cyclophosphamide: 

• Cyclophosphamide is an immunosuppressive agent used in certain cases of severe or rapidly growing Keratoacanthomas that are not responsive to other treatments. 
• It works by inhibiting cell growth and reducing the immune response. 

Intravenous Fluorouracil: 

• In some special cases, intravenous (IV) fluorouracil may be used to treat multiple or extensive Keratoacanthomas. 
• IV administration allows for systemic delivery of the medication to control the growth of the lesions. 

treatment for Subungual keratoacanthoma and Muir-Torre syndrome

Subungual Keratoacanthoma Treatment:  

Curettage with or without Electrodesiccation: 

• For subungual keratoacanthoma, curettage is a commonly used treatment approach. During the procedure, the dermatologist uses a curette to scrape off the lesion from the subungual region. 
• In some cases, electrodesiccation may follow the curettage to cauterize the base of the lesion, destroying any remaining abnormal cells and minimizing bleeding. 
• Subungual keratoacanthomas can be challenging to completely remove, and recurrence is possible. Therefore, close follow-up is crucial to monitor for any signs of lesion persistence or recurrence. 

Systemic Methotrexate: 

• Systemic methotrexate, an immunosuppressive drug, may be considered for subungual keratoacanthoma cases that are challenging to manage with local procedures alone. 
• Methotrexate can help control the growth of the lesion and reduce inflammation, particularly in cases where the lesion is extensive or recurrent. 

Muir-Torre Syndrome: 

• Muir-Torre syndrome is a rare hereditary condition characterized by the presence of multiple sebaceous neoplasms (adenomas or carcinomas) and internal malignancies, along with keratoacanthomas and other skin tumors. 
• Treatment of Keratoacanthoma in individuals with Muir-Torre syndrome may require a multidisciplinary approach due to the potential for other malignancies and the complexity of the condition. 
• Management may involve a combination of treatments, including surgical excision, topical therapies, and systemic treatments, depending on the extent and aggressiveness of the lesions and associated tumors. 

use-of-surgical-procedures-as-a-first-line-therapy-for-keratoacanthoma

First-line therapy for Keratoacanthoma typically involves conventional surgical excision and, in certain cases, Mohs surgery. These two surgical procedures are considered effective and widely used approaches for removing the lesion while ensuring complete excision and minimizing the risk of recurrence. 

Electrodesiccation and Curettage (ED&C): 

• ED&C is a procedure in which the dermatologist first scrapes off the Keratoacanthoma using a sharp instrument called a curette. 
• After curettage, the base of the lesion is cauterized using an electrical current (electrodesiccation) to destroy any remaining abnormal cells and stop bleeding. 
• ED&C is a simple and cost-effective procedure suitable for smaller and superficial Keratoacanthomas. 

Conventional Surgical Excision: 

• Conventional surgical excision is a standard first-line treatment for most Keratoacanthomas. During the procedure, the dermatologist or surgeon removes the lesion along with a margin of healthy surrounding tissue to ensure complete excision. 
• The excised tissue is sent for histopathological examination to confirm the absence of tumor cells, ensuring the lesion’s full removal. 
• This technique is suitable for most Keratoacanthomas and provides a high cure rate with minimal scarring when performed by experienced healthcare professionals. 

Mohs Surgery: 

• Mohs surgery is a surgical technique often used for larger, recurrent, or challenging Keratoacanthomas, especially those in cosmetically sensitive areas or near critical structures. 
• During Mohs surgery, thin layers of the tumor are removed one at a time, and each layer is immediately examined under a microscope by the surgeon. 
• This process continues until the surgeon determines that no cancer cells remain, achieving precise tumor removal while preserving healthy tissue. 
• Mohs surgery offers high cure rates and is particularly beneficial for tumors with indistinct borders or aggressive behavior. 

various-phases-of-management-in-the-treatment-of-keratoacanthoma

Evaluation and Diagnosis: 

• The management process begins with a thorough evaluation of the skin lesion by a dermatologist or healthcare professional. 
• Clinical examination helps in identifying the characteristic features of Keratoacanthoma and differentiating it from other skin conditions. 

Confirmation through Biopsy: 

• A skin biopsy is usually performed. A small tissue sample is taken from the lesion and sent to a laboratory for histopathological examination. 
• The biopsy results help establish a definitive diagnosis of Keratoacanthoma and rule out other skin conditions, including more aggressive forms of skin cancer. 

Treatment Planning: 

• Based on the biopsy results and the characteristics of Keratoacanthoma, the dermatologist formulates an appropriate treatment plan. 

• Treatment options are based on factors such as the lesion’s size, location, aggressiveness, and overall health and preferences. 

Treatment Phase: 

• The chosen treatment method is implemented during this phase. The treatment may involve surgical excision, cryotherapy, electrodesiccation and curettage, laser therapy, topical therapies, systemic medications, or a combination of these approaches. 
• The goal of treatment is to remove the Keratoacanthoma completely, minimize scarring, and prevent recurrence. 

Healing and Follow-up: 

• After the treatment, the patient is monitored for proper healing and to detect any signs of recurrence or complications. 
• Regular follow-up visits with the dermatologist are essential to assess the treated area’s response, evaluate for recurrence, and address any concerns or side effects. 

Long-term Surveillance: 

• Depending on the patient’s risk factors and history of skin lesions, long-term surveillance may be necessary to monitor for potential new skin changes or the development of new Keratoacanthomas. 
• The dermatologist may provide recommendations for skin self-examination and educate the patient about potential warning signs.

Medication

Future Trends

Media Gallary

References

• www.keratoacanthoma.ncbi.nlm.nih.gov 
• www.An Updated Review of the Therapeutic Management of Keratoacanthomas.ncbi.nlm.nih.gov 
• www.keratoacanthoma.dermnetnz.org