Continuing Education Activity

A Marjolin ulcer is a cutaneous malignancy that arises in the setting of previously injured skin, longstanding scars, and chronic wounds. Historically, Marjolin ulcers are named for French surgeon Jean Nicolas Marjolin and first described as ulcerations with dense villi arising within a burn cicatrix. Squamous cell carcinoma is the most frequent malignancy identified, although other cell types have been described (i.e., basal cell carcinoma). Lesions are aggressive and carry a poor prognosis with a high rate of recurrence. This activity reviews the cause, pathophysiology, and presentation of Marjolin ulcer and highlights the role of the interprofessional team in its management.

Objectives:

• Describe the pathophysiology of Marjolin ulcer.
• Review the evaluation of a patient with Marjolin ulcer.
• Summarize the treatment options for Marjolin ulcer.
• Outline the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by Marjolin ulcers.

Introduction

A Marjolin ulcer is a cutaneous malignancy that arises in the setting of previously injured skin, longstanding scars, and chronic wounds. Historically, Marjolin ulcers are named for French surgeon Jean Nicolas Marjolin and first described as ulcerations with dense villi arising within a burn cicatrix.[1] Squamous cell carcinoma is the most frequent malignancy identified, although other cell types have been described (i.e., basal cell carcinoma). Lesions are aggressive and carry a poor prognosis with a high rate of recurrence. Prevention with proper burn wound management and early recognition of malignant conversion followed by surgical resection, if possible, are of the utmost importance.

Etiology

Burn scars are the most common inciting condition that leads to the development of Marjolin ulcers.[2] Malignant degeneration occurs in 0.7% to 2.0% of burn scars that have been allowed to heal by secondary intention.[3][4] Other chronic inflammatory etiologies that lead to Marjolin ulcers include traumatic wounds, venous stasis ulcers, osteomyelitis, pressure ulcers, radiation dermatitis, stings, bites, and hidradenitis suppurativa.[1][3][4][5] Individuals that are immunocompromised, either due to disease state or medication, are at increased risk for malignant conversion.[5]

Epidemiology

Marjolin ulcers occur in all age groups, sexes, and races. The average latency period from the time of the initial inciting wound to the discovery of malignant degeneration is between 30 and 35 years, with the average age at presentation being 59 years.[6][7] Men are more commonly affected than women (3:1), perhaps due to the increased frequency of burns in this population in general.[2] Unlike other forms of skin cancer, the risk is equal in all races and ethnicities.[8]

Pathophysiology

The pathophysiology has not been completely elucidated, but several mechanisms have been proposed, including chronic irritation, repeated re-epithelization, local damage to immune mechanisms of the skin, genetic predisposition, and toxins from local cell damage.[1] Burn scars tend to be raised above the natural skin, leading to chronic irritation. Obliteration of local lymphatic vessels, poor vascularization, and reduced Langerhans cell activity have been observed, allowing developing lesions to avoid immune detection.[9] Overall, the pathogenesis is likely multifactorial, with chronic irritation and local toxins leading to neoplastic changes that are allowed to proliferate in the setting of altered immune mechanisms.

Histopathology

Squamous cell carcinoma is the most frequent malignancy identified on histopathologic examination (80 to 90%).[2] Most lesions are well-differentiated, but poorly differentiated subtypes have also been identified. The second most common cell type is basal cell carcinoma (9.6%), followed by melanoma (2.4%). Rare cases of sarcoma, dermatofibrosarcoma, mucoepidermoid carcinoma, and leiomyosarcoma have been described.[10]

History and Physical

A nonhealing, ulcerative, or indurated lesion appearing in a chronic wound or scar should raise suspicion for malignant degeneration to a Marjolin ulcer.[2][7] Visually, the lesions have been described as ulcerative and foul-smelling with rapid growth and rolled elevated margins.[7] Other clinical signs that suggest Marjolin ulcer formation include exophytic granulation tissue, bleeding, and regional lymphadenopathy.[4] The ulcerative form is more common and more aggressive than the exophytic form. Superinfection of the wound may be the first presenting symptom. Lesions can occur anywhere but most frequently affect the lower extremities, followed by the scalp, upper extremities, torso, and face.[3][10] Clinicians should pay close attention to all old scars on routine physical examinations and carefully note changes from prior visits.

Evaluation

Any suspicious nonhealing or ulcerative lesion that appears in a chronic scar should be biopsied to confirm the diagnosis. Physical examination of local lymph nodes should be performed. Some centers perform an ultrasound of regional nodes due to the high rate of nodal involvement.[11] Lymphatic mapping and sentinel node biopsy have also been suggested.[3] Other imaging (i.e., chest radiograph, brain computed tomography) can be considered on a case-by-case basis to assess for metastases.

Treatment / Management

Management should focus on prevention as unresected burn wounds that heal by secondary intention are at increased risk for malignant degeneration.[2] Once discovered, no definitive treatment protocol exists for the management of Marjolin ulcers. The most widely accepted treatment options include Mohs surgery, wide local excision with 1 to 2 cm margins, and amputation proximal to the lesion.

Mohs surgery can be considered in lesions on the face, scalp, hands, feet, areolae, and other areas where improved cosmesis is desired.[12][13] Amputation is reserved for advanced-stage disease when wide local excision and Mohs surgery are not possible.[14] Defect coverage with local flap, free flap, or avascular graft is often performed but remains controversial as some studies have shown an increased risk of recurrence with incomplete resection.[3][7][15] After resection, close follow-up is necessary due to the high risk of recurrence.

Lymph node dissection is controversial but can be considered with positive lymph nodes on physical or ultrasound examination.[3][11] Adjuvant radiation and chemotherapy are indicated if surgical resection is not possible. Agents that have been suggested include topical 5-fluorouracil, methotrexate, l-phenylalanine, and platinum-based therapy.[2][11] Radiotherapy is recommended with regional lymph node metastases, high-grade lesions (grade III), and lesions greater than 10 cm in diameter.[3]

Differential Diagnosis

• Actinic keratosis
• Allergic contact dermatitis
• Atopic dermatitis
• Atypical fibroxanthoma
• Basal cell carcinoma
• Benign cell lesions
• Bowenoid papulosis
• Chemical burns
• Limbal dermoid

Staging

No specific TNM staging criteria exist for Marjolin ulcers. After a biopsy has been performed, the histopathologic type of tumor can be used to stage the disease. For example, if the biopsy reveals squamous cell carcinoma, existing criteria established by the American Joint Committee on Cancer (AJCC) can be used.[2]

Prognosis

Although most Marjolin ulcers are well-differentiated, lesions are aggressive and carry a poor prognosis. Metastases are found in up to 27% of patients compared to 3% for other causes of squamous cell carcinoma.[3][7][10] The recurrence rate after surgical resection is up to 50%[7][10]. High grade (grade II or III), the presence of nodal metastases, and lower extremity location indicate a worse prognosis.[1][3][10] The 5-year survival rate is 43 to 58%.[12]

Pearls and Other Issues

• Marjolin ulcers most commonly arise from burn scars.
• The most common cell type identified is squamous cell carcinoma.
• All suspicious lesions should be biopsied.
• Confirmed cases of Marjolin ulcers should be excised with clear margins.
• Marjolin ulcers can be prevented with early excision and grafting of burn wounds.
• Prognosis is poor with a high rate of recurrence.

Enhancing Healthcare Team Outcomes

Prevention and management of Marjolin ulcers require an interprofessional team approach, including providers from surgery, primary care, oncology, and dermatology. Burn scars should be excised, and the surrounding skin should be reconstructed by a surgeon trained in the reconstruction (i.e., plastic surgeon) to prevent malignant conversion. For burn scars that have been allowed to heal by secondary intention, primary care providers (physicians, nurse practitioners, and physician assistants) must be aware that burn scars are at risk for malignant conversion. All burn scars should be monitored on routine physical examination, and patients should be educated on symptoms to prompt earlier presentation.[12] [Level 5]

Wound changes that are suspicious for Marjolin ulcers should be immediately biopsied. Once malignancy has been identified, a team approach to management should be initiated. Staging should involve an examination of the regional lymph nodes, either by physical or ultrasound examination. If the malignancy is thought to be confined to the scar, treatment should be discussed with a surgical oncologist, plastic surgeon, and Mohs surgeon. Resection with wide margins or Mohs technique should be performed depending on the location and desired cosmesis.[12] Radiation oncology and medical oncology should be consulted for adjuvant radiotherapy/chemotherapy for those with positive lymph nodes.

After treatment, follow-up surveillance should occur regularly with a primary care provider or dermatologist to note any evidence of recurrence.