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Marjolin ulcers are aggressive cutaneous malignancies that arise in areas of previously traumatized, chronically inflamed, or scarred skin, most commonly following burn injuries. These lesions, while often presenting as squamous cell carcinoma, may also manifest as basal cell carcinoma, melanoma, or sarcoma. The pathogenesis involves malignant transformation due to chronic inflammation, repeated injury, and impaired immune surveillance within nonhealing wounds or scars. Characterized by a poor prognosis and high rates of recurrence and metastasis, Marjolin ulcers typically present late due to delayed recognition. Risk factors include chronic ulcers, osteomyelitis, and long-standing scars. Diagnosis relies on clinical suspicion and is confirmed through biopsy, with imaging used to assess local invasion and distant spread. Early detection and intervention remain crucial, as delayed diagnosis often necessitates more extensive treatments such as wide local excision, Mohs surgery, or even amputation. This continuing medical education activity provides participants with comprehensive information on Marjolin ulcers, focusing on prevention, early detection, and current treatment strategies. Learners gain knowledge about the clinical presentation and high-risk features of malignant transformation in chronic wounds, along with the importance of timely biopsy and imaging. The course highlights the variability in treatment approaches and the lack of standardized protocols, emphasizing the need for individualized care based on tumor characteristics and patient factors. Participants also explore the role of adjuvant therapies and emerging treatments, such as immune checkpoint inhibitors, in improving outcomes. Collaboration with an interprofessional team—including dermatologists, oncologists, plastic surgeons, radiologists, and wound care specialists—enhances patient outcomes by ensuring comprehensive evaluation, coordinated treatment planning, and long-term surveillance to monitor for recurrence or metastasis. Objectives: Screen for early signs of malignant conversion in chronic wounds, ensuring timely intervention. Identify patients at risk for Marjolin ulcer, including those with chronic wounds, burn scars, or long-standing ulcers. Assess the extent of local and regional disease involvement through imaging and lymph node evaluation.

This continuing medical education activity provides participants with comprehensive information on Marjolin ulcers, focusing on prevention, early detection, and current treatment strategies. Learners gain knowledge about the clinical presentation and high-risk features of malignant transformation in chronic wounds, along with the importance of timely biopsy and imaging. The course highlights the variability in treatment approaches and the lack of standardized protocols, emphasizing the need for individualized care based on tumor characteristics and patient factors. Participants also explore the role of adjuvant therapies and emerging treatments, such as immune checkpoint inhibitors, in improving outcomes. Collaboration with an interprofessional team—including dermatologists, oncologists, plastic surgeons, radiologists, and wound care specialists—enhances patient outcomes by ensuring comprehensive evaluation, coordinated treatment planning, and long-term surveillance to monitor for recurrence or metastasis. Objectives: Screen for early signs of malignant conversion in chronic wounds, ensuring timely intervention. Identify patients at risk for Marjolin ulcer, including those with chronic wounds, burn scars, or long-standing ulcers. Assess the extent of local and regional disease involvement through imaging and lymph node evaluation. Collaborate with an interprofessional team, including surgeons, oncologists, and pathologists, to optimize patient care for Marjolin ulcers. Access free multiple choice questions on this topic.

A Marjolin ulcer, named after French surgeon Jean Nioclas Marjolin, historically referred to a squamous cell carcinoma within a burn scar, but the definition evolved to incorporate all skin malignancies arising within damaged tissue. Squamous cell carcinoma remains the most common malignancy, but many cutaneous cancer types have been identified in inflamed or injured tissue, including trauma, osteomyelitis, and chronic ulcers.[1][2] Most common sites of marjolin ulcer, in order of decreasing frequency, include the lower extremities, head and neck, upper extremity and trunk, with rare occurrences on the face, foot and digits.[3] Marjolin lesions are aggressive, have a poor prognosis compared to their non-Marjolin counterparts, and have a high recurrence rate. Marjolin ulcers can occur many years, even decades, following the initial injury. A subset of Marjolin ulcers appears within months of initial injury and is termed "acute," often having basal cell histology. Prevention with proper burn wound management, routine surveillance, and early recognition of malignant conversion are critical to reducing morbidity and mortality.[4]

Marjolin ulcers most commonly arise from burn scars.[5] Malignant degeneration occurs in 0.7% to 2.0% of burn scars that have been allowed to heal by secondary intention.[6][7] Other conditions that lead to Marjolin ulcers include traumatic wounds, venous stasis ulcers, osteomyelitis, pressure ulcers, skin impacted by radiation dermatitis, stings, bites, and hidradenitis suppurativa.[2][6][7][8] Immunocompromised persons are at increased risk for malignant conversion.[8] Malignancies can develop within oral mucosa from areas of inflammation, including lichen planus, oral lesions of graft-versus-host, discoid lupus, and syphilis, and in follicular disorders such as chronic scalp cellulitis, featuring sinus tracts and sterile abscess collections.[9] Chronic pressure and friction give rise to dermatological conditions that may predispose to malignancy.[10][11]

Marjolin ulcers most commonly affect persons in the fifth decade, men more than women, in a 2:1 or 3:1 ratio, perhaps due to the increased frequency of burns in this cohort. Marjolin ulcers occur equally throughout ethnicities, but vary in cultures consistent with the prevalence of certain practices. For example, in areas where heating pads are customary, associated burns result in a 6.8% prevalence of Marjolin ulcers.[3][12] The period from initial wound to malignant degeneration is between 5 and 51 years, with an average latency of 29 years. Shorter latency periods are common in older persons, but younger persons present often decades following the initial injury.[13][14][15] Most Marjolin ulcers are squamous cell carcinoma, although basal cell carcinoma and melanoma are not rare. Approximately 2.5% of squamous cell carcinomas, compromising 0.05% of lower extremity cutaneous squamous malignancy, and 0.3% of basal cell carcinomas present within burn scars. Chronic osteomyelitis degenerates into malignancy at a rate of 0.2% to 1.7%.  One in 300 leg ulcers contains malignancy, and epidermoid malignancy accounts for 0.21% to 0.34% of cancers that develop within leg ulcers. The relative risk for venous leg ulcers to transform to nonmelanoma skin cancer is 5.8% compared with the population at large.[5][16] Marjolin ulcers have higher metastatic potential and greater recurrence rate than a de novo cutaneous malignancy, with 30% to 40% of squamous cell Marjolin ulcers metastasizing compared with 0.5% to 3% of nonMarjolin squamous cell carcinoma.[17] Recurrence is associated with a higher mortality than other metastatic squamous cell carcinomas.[5]

Several pathophysiologic mechanisms have been proposed to explain the aggressive nature of these malignancies based on hyperproliferation seen with rapid destruction and reepithelialization.[9] Chronic inflammation promotes cellular division and growth factor secretion, and inhibits apoptosis.[18] Damage to immune mechanisms of the skin results in incomplete healing, and cells damaged from poor perfusion and chronic inflammation release toxins that promote mutations.[2] Dysregulation of cell adhesion molecules is thought to contribute to pathogenesis. Upregulation of growth factors contributes to the fibroblast-mediated epithelial-mesenchymal transition that promotes metastases.[19] Malignant cell lines that develop from the mutations are relatively shielded from immune detection secondary to decreased perfusion and obliteration of local lymphatic vessels and reduced Langerhans cell activity within the chronic scar. A decrement in natural killer cells contributes to the avoidance of immune detection.[3] Genetic predisposition to malignancy involving the HLA-DR4 and p53 genes has been identified, including, for example, the TP53 gene mutations in Li-Fraumeni syndrome.[20] The cycle of inflammation and healing that involves rapid cellular turnover renders the repair mechanisms particularly vulnerable to mutation, especially at wound edges. Mutations within FasR result in decreased programmed cell death and dysregulated cellular proliferation. A procarcinogenic environment is further promoted by increased exposure to radiation and ultraviolet light.[3][16] Spread is mainly via lymphatics rather than hematologic. The fibrous tissue surrounding the ulcer can serve as a mechanical or immunological barrier to tumor spread, and lymphatic spread may be increased following excision.[16] Full-thickness burns are particularly susceptible to malignant degeneration.[3][13] Wounds across joint spaces may be more prone to malignancy due to chronic friction.[21]

Squamous cell carcinoma is identified on histopathologic examination in 80% to 90% of Marjolin ulcer specimens, basal cell carcinoma in 9.6%, and melanoma in 2.45%. Rare cases of sarcoma, dermatofibrosarcoma, mucoepidermoid carcinoma, angiosarcoma, fibrosarcoma, osteosarcoma, malignant fibrous histiocytoma, liposarcoma, malignant schwannoma, and leiomyosarcoma have been described.[5][22] Lesions range from well-differentiated to poorly-differentiated. Squamous cell carcinoma features irregular squamous cells with increased mitoses. Squamous cell carcinoma is graded from I to III depending on the degree of differentiation, where grade I contains 75% well-differentiated cells, grade II 25% to 75%, and grade III less than 25% well-differentiated cells.[13] Well and moderately-differentiated squamous cell carcinoma exhibits pseudo-epitheliomatous hyperplasia with increased epidermal thickness and irregular cellular proliferation with minimal or absent typia and monocyte infiltration. While this is seen in a benign spectrum or the early stage of squamous cell carcinoma, this histology should be regarded with suspicion for the presence of more aggressive cancer. The squamous tumor is overlying irregular collagen consistent with scar. Many lesions arising from radiation dermatitis are basal cell carcinoma, characterized by islands of dermal basaloid cells within a mucinous stroma. Tumor cells are round with hyperchromatic nuclei and increased mitotic bodies. Adjacent hair follicles and sweat glands are often preserved. Basosquamous carcinoma has histopathological features of both basal and squamous cell carcinoma, with a high metastatic rate, cytologically similar to squamous cells.[16] Distinction is made between nonMarjolin ulcer cutaneous squamous cell malignancies and those from burns and scars. The cutaneous denovo squamous cell cancers are characterized by solar damage and are quite responsive to programmed cell death protein 1 (PD-1) blockade immunotherapy, whereas those from scars have less solar exposure and are not responsive to PD-1 blockade therapy.[23]

A person presenting with a Marjolin ulcer has a burn wound, traumatic scar, or other tissue injury, may describe a nonhealing area, often longstanding, who notes recent or growing changes to the area, possibly with ulceration, pain, bleeding, or drainage, and an increase in size or exophytic growth.[20] The lower extremity is the most common site, followed by the scalp, upper extremities, torso, and face.[6][22] A nonhealing, ulcerative, or indurated lesion appearing in a chronic wound or scar should raise suspicion for malignant degeneration.[5][15] Two forms of Marjolin ulcer are a milder exophytic variant and the more common ulcerative type that is typically poorly differentiated and has a worse prognosis due to invasion at the time of diagnosis. Clinicians should pay close attention to all scars on routine physical examinations, note changes from prior visits, and check for regional and systemic adenopathy.[24] Superinfection of a wound or scar may be the first presenting symptom of a Marjolin ulcer.[3] Burn scars tend to be raised above uninjured skin, leading to chronic irritation.[3] Presentation may include irregular growth, an ulcerative and foul-smelling lesion with surrounding induration and rolled elevated margins.[15] Other clinical signs that suggest Marjolin ulcer formation include exophytic granulation tissue, bleeding, poor response to conventional wound therapy, and regional lymphadenopathy. One-third of affected persons have a palpable lymph node.[3][6][7][22]

Any chronic wound, nonhealing or ulcerative, irregular or growing lesion that appears within or in proximity to a scar should be biopsied via excision, incision, or punch. If incisional or punch biopsies are taken, multiple areas are sampled in a 4-quadrant distribution. Examination of local and regional lymph nodes is performed by ultrasound or lymphatic mapping. Sentinel node biopsy can be performed before any excision or incision of the lesion.[6][25] Additional imaging, including x-ray, computed tomography, magnetic resonance, and positron emission tomography, is performed to clarify soft tissue involvement and evaluate for metastatic disease, including the presence of any pathologic fractures.[20][26]

Prevention and early detection of Marjolin ulcer is the best practice. Prevention includes excision and reconstruction or regular surveillance of burn scars and other chronic wounds.[3] There is no standardized treatment protocol for a Marjolin ulcer.[5] The most common treatment for nonmetastatic disease is wide local excision with 2 cm to 3 cm margins, with most clinicians recommending 3 cm margins, ideally with intraoperative frozen sections to confirm negative margins. Lesions within the subcutaneous layer are excised to the fascia, and those invading fascia or muscle are excised to the periosteium. Amputation is reserved for bony involvement or any advanced-stage disease when wide local excision is not possible.[27] Amputation may be associated with lower recurrence, but other results have demonstrated an increased or similar recurrence rate.[13] Lymph node involvement is treated with lymphadenectomy plus radiation or radiation alone.[6][15][25][28] Prophylactic lymph node dissection remains a topic of debate.[6][16] Nonexcisional procedures, such as curettage and cryotherapy, are not recommended due to the probability of a Marjolin lesion invading deep tissue. Mohs surgery can be considered in cosmetically sensitive areas such as the face, scalp, hands, feet, and areolae.[29][30]  Close follow-up is necessary following any intervention due to the high recurrence risk. A suggested follow-up protocol involves surveillance every 2 weeks for 2 months, every 2 months for 6 months, every 6 months for 5 years, with imaging and labwork for any suspicion of recurrence.[3][16] No randomized controlled trials exist for Marjolin ulcer adjuvant or neoadjuvant treatment. Indications for chemoradiation include widespread disease with lymph node involvement, tumor size greater than 10 cm, and lesions of the head and neck with lymph node involvement. Chemotherapy is often reserved for those with widespread disease or for those who cannot undergo surgery. Suggested agents include topical or systemic 5-fluorouracil with cisplatin, methotrexate, bleomycin, l-phenylalanine, and platinum-based therapy.[5][25] Radiotherapy is given for recurrence, poorly differentiated or high-grade tumor, inoperability, or patient refusal, a tumor size greater than 10 cm with lymph node involvement, or head and neck tumors with nodal involvement.[16]

No randomized controlled trials exist for Marjolin ulcer adjuvant or neoadjuvant treatment. Indications for chemoradiation include widespread disease with lymph node involvement, tumor size greater than 10 cm, and lesions of the head and neck with lymph node involvement. Chemotherapy is often reserved for those with widespread disease or for those who cannot undergo surgery. Suggested agents include topical or systemic 5-fluorouracil with cisplatin, methotrexate, bleomycin, l-phenylalanine, and platinum-based therapy.[5][25] Radiotherapy is given for recurrence, poorly differentiated or high-grade tumor, inoperability, or patient refusal, a tumor size greater than 10 cm with lymph node involvement, or head and neck tumors with nodal involvement.[16] Hyperthermic intraarterial limb perfusion with methotrexate is also considered in certain circumstances. While surgery controls lymphatic spread in 40% to 45% of cases, adjuvant radiotherapy has been the only effective intervention for disease progression in others.[6] Immune checkpoint inhibitors such as cemiplimab and pembrolizumab for metastatic squamous cell Marjolin ulcer show some early efficacy in trials, but additional studies are needed, and cost is a factor.[17]

Differential diagnosis to be considered in the evaluation of a possible Marjolin ulcer includes pressure ulcers, abscess, arterial or venous insufficiency, vasculitis, contact dermatitis, actinic keratosis, atypical fibroxanthoma, Bowen papulosis, trauma to skin and subcutaneous tissues such as a chemical burn, and other benign lesions.[29][31]

A meta-analysis of 16 studies evaluated 670 persons with skin injury from burn, trauma, and infection. The results showed that the anatomical location was divided by 57% on the lower extremity, 21% on the head and neck, 14% on the upper extremity, and 7% on the trunk. Histologic diagnosis included 86% squamous cell, 6% basal cell, and the remainder verrucous lesion, melanoma, and sarcoma. Pathologic grading included 64% grade I, 24% grade II, and 11% grade III. Those on the upper extremity and head and neck demonstrated a higher recurrence rate, and in this study, amputation was associated with a higher likelihood of recurrence than wide excision. Lower grade lesions, absence of lymph node involvement, and smaller size were associated with lower recurrence risk. Older age was associated with a shorter latency period before the development of Marjolin ulcer. Histologic grade was the most significant overall predictor of recurrence.[13] A case illustrating the genesis of Marjolin ulcer involves a 22-year-old Asian man with a history of extensive burns, who, after recurrent trauma to one of the burned areas, developed a large exophytic mass that was diagnosed as a squamous cell carcinoma on biopsy with local lymph node involvement without metastases. The lesion was widely excised with 2 cm margins and covered with a split-thickness skin graft followed by adjuvant radiation.[24] A study of 226 persons with burn site ulceration included 19 persons with a Marjolin ulcer, with a mean latency of 29 years, recurrence of disease following treatment in 8 cases, 6 of whom died. In this study, timely diagnosis, lower tumor grade, and customized surgical approach with adjuvant radiation resulted in the best prognosis.[16]

No specific TNM staging criteria exist for Marjolin ulcers, but the disease can be staged according to the histopathology. For example, if the biopsy reveals squamous cell carcinoma, existing criteria established by the American Joint Committee on Cancer can be used.[5]

Persons with well-differentiated Marjolin ulcers have a 3-year survival rate of 65% to 75%, and a 5-year survival rate of 43% to 58%.[29] Those with metastases at the time of diagnosis have a 3-year survival of 35% to 50%. The overall 20-year survival is 52%, but 23% with metastatic disease. The prognosis of a Marjolin ulcer is worse than a de novo lesion of similar histology. The risk for metastatic disease is correlated with tumor differentiation. The European Dermatology Forum, European Association of Dermato-Oncology, and European Organisation for Research and Treatment of Cancer note that tumor diameter greater than 2 cm and depth of invasion greater than 6 mm are poor prognostic indicators.[17] Metastatic disease is reported in 27.5% and 40% of all Marjolin ulcers, but varies between etiologies, greatest for pressure ulcers, followed by burns. Metastases are found in up to 27% of persons with squamous cell Marjolin ulcer, compared to 3% for non-Marjolin squamous cell carcinoma. The overall mortality for a Marjolin ulcer is reported to be 21%.[6][15][22] Head and neck Marjolin tumors are aggressive, poorly responsive to chemoradiation, and have a higher recurrence risk.[13] This is illustrated by the case of a 20-year-old who developed malignancy in a scalp burn sustained at 3 years of age and, despite initial surgical treatment, brachytherapy, chemoradiation, metastectomy, and neck dissection, subsequently developed locoregional and systemic metastases.[17] The recurrence rate after surgical resection of a Marjolin ulcer is up to 50%.[2][6][15][22] The 5-year survival reported for those with a recurrence after excision is 20% to 50%, and the 10-year survival is 34%. Lymphatic invasion identified postoperatively confers a poor prognosis and is often associated with rapid deterioration, with a 3-year survival of 35% to 50%.[3][16]

Marjolin ulcer is a complication of scar tissue or areas subject to chronic irritation and inflammation. Complications from the Marjolin ulcer include infection and compromise to function and cosmesis.[32]

Any person with a chronic wound or scarring should be counseled on the importance of monitoring for signs of change to the area, including increased size, pain, altered appearance or texture, or bleeding. Vigilance and regular inspection decrease the risk of a Marjolin ulcer.[24] Those with scalp wounds and scars should be advised regarding the potential for rapid progression of a Marjolin ulcer of the scalp.[1]

Thorough excision and grafting of wounds, particularly burn wounds, help prevent the formation of a Marjolin ulcer. The incidence of Marjolin ulcer is significantly higher in areas of unreconstructed scar versus scar that undergoes excision and reconstruction.[16] All areas of inadequate or incomplete healing, and any changes within longstanding scars or wounds, should be biopsied in four quadrants. Any areas that remain suspicious warrant routine surveillance and biopsy as warranted. Sampling error may result in false negatives. It is important to be cognizant of the clinical implications of a delay in diagnosis in these malignancies, especially in areas of chronic inflammation where changes may be difficult to identify.[9][24] Marjolin ulcer has a high rate of recurrence, and treated persons should undergo routine surveillance. NCCN 2023 guidelines recommend clinical assessment every 2-3 months within the first year following treatment, every 2 to 4 months in the second year, every 4 to 6 months in year 3, and every 6 to 12 months thereafter.[17] Amputation sites are more prone to the development of a Marjolin ulcer within the scar, and these malignancies have a high rate of metastasis. This is especially true in the setting of a prosthesis where amputation sites are subject to compression and friction. Squamous, basal, lymphangiosarcoma and a case of melanoma have all been reported at amputation sites.[18]

Prevention and management of Marjolin ulcers require an interprofessional team approach, including clinicians from several surgical specialties, primary care, radiation and medical oncology, radiology, pathology, and dermatology. Burn scars should be excised and revised to prevent malignant conversion. Those scars that have healed by secondary intention should be monitored routinely, and patients should be educated on symptoms to prompt early recognition of any malignant changes. Successful prevention requires a collaborative interdisciplinary approach and communication.[29] Successful management of a Marjolin ulcer relies on prompt and thorough evaluation and treatment.[29] Following treatment, regular surveillance is imperative. All clinicians should be aware of the possibility of malignant transformation in chronic wounds and scars.[3]