Marjolin ulcer: an overlooked entity

Abstract

Marjolin ulcer is a well‐defined, but uncommon malignant ulcer that occurs in chronic wounds and cutaneous scars. Jean‐Nicolas Marjolin was credited with describing this phenomenon in 1828. This entity is frequently overlooked and therefore inadequately treated leading to a poor prognosis. The malignant transformation of an ulcer is most commonly associated with burn scars, but has been reported in many other types of chronic, non healing wounds such as traumatic wounds, venous stasis and chronic pressure ulcers, fistulas, lacerations and leprosy ulcers. Development of malignancy tends to be slow with an average time of approximately 25 years. Various theories concerning pathogenesis of Marjolin ulcer have been proposed. Well‐differentiated squamous cell carcinoma (SCC) is the most common histological type of Marjolin ulcer. Biopsy with histopathologic interpretation remains the gold standard for the diagnosis, with radical surgical excision being the treatment of choice. A high index of suspicion should be held by any health care provider when evaluating a chronic, non healing wound. This is a case report of a Marjolin ulcer arising on the left buttock of a patient with a long‐standing history of a traumatic wound.

INTRODUCTION

Marjolin ulcer is a rare malignant ulcer that originates in chronic non healing wounds and cutaneous scars 1, 2. This malignant transformation is most commonly associated with burn wounds, but has been reported in many other types of non healing wounds, such as traumatic wounds (3), pressure sores (4), osteomyelitis (5), venous stasis ulcers (6), fistulas (7), lacerations (1) and chronic trophic ulcers (8) in leprosy. The development of malignancy tends to be slow, with an average time to malignant transformation of 25 years 9, 10. Well‐differentiated squamous cell carcinoma (SCC) is the major histopathologic type of Marjolin ulcer 11, 12. Marjolin ulcer is frequently an overlooked entity, and therefore inadequately treated leading to a poor prognosis. In this report, we describe clinicopathologic features and the differential diagnosis of this unusual lesion.

CASE REPORT

The patient is a 45‐year‐old male with a medical history of a non insulin‐dependent diabetes mellitus, asthma and hypertension who presented with a purulent drainage in the left gluteal area. He suffered a motorcycle accident 20 years ago, resulting in a left hip wound (haematoma) and rectal tear. At the time of initial injury, the patient had debridement with local dressing changes, as well as diverting colostomy which was later reversed within 1 year. Four years prior to the current admission, the patient had presented with multiple abscesses in the same area when he underwent multiple incisions and drainage procedures and local advancement flap. At the current admission, physical examination revealed a 16‐cm open wound in the left gluteal area that was tender to palpation, warm and swollen (Figure 1). Magnetic resonance imaging (MRI) showed a superficial ulcer over the left buttock with multiple fluid collections, as well as a sinus tract, with extensive inflammation of the underlying superficial and deep musculature. There was no gross evidence of osteomyelitis (Figure 2). Given the patient's history of multiple abscesses in the area, he was evaluated by the colorectal surgery team, and the exam was negative for fistulas. The patient underwent debridement of the wound and the initial histologic examination revealed skin and subcutaneous tissue with pseudoepitheliomatous hyperplasia (PEH) and acute inflammatory cell infiltrate (Figure 3A). The cytologic atypia was not histologically identified in tissue sections. Wound cultures were positive for Serratia marcescens and Pseudomonas aeruginosa. Therefore, the patient was placed on a 2‐week course of intravenous antibiotic treatment. Subsequent biopsy revealed nests and strands of squamous epithelial cells arising from the epidermis and extending into the reticular dermis and subcutaneous tissue. Some of the squamous epithelial cells were large with abundant eosinophilic cytoplasm, and numerous keratinising pearls were present (Figure 3B). The higher power magnification revealed invasion of the dermis by atypical, hyperchromatic keratinocytes, with mitotic figures present (Figure 3C). These findings were consistent with infiltrating well‐differentiated SCC. Several days later, the patient underwent radical excision of the lesion (Figure 4) by the surgical oncology service, with simultaneous layered closure of the defect by the plastic surgery service. Briefly, the gluteus maximus, gluteus minimus and lower gluteus medius muscles were dissected of the sacrum sparing the sciatic nerve. The muscle remnants were sutured over the inferior portion of the sciatic nerve. The skin flaps with underlying subcutaneous fat were brought together over the wound without tension. The excisional specimen showed identical histological features. Taking into account the patient's medical history and the radiological and histological features, the diagnosis of Marjolin ulcer was rendered.

Figure 1.

Physical examination revealed a 16‐cm non healing open wound with irregular margins and base in the left gluteal area that was swollen and tender to palpation.

Figure 2.

Magnetic resonance imaging (MRI) of the left gluteal area showing superficial ulcer (arrow) with a sinus tract (arrowhead).

Figure 3.

Wound debridement tissue showing skin with extensive hyperkeratosis and irregular strands of epidermal proliferation with absence of cytologic atypia consistent with pseudoepitheliomatous hyperplasia (PEH) [(A) haematoxylin and eosin (H&E) stain, ×40]. Subsequent biopsy showed nests and irregular strands of squamous epithelial cells which arise from the epidermis and extend into the deep dermis, with abundant eosinophilic cytoplasm and numerous keratinising pearls [(B) H&E stain, ×20)]. Higher power magnification of the area highlighted by the red square [(C) H&E stain, ×400)] shows dermal invasion by atypical keratinocytes (arrows).

Figure 4.

The radical excision specimen showing a deep ulcerated lesion.

DISCUSSION

Marjolin ulcer is a well‐defined, uncommon lesion that represents malignant transformation arising in chronic wounds and cutaneous scars 1, 2. Clinically, this type of ulcer is frequently overlooked and therefore inadequately treated. Early recognition of these lesions is essential because a delay in diagnosis can convert a potentially curable lesion into an incurable one. Malignant transformation of an ulcer is most commonly associated with burn wounds, but has been reported in many other types of non healing wounds, such as traumatic wounds (3), pressure sores (4), osteomyelitis (5), venous stasis ulcers (6), fistulas (7), lacerations (1) and chronic trophic ulcers (8) in leprosy. After burn scars, traumatic wounds constitute the second most common cause of malignant ulcers (13). The development of malignancy tends to be slow, with an average time to malignant transformation of 25 years 9, 10. Overall, malignant transformation of chronic ulcers is related to the duration of the ulcer, i.e. the longer the ulcer duration, higher the risk for malignant change (6).

In 1828, a French physician, Jean‐Nicolas Marjolin published four examples of a distinct ulcer that he termed ‘ulcere verrequeux’(14). He provided the classic description of chronic ulcers which arise from scar tissue, though he failed to attribute malignant potential to these lesions. It was not until 1903 that John Chalmers DeCosta coined the term ‘Marjolin ulcer’ to describe carcinomatous degeneration of burn scars (15). Today, the term ‘Marjolin ulcer’ has entered common medical parlance to refer to long‐term malignant complications in many different types of cutaneous scars and chronic wounds.

Well‐differentiated SCC is the major histopathologic type of Marjolin ulcer, that is found in the vast majority of patients 11, 12. Less than 2% of all SCCs arise within chronic wounds without actinic damage (16). Basal cell carcinoma is next in frequency (17), but many other cellular malignancies, such as malignant melanoma (18), osteogenic sarcoma, fibrosarcoma and liposarcoma (19) have also been reported to occur in Marjolin ulcer. There is scant data on possible exacerbating factors, which include trauma or ultraviolet radiation, both of which may be relevant because Marjolin ulcer is usually located on the extremities, the scalp and neck (20). Other less common anatomical sites, such as the nose, the eyelids and the lip have also been reported in the literature 21, 22, 23.

The exact pathogenesis of Marjolin ulcer is still unknown. Several theories have been postulated. It has been suggested that decreased vascularity combined with weakened epithelium makes non healing chronic wounds more susceptible to carcinogens (24). Many authors believe that chronic irritation with repeated damage and attempted repair of the damaged cutaneous tissue lead to malignancy (25). Other researchers have proposed that toxins released from damaged tissue lead to mutation of cells and eventually a tumour (26). Furthermore, elevated expression of proto‐oncogenes which could be favoured by chronic inflammation, has been suggested as a mechanism for malignant degeneration in Marjolin ulcers 6, 27.

Biopsy of the suspicious non healing lesions and histopathologic interpretation remain the gold standard for the diagnosis of Marjolin ulcer (28). However, confounding characteristics of both benign and malignant ulcers can result in the delay of biopsy and diagnosis. The clinical features of an ulcer undergoing malignant transformation into SCC, though recognised, are not well described. Some of the features that may suggest a malignant transformation within an ulcer are everted edges, exophytic growth, irregular base or margin and excess granulation tissue extending beyond the margins (28). In the case of our patient, the ulcer had irregular margins and base without an overt tumour growth, but had a protracted course despite an appropriate treatment. Therefore, any chronic, ‘ugly‐looking’ ulcer that is failing to heal in spite of appropriate treatment should be considered as Marjolin ulcer unless proven otherwise (29). Malignant transformation or dysplastic changes in chronic ulcers occur mainly at the edges where there is a rapid turnover of cells. In chronic, non healing ulcers, only one edge may undergo dysplastic changes, while the rest of the ulcer may lack cytologic atypia (28). Therefore, it is of utmost importance to sample the lesions at multiple sites and depths in order not to miss the diagnosis of SCC. Grauwin (8) reported that in his study of chronic trophic ulcers in leprosy patients, several cases showed PEH at the ulcer edge, but when the depth of the lesion was sampled, SCC was identified. PEH can closely mimic a well‐differentiated SCC and on numerous occasions, both clinical findings and histopathology need to be correlated in order to differentiate these two entities. The characteristic histopathology of PEH is that of extensive epithelial hyperplasia with dermal extension of ‘tongue‐like’, anastomosing epithelial masses, which are often surrounded by inflammatory cells. Mitotic figures in PEH are very few, and never atypical. A few keratin pearls may be present, but the squamous cell nuclei are not pleomorphic. Furthermore, vascular, lymphatic or perineural invasion is never present 30, 31. In contrast to PEH, well‐differentiated SCC is characterised by long irregular strands of atypical epidermal cells that infiltrate into the dermis in all directions with numerous keratinising pearls. The tumour cells arise from epidermis or ulcer base and can extend into the reticular dermis, as well as adjacent tissues in a haphazard fashion. Numerous mitotic figures, including atypical ones, are usually present 30, 31, 32.

Computed tomography and MRI can be very useful diagnostic methods to help make an accurate preoperative diagnosis in the evaluation of Marjolin ulcer. Moreover, it is an effective means of excluding a metastatic process. MRI may be performed as a safe and rapid method, especially in tumours that aggressively invade surrounding tissue (33). In addition, lymph nodes should be carefully examined in all patients.

Marjolin ulcers are recognised as aggressive skin cancers. They tend to be more aggressive than other types of skin cancer with higher fatality rate (34). The metastatic potential of SCCs arising from chronic ulcers and scars is significantly greater than that of SCCs arising in normal skin (30% versus 3%) 34, 35, with the lymph nodes being the most commonly involved. Metastases to lymph nodes are often due to underestimation of clinical findings and therefore, a delayed diagnosis. Some authors (36) advocate the use of sentinel lymph node biopsy as an efficient and minimally invasive method for the identification of metastasis in patients without clinical signs of lymph node involvement. Studies have shown that a 5‐year survival rate is about 90% in case of SCCs without lymph node metastasis, as compared to 39% in SCCs with lymph node metastasis 36, 37. Metastases have been reported to involve the brain, lung, liver, bone and kidney 27, 38. Additionally, local recurrence rate is higher in patients with Marjolin type SCC than in other skin malignancies (39).

Wide local excision with a margin of at least 2 cm of normal appearing tissue, and subsequent skin grafting is the treatment of choice for Marjolin ulcer (40). Most studies (25) do not support a prophylactic lymph node dissection, but regional node dissection is recommended when a clinically palpable lymphadenopathy is present. Wide local excision is usually followed with radiation therapy (41). Any delay in diagnosis may necessitate the amputation due to deep bone involvement (42).

In the end, we would like to summarise that Marjolin ulcer is a rare malignancy that originates in chronic non healing wounds and cutaneous scars. It is a preventable, but unfortunately frequently overlooked complication, causing a delay in diagnosis and proper management. While the cause of Marjolin ulcer is still being investigated, several theories have been postulated. The most common histopathologic type of carcinoma found in Marjolin ulcer is well‐differentiated SCC followed by basal cell carcinoma. SCC may be masqueraded by PEH if the tissue sampling is not adequate. This can be a diagnostic pitfall, especially when the pathologist is not informed of the patient's clinical history of a non healing wound. Because chronic, non healing ulcers may transform into SCC, a high index of suspicion should be employed by any clinician evaluating a chronic wound. Multiple biopsies of the suspicious non healing lesions should be sent to the pathologists for thorough evaluation. Histopathologic interpretation, together with clinical correlation, remains the gold standard for the diagnosis of Marjolin ulcer. Marjolin SCCs tend to be more aggressive than other types of skin cancer, and have a higher fatality rate. Wide local excision with a margin of at least 2 cm is the treatment of choice for Marjolin ulcer. A delay in diagnosis, may cause deep bone involvement necessitating amputation, or may lead to metastases and even death. Therefore, health care providers should be aware of this rare entity and should exclude a Marjolin ulcer when confronted with a long‐standing ulcer that is failing to heal despite the appropriate treatment.