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Squamous cell carcinoma arising on a skin graft 64 years after primary injury

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Squamous cell carcinoma arising on a skin graft 64 years after primary injury
Nina Guenther MD, Charalambos Menenakos MD, Chris Braumann MD, Rolf Buettemeyer MD PhD
Dermatology Online Journal 13 (2): 27

Department of General, Visceral, Vascular and Thoracic Surgery, Universitaetsmedizin Berlin, Berlin, Germany.


Malignant degeneration of a chronic wound is often described by the term, Marjolin's ulcer. We present a case of a squamous cell carcinoma that developed in a patient 64 years after the initial injury during World War II. Tissue contusion and detachment required repeated surgery and full skin grafting in several hospitals. The patient had a persistent ulcer in the right popliteal region for the last 3 years. Excisional biopsy in our department showed a bifocal low-grade invasive squamous cell carcinoma of the skin. Because of extensive inflammation and previous scar formation it was difficult to determine the status of the surgical margins. Therefore, we proceeded with amputation at the right thigh. Some 6 months after surgery the general condition of the patient remains excellent.

Clinical synopsis

A 70-year-old man was referred to our department with an ulcerated plaque extending over the entire right popliteal region adjacent to a scar from a previous injury. The wound was secondarily infected (Fig. 1).

In 1942, at the age of 6 the patient suffered a severe injury with tissue contusion and detachment during an attempt to escape army troops. Since that time repeated surgeries with grafting have been required.

Figure 1
Ulcerated fragile wound (10x5 cm) extending over the whole right popliteal region adjacent to a previous injury scar (15x12 cm). Initial injury happened in 1942 during World War II.

Approximately 61 years after the injury the scar began to ulcerate. The patient sought medical advice 3 years later because the ulcer continued to enlarge and he developed erysipelas of the right lower limb. In February 2006 the patient was referred to our Surgical Department because of recurrence of the ulcer at the site of the previous skin grafting. The clinical characteristics were highly suspicious of a carcinoma. MRI of both limbs, inguinal sonography, and CT-scan (thorax, abdomen, and pelvis) showed no distant metastasis.

A bifocal low grade invasive squamous cell carcinoma (SCC) of the skin was detected in the excisional biopsy. Owing to extensive inflammation and scarring, adequacy of the surgical margin was difficult to determine. Because the tumor was regionally extensive and its full excision could not be confirmed we proceeded with amputation at the right thigh. The patient was thoroughly informed about possible therapeutic options and gave his written consent to the amputation; he had already sustained several operations and wound debridements. Additionally the idea of a possible recurrence after a more conservative surgery had caused the patient and his family significant psychological strain. The postoperative course was uneventful and the patient was discharged on the 8th day after surgery in good condition.


Marjolin's ulcer is a malignant transformation of scarred injury sites [1, 2]. The most common histological type of cancer in this setting is the SCC, the second leading cause of skin cancer death after melanoma and the second most common type of skin cancer after basal cell carcinoma (BCC) [3]. Frequent exposure to sun light (UVR), fair skin, reduced immunity and gene mutations are major risk factors [4]. Malignant melanoma, sarcoma or adenocarcinoma are extremely rare [5]. Acute scar carcinoma occurs sooner than one year after injury [2] whereas the mean average period of chronic carcinoma development is 35.5 years [6].

To our knowledge our case is the longest interval between injury and cancer formation ever reported in the literature. Risk factors include healing by secondary intention, non-healing wounds, fragile, easily traumatized, ulcerated scars with obliterated lymphatics and poor local immune resistance [7]. Immunological or genetic factors may play a role leading to a shortened latency period in some cases [8]. Most SCCs are associated with abnormalities of tumor suppressor genes, particularly p53 [9, 10]. The p53 appears to protect from irreparable DNA damage by signaling for apoptosis of mutated, precancerous cells in various tissues and organs and its loss correlates with increased aggressiveness and decreased survival rate [9]. P53 gene mutations may play an important role in carcinogenesis of skin cancer, but it seems to be insignificant when an underlying disorder (injury or burn) exists [11]. Unlike burn scars (mutations of Fas-Apo-1/CD 95 gene in 14.3 %) no mutations were detected in squamous cell carcinomas [12]. It is most interesting that in our patient the cancer arose at the site of the skin graft and not from the injury site itself.

In our case the patient was initially treated by surgical methods that were appropriate in 1942. When SCC develops radical excision with standard margins more than 7 mm and skin grafting if necessary, or even amputation of the extremity are recommended [8]. Delay in diagnosis could result in loss of the affected limb and metastatic SCC can be life threatening [1]. The incidence of ymph node metastasis of Marjolin's ulcer ranges from 10 to 44 percent and is treated with comprehensive nodal dissection, sometimes followed by radiation and/or chemotherapy [13].

In the present case following surgical excision of the lesion and histological confirmation of the SCC we initially performed consecutive debridement sessions of the wound in an attempt to facilitate plastic repair on healthy tissue. The patient had unfortunately suffered several episodes of lymphangitis that made this difficult. In addition, we considered the risk of recurrence and metastatic disease to be high. After detailed counseling the patient himself wished an amputation. Although amputation has mainly a palliative role in the treatment of SCC, there have been a few cases of major extremity amputation for SCC with curative intent reported in the literature [14, 15].


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