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Abstract: Marjolin’s ulcer is an epidermoid carcinoma arising in chronic ulcers. This condition is most commonly seen post burn scar formation as originally described by Jean Nicholas Marjolin in the 19th century. However, it can originate from other chronic wounds of long duration. The authors present 2 cases in which the cause of the scar was burn injury. In 1 case, multiple biopsies were the key for final diagnosis. In the second case, because of the location of the lesion, the use of the sentinel node biopsy technique was appropriate. The authors encourage liberal use of biopsies in long standing chronic ulcers and repeated biopsies if necessary.
The 2 cases presented here represent extremes in the presentation of malignant transformation in chronic wounds and serve as important reminders of the need for wound care clinicians to aggressively evaluate and manage chronic wounds of any etiology that follow a stagnant or progressive course.
Case 1 A 67-year-old black man was referred to the Wound Healing Center in El Dorado, Arkansas, for chronic ulcers on the right leg of approximately 20 years duration. The patient reported having suffered a burn caused by a gasoline explosion. Since then, the wounds never healed completely despite skin grafting and debridement completed in another institution. The patient’s physical examination was otherwise unremarkable. There was no evidence of lymphadenopathy in the ipsilateral groin. Laboratory work was also unremarkable. His diabetes mellitus was well controlled with oral medications. Interestingly, a radiograph of the involved leg suggested osteomyelitis involving the tibia and fibula. An indium-labeled white cell scan was completed. The results of the scan were suspicious but not definitive of harboring osteomyelitis. Because of the duration of the ulcers, several sample biopsies were taken from the most suspicious ulcer, but the final report indicated no evidence of malignancy (Figure 1).
The patient was treated with long-term antibiotics for approximately 4 weeks, then surgical debridements, application of silver dressings, and a skin substitute at one point, which resulted in partial healing (Figure 2). The size of the ulcers diminished. Since the patient was noncompliant, his attendance at the Wound Healing Center was sporadic, and weeks passed with no evidence of healing. The most proximal ulcer became more exophytic and infected. Therefore, a repeat and more extensive biopsy was completed, which proved to be positive for squamous cell carcinoma. Again, other than the leg ulcers, the patient’s physical examination was considered unremarkable. A complete surgical excision of the ulcers was performed; however, the malignant ulcer had invaded the periostium of the tibia of the right leg with exposure of the bone (Figure 3). The histological report also showed extensive osteomyelitis. The other ulcer was benign.Figures 1–3
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The patient had an uneventful below-knee amputation of the right leg. Histologically, there was local periosteal invasion by the squamous cell carcinoma, while the rest of the tibia showed chronic osteomyelitis. The final pathological report of the ulcer was moderately differentiated squamous cell carcinoma. Currently, the patient displays no evidence of local, regional, or distant metastasis. The patient now wears a leg prosthesis and is active with little limitation.
Case 2 A 72-year-old white woman was referred to the Wound Healing Center for a chronic wound located in an old scar on the lateral aspect of the chest, below the left breast. The patient suffered an extensive burn on the chest at 4 years of age. Approximately 1 year before presentation at the Wound Healing Center, the patient noticed a small ulceration on the scar tissue that she attributed to irritation from her brassiere strap. Despite local and systemic therapy, the ulcer became larger. Her primary care physician treated her for approximately 1 year before referring her to the authors’ Wound Healing Center. The ulcer was biopsied promptly and proved to be a squamous cell carcinoma arising from an old burn scar.
The physical examination revealed a scar on the lateral aspect of the left chest below and distal to the left breast. The ulcer was located in the middle of the burn scar tissue and measured 5.3 cm x 2.5 cm with elevated, inflamed edges and a fragile wound bed with some necrosis (Figure 4). No enlarged axillary or inguinal nodes were palpated. The remainder of the physical examination was unremarkable. The ancillary laboratory workup and radiological studies were negative. However, a preoperative scintigram suggested “hot” nodes in the left axilla (Figure 5).
The patient underwent complete excision of the lesion with wide margins and sentinel node biopsy. Only a left axilla biopsy was performed, since the gamma probe demonstrated marked activity solely in this area. A large sentinel lymph node was found but proved to be nonmalignant. The patient underwent a skin graft after the excision. She is now recovering well with no signs of recurrence or metastases.Figures 4–5
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Discussion Marjolin’s ulcers are the malignant transformation of chronic wounds.1,2 Malignant transformation, as demonstrated in these cases, has been recognized since the 19th century. In 1828, Jean Nicholas Marjolin2,3 first described an indolent ulcer arising in a burn scar. Usually, the ulcers are squamous cell carcinomas that occur at sites of previous burns, scars, sinuses, pressure ulcers, trauma, or sites of osteomyelitis,4 but other less common malignancies, such as basal cell carcinomas or melanomas,3 have been reported. In a retrospective study, Snyder et al5 found several cases of Marjolin’s ulcers in patients with clinical features that mimicked chronic venous ulcers. Although Marjolin initially described malignant transformation of a chronic scar from a burn wound, the term Marjolin’s ulcer has been used interchangeably for malignant transformation of any chronic wound, including pressure ulcers, osteomyelitis, venous stasis ulcers, urethral fistulas, anal fistulas, and other traumatic wounds.6 This malignant transformation is histologically a well-differentiated squamous cell carcinoma; however, its behavior is aggressive when arising in pressure ulcers as compared to burns or osteomyelitis.7,8 In a retrospective analysis at MD Anderson Cancer Center, carcinoma arose from thermal burns of irradiation dermatitis in 3.4% of 1,200 patients with squamous cell carcinoma.7 In a review of 264 burn cases, Copcu6 found 31 cases of Marjolin’s ulcer and 14 cases of nonmalignant ulceration at previous burn sites. In the same study, 18 Marjolin’s ulcers were located on the extremities, 6 on the scalp, 6 on the trunk, and 1 on the nose.6 There are several other common dermatologic conditions that occasionally have been linked to the development of squamous cell carcinoma. These include genital lichen sclerosus et atrophicus, oral lichen planus, erythema ab igne, and burn scars. Of these conditions, burn scars are the most likely to become malignant. A Marjolin’s ulcer has a 30% to 40% rate of metastasis.9 A case of a squamous cell carcinoma at the site of the extravasation of a chemotherapy agent has been reported.10 More aggressive than other skin cancers of the same cell type, Marjolin’s ulcers are thought to be due to long-term, continuous mitotic activity as the epidermal cells attempt to resurface the open defect.11 Despite the wide prevalence of wounds in which this malignancy may develop, Marjolin’s ulcer remains rare.12 Incidence varies, but an estimated 1.7% of chronic wounds undergo malignant degeneration.2 However, according to Smith et al,13 a chronic ulcer present for decades that ultimately undergoes malignant change is more prevalent in developing countries where patients only consult physicians after they experience complications, such as pain, bleeding, or tissue necrosis. At the Wound Healing Center, out of hundreds of patients with various types of wounds, these were the first 2 cases of Marjolin’s ulcers that developed into chronic wounds.
The latent transformation period of Marjolin’s ulcers ranges between 25 to 40 years.14 Other authors report an average of 32.5 years.1 In the early 19th century, attempts were made to classify Marjolin’s ulcers into 2 subgroups: scars that underwent malignant transformation less than 1 year after the initial injury and scars that degenerated after 1 year. In another study, 6 out of 28 cases were considered acute, with a latency average of 0.3 years.15 Although controversy exists regarding whether or not a clear differentiation exists between early and late malignant transformation, the critical issues are a high index of suspicion and biopsy of suspicious cases including longstanding chronic ulcers, ulcers following healing of cutaneous burns or other traumatic injuries, or those complicated by osteomyelitis. In these cases, biopsies should be taken at multiple sites and repeated if the ulcer does not respond to the standard therapy.
In the authors’ first case, the initial biopsy was completed when the patient was first admitted to the Wound Healing Center, but it proved to be negative. In fact, with standard therapy, the ulcer initially showed signs of healing. Either this patient developed an acute Marjolin’s ulcer or, more likely, the first biopsy failed to show the malignant tumor based on the tissue sample location. This emphasizes the importance of taking samples from multiple biopsy sites to reduce the likelihood that sampling errors led to a delay in making the correct diagnosis. Because of the invasive character of the malignant ulcer, the wound necrosis, the poor patient compliance, associated periostium invasion, and diffuse bone changes, an amputation of the leg was scheduled. Appropriate treatment of a Marjolin’s ulcer is wide excision with a margin of at least 1 cm of healthy tissue, and amputation has been the treatment of choice only when excision is complicated by bone or joint involvement, extensive infection, and chronic osteomyelitis.3 However, reports have shown that other methods of ensuring complete local excision are also useful, including the Mohs micrographic surgery technique.16 Due to lack of specialists in the area and the patient’s poor compliance, amputation of the leg was the only alternative. Marjolin’s ulcer is a more aggressive malignancy and carries a high incidence of metastases; therefore, extensive surgical excision, including amputation, can also be recommended to treat the tumor and the chronic infection.13,17 The patient was satisfied with this decision, since he desired healing of the longstanding chronic wound.
In the second case, however, the histological diagnosis was made promptly due to the authors’ previous experience. Biopsy remains the most important definitive diagnostic procedure, and it should be performed on any suspicious lesion or any chronic wound, especially those with any recent change in appearance or considerable drainage. Biopsy should extract material from multiple sites, including the central area of the wound as well as the margins.18
The pathogenesis of malignant transformation in chronic wounds remains controversial and poorly understood. It has been suggested that cellular mutations are responsible for neoplastic changes.14,15 One theory suggested that burn exudate, which contains endogenous growth-promoting factors, may act as a cocarcinogen19 and infection might serve as a cocarcinogen in scar tissue.14 It has also been suggested that patients with inherent immune deficiency are at higher risk for developing malignant ulcers.
The most logical treatment for burn carcinoma seems to be prophylaxis.18 Once a burn or skin trauma has occurred, care must be taken to ensure rapid and stable healing by skin graft or flap coverage. The involved skin lesions will not heal in the presence of tumor cells. Wide local excision with a margin of at least 1 cm of healthy tissue should be done in cases of Marjolin’s ulcer. Amputation is indicated when wide local excision is prevented by deep invasion, bone or joint space involvement, infection or hemorrhage, or when excision would impair function and encumber the patient. Lifeso stated that wide local excision can be unreliable for grade II and grade III disease; therefore, amputation and prophylactic node irradiation is recommended.20 The advent of the sentinel lymph node biopsy technique has been useful in the management of this condition as reported by Eastman et al.21 The second case in the Wound Healing Center also demonstrated the benefit of this technique.
Long-term follow-up is recommended in all cases of Marjolin’s ulcer. Most series indicate that the incidence of recurrence is in the range of 20% to 50%.14
Currently, clinicians at the Wound Healing Center are liberal in performing aggressive biopsies in longstanding or suspicious ulcers.
Conclusion Chronic ulcers are at constant risk of developing squamous cell carcinoma. Fortunately, this condition is considered rare, but when it occurs, it is more aggressive than other squamous cell carcinomas appearing de novo. Also, since this condition is rare, the general practitioner should refer patients with longstanding chronic ulcers or lesions that do not heal to a wound center or to proper specialists to avoid delay in treatments. Biopsies of suspicious ulcers and re-biopsies of the lesions should be a standard of care in institutions caring for chronic wounds.
Acknowledgment The authors express their gratitude to Brenda Murphree, RN, for the completion of this manuscript.
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References
1. Sabin SR, Goldstein G, Rosenthal HG, Haynes KK. Aggressive squamous cell carcinoma originating as a Marjolin’s ulcer. Dermatol Surg. 2004;30(2 Pt 1):229–230.
2. Trent JT, Kirsner RS. Wounds and malignancy. Adv Skin Wound Care. 2003;16(1):31–34.
3. Christopher JW, Li BD, Gonzalez E, Valiulis JP, Cunningham M, McCulloch J. Nonhealing ulcer in a diabetic foot. WOUNDS. 2004;16(6):212–217.
4. Dupree MT, Boyer JD, Cobb MW. Marjolin’s ulcer arising in a burn scar. Cutis. 1998;62(1):49–51.
5. Snyder RJ, Stillman RM, Weiss SD. Epidermoid cancers that masquerade as venous ulcer disease. Ostomy Wound Manage. 2003;49(4):63–66.
6. Copcu E, Aktas A, Sisman N, Oztan Y. Thirty-one cases of Marjolin’s ulcer. Clin Exp Dermatol. 2003;28(2):138–141.
7. Wilhelmi BJ, Neumeister M. Pressure ulcers, surgical treatment and principles. Available at: http://www.emedicine.com/plastic/topic462.htm. Accessed February 9, 2004.
8. Ratliff CR. Two case studies of Marjolin’s ulcers in patients referred for management of chronic pressure ulcers. J Wound Ostomy Continence Nurs. 2002;29(5):266–268.
9. Habif TP. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 4th ed. St Louis, MO: Mosby Inc; 2004:744–747.
10. Lauvin R, Miglianico L, Hellegouarc’h R. Skin cancer occurring 10 years after the extravasation of doxorubicin. N Engl J Med. 1995;332(11):754.
11. Lawrence WT. Clinical management of nonhealing wounds. In: Cohen IK, Diegelmann RF, Lindblad WJ, eds. Wound Healing. Philadelphia, Pa: WB Saunders Co; 1992:541–546.
12. Snyder R. The importance of biopsy in wound management: lesion biopsy should be an essential part of the wound-healing algorithm. Podiatry Management. March 2003.
13. Smith J, Mello LF, Nogueira Neto NC, et al. Malignancy in chronic ulcers and scars of the leg (Marjolin’s ulcer): a study of 21 patients. Skeletal Radiol. 2001;30(6):331–337.
14. Hill BB, Sloan DA, Lee EY, McGrath PC, Kenady DE. Marjolin’s ulcer of the foot caused by nonburn trauma. South Med J. 1996;89(7):707–710.
15. Thio D, Clarkson JH, Misra A, Srivastava S. Malignant change after 18 months in a lower limb ulcer: acute Marjolin’s revisited. Br J Plast Surg. 2003;56(8):825–828.
16. Rahimizadeh A, Shelton R, Weinberg H, Sadick N. The development of a Marjolin’s cancer in a human immunodeficiency virus-positive hemophilic man and review of the literature. Dermatol Surg. 1997;23(7):560–563.
17. McGrory JE, Pritchard DJ, Unni KK, Ilstrup D, Rowland CM. Malignant lesions arising in chronic osteomyelitis. Clin Orthop Relat Res. 1999;(362):181–189.
18. Konigova R, Rychterova V. Marjolin’s ulcer. Acta Chir Plast. 2000;42(3):91–94.
19. Ozek C, Celik N, Bilkay U, Akalin T, Erdem O, Cagdas A. Marjolin’s ulcer of the scalp: report of 5 cases and review of the literature. J Burn Care Rehabil. 2001;22(1):65–69.
20. Lifeso RM, Bull CA. Squamous cell carcinoma of the extremities. Cancer. 1985;55(12):2862–2867.
21. Eastman AL, Erdman WA, Lindberg GM, Hunt JL, Purdue GF, Fleming JB. Sentinel lymph node biopsy identifies occult nodal metastases in patients with Marjolin’s ulcer. J Burn Care Rehabil. 2004;25(3):241–245.
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