Chronic Ulcers: When to Consider Malignancy?

August 2012 | Volume 11 | Issue 8 | Features | 1006 | Copyright © August 2012

Kendra Gail Bergstrom MD FAAD

Chronic wound management is challenging for patients and physicians alike. As our population ages, the prevalence of both chronic wounds and skin cancer is increasing. Management of chronic wounds is complicated in many cases by comorbidities such as diabetes, vascular disease, or immunosuppression. When a chronic ulcer fails to respond to treatment, cutaneous malignancy should be a consideration either as a primary cause or secondary complication. Missed diagnosis of malignancy inside a leg ulcer can lead to non-healing of ulcer, potential for skin cancer metastasis, putting a patient at risk of amputation for aggressive treatment for local disease. New data helps to refine recommendations for timing and location of potential surveillance biopsies.


Chronic leg wounds, associated at times with leg edema, vascular disease, immunosuppression, or chronic skin conditions, are a source of patient suffering and often a challenge for physicians. Many times, ulcers can fail to respond to treatment for a variety of reasons, including underlying medical conditions, superinfection, and cutaneous malignancies. The prevalence of cutaneous malignancy in chronic ulcers is hard to quantify, but new data adds to our ability to predict and identify skin cancer in leg ulcers in a timely way.
The potential for squamous cell carcinoma to arise in a chronic wound is well established, and was first described by the French surgeon Dr. Jean-Nicholas Marjolin in 1828. He first noticed the appearance of ulcerating skin lesions in old scars. The phenomenon was coined as “Marjolin's Ulcer” almost 100 years later and the definition was later widened to describe ulcerating squamous cell carcinomas appearing in chronic wounds, chronic inflammation, ulcers of osteomyelitis, pressure ulcers, and radiation burn scars. Rare cases have even been described in chronic wounds of hidradenitis suppurativa1 and untreated tinea capitis.2
Squamous cell carcinomas arising in ulcers appear to be more aggressive than those arising de novo on similar regions of the body. The reasons for this are not completely understood, and several hypotheses exist. One hypothesis is that that scars may have an immunologically protected status that can lead cancer to progress without significant host response, and another is that the chronic low grade inflammation and cell proliferation in wound healing can promote DNA damage leading to malignancy.
A second challenge is early detection of these malignancies that may look just like a skin ulcer. Malignant transformation of chronic ulcers is often unrecognized for months or years. This delay in diagnosis leads to a higher incidence of larger sized tumors, invasive disease, and metastases to lymph nodes or beyond. Several large population based studies have tried to characterize the frequency of and risk factors for malignant transformation. A new study published June 20123 was able to follow patients prospectively and highlights the value of surveillance biopsies for detection of malignancy.

Prevalence of Malignancy in Chronic Ulcers

Before the publication of this prospective study, 3 large retrospective studies in the past 20 years have tried to quantify the risk of chronic ulcers' malignant transformation. One large retrospective case-control study4 from Sweden showed that out of 10,913 patients with venous leg ulcers, the diagnosis of squamous cell skin cancer was made in only 33 cases. Among this group, the absolute risk was calculated at approximately 0.3%, and the mean duration of time between ulcer formation and skin cancer diagnosis was 25 years. Limitations of this study include the fact that all venous ulcers were included, regardless of duration of disease or response to treatment and that evaluation was performed by a diverse group of physicians in regard to diagnosis and treatment. Because this was a retrospective study of multiple medical centers, no standardization of initial evaluation and treatment protocols was possible.
A second large study from Australia4 retrospectively analyzed 981 consecutive patients over a 7-year period who were referred to a leg ulcer clinic and underwent a tissue biopsy. Leg ulcers were biopsied based on clinical suspicion or lack of response to treatment. Among this group, 43 patients were diagnosed with 55 malignancies, yielding a prevalence among that group of 4.4% per patient or 2.2% per ulcer. In contrast to the above, previous studies, 75% of the malignancies were basal cell carcinomas and only 25% were squamous cell carcinomas.
A third retrospective study,5 also from France, evaluated patients who had already been diagnosed with skin cancer after a longstanding vascular leg ulcer. Eighty patients with 85 malignancies were analyzed retrospectively. The average age in this group was 75 years; women outnumbered men. Eighty-five percent of the ulcers were venous in origin and their mean duration was striking at over 27 years. Five of the eighty patients, or 6.2%, developed bilateral cancers; these were in patients who also had bilateral leg ulcers.
Consistent with previous studies, 98% of these cancers were squamous cell carcinoma. Of this group, 82% were well differentiated and 18% were poorly differentiated. Surgical excision was performed where possible, in well differentiated or localized tumors. Despite this conservative intent, 29 of 51 patients