Malignant Transformation in Diabetic Foot Ulcers—Case Reports and Review of the Literature

Abstract

An imbalance of regeneration and destruction of the extracellular matrix due to a plethora of chemo- and cytokines, elevated matrix metalloproteinases, bacterial contamination and repetitive painless tissue damage can lead the chronicity of a wound, especially in diabetic foot ulcers (DFU). Along general lines, wound healing and cancer development are similar. Therefore chronic wounds prepare a breeding ground for cancer development. Several characteristics such as increase in size, verrucous everted margins and contact bleeding are suspicious for malignant growth in a chronic wound. While previously the term Marjolin’s ulcer was attributed to a malignant tumor in (burn) scars, it is nowadays used for every malignant tumor in chronic wounds. Furthermore, chronic ulcers in diabetic feet are susceptible for malignant transformation. We describe two cases of squamous cell carcinoma in patients with DFU—a 71 year-old woman and a 67 year old man. Both received total tumor excision and split-skin grafts with good short-time results.

Predictive Effect of Inflammatory Response and Foot Ulcer Localization on Outcome in Younger and Older Individuals with Infected Diabetic Foot Syndrome

“…Further, wound healing is disturbed in diabetics due to an imbalance of de-and regeneration of extracellular matrix. Additionally, an intrinsic granulocyte dysfunction in diabetics [11,13,14] leads to a deranged release of growth factors. Hence, patients with infected DFS often appear with normal or only marginal elevated inflammation markers, although in the clinical examination bone and soft tissue involvement is provable.…”

Verrucous Carcinoma Arising Secondary to Diabetic Foot Lesions: A Systematic Review of the Literature

“…14 Verrucous carcinoma was diagnosed over a very short or long period following initial ulcer development, presenting in a range from 1 month 14 to 8 years. 12 Only a single patient 13 reported pain in the lesion, with the rest reporting painless presentation throughout the disease course, a finding which may be explained by concurrent peripheral neuropathy. Case 3 illustrates that it is possible for verrucous carcinoma to develop even after a previously active ulcer is considered healed and closed, as carcinomatous transformation in this patient was noted at the 1 month follow up appointment post wound closure.…”

“…Patients included both men 11,14,15,16 and women, 12,13 with ages ranging from 44 to 72 years old (Table 1). Across the six reported cases, all patients had a past history of diabetic foot ulcers followed by histopathological confirmed diagnosis of verrucous carcinoma arising in the region of the ulcer.…”

“…Patient ulcers had a peripheral hyperkeratotic border with subsequent wart or cauliflower-like transformation. Malodorous secretions were described in several cases, 12,13,16 although one case specifically noted a lack of malodor or drainage. 14 Verrucous carcinoma was diagnosed over a very short or long period following initial ulcer development, presenting in a range from 1 month 14 to 8 years.…”

“…The requirement for inclusion in our report were that the patient data had been documented in a case-related manner and the patient diagnosed with verrucous carcinoma secondary to diabetic foot lesion. One case of carcinoma cuniculatum 11 and one case of Ackerman carcinoma 12 were included in our analysis, as these are classified as alternate names for verrucous carcinoma. 6 One case report 13 included two separate cases of verrucous carcinoma secondary to diabetic ulcer in the same patient, for a total of seven such cases across six case reports.…”