Malignant Melanoma Misdiagnosed as a Diabetic Foot Ulcer

Index: WOUNDS 2012;24(2):43–46

Presentation

  Malignant melanoma, although rare, is a skin cancer with the highest mortality. This report presents a 55-year-old man who had been followed-up for diabetes mellitus for 14 years, and was diagnosed with a malignant melanoma that had developed on the base of a diabetic foot ulcer. The major common characteristic of malignant melanomas misdiagnosed as foot ulcer in the literature was that these cases have a very aggressive course, and metastasize in a short time. Thus, early biopsy is required in painful, pigmented foot ulcers with atypical localization that do not respond to standard treatment in patients with diabetes.

Diagnosis

  Malignant melanoma misdiagnosed as a diabetic foot ulcer.

Discussion

  Although it accounts for only 4% of skin cancers, 80% of deaths due to skin cancer are attributed to malignant melanoma.¹ Until recently, it has been considered a definitively fatal condition. However, owing to the efforts of training and raising awareness, patients who are diagnosed early may be cured with surgical treatment. Delayed diagnosis is still associated with high mortality rates.   Micro- and macrovascular complications due to diabetes mellitus are the major long-term morbidities of this condition. Ulcers of the lower limbs due to peripheral neuropathy, angiopathy, and infections are more frequent than in nondiabetics. The most common conditions causing foot ulcers, other than diabetic complications in diabetes patients, are Charcot Marie Tooth disease, spina bifida, spinal trauma, and Hansen’s disease (leprosy).²   Malignant melanoma is an invasive and metastatic tumor with an increasing frequency and high mortality. More than 33% of all melanomas develop on the lower limbs.^3,4 The most common site of involvement of malignant melanomas of the foot is the plantar region.⁵ Plantar melanomas are still rare in the melanoma population, as only 0.9%–7% have invasive primary cutaneous melanomas located on the plantar region.^1,6 There is no significant difference between mean tumor thickness on the plantar surface and that on the leg.7 Five-year survival rates are between 56% and 71%.⁸ Unsurprisingly, earlier stage and thinner tumors (< 4 mm) have a better prognosis.⁸ In another study, the survival rates of palmoplantar melanomas were lower compared to other regions.⁹   Misdiagnosis of palmoplantar melanomas was reported to delay treatment for 12 months, increase tumor thickness, and decrease the 5-year survival rate for up to 68.9%.¹⁰ In a study reviewing 53 cases of lower limb melanomas in plantar region, melanoma was misdiagnosed in 11 out of 18 patients (61%).¹¹ Thus, rapid diagnosis and treatment are critical in these patients.   Malignant melanomas are most frequently confused with nonhealing ulcers, warts, blisters, hyperkeratotic lesions, foreign bodies, pyogenic granules, benign nevi, tinea pedis, and onychomycosis.¹² Diabetic foot ulcers are not yet included on this list. Plantar ulceration is frequent in diabetic patients because small lesions developing with high pressure or trauma go unnoticed due to diabetic sensorial neuropathy and transform into diabetic foot ulcers with microangiopathic ischemia in time.   A recent large cohort study found that colon, rectum, liver, biliary tract, pancreas, kidney, leukemia, and melanoma are significantly elevated among men with diabetes.¹³ In 1985, O’Mara et al¹⁴ noted a raised risk of melanoma and nonmelanoma skin cancers in women with diabetes. The hypothesized biological mechanisms are related to the effect of insulin and insulin-like growth factors on tumoral cell proliferation.^15,16 Additionally, advanced glycation end products (AGE) have been implicated in the growth and migration of human melanoma cells.¹⁷ In the same study, AGE were present in beds of human melanoma tumor, where as barely detected in normal skin. However, in Canada, Rousseau et al¹⁸ found that diabetes was associated with an increased risk of liver cancer among diabetics with no other types of cancer, including melanoma. A link between cancer and diabetes remains controversial.   Biopsy rates for lesions in the plantar area have increased recently. There are 13 malignant melanoma cases misdiagnosed as diabetic foot ulcers in the literature, and our patient is the 14th case. The characteristics of the all misdiagnosed patients reported in the English literature are summarized in the Table 1. Data on various parameters, such as the duration of diabetes mellitus, history of trauma on the foot, presence of peripheral neuropathy, or ischemia were not available for previous cases; therefore, commenting on the common points of cases is difficult. The possible correlations between the duration of diabetes mellitus, duration of foot ulcers, location of ulcers, development of malignant lesions, age and sex of patients, frequencies of malignancy, and poor/good control of blood glucose levels, will be unraveled as the number of cases in the literature increases.   Kong et al² suggested that early biopsy was indicated if neuropathy or ischemia was not present, if the ulcer had an atypical localization, if it was painful/pigmented, and did not respond to standard treatment. Excisional biopsy should be performed to allow staging of the malignant melanoma. A significant cause of misdiagnosis is that a dermatologist does not usually examine these patients. All atypical, suspicious ulcers should be consulted with a dermatologist.¹⁰

Treatment

  A 55-year-old man who has been followed-up for Type 2 diabetes mellitus for 5 years presented with an ulcer of the right heel. The lesion had started with a skin abrasion 5 months previously, and had enlarged and become a painless ulcer with serous fluid. Extensive debridement, oral antibiotic, and silver-based topical agents were used, but were not successful. Secondary debridement and intravenous antibiotics were started. All of these efforts were not useful to minimize ulcer dimensions and an incisional biopsy was taken from the ulcer base. The histopathological examination showed malignant melanoma cells (stained with HMB-45) with a Breslow depth of 5 mm (Figure 1).   The conditions including peripheral neuropathy, peripheral ischemic disease, and trauma were not detected. Physical examination revealed hepatosplenomegaly, ascites, painful lymph node enlargement in the right inguinal region, and a 6-cm diameter ulcerative lesion of the right heel with small, pigmented areas and an irregular border (Figure 2). Reactive Achilles reflexes, rosy-pink skin color, normal skin temperature, and hair loss were detected on both lower extremities. Direct x-rays did not reveal any evidence of osteomyelitis. Blood glucose levels were high and not regulated and serum HbA1C was 9 mg/dL. A biopsy taken from the right inguinal lymph node revealed metastasis of melanoma, liver, and brain metastases were detected. The patient died within a few weeks.

Conclusion

  A patient may have more than one medical condition concurrently. Thus, considering the worst scenario may be life saving.

References

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