The importance of biopsy in wound management: lesion biopsy should be an essential part of the wound healing algorithm

The importance of biopsy in wound management: lesion biopsy should be an essential part of the wound healing algorithm – Wound Care & Diabetes Q&A

Robert J. Snyder

Case Study:

JB, a 76-year-old African-American male, presented with a chronic wound at the dorsal-lateral aspect of the fifth metatarsal head of the right foot. Symptoms had been present for two years and the patient related a shoe irritation as the catalyst. Previous treatments were heroic and included several interventions. The patient was thought to have significant peripheral vascular disease and subsequently had a femoral-popliteal bypass performed. This treatment was combined with local debridements, topical antibiotics, the use of a hydrogel, and offloading. He also was given a course of intravenous vancomycin for two weeks. The wound, however, remained recalcitrant and he was referred for further evaluation and treatment.

After a complete history and physical, x-rays and an MRI were ordered and proved negative for osteomyelitis. The patient related a history of insulin-dependent diabetes with lower extremity neuropathy; however, he was in otherwise good health. Pedal pulses were palpable and the foot was warm to touch. The wound measured 10mm x 5mm x 1mm and consisted of beefy red granulation tissue with no signs of infection. Multiple biopsies were performed in light of wound chronicity and raised borders. The pathology report revealed malignant melanoma, Clark’s Level III, Breslow’s Level I (1-1.65 mm). The tumor extended to the lateral edges of resection.

Q Why is it important to biopsy lesions in the lower extremities?

Although the above case represents the most devastating result, wound biopsy may also play a role in the diagnosis of many maladies thus influencing treatment protocols and prognosis.

Squamous cell cancer (SCC) represents a specific type of epidermoid lesion of the skin, second only to basal cell cancers (BCC). Clinicians in the United States diagnose more than 600,000 new cases each year. Although sun-exposed surfaces such as the head and neck appear most vulnerable, tumors may also arise from non-sun-exposed areas. Immunosuppression resulting from human papilloma virus (HPV) represents another causative factor.

Although occurrence of these lesions appears less prevalent in the lower extremities, they still represent a significant risk. Snyder et al. (1) noted that many lesions originally diagnosed as venous ulcers showed characteristics strikingly similar to skin cancers and might represent sites of primary malignancies. A pilot study concluded that epidermoid cancers may mimic venous ulcers in appearance, location and symptoms. A literature review supports the premise that sun damage may manifest many years after exposure. The research further suggests that those patients presenting with venous ulcer disease and a history of current or previous domicile in a tropical climate may benefit from lesion biopsies.

Typically, Marjolin’s ulcers represent SCC that arise from chronic wounds such as pressure ulcers or burn scars, although BCC and malignant melanomas have also been reported. Conditions such as venous ulcers, sinus tracts secondary to osteomyelitis, and fistulas also have a propensity to develop Marjolin’s ulcers. Clinicians historically observe these cancers in patients with syphilis, lupus, sites of amputation, small pox vaccination sites, skin graft donor sites, puncture wounds, dog bites, and blunt trauma, among others.

The average lesion undergoes malignant transformation over a period of 25-40 years with a male to female ratio of almost 3:1. Despite the wide prevalence of wounds in which this entity may develop, Marjolin’s ulcer remains rare. (2,3)

Pyoderma Gangrenosum

Pyoderma gangrenosum (PG) represents an autoimmune disease usually characterized by one or more ragged violaceous plaques with undermined borders. Fifty percent of cases are associated with but not limited to chronic systemic diseases, including ulcerative colitis, Crohn’s disease, rheumatoid arthritis, and diabetes. Conversely, the other 50% of cases have no associated disease, rendering them idiopathic. PG is often difficult to diagnosis and usually requires a multidisciplinary treatment approach. Although there are no specific pathologic findings biopsy is important because the diagnosis is usually one of exclusion of other known causes of cutaneous disease. (4)

Subungual Malignant Melanoma

Subungual malignant melanoma has been reported in the Literature. Many cutaneous manifestations mirror systemic disease; therefore, a complete history and physical is mandatory. The diagnoses of conditions such as calciphalyxis, Necroblosis Lipodica Diabeticorium (NLD), lesions associated with rheumatoid arthritis, and vasculitis, may be facilitated with appropriate biopsy.

Q How does the clinician make a decision to biopsy a particular ulcer?

The decision to biopsy is multifactorial. If the history is specific for but not limited to such conditions as chronic renal failure requiring dialysis, diabetes, autoimmune disease, history of previous skin cancers, family history of cutaneous cancer, or a longstanding chronic wound, than a biopsy may be helpful in making a diagnosis. If the wound has changed in appearance, color, or drainage, or becomes exquisitely painful, a pathological evaluation becomes important. Wounds exhibiting violaceous rings and exquisite pain may represent Recluse spider bites and should be verified with a tissue sample. Cutaneous lesions with raised borders as well as those wounds that scab over and continually re-open should be considered suspicious for cancers.

Q What techniques may he utilized in taking a wound biopsy?

There are many acceptable techniques utilized to take these biopsies, including punch biopsy, shave technique, or excisional biopsy with or without primary closure. This author prefers the following methodology:

a) The ulcer is prepped and draped in the usual sterile manner.

b) A 4mm disposable biopsy instrument is utilized.

c) Multiple biopsy sites are usually taken when feasible, usually at 12 o’clock and 6 o’clock. A portion of normal skin margin is usually incorporated into the specimen. In large lesions, a central specimen may also be taken.

d) Shave biopsies are usually discouraged and the procedure is performed through subcutaneous tissue where appropriate. Snyder et al reported a case of subcutaneous T-cell lymphoma that was originally missed with shave biopsy.

Lesion biopsy represents a simple and reliable technique and should be considered an essential part of the wound healing algorithm.


(1.) Snyder RJ, Stillman R, Weiss SD. Epidermoid cancers that masquerade as venous ulcer disease in the lower extremities. Accepted for publication in Ostomy Wound Management, April 2003.

(2.) Lifeso RM, Bull CA. Squamous cell carcinoma of the extremities. Cancer 55: 2862-2867, 1985.

(3.) Van Eygen P, Stuyck J. Marjolin’s ulcer presenting as a pathological fracture. Belgian Orthoweb, 12/23/2001.

(4.) Snyder RJ, Kimmel SC, Weiss SD, Glick B. Pyoderma Gangrenosum. Podiatry Management, Aug. 75-82 2002.

Robert J. Snyder, DPM, CWS is a diplomate of the American Board of Podiatric Surgery and his practice Is limited to wound management and limb salvage. He Is a diplomate of the American Academy of Wound Management and has the designation of Certified Wound Specialist. Dr. Snyder serves as the Director of Wound Management Education at Northwest Medical Center In Margate, FL and Is a faculty physician at the Wound Healing Center at University Hospital In Tamarac, FL.

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