The Value of a Biopsy in Chronic Ulcers: A Case Series

Jocelyn Tisch Mendes, MD; Robert J. Klein, DPM


Wounds. 2022;34(4):119-123. 

In This Article

Abstract and Introduction


Chronic wounds affect millions of individuals in the United States. Chronic wounds of the lower extremity and foot are commonly associated with vascular insufficiency, diabetes, pressure, and neuropathy. Nonhealing wounds are at risk of severe complications, including infection, gangrene, amputation, and malignant transformation. Primary cutaneous malignancies may masquerade as nonhealing ulcers; thus, it can be challenging to differentiate between the malignant transformation of a chronic wound and a primary cutaneous malignancy with ulceration. A biopsy can be a safe, valuable tool in investigating underlying pathology in chronic wounds. Early biopsy diagnosis of malignant transformation can prevent diagnostic and treatment delays. Presented is a review of biopsy and its need and timing to identify malignant transformation in chronic wounds. The authors present 3 patient cases in which biopsies confirmed presence of malignancy in chronic ulcers.


In the United States, chronic wounds affect more than 6 million individuals, and chronic lower extremity wounds affect between 2.5 million and 4.5 million people.[1–3] Chronic wounds are defined as wounds that do not exhibit significant evidence of healing within 3 months, despite standard treatment.[4] Malignant transformation of chronic lower extremity ulcers is rare, and skin cancer identification in chronic foot ulcers is even more so, possibly due to lacking guidelines.[1–3] The importance of early diagnosis and implementation of biopsy plays an important role in identifying the underlying pathology of nonhealing ulcers, as primary cutaneous malignancies may mimic chronic ulcers and can go untreated if misdiagnosed.[2,5] It can be especially difficult to differentiate between the malignant transformation of a chronic wound and a primary malignancy with ulceration. Biopsy of chronic wounds can identify malignancy and help clarify the nature of the wound, especially the barriers to healing and increased risk of infections.[6–8] Some clinicians may be hesitant to perform a biopsy because the resulting wound may have delayed healing. However, the US Food and Drug Administration recommends biopsy as an objective tool to exclude infectious, immunologic, or neoplastic disease in chronic wounds.[9]


A biopsy is performed to examine a removed sample of involved tissue for the presence of disease. Skin biopsies most often include punch biopsy, tangential shaving of the skin, or excising a sample with a scalpel.[10]

Based on the level of difficulty of the procedure, a biopsy can be performed in various clinical settings.[10] To safely perform more difficult biopsies, such as liver, bone, or kidney biopsies, and determine where exactly to perform the extraction of tissue, imaging guidance is often used; such imaging includes ultrasound, x-ray, computed tomography, and magnetic resonance imaging (MRI).[10] For skin lesions, imaging guidance is unnecessary, and the procedures are most often performed in an ambulatory setting. [10]

The National Comprehensive Cancer Network (NCCN) recommends that a skin biopsy be performed on any suspicious lesions, and the biopsy should include a specimen obtaining deep reticular dermis.[11] Superficial biopsies often miss the causative component of the infiltrative histology of the tumor, especially in wounds and scars.[11]

Malignant Transformations of Chronic Ulcers

A Marjolin ulcer (MU) is a cutaneous squamous cell carcinoma (SCC) associated with chronic wounds.[6,7,12] These carcinomas arise after the malignant transformation of chronic ulcers associated with scars and chronic wounds.[12] Marjolin ulcers are classified as either acute or chronic.[15] Acute MUs are extremely rare and occur within 12 months of the development of an ulcer, whereas chronic MUs most commonly occur after 12 months.[15] Although basal cell carcinoma (BCC) is more common than SCC, SCC is a more common type of malignancy that develops in chronic wounds and scars.[10,12,13] Marjolin ulcers are more difficult to manage, and in general, have a poor prognosis.[12]

The NCCN recommends that cutaneous squamous cell carcinoma (cSCC) workup begins with the collection of medical history and physical examination and includes a full-thickness biopsy of the epidermal atypia, excluding actinic keratosis.[11] The NCCN also states that if the incisional biopsy only provides clinical information for micro-staging the tumor, narrow margin excisional biopsy should be obtained, including the accurate measurement of thickness and anatomic level of invasion.[11]

Primary cutaneous malignancies may mimic chronic ulcers.[7] Thus, it can be challenging to differentiate between the malignant transformation of a chronic wound and a primary malignancy with ulceration. The authors present 3 cases of biopsy-proven cutaneous malignancy in chronic foot ulcers, where 1 case represents the malignant transformation of a wound and 2 cases demonstrate primary malignancy masquerading as chronic wounds.