A 72-year-old man is evaluated due to a scaly lesion behind his right ear. A diagnosis of squamous cell carcinoma is confirmed on biopsy, and the patient undergoes excision of the lesion with clear margins. The wound is left to heal by secondary intention. Three weeks later, the patient returns to the office with a 2.5-cm raised, soft, granular lesion at the excision site. Biopsy of a representative lesion is shown in the image below:
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Which of the following is most likely responsible for this patient's postoperative changes?
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This patient has a lesion with abundant capillaries and fibroblasts, which is characteristic of granulation tissue. Raising of the lesion above the surrounding skin (tissue overgrowth) is further consistent with excessive proliferation of granulation tissue (ie, hypergranulation tissue) at the site of wound healing.
Granulation tissue is an essential component of the proliferative phase of normal wound healing, providing the nutrients and structure needed for a wound to fill and reepithelialize. Platelets and macrophages in and around a healing wound produce vascular endothelial growth factor (VEGF), which induces the vascular and fibroblast proliferation of granulation tissue.
However, if VEGF-induced tissue proliferation continues unchecked, the resulting hypergranulation tissue prevents wound epithelialization and remodeling. These lesions most often occur at the site of nasogastric tubes or wounds left to heal by secondary intention (ie, the wound is purposely left open).
(Choice A) Cutaneous amyloidosis is caused by the deposition of insoluble fibers derived from precursor proteins (eg, immunoglobulin light chains) into the superficial dermis. It can have a varied gross appearance (eg, macular, nodular, lichenous) but would be characterized histologically by homogenous, eosinophilic dermal deposits.
(Choice B) During the remodeling phase of wound healing, fibroblasts and type III collagen in granulation tissue are gradually (ie, over weeks to years) replaced with myofibroblasts and type I collagen, forming a scar. Abnormalities in this process result in unchecked production of collagen fibers, forming a hypertrophic scar or keloid months after the initial wound.
(Choice C) Individuals with a resected squamous cell carcinoma lesion are at risk of developing a secondary lesion at the same site. However, these recurrences typically develop years postresection, and histology would typically show acanthosis, keratinization, and evidence of keratinocyte dysplasia (eg, keratinocytes with pleomorphic nuclei and abundant cytoplasm).
(Choice D) Neutrophils are essential to the normal inflammatory response in wound healing; they prevent infection and release cytokines and growth factors that allow wound healing to progress. However, protracted inflammation and excessive release of reactive oxygen species by neutrophils in a wound can cause tissue damage that delays wound healing, resulting in a chronic, nonhealing wound.
Educational objective:
Fibroblast and vascular proliferation (ie, granulation tissue) induced by vascular endothelial growth factor (VEGF) is essential to normal wound healing. However, if this tissue proliferation becomes excessive (eg, in wounds left to heal by secondary intention), the resulting hypergranulation tissue can impair wound reepithelization and remodeling.