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Skin Cancers and Wounds in the Geriatric Population: A Review
Abstract
Diagnosis of wound malignancy often remains elusive and is of particular concern in the geriatric population because the average age for presentation of squamous cell cancer is 70 years. Basal and squamous cell carcinoma, as well as Marjolin’s ulcer, may look like a chronic or acute wound, can develop in the wound itself, or be found in the scar tissue of these wounds.
A complete patient history should include questions about sun exposure and personal and family history of skin cancer. Some wounds exhibit typical clinical signs of cancer — ie, raised borders, crusting — but many do not, making diagnosis more challenging. A punch, excisional, or ellipse biopsy from all ulcers and wounds that do not respond to appropriate protocols of care should be obtained. An accurate diagnosis is crucial to positive treatment outcomes.
Chronic wounds in the elderly often represent serious medical maladies, result in significant morbidity and skyrocketing medical costs, and affect approximately 4 million patients in the United States. Many potential wound etiologies exist (sequelae from diabetes, venous, and arterial disease, pressure, and trauma) and a host of diseases (eg, Crohn’s disease, rheumatoid arthritis, and antiphospholipid antibody syndrome) may predispose to wounds. Diagnosis of wound malignancy, especially in the venous leg ulcer, often is illusive. Because epidermoid (skin) cancers may masquerade as chronic ulcers, particularly in the elderly, these cancers often are overlooked. The purpose of this overview is to help clinicians decide when to biopsy chronic wounds. 
Epidemiology of Skin Cancers
More than 1 million new cases of non-melanoma skin cancers (NMSC) occur in the United States yearly.1 Among these, basal cell cancers (BCC) predominate and occur in approximately 80% of the cases; the remaining 20% of patients show evidence of squamous cell cancer (SCC), most of which has been found to be related to precancerous lesions called actinic keratoses (AK).2 Sun-exposed surfaces of the head and neck on fair-skinned individuals appear most vulnerable, although tumors arising from areas not exposed to the sun have been reported.1 Immunosuppression plays a pivotal role and many skin cancers have been found to develop secondary to human papilloma virus (HPV) types 5 and 8.3 Ultraviolet (UV) radiation exposure represents the major known risk factor for NMSC. Clinicians have observed a small yet definitive risk of metastasis with SCC; however, this varies with site and histology.4
SCC are responsible for more than 2,500 deaths annually. Researchers hypothesize these numbers likely will escalate secondary to aging “baby boomers” in general and to persons requiring organ transplantation — and subsequent use of immunosuppressive medications — in particular. The catastrophic effects of a population with record rates of diabetes and immunopathy most certainly predispose to the proliferation of epidermoid cancers in the geriatric population.5
An Overview of Types of Skin Cancers
Basal cell cancer. BCC represents the most common type of malignancy. It typically occurs in areas of chronic sun exposure. Basal cell tumors rarely metastasize and are slow growing; however, inadequate treatment or neglect may lead to significant local disfigurement and tissue destruction. BCC usually occurs in fair-skinned Caucasians and remains rare in dark-skinned individuals. The lesions predominate in a male-to-female ratio of 3:2. Areas of the face, ears, scalp, neck, and trunk are the most frequently affected.6 Clinicians may observe a very friable neoplasm with a propensity for ulceration that provides a nidus for infection.
Nodular BCC represents the most common variety; features include waxy papule(s), pearly appearance, erosion/ulceration, bleeding or crusting, rolled border(s), translucency, telangiectases, and a history of bleeding with insidious trauma.7 In the US, BCC occurs in approximately 900,000 people annually, most commonly in adults, especially the elderly population. There can be a latency period of 20 to 50 years between UV damage and the clinical onset of these malignancies.8
Squamous cell cancer. SCC (see Figure 1), the second most common form of 
skin cancer, represents a malignant tumor of keratinocytes. Most SCC arises from sun-induced AK lesions. Statistics from earlier in this decade show the annual incidence of SCC in the US was 105 cases per 100,000 population.9 SCC is capable of local extension, regional lymph node metastasis, and distant metastasis. These cancers usually spread to the regional lymph nodes but rarely to the lungs. Practitioners observe that SCC is common in Caucasians and rare in African Americans. These lesions predominate in men versus women (2:1). Typical age at presentation of SCC is approximately 70 years, underscoring the importance of appropriate diagnosis and treatment in this population.9
Marjolin’s ulcer. Marjolin’s ulcer historically represents SCC that proliferates or transforms from a chronic wound. These cancers traditionally are observed in pressure ulcers (decubiti) and in burn scars. However, lesions may develop in a host of other wound types including those related to thermal injuries,10 amputation stumps, small pox vaccinations, skin graft donor sites, puncture wounds, dog bites, snake bites,11 blunt trauma, sinus tracts secondary to osteomyelitis, venous ulcers, and fistulas, as well as in patients with spinal cord injuries.12 Clinicians also have reported these tumors in patients with syphilis and lupus vulgaris, epidermolysis bullosa scars, granuloma inguinale, and pilonidal sinus tracts, among other conditions and diseases.13 The average latency between ulcer formation and documented malignancy is 30 years (range 25 to 70 years); the male-female ratio has been reported to be as high as 3:1.12
Burn scar carcinomas may present as flat, indolent lesions with indurated and elevated margins and may exhibit foul-smelling drainage and underlying bone destruction. These lesions easily may be mistaken for infection.14 The tumors are often aggressive with a propensity for local recurrence and lymph node metastasis. Clinicians usually link Marjolin’s ulcer to SCC; other tumors also have been reported (eg, BCC, malignant melanoma15,16). Most Marjolin’s ulcers occur on the extremities; whereas, more than 90% of other epidermoid cancers occur on the face and neck.17 Despite the wide prevalence of wounds in which they may develop, these lesions remain rare.
An Overview of Predisposition to Developing Skin Cancer by Wound Type
Wounds may develop secondary to many conditions including diabetes, venous disease, arterial insufficiency, immunopathy, malignancy, rheumatoid arthritis and Crohn’s disease. Geriatric populations are predisposed to many of these illnesses. Ulcerations also form secondary to pressure (predominately in the elderly nursing home or hospital populations), insect bites, and wound healing complications following surgery. Additionally, vasculitis, pyoderma gangrenosum, and cryoglobinemias may cause wounds. Patients on dialysis may develop calciphylaxis.18
Appropriate diagnosis before treatment is mandatory. Clinicians must perform a complete history and physical examination including a vascular, neurological, and orthopedic evaluation of the lower extremities. The history should include specific questions about the ulcer such as etiology, duration, previous treatment, history of similar wounds, ethnic background, pain, and patient history of skin cancer in order to establish a diagnostic pathway. Clinicians find this particularly important in the geriatric population where presentations of cancers are typically observed.
Unfortunately, many “wounds” represent primary or secondary cancers (see Figure 2) while others ultimately convert to malignancies such as Marjolin’s ulcer. The literature is replete with examples of these cancers. In a retrospective study involving 4,020 patients with metastatic disease, Lookingbill et al19 concluded that cutaneous metastasis was not uncommon and frequently represented the first signs of extranodal metastatic disease. Amelanotic melanoma can masquerade as a variety of other conditions, often delaying diagnosis.20 Arroyo et al21 underscored the importance of having a high index of suspicion in cases of verrucous plaques in the foot that did not behave as clinically expected; Yoshitatsu et al,22 Schroven et al,23 and others24,25 have reported similar experiences, heightening awareness that certain persistent “warts” could actually represent cancers.26
Diabetic foot ulcers. Patients with diabetes mellitus often develop foot ulcers secondary to multiple underlying etiologies; neuropathy is present in 85% of foot ulcers.27 Additional comorbidities and complications of diabetes mellitus include large and small peripheral vascular disease, immunopathy, poor glycemic control, and use of tobacco products.28 Utani et al29 reported on a patient with diabetes mellitus and reactive eccrine syringofibroadenoma 
associated with a chronic skin ulcer on the foot. Several case studies of patients with SCC that developed within necrobiosis lipoidica have been published.30-32 (see Figure 3). Gregson and Allain33 discussed a case of amelanotic malignant melanoma that resembled a diabetic foot ulcer. SCCs also have been associated with osteomyelitis and chronic foot wounds34; reports of primary squamous cell tumors of the plantar surface of the foot have been published.35
Pressure ulcers. Pressure ulcers often occur secondary to friction, stress, shear, and moisture.36 Clinicians observe these wounds in patients with limited mobility. Nutritional deficiencies, especially protein malnutrition, often exacerbate or even precipitate these lesions.37 Patients recovering from hip fractures and pneumonia and patients with chronic obstructive pulmonary disease (COPD) and steroid dependency or diabetes also may be at greater risk.
Many case reports discuss potential cancers (including Marjolin’s) emanating from pressure ulcers. Mustoe et al38 described four cases of SCC arising from chronic pressure ulcers; a short latency period and fulminant clinical course with high metastatic rates was observed. Berkwits et al39 and Ratliff40 reported similar observations. Early diagnosis is imperative and tumor removal (ie, excision and radiation) is crucial.41 Due to increased survival rates of spinal cord injured/disabled patients (and elderly patients residing in nursing homes), pressure ulcer malignancies may become more widespread.39
Venous ulcers. The etiology of venous ulcer disease is multifactorial. Increases in vein pressure predispose to edema and subsequent lower extremity ulceration. These sequelae usually occur secondary to valve incompetence and subsequent failure of the pumping action of the skeletal musculature. Additional factors include microvascular compromise, venous hypertension, family and patient history of deep vein thrombosis, obesity, increased age, and pregnancy42,43 (see Figure 4). Higher rates of skin cancer have been associated with venous leg ulcers.44,45 A cohort study45 of 60 patients with typical venous leg ulcers demonstrated some intriguing parallels between venous and Marjolin’s ulcer, including poor nutritional support, tissue hypoxia, lack of blood supply, decreased tissue immunity, and repetitive micro-trauma.
Lag time represents the primary difference in the development of symptoms.17 Baldursson et al46 reviewed 25 cases of SCC arising from venous ulcers (mean age at cancer diagnosis was 78.5 years. See Figure 5). Based on their findings, aggressive treatment of patients with poorly differentiated and some moderately differentiated tumors wasrecommended to prevent fatalities.
Primary epidermoid cancers may mimic venous ulcers in appearance, location, and symptoms47,48 (see Figure 6). In a study by Snyder et al,49 25% of wounds initially diagnosed as venous ulcers were found to be malignant. The results suggested that clinicians consider including sun exposure questions in the patient history and obtaining biopsies when ulcers fail to heal.
Subungual tumors. Subungual (ie, under toe- and fingernails) tumors with metastasis50-53 are difficult to diagnose because some lesions present with minimal nail changes and mimic other diseases, particularly fungal infections.54 Clinical experience underscores the importance of nail plate removal, nail bed inspection, and appropriate biopsy.55
Traumatic wounds. Clinicians frequently dismiss the notion that traumatically induced wounds may represent potential sites of malignancies; clinically, the etiology appears straight-forward. However, many published reports conclude that trauma might be considered an additional etiological variable for tumors in both acute and chronic ulcers. Ozyazgan and Kontas56 assessed the relationship between the development of BCC and trauma in a retrospective review of 92 patients, 12 of whom gave a history of previous injury, and concluded that malignancies could develop directly after sharp or blunt injury or in scar tissue resulting from previous surgical incisions, burns, or dog bites (see Figure 7). Noodleman et al57 substantiated these findings in chicken pox scars, burns, sharp trauma, blunt traumas, and vaccinations. Wilkin and Strobel58 observed BCC at 
the site of venipuncture; this case report substantiated the premise that cancers not only could occur at sites of chronic trauma, inflammation, and scarring, but also could be precipitated by a single injury.
SCC often has been observed at sites of acute and chronic trauma. In a retrospective study of 406 patients, Mohrle and Hafner59 concluded that trauma could be an etiologic factor in subungual melanoma. Snyder60 reported several cases of SCC arising from insidious trauma.
The biochemical mechanisms producing cancers at sites of trauma are not clearly understood. Tumors might be explained by coincidence, increased attention to a dark area under a nail, or traumatic bleeding versus cell mutation and proliferation precipitated by trauma.
Summary. Malignant skin changes are common in many chronic ulcers. Biopsies should be obtained from all suspicious ulcers and from wounds that do not respond to appropriate treatment.61 Clinicians must function as medical detectives when dealing with seemingly innocuous clinical presentations such as warts that may represent fulminant skin cancers. Early detection and intervention increase the probability for successful outcomes.62
When to Biopsy?
Clinicians must be astute in determining which lesions require testing and when to biopsy. Foremost, some wounds may show clinical characteristics of carcinoma (eg, raised boarders and crusting); these indications combined with a patient history of chronic sun exposure, a change in shape/color of the lesion, or family history of skin cancer should prompt further investigation. If clinical signs lead to a suspicion of skin cancer, wound biopsy on the first patient encounter is appropriate. Additionally, if a wound is not responding to traditional and specific treatment protocols63 (eg, a venous ulcer that fails to respond to several weeks of compression therapy or a pressure ulcer that 
fails to respond to offloading, re-positioning, moisture control, and nutritional support within a reasonable period of time), practitioners must consider alternative causes and obtain a biopsy. Multiple tissue samples may be required to rule out underlying cancer, especially if the lesions have been present for years (Marjolin’s ulcer) or diabetic foot ulcer has been diagnosed.
Organ transplantation patients are at high risk for developing skin cancer; the importance of biopsy cannot be overstated. Walder et al64 found a 14% increase in skin cancers in transplant recipients, with squamous cell lesions outnumbering basal cell tumors 5 to 1.
Pyoderma gangrenosum represents a diagnosis of exclusion. Misdiagnosis is not uncommon and may result in substantial complications65 and disfiguring surgery. Biopsy should be performed to confirm the absence of carcinoma (see Figure 8).
Generally, if biopsies are negative and the wound continues to languish, additional or re-biopsy is recommended (perhaps with a wider excision).66 In such cases, the clinician should “think like an internist, but act like a surgeon”.67
Clinical Experience: Types of Biopsies
Skin biopsy is required to confirm a diagnosis of carcinoma. Several viable biopsy options are available to clinicians — ie, shave, incisional, excisional, and punch. Although the shave technique may suffice for the diagnosis of a solitary lesion such as BCC, chronic wounds usually require deeper sections. Examination of the deeper tissues in lesions with pseudoepitheliomatous hyperplasia is necessary to ascertain malignancy does not go undetected.68 Snyder69 reported a case of subcutaneous T-cell lymphoma initially missed by shave biopsy (see Figure 9). De 
Faria70 described BCC of the skin along with areas of SCC, termed basosquamous cell carcinoma. Findings of basal cell tumor with a solitary biopsy could prompt a vastly different treatment protocol than one used to treat a squamous cell lesion discovered at a different site (see Figure 10). Punch biopsies traversing the subcutaneous tissue represent a simple and straight-forward technique that yields consistent and reproducible results.
The need for multiple biopsies cannot be overstated.71 Procedures performed in one suspicious section may yield, for example, venous stasis and at another section the findings may be SCC (see Figure 11). If the lesion is approached as a clock — the area closest to the head is 12 o clock — biopsies could be taken at 6 and 12 o clock (for example) with a 4-mm punch and include subcutaneous tissue. A disposable punch should be held perpendicular to the skin and used in a “twisting” motion until the tissue traversing the subcutaneous layer is obtained. The clinician needs to make certain not to crush the specimen while it is being removed. The site may be left to heal by secondary intention or closed with a suture or steri-strip. A small margin of normal tissue should be included to facilitate 
comparison (see Figure 12a-d, Figure 13a,b); excisional or ellipse biopsy through the entire lesion also may yield acceptable diagnostic results.72
In real estate, the mantra is “location, location, location”; in wound management, it is “biopsy, biopsy, biopsy”. 
Treatment Protocols for Typical Skin Cancers
Electrodesiccation and curettage (ED&C).73 Electrodesiccation is used to remove small superficial growths; when combined with curettage, it can eliminate abnormal tissue found deeper in the skin.
Cryosurgery (liquid nitrogen).74 In cryosurgery, tissue is destroyed using subfreezing temperatures. Curettage and cryosurgery may be combined.
Mohs micrographic surgery (see Figure 14). Mohs is considered for moderate- to high-risk lesions where tissue conservation is required and offers very high cure rates in an outpatient setting when performed by fellowship-trained Mohs surgeons.75
Excision of skin cancer,72 frozen section (4- to 6-mm margins), followed by split-thickness skin graft (STSG). This approach offers excellent cure rates in low-risk tumors, especially in the lower extremities. Disadvantages include arbitrary margin control. Frozen sections are recommended before application of STSG.
Radiation therapy76 (see Figure 15). Radiation therapy is considered a primary modality for inoperable tumors and for patients unable to tolerate surgical excision. Disadvantages include poor margin control/development of multiple adjacent tumors.
Topical preparations. (eg, Imiquimod77 topical photodynamic therapy ablative skin resurfacing78). These therapies are effective in the treatment of superficial BCC.
Reconstructive surgery. Epidermoid cancers typically range from 0.5 cm to 1.5 cm; however, clinicians frequently encounter much larger lesions at sites of chronic wounds. Surgical removal, either via Mohs surgery or excision, often creates a large defect that must be managed. Geriatric patients may have atrophic skin that can delay healing.
Historically, surgeons predicate wound closure technique on the Reconstructive Ladder.79 First, healing via secondary intention should be initiated, followed by skin grafting, and rotational flaps and culminated by performing free flaps, if necessary (see Figure 16a,b,c).
Collaborative approach. Generally, the diagnosis and treatment of chronic wounds in the elderly patient requires a holistic collaboration between different physician specialists 
including internists; geriatricians; diabetologists; vascular, podiatric, general, plastic, and orthopedic surgeons; dermatologists; and infectious disease. Additional professionals may include nurses, physical medicine physicians, physical therapists, social workers, pedorthists, diabetic educators, and nutritionists. Clinical experience has shown that consultations with cardiologists, nephrologists, neurologists, radiologists, and physicians trained in hyperbaric medicine often are required.80 Patient outcomes should be reviewed by the wound team and treatments adjusted on a regular basis, as needed.
Treating patients with epidermoid cancers creates a slightly different dynamic that should involve numerous health professionals. Ideally, all evaluations, prevention, and treatment strategies comprise a multidisciplinary and collaborative approach between wound care specialists, primary care and transplant physicians, dermatologists, oncologic surgeons, pathologists, and medical and radiation oncologists.81
Conclusion
A search of the relevant literature yielded practical information on the diagnosis and management of wound-related cancers. Elderly patients are predisposed to chronic illnesses, many of which are factors in the development and healing of acute and chronic wounds. Many wounds, including diabetic foot ulcers, pressure ulcers, venous ulcers, and traumatic wounds may predispose to epidermoid cancer formation. Appropriate diagnosis requires a complete history and physical examination including questions about previous skin cancers and sun exposure. Skin cancer types include basal cell, squamous cell, Marjolin’s ulcer, and malignant melanoma; elderly patients are at risk for all of these tumors.
When a wound exhibits typical clinical signs of cancer (ie, raised boarders, crusting) a biopsy should be obtained on the first patient encounter. Ulcers not responding to appropriate disease-specific algorithms for care also warrant biopsy. Furthermore, if lesion biopsies are negative and the wound continues to languish, clinicians should procure additional tissue samples over time. Biopsy remains an essential diagnostic tool; in the author’s opinion, punch biopsies traversing the subcutaneous tissue should be procured at multiple sites (at 6 and 12 on the wound “clock”) including a small amount of normal tissue margin to facilitate comparison. Excisional biopsy or ellipse through the entire lesion also may yield acceptable diagnostic results.
Treatment protocols include electrodesiccation and curettage, cryosurgery, Mohs micrographic surgery, excision, radiation therapy, and topical preparations. A multidisciplinary and collaborative approach remains the mainstay of therapy.
Dr. Snyder is Medical Director, Wound Healing Center at University Hospital, Tamarac, FL. Please address correspondence to: Robert Jay Snyder, DPM, FACFAS, CWS, FCCWS, 7301 N. University Drive, Suite 305, Tamarac, FL 33321; email: drwound@aol.com.
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