Chapter 42
Pigmented Skin Lesions (Case 34)
James G. Bittner IV MD, Joan R. Johnson MD, MMS, and D. Scott Lind MD
Case: A 68-year-old woman presents with a pigmented skin lesion on her right thigh.
Differential Diagnosis
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Basal cell carcinoma (BCC) |
Atypical nevus |
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Squamous cell carcinoma (SCC) |
Actinic keratosis |
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Malignant melanoma |
Benign nevus |
Speaking Intelligently
When asked to see a patient who presents with a pigmented skin lesion, we start by asking the patient what she thinks the lesion may be and reassuring her that as a team we will “find out” the answer. This allows us to quickly assess the patient’s level of concern regarding the pigmented skin lesion. Next, we find out when she first noticed the lesion; if it has changed in shape, size, or color; whether or not it is painful; and whether the patient noticed any similar lesions recently or in the past. We also ask whether the lesion has been itching or bleeding and whether she has had any prior biopsies, laboratory tests, or imaging studies ordered by other physicians. It is important to ask about a prior personal or family history of skin cancer.
PATIENT CARE
Clinical Thinking
• Most patients think cancer first (perhaps rightfully so), and they want an answer—yesterday. That said, it is up to you, the physician, to reassure the patient that the ideal scenario is a correct diagnosis based on clinical, radiographic, and pathologic evidence. A timely but inaccurate answer may result in lost credibility, increased patient anxiety, and a strain on the physician-patient relationship. Most of all, you don’t want to miss a skin cancer. Therefore, if a lesion is suspicious, you should perform a biopsy. If a biopsy is required, be sure to check the patient’s history for coagulopathy or medications that might cause bleeding such as clopidogrel, aspirin, and warfarin.
History
It is crucial to obtain a thorough history, including past medical history, family history (especially including skin cancers), surgical history, and medications; of particular interest are the following skin cancer risk factors:
• Occupation: Patients with prolonged ultraviolet exposure are at increased risk.
• Radiation: History of industrial, therapeutic, and occupational exposure constitutes high risk.
Physical Examination
• Most patients with a skin lesion present with normal vital signs.
• A complete skin examination in a well-lighted room includes inspection from the scalp to the toes, paying careful attention to those areas most notable for harboring cutaneous malignancies such as the face, neck, upper back, upper and lower extremities, and dorsal and ventral aspects of the hands and feet.
Tests for Consideration
| Clinical Entities | Medical Knowledge |
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Basal Cell Carcinoma |
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Pφ |
BCC is the most common skin cancer worldwide. It is a slow-growing tumor that arises from abnormal epidermal keratinocyte growth and is divided into three types: nodular (70%–80%), superficial, and morpheaform. The histology is unique for aggregations of basophils at the tumor periphery called “peripheral palisading.” |
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TP |
Nodular BCC usually presents as a waxy, raised, pearl- or cream-colored lesion with heaped borders and often exhibits central ulceration. Superficial BCC presents as an erythematous, scaling lesion usually on the trunk. BCC may also contain pigment and appear tan or black. These lesions must be differentiated from melanoma by biopsy. |
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Dx |
Most lesions can be diagnosed based on clinical presentation, but biopsy of any pigmented BCC is required to exclude melanoma. |
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Tx |
The gold standard treatment for BCC is complete surgical excision with negative margins. However, newer therapies include curettage/electrodesiccation, Mohs micrographic surgery, cryosurgery, radiation, and topical chemotherapy or immunomodulator therapy. Mohs surgery can be offered to patients with BCC size >2 cm, contiguous lesions in high-risk locations (eyelids, ears, nose), recurrent tumors, and tumors with little metastatic potential. See Cecil Essentials 57. |
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Pφ |
SCC is the second most common skin cancer worldwide. It arises from abnormal epidermal keratinocyte growth and is divided into two types—in situ (Bowen disease or erythroplasia of Queyrat) and invasive. The histology demonstrates atypical squamous cells of the epidermis with possible extension into the reticular dermis. |
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TP |
SCC most often presents as a hyperkeratotic, raised, flesh-colored lesion with associated ulceration and erythema commonly located on the face, ear, trunk, or regions of skin pathology. Predisposing skin lesions for SCC include Marjolin ulcers, decubitus ulcers, bullous disease, and areas of chronic osteomyelitis. |
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Dx |
Most lesions can be diagnosed based on clinical presentation, but biopsy of any SCC is required to exclude amelanotic melanoma. |
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Tx |
The gold standard treatment for SCC is complete surgical excision with negative margins with or without lymph node biopsy. However, newer therapies include curettage/electrodesiccation (if epidermis involvement only), Mohs micrographic surgery, cryosurgery, and topical chemotherapy or immunomodulator therapy for multiple lesions. Mohs surgery can be offered to patients with SCC diameter > 2 cm, contiguous lesions in high-risk locations (eyelids, ears, nose, lips), recurrent tumors, and tumors with little metastatic potential. Radiation can be used alone for moderate-risk locations (with lesions < 20 mm diameter) and high-risk locations (<15 mm diameter), or in combination with cisplatin-based chemotherapy regimens. Postoperative chemotherapy and radiation are used for high-risk lesions, nodal involvement, and incompletely resected margins. See Cecil Essentials 57. |
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Malignant Melanoma |
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Pφ |
Malignant melanoma is now the fifth most common cancer in men and seventh in women, with approximately 68,000 new cases of invasive melanoma diagnosed and 8400 deaths reported annually in the United States. At the time of diagnosis, about 84% present with localized disease, 8% have regional disease, and 4% have distant metastases. Melanoma arises from mutated melanocytes, and four common types are classified: superficial spreading (70%), nodular (15%–30%), lentigo maligna (4%–15%), and acral lentiginous (5%). |
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Superficial spreading melanoma presents as a flat, pigmented lesion with variegated pigmentation, irregular borders, and areas of tumor regression anywhere on the body except the hands and feet. Nodular melanoma typically contains more pigmentation and appears raised without evidence of radial spread. The lentigo maligna type occurs on the face, neck, and hands of elderly patients. Acral lentiginous type occurs on the palms and soles as well as the subungual region of predominantly dark-skinned people (African Americans, Asians, and Hispanics). |
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Dx |
Most lesions can be grossly diagnosed based on clinical presentation, but biopsy of every melanoma is required for type-specific identification. Breslow depth of invasion determines the T classification using the TNM system: T1 lesion < 1 mm in depth, T2 lesion 1–2 mm in depth, T3 lesion 2–4 mm in depth, and T4 lesion > 4 mm in depth. Current pathologic T staging differentiates between (a) nonulcerated and (b) ulcerated. Also, pathologic N staging differentiates between (a) micrometastasis, (b) macrometastasis, and (c) in-transit metastasis. |
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Tx |
The gold standard treatment for malignant melanoma is wide local excision with tumor-free margins. For patients with melanoma of stage IB or higher, consider sentinel lymph node biopsy. Systemic treatment options for advanced or metastatic melanoma include a clinical trial, interferon-α, ipilimunab, vemurafenib, dacarbazine, temozolomide, high-dose interleukin-2, paclitaxel, cisplatin, or carboplatin. Genetic testing is available and should be offered to patients who meet any of the following criteria: • Patients with strong personal or family history of melanoma • Patients diagnosed with melanoma + family history of melanoma • Patients diagnosed with multiple primary melanomas • Patients diagnosed with multiple dysplastic nevi + family history • Patients with relatives who tested positive for p16 mutation See Cecil Essentials 57. |
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Pφ |
Atypical nevi are either inherited or sporadic precursors to cutaneous malignant melanoma with a prevalence of 2% to 5% in light-skinned people in the United States. The greater the number of atypical nevi present, the higher the risk of developing melanoma; however, the greatest risk is a strong family history of atypical nevi and melanoma. |
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TP |
Atypical nevi present as large, variably pigmented lesions with ill-defined borders most commonly in sun-exposed areas similar to melanoma. Ultraviolet light exposure is an independent risk factor for the development of sporadic atypical nevi. |
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Dx |
Most lesions can be grossly diagnosed based on clinical presentation, but biopsy of a melanoma precursor is required for identification. Only the most concerning lesion should be excised with narrow margins for histologic identification. |
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Tx |
The gold standard treatment for atypical nevi is excision. |
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Actinic Keratosis |
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Pφ |
Actinic keratosis is the most common sun-related premalignant skin lesion worldwide, with prevalence directly related to ultraviolet light exposure and light skin color. Histologically, epidermal changes include acanthosis and cellular atypia of keratinocytes. |
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TP |
Actinic keratosis presents as a discrete, verrucous, hyperkeratotic lesion usually on a sun-exposed area of the face, ears, forearms, and hands. More advanced lesions form keratotic horns. Ultraviolet light exposure is an independent risk factor for the development of actinic keratosis. |
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Dx |
Most lesions can be grossly diagnosed based on clinical presentation, but biopsy of a melanoma precursor is required for identification. |
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Tx |
The gold standard treatment for advanced actinic keratosis is surgical excision. However, early small lesions may be treated initially with topical 5-fluorouracil for approximately 1 month. If the lesion continues to improve with medical management, a repeat course of 5-fluorouracil is indicated before excision. For smaller lesions that fail repeated attempts at medical management, cryotherapy with liquid nitrogen is an effective means of removing the cutaneous lesion. |
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Pφ |
Benign melanocytic nevi represent nests of neural crest–derived melanocytes with no evidence of cytogenetic flaws or contact inhibition, which are present in most dysplastic nevi. In light-skinned individuals, benign nevi are so prevalent that they may not even be considered pathologic. |
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TP |
Benign melanocytic nevi present as small (<1 cm), well-circumscribed, uniformly pigmented, flat lesions usually on sun-exposed areas. Ultraviolet light exposure is an independent risk factor for the development of benign melanocytic nevi. |
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Dx |
Most lesions can be grossly diagnosed based on clinical presentation, but biopsy of a benign melanocytic nevus is required for identification. |
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Tx |
The gold standard treatment for benign melanocytic nevus is to rule out malignancy. Since these lesions may be difficult to distinguish from melanoma clinically, an appropriate biopsy should be performed. Medical management is usually ineffective and generates no pathologic specimen for lesion identification. |
Practice-Based Learning and Improvement: Evidence-Based Medicine
Title
Excision margins in high-risk malignant melanoma
Authors
Thomas JM, Newton-Bishop J, A’Hern R, et al.
Institution
United Kingdom Melanoma Study Group
Reference
N Engl J Med 2004;350:757–766
Problem
Controversy exists regarding the appropriate margin of resection for cutaneous melanoma of 2 mm or greater in depth. This multicenter, prospective, clinical trial investigated the significance of excision margins on loco-regional recurrence and disease-free survival in high-risk melanoma patients. Loco-regional recurrence was defined as recurrence within 2 cm of the excision site, in-transit recurrence, and regional node metastases.
Intervention
Using the intention-to-treat principle, eligible adults with cutaneous melanoma greater than or equal to 2 mm in depth on the trunk/limbs and no prior history of cancer or immunotherapy were randomized to resection with 1-cm or 3-cm margins. No sentinel lymph node biopsies or lymphadenectomies were performed. Patients did not receive adjuvant interferon.
Quality of evidence
Like the Swedish Melanoma Study Group, which supports 2-cm margins of excision for melanomas 0.8–2 mm in depth, and the Intergroup Melanoma Surgical Trial, which recommends 2-cm margins for tumors 1–4 mm in depth, the quality of evidence for this study is high.
Outcome/effect
In adults with cutaneous malignant melanoma of the trunk or limbs at least 2 mm in depth, a 1-cm margin of excision increases risk of loco-regional recurrence but does not alter disease-free survival compared to 3-cm margins. Overall survival decreased in those patients who did experience recurrence after excision with 3-cm margins.
Historical significance/comments
This article supports the use of wide local excision with margins greater than 1 cm for all cutaneous melanomas of the trunk and limbs at least 2 mm in depth. It stands to reason that patients who develop melanoma greater than 4 mm in depth may benefit from wider margins (3 cm) than those with tumor of 4 mm or less in depth. This is because deeper tumors (>4 mm) have a significantly higher rate of loco-regional recurrence and decreased overall survival.
Interpersonal and Communication Skills
Preoperative and Postoperative Discussions Are Essential to the Patient-Physician Relationship
Preoperatively, patients with pigmented skin lesions are usually concerned with the overall risk of the procedure, the aesthetic results, and the likelihood of cure. A realistic, positive discussion addressing the risks and benefits, as well as the scar and aesthetics, is the best approach. Postoperatively, a candid and compassionate disclosure of the pathologic results, the disease stage if completely determined, the natural history of the disease process, and appropriate future management facilitates patient satisfaction and promotes an ongoing physician-patient relationship.
Professionalism
Cell Phone Etiquette: A Skill to Develop
You are in the process of discussing a new diagnosis and prognosis with a patient, and your cell phone rings. Do you answer it? What if you see on the face of your phone that it is a medical student? What if it is the chief resident? The attending physician? What do you do if it’s a text message, “Call me ASAP about Mr. Jones.”? These are difficult questions to answer definitively. Although, of course, patients are aware that a physician’s beeper or cell phone might ring—after all, this is how they reach the doctor in an emergency—certain conversations will not lend themselves to interruption. In the case of an emergency, simply explaining that fact and excusing yourself momentarily may be the best option. As a medical community, it will become important to cultivate behavioral guidelines for our use of technology so that our technologic achievements in communication do not interfere with physician-patient interactions.
Community Education Benefits Community Health
Individual and community-based education programs specifically outlining the independent risk factors of cutaneous malignancy significantly impact the overall prevention of skin neoplasms. School-aged children and adolescents should be taught about the use of ultraviolet protection in sun-exposed areas, minimizing unprotected time in the sun during the midday, and performing early skin self-examination. Adults should receive similar education, with particular attention to close observation of existing pigmented skin lesions. Finally, community-based programs designed to screen individuals at risk are available and aid in early diagnosis and possibly improved mortality associated with malignant skin neoplasms.
