Cancer, Skin (Integument)


Article Author:
Paul Gruber
Muneeb Shah


Article Editor:
Patrick Zito


Editors In Chief:
Susan Jeno
Sarah Fabiano


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
4/24/2019 12:11:00 AM

Introduction

Precancerous changes and non-melanoma skin cancers represent the most frequently observed malignancy amongst Caucasians.  The exact incidence, however, of nonmelanoma skin cancers may be difficult to determine due to issues such as diagnostic accuracy and diagnostic criteria. While these carcinomas are regarded as demonstrating low risk for invasive behavior, the incidence of these as well as the more aggressive malignant melanoma continues to rise annually worldwide. The diagnosis and treatment of these neoplasms represent a significant health problem from the standpoint of patient well-being and healthcare expenditures. Skin cancers frequently are located on the sun-exposed head and neck regions which can result in significant morbidity during their diagnosis and treatment. Chemopreventative tactics and non-surgical intervention of these malignancies can be considered in appropriate clinical scenarios.

Etiology

UV solar radiation is also a major etiologic factor in the development of cutaneous carcinomas.  UV exposure induces carcinogenesis by a twofold mechanism; it generates DNA damage that leads to mutation formation and malignant transformation, but it also reduces the ability of the host immune defense system to recognize and remove malignant cells. Actinic keratosis, basal cell carcinoma, and squamous cell carcinoma are the result of epidermal keratinocytes which undergo malignant transformation due to substantial ultraviolet light exposure. In contrast to squamous cell carcinomas which are related to the cumulative dose of UV radiation an individual receives over time, a more complex relationship exists for basal cell carcinomas and melanomas with consideration for sun exposure early in life and sunburns. Immunosuppressed solid organ transplant patients and those receiving immunomodulating treatment for metastatic melanoma are at increased risk due to alterations in cutaneous immune surveillance.  

Epidemiology

There are more skin cancers in the United States population than all other cancers combined. These cancers are on the rise, representing a significant health problem for the standpoint of patient well-being and from the prospect of health expenditures. Nonmelanoma skin cancer occurs in all races worldwide, and the most important factor related to the development of these malignancies is skin type. However, other risk factors include UV exposure, chemical exposure, tanning bed use, human papillomavirus (HPV) infection, immunosuppression, and others. The amount of average annual ultraviolet radiation correlates with the incidence of skin cancer. In individuals with fair skin, approximately 75% to 80% of non-melanoma skin cancers are basal cell carcinomas, and up to 25% are squamous cell carcinomas. Heritable defects in DNA repair mechanisms, as seen in xeroderma pigmentosum and Muir-Torre Syndrome, also make afflicted individuals at high risk for cutaneous carcinomas. 

Pathophysiology

Intermittent, recreational sun exposure, more so than cumulative UV radiation is a significant risk factor for the development of basal cell carcinoma. The gene most often altered in basal cell carcinoma is the PTCH gene and the second most common alteration is point mutations in the p53 gene. Unlike the complex relationship between basal cell carcinoma and UV radiation, squamous cell carcinoma is related to the cumulative lifetime dose of UV radiation. Current opinion favors clonal expansion of keratinocytes with a p53 mutation causing precancerous actinic keratosis lesions with slight dysplasia which precede further severe dysplasia and transformation into invasive squamous cell carcinoma.

History and Physical

Premalignant actinic keratoses often present as rough, gritty skin papules on an erythematous base, while basal cell carcinomas usually appear as pink pearly papules with telangiectasias; and squamous cell carcinomas are pink rough papules, patches, and plaques. The distribution of these lesions reflects areas of the body that are most sun exposed, namely the face, scalp, and arms. Within these regions, lesions often are found in sun-damaged skin, and premalignant actinic keratoses can be widespread or present adjacent to a skin cancer. Basal cell carcinomas and squamous cell carcinomas commonly are noted on parts of the head and neck which receive the most cumulative ultraviolet radiation over the course of a lifetime such as a nose, ear, and upper lip.  Melanomas, given their complex genetic background, can occur anywhere on the body which melanocytes are located.

Evaluation

Evaluation of the patients at risk for cutaneous carcinoma usually includes a full body skin examination by a medical professional.  This can be done by most primary care providers; however, the evaluation often is performed by specialists with three years of post-medical school advanced dermatology training. The vast majority of concerning lesions on physical examination will undergo an office procedure called a skin biopsy. This is done under location anesthesia during an outpatient office visit. The specimen is then sent for special interpretation by a trained dermatopathologist. If the pathologist reading the tissue specimen under the microscope confirms the diagnosis of cutaneous malignancy, further intervention is usually warranted based upon the pathologic diagnosis and clinical scenario.

Treatment / Management

Treatment of precancerous lesions and cutaneous carcinoma should be tailored toward the individual patient scenario and the best clinical outcome. If presenting as isolated lesions, precancerous actinic keratoses can be treated individually with lesion-directed therapies such as cryotherapy. Often patients may present with numerous lesions and diffuse actinic damage which require field-directed therapy as opposed to individually treating each lesion.  This can be done with topical agents (5-fluorouracil, imiquimod, and ingenol mebutate) or with photodynamic therapy after sensitizing the skin with a topical agent. Initial pre-emptive efforts should be made to reduce the patient's risk profile for developing cutaneous carcinoma including optimizing the immunosuppressant regimen in solid organ transplant patients, proper surveillance schedules in patients treated with immunomodulatory therapies, and adequate therapy of precancerous lesions. 

Basal cell carcinomas and squamous cell carcinomas, if superficial, can be treated with topical therapies depending on provider preference. However, the standard practice is to surgically treat these lesions with destructive means such as electrodesiccation and curettage or surgical excision. Skin cancers greater than 2 cm in diameter and those located on functionally and cosmetically sensitive sites (head/neck, hands, and feet, genitalia) usually are referred for a special surgical procedure called Mohs micrographic surgery. Some patients with aggressive and recurrent forms of basal cell carcinoma who would not be good surgical candidates are treated with radiation therapy or a systemic medication called Vismodegib which inhibits cellular proliferation.

Melanomas are the most aggressive form of skin cancer; the gold standard of treatment is surgical excision. If caught early, surgical excision can be curative.  Later stage tumors portend a poor prognosis and often require adjuvant immunotherapy.

Enhancing Healthcare Team Outcomes

Skin cancers are freuently encountered in clinical practice by the primary care provider, nurse practitioner, and the internist. In all cases, the patient should be referred to a dermatologist for final confirmation. While the treatment of skin cancer is done by an oncologist and a dermatologist, the primary care providers play a vital role in prevention. Patients should be educated about avoiding too much sun, wearing appropriate garments when going outdoors and applying sunscreen. Finally, patients should be educated on how to inspect their skin and when to seek medical assistance. [1]


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Cancer, Skin (Integument) - Questions

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What is the most common malignancy in post-transplant patients?



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A 64-year-old farmer presents with a 1-month history of enlarging skin lesion on his face. He denies any recent injury. He has a history of diabetes mellitus, well-controlled with metformin. Vital signs are within normal limits. Physical examination reveals a 2-cm pearly lesion on the upper lip. The lesion is not tender to palpation. The practitioner is concerned that the lesion could be cancerous and recommends a biopsy. A biopsy is most likely to reveal which of the following?



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A 65-year-old woman comes to the physician because of a 9-mm papule that has changed considerably in size and color over the past couple of months. There is no personal or family history of skin cancer. Physical examination reveals a flat, heterogeneous, brown-to-black lesion with irregular borders on the dorsum of the hand. Which of the following would be the most appropriate next step in management for this patient?



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A 68-year-old white man comes to the physician for a follow-up examination. He has no complaints. He has smoked 1 pack of cigarettes daily for the past 30 years. Also, his last colonoscopy was 8 years ago. The vital signs today are within normal limits. Physical examination is unremarkable. He is at the highest risk for developing which of the following forms of cancer?



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A 68-year-old woman comes to the physician because of palpable lymph nodes in the left axilla. She denies weight loss, and her vital signs are within normal limits. Mammography is negative for breast malignancy. A biopsy is performed on the left axillary lymph nodes. Histopathology shows a malignancy with multiple sites with pyrimidine cross-linking forming pyrimidine dimers. Which of the following is the most likely site of origin of this cancer?



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A 32-year-old woman comes to her primary care physician for a wellness examination. She reports a family history of cancer and is concerned about her risk of developing cancer. After discussing primary prevention measures, the physician recommends a healthy diet, exercise, daily sunscreen use, and a pap smear. This woman is at risk of developing which of following cancer in the future?



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Cancer, Skin (Integument) - References

References

Skin Cancer Prevention (PDQ®): Health Professional Version 2002;     [PubMed]
Rogers HW,Weinstock MA,Feldman SR,Coldiron BM, Incidence Estimate of Nonmelanoma Skin Cancer (Keratinocyte Carcinomas) in the U.S. Population, 2012. JAMA dermatology. 2015 Oct;     [PubMed]
Glazer AM,Winkelmann RR,Farberg AS,Rigel DS, Analysis of Trends in US Melanoma Incidence and Mortality. JAMA dermatology. 2017 Feb 1;     [PubMed]

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