Cancer, Basal Cell


Article Author:
Jake Fagan


Article Editor:
Michael Ramsey


Editors In Chief:
Jasleen Jhajj
Cliff Caudill
Evan Kaufman


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
11/15/2018 4:30:40 PM

Introduction

Basal cell carcinoma is the most common cutaneous malignancy, affecting close to one in five Americans. Basal cell carcinoma rarely metastasizes, but it can cause significant local destruction and morbidity if not recognized and adequately treated.[1][2]

Etiology

Basal cell carcinoma occurs most commonly on sun-damaged skin of the head, neck, and trunk. Basal cell carcinoma develops at sites of prior ultraviolet light exposure; the latency period extends from 10 to 40 years, and no known precursor lesion exists. Individuals with light skin and lighter-colored eyes are at the greatest risk of developing these tumors. Longer life spans and an increase in the use of immunosuppressant medications has further added to the incidence of patients with basal cell carcinoma.[3]

Epidemiology

Basal cell carcinoma is the most common skin malignancy with a lifetime risk of close to 20% in the United States. An estimated more than four million basal cell carcinomas are diagnosed yearly in the United States, which makes up 80% of all non-melanoma-type skin cancers. The number of diagnosed basal cell carcinomas in all age groups has increased at an annual rate of close to 10%. An increase in natural and artificial ultraviolet light exposure has been associated with this increased incidence of basal cell carcinoma in younger age groups, especially females.[4]

Pathophysiology

The exact cell of origin from which basal cell carcinoma proceeds is still a topic for debate. A popular hypothesis is that basal cell carcinoma arises from basal keratinocyte stem cells that lie between hair follicles of the dermal-epidermal junction and in the bulge of the hair follicle.  It is hypothesized that unregulated cell growth among these stem cells leads to tumor formation. Mutations in the sonic hedgehog pathway are implicated in up to 80% to 90% of sporadic basal cell carcinoma and predisposing genetic syndromes, including basal cell nevus syndrome. Mutations in this pathway lead to unregulated cell growth due to dysregulation of the PTCH gene. PTCH works as a tumor suppressor with specific suppression of the smoothened protein. 

History and Physical

Basal cell carcinoma can be broken into three main categories: superficial, nodular, and infiltrative. Nodular basal cell carcinoma is the most common subtype and presents as a pink, pearly papule with overlying telangiectasias and rolled borders. It commonly occurs on the head and neck, and it is a slow-growing papule that will often ulcerate and bleed. The latter may mislead male patients to dismiss the neoplasm as a cut while shaving. Superficial basal cell carcinoma presents as a thin, pink plaque, papule, or macule with a pink, pearly border that is most commonly seen on the chest, back, or extremities. Infiltrative basal cell carcinomas include infiltrative, micronodular, and morpheaform subtypes. Morpheaform basal cell carcinoma presents as a firm, scar-like plaque and should be considered in the presentation of a new scar without previous trauma to the area. Infiltrative and micronodular basal cell carcinoma present similarly to nodular basal cell carcinoma as pink, pearly papules with overlying telangiectasias.

Evaluation

Basal cell carcinoma is in the differential for a new, pink, pearly papule of the head, neck, or trunk. Papules will often ulcerate and bleed. The clinical history can assist in ruling out more acute lesions, such as acneiform papules, as patients often report a nonhealing or intermittently bleeding lesion noticeable for several weeks to months.  A biopsy and histopathologic review can confirm the diagnosis of a clinically suspicious lesion. On histology, the three main categories differ in their microscopic presentation. Nodular basal cell carcinoma presents as large, blue islands with peripheral palisading of cells. Clefting between the collagen and the palisaded cells is common. Basal cell carcinoma has a distinct fibromyxoid stroma on histology.  Superficial basal cell carcinoma shows a palisaded border of blue basal cells budding from the epidermis. The infiltrative types of basal cell carcinoma show small islands of blue tumor cells diving between collagen bundles. The morpheaform subtype has a sclerotic stroma, which correlates with the scar-like clinical appearance.[5][6]

Treatment / Management

Surgical excision is the gold standard for basal cell carcinoma treatment. Mohs micrographic surgery (MMS) for basal cell carcinoma has the highest cure rate with a 2.5% 5-year recurrence rate. MMS is most appropriate in infiltrative basal cell carcinoma, recurrent lesions, tumors with poorly-defined borders, or in anatomical areas in need of tissue conservation. For tumors that do not meet MMS-appropriate criteria, surgical excision with 4-mm margins is recommended, which portends a 4.1% 5-year recurrence rate. Curettage with electrodesiccation for nodular or superficial basal cell carcinoma is a common treatment option at the time of biopsy when clinical suspicion is high. This method has a 5-year recurrence rate of 7.7%. [7][8]

Chemotherapy creams, including imiquimod 5% cream and 5-Fluorouracil 5% cream are FDA approved for the treatment of superficial basal cell carcinoma. Imiquimod stimulates toll-like receptor 7, which modifies the local innate and adaptive immune response. 5-Fluorouracil is a thymidylate synthase inhibitor, and application leads to a local decrease in the formation of thymidine. Thymidine is a purine that is necessary for DNA replication. Treatment regimens vary, but on average, both creams require application over multiple weeks. A major benefit over surgical intervention is that they can be used in cosmetically sensitive areas as they are less likely to cause scarring.

Vismodegib was approved by the Food and Drug Administration (FDA) in 2012 for locally advanced and metastatic lesions of basal cell carcinoma. Vismodegib works on the sonic hedgehog pathway by acting as a smoothened inhibitor, which decreases unregulated cell growth in both sporadic and syndromic basal cell carcinoma lesions.

Pearls and Other Issues

The best treatment of basal cell carcinoma of any type is prevention with adequate protection from ultraviolet light exposure. The American Academy of Dermatology recommends a broad-spectrum sunscreen with a sun protection factor (SPF) 30 or greater, reapplied every two hours while outdoors. Daily sunscreen should be encouraged to all patients, especially those who spend increased time outside. Many daily facial moisturizers and foundational makeup have SPF sun protection; these cosmeceuticals should not replace regular sunscreen application when outside, but rather they should be viewed as an additional layer of protection. Other sun-protective measures include wearing a hat that shades the ears and neck and sunglasses. Tanning bed use should be strongly discouraged as it greatly increases the risk for all types of skin cancer.

Enhancing Healthcare Team Outcomes

Basal cell cancer is a common presentation in the outpatient clinic. While the majority of basal cell cancers are managed by the dermatologist or the plastic surgeon, other healthcare workers need to know the presenting features- so that an appropriate referral can be made. The majority of basal cell cancers remain localized, and metastatic spread is rare. However, if treatment is delayed, these cancers can invade local tissue and cause severe cosmetic problems including loss of vision. The best way to treat basal cell cancers is to prevent them in the first place, and this means patient education. Patients should be told to avoid direct sunlight and wear a sunscreen when going outdoors. In addition, a wide brim hat and long-sleeved garments can also protect against the harmful effects of UV light. Finally, patients should be taught the warning signs of a basal cell cancer and when to seek medical help. The outcomes for most patients with basal cell cancer are excellent, but long-term follow up is necessary as there is a chance of recurrence.[9][1]


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Cancer, Basal Cell - Questions

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A 65-year-old farmer presents with a lesion on his face. He has noticed that the lesion occasionally bleeds when he towel dries his face, and the lesion has slowly grown over time. He denies any medical problems and does not smoke. The lesion is about 1 cm by 2 cm and has an uneven border. It is slightly elevated, pink and translucent and has a few crusted areas of erosion within its borders. The lesion is located next to the base of the nose. What is the most likely diagnosis?



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What is the principal etiologic factor of basal cell carcinoma (BCC)?



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What is the incidence of lymph node metastasis in a patient with a 4 cm morpheaform basal cell carcinoma lesion of the nose?



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A 65-year-old white man presents with a small ulcerated papule adjacent to an old surgical scar on his nose. A skin biopsy is performed, and the diagnosis is a basal cell carcinoma (BCC). Which of the following treatment options is best?



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A 78-year-old white man presents with a 0.5 cm erythematous plaque on his arm. Skin biopsy results reveal a nodular basal cell carcinoma. Which of the following is the best treatment option?

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Which of these basal cell carcinoma subtypes is clinically the most aggressive?



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What treatment for basal cell carcinomas has the highest cure rate?



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On what part of the body do the majority of basal cell cancers occur?



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The majority of basal cell cancers have mutations in which gene?



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What is the most common site of the spread of basal cell cancer?



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What is the most common subtype of basal cell cancer?



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Topical 5 fluorouracil (5-FU) is only recommended for treatment of which type of basal cell cancer?

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Which treatment for basal cell cancer has the lowest recurrence rate?



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How can cryotherapy for basal cell carcinomas be used?



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Which is not true of treatment of basal cell carcinoma?



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What is the most common skin cancer in the United States?



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What is the most common skin cancer in the geriatric population?



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Which of the following is true of basal cell carcinoma?



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Which of the following is true of basal cell carcinoma?



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A 69 year old female presents with a skin lesion on her forearm that has been growing slowly. It is a pearly papule with a central ulcer and raised margins. What is the histology of the lesion most likely to show?



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A 78-year-old male has a pearly nodule with telangiectasias on the face. Which of the following is the most likely diagnosis?



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What is the most common skin cancer?



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A patient has a 1 cm ulceration on the forehead with telangiectasias. What is the most likely diagnosis?



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What is the rate of metastasis of basal cell carcinoma?



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A pearly papule with raised, "rolled" borders, central erosion and superficial telangiectases is noted in a sun-exposed area. What is the most likely diagnosis?



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A 60-year old farmer presents with several lesions on his head, neck, and nose. He says he has had these skin lesions for many years, but they do not seem to be going away. He has been a farmer all his life and has no other pertinent medical history. On physical exam, you note two lesions that appear waxy and have a central depression. The edges have a pearly appearance. Excisional biopsy of one of the lesions reveals that it is a malignancy. What is the most common subtype of malignancy in people with such lesions?



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A 60-year old farmer presents with several lesions on his head, neck, and nose. He says he has had these skin lesions for many years but they do not seem to be going away. He has been a farmer all his life and has no other pertinent medical history. On physical exam you note two lesions that appear waxy and have a central depression. The edges have a pearly appearance. Excisional biopsy reveals a malignancy. If this lesion occurred on the eye, which is the most common site of involvement?



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Which subtype of basal cell cancer is the most difficult to diagnose?



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A 55-year-old male presents with a 1 cm skin lesion on his forehead. He says he worked as a farmer in the past. The lesion appears pearly, with central ulceration, and the edges are rolled up into a border. Which of the following is not an option in the initial workup?



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Dysregulation in what pathway is thought to lead to unregulated cell growth in basal cell carcinoma?



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A new scar-like lesion on the cheek without previous trauma to the area would be most consistent with what type of basal cell carcinoma?



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What the range for the latency period from UV radiation exposure to the presentation of basal cell carcinoma?



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Which FDA-approved therapy for superficial basal cell carcinoma is non-surgical?



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Which type of treatment has the lowest rate of recurrence for basal cell carcinoma?



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Cancer, Basal Cell - References

References

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Okhovat JP,Beaulieu D,Tsao H,Halpern AC,Michaud DS,Shaykevich S,Geller AC, The first 30 years of the American Academy of Dermatology skin cancer screening program: 1985-2014. Journal of the American Academy of Dermatology. 2018 Nov     [PubMed]
Peccerillo F,Mandel VD,Di Tullio F,Ciardo S,Chester J,Kaleci S,de Carvalho N,Del Duca E,Giannetti L,Mazzoni L,Nisticò SP,Stanganelli I,Pellacani G,Farnetani F, Lesions Mimicking Melanoma at Dermoscopy Confirmed Basal Cell Carcinoma: Evaluation with Reflectance Confocal Microscopy. Dermatology (Basel, Switzerland). 2018 Nov 7     [PubMed]
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Morton CA, A synthesis of the world's guidelines on photodynamic therapy for non-melanoma skin cancer. Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. 2018 Feb 7     [PubMed]
Kim JYS,Kozlow JH,Mittal B,Moyer J,Olencki T,Rodgers P, Guidelines of care for the management of basal cell carcinoma. Journal of the American Academy of Dermatology. 2018 Mar     [PubMed]
Dalal AJ,Ingham J,Collard B,Merrick G, Review of outcomes of 500 consecutive cases of non-melanoma skin cancer of the head and neck managed in an oral and maxillofacial surgical unit in a District General Hospital. The British journal of oral     [PubMed]

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