Skin cancer: Pathology review

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Skin cancer: Pathology review

USMLE® Step 1 questions

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A 55-year-old woman is brought to the emergency department by her partner following generalized tonic-clonic seizure activity. Her partner states that the patient has generally been in good health, but states that she has mentioned right-sided weakness over the past week. She has no significant past medical history. Temperature is 37.0°C (98.6°F), pulse is 96/min, respirations are 22/min, and blood pressure is 125/85 mmHg. Physical examination reveals a stuporous woman who is unable to speak coherently. Physical examination reveals mild right-sided weakness. A hyperpigmented lesion is noted on the dorsum of the right hand with irregular borders measuring 8-mm in diameter. Noncontrast CT of the brain is shown:

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After confirming the diagnosis, a decision is made to start this patient on vemurafenib. Which of the following is the most likely mechanism of action of this drug?


62 year old William comes to the dermatology clinic for a routine skin examination. He has been working as a farmer since the age of 20 and rarely wears a hat or sunscreen. Physical examination reveals a pink, pearly lesion with surrounding telangiectasias on his right upper lip. Right after him, 47 year old Shelby comes in because of a large mole on her right shoulder that has recently grown in size. She is light skinned and has many freckles. Physical examination shows an asymmetric lesion, 8 millimeters in diameter, with irregular borders and variegated brown to black pigmentation.

Based on the initial presentation, both William and Shelby seem to have some form of skin cancer. Okay, first, let’s talk about physiology real quick. Normally, the skin is divided into three main layers, the epidermis, dermis, and hypodermis. The hypodermis is made of fat and connective tissue that anchors the skin to the underlying muscle. Above the hypodermis is the dermis, containing hair follicles, nerve endings, glands, blood vessels and lymphatics. And above the dermis is the epidermis, which contains 5 layers of developing keratinocytes. Keratinocytes start their life at the lowest layer of the epidermis, so the stratum basale or basal layer. As keratinocytes in the stratum basale mature, they migrate into the next layers of the epidermis, called the stratum spinosum, stratum granulosum, stratum lucidum, and finally, the stratum corneum, which is the uppermost and thickest epidermal layer.

Now, the stratum basale also contains the melanocytes, which produce a pigment called melanin from tyrosine. Melanin is then taken up by surrounding keratinocytes, and it contributes to the color of our skin, hair, and eyes. Now, what’s high yield is that melanin acts as a natural sunscreen that absorbs and dissipates, or scatters, UV radiation from the sun or other sources such as tanning booths, preventing it from penetrating the skin.

Now, this is important because UV radiation can damage the DNA of keratinocytes. This occurs mostly through the formation of pyrimidine dimers. Fortunately, most pyrimidine dimers are recognized and repaired by nucleotide excision repair enzymes, which can remove the damaged strand on both sides of the pyrimidine dimer. Now, what’s high yield is that sometimes the repair process doesn’t work and may leave transcriptional errors and mutations. These errors can occur in proto-oncogenes and tumor suppressor genes, increasing the risk of skin cancer. All right, so UV radiation exposure is definitely the number one risk factor for skin cancer, which is why most cases of skin cancer occur on sun-exposed skin regions, particularly the face, ears, neck, and hands. In general, fair skinned individuals are considered to be at a higher risk of developing skin cancer, and the risk increases with sun exposure over time. Other risk factors that affect the protection and repair mechanisms of the skin can also increase the risk of cancer and this include diseases like albinism and xeroderma pigmentosum. Albinism is caused by an autosomal recessive gene mutation encoding any one of the enzymes needed to produce melanin, typically tyrosinase. The result is a dysfunctional or deficient enzyme that drastically decreases the amount of melanin that’s made within normal melanocytes. As a result, there’s reduced or obliterated pigmentation of the skin, hair, and eyes, as well as increased risk of skin cancer. On the other hand, xeroderma pigmentosum is a rare inherited autosomal recessive disorder in which nucleotide excision repair enzymes are defective and cannot repair pyrimidine dimers. Individuals affected by xeroderma pigmentosum are at much higher risk of developing skin cancer. In addition, they can present dry skin, extreme sensitivity to light, and hyperpigmentation in sun exposed areas.


Skin cancer is a type of cancer that develops in the cells of the skin. Three main types of skin cancer are basal cell carcinoma (the most common), squamous cell carcinoma (the second most common), and the least common but most deadly, melanoma. Risk factors for skin cancer include exposure to UV radiation, a history of sunburns, fair skin, and a weakened immune system. Diagnosis is made with a tissue biopsy and treatments can include physically removing cells with a high risk of developing into skin cancer. Tumor cells are also commonly removed and treated with radiation, chemotherapy, or immunotherapy.


  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Skin Cancer Epidemiology, Detection, and Management" Medical Clinics of North America (2015)
  4. "Epidemiology and Economic Burden of Nonmelanoma Skin Cancer" Facial Plastic Surgery Clinics of North America (2012)
  5. "World Cancer Report 2014" NA (2014)
  6. "Ultraviolet radiation" Chronic Diseases and Injuries in Canada (2010)
  7. "Nonmelanoma Skin Cancer" Facial Plastic Surgery Clinics of North America (2013)
  8. "A Clinical Atlas of 101 Common Skin Diseases" NA (2000)
  9. "Basal Cell Carcinoma and Seborrheic Keratosis" International Journal of Surgical Pathology (2015)

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