Skin cancer

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Skin cancer

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A 75-year-old man presents to the office for the evaluation of a lesion on his right forearm. He first noticed the lesion 9 months ago, and it has gradually increased in size since then. He has worked on various construction sites for the past 45 years. Past medical history is noncontributory. Family history is significant for skin cancer in his father. Physical examination shows a 1.5 cm nodule with a thick and rough surface on his right forearm. Biopsy of the lesion is shown below.



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Which of the following additional features is most likely to be present in this patient?

External References

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BRAF gene p. 220, 394

melanomas and p. 493

Malignant melanomas

IFN- αfor p. 200

Melanoma

common metastases p. 202

immunohistochemical stain for p. 218

nomenclature for p. 223

oncogene p. 220

origin of p. 223

tumor suppressor gene p. 220

Metastatic melanoma

recombinant cytokines for p. NaN

Melanomas

of skin p. 493

sunburn and p. 492

Metastatic melanomas

vemurafenib for p. 445

Transcripción

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Skin cancer is an uncontrolled growth of cells within the skin.

There are three main types: basal cell carcinoma, squamous cell carcinoma, and melanoma.

Some skin cancers can spread to other locations in the body and can be fatal, as seen with singer-songwriter Bob Marley, who died shortly after being diagnosed with melanoma.

The skin is divided into three layers--the epidermis, dermis, and hypodermis.

The hypodermis is made of fat and connective tissue that anchors the skin to the underlying muscle.

Just above is the dermis, which contains hair follicles, nerves and blood vessels.

And just above that, the outermost layer of skin, is the epidermis.

The epidermis itself has multiple cell layers that are mostly keratinocytes - which are named for the keratin protein that they’re filled with.

Keratin is a strong, fibrous protein that allows keratinocytes to protect themselves from getting destroyed, when you rub your hands through the sand at the beach.

Keratinocytes start their life at the deepest layer of the epidermis called the stratum basale, or basal layer, which is made of a single layer of small, cuboidal to low columnar stem cells that continually divide and produce new keratinocytes that continue to mature as they migrate up through the epidermal layers, flattening out to a pancake-like squamous shape as they ascend.

But the stratum basale also contains another group of cells - melanocytes, which secrete a protein pigment, or coloring substance, called melanin.

Melanin is actually a broad term that constitutes several types of melanin found in people of differing skin color.

These subtypes of melanin range in color from black to reddish yellow and their relative quantity and rate at which they are metabolized define a person’s skin color.

When keratinocytes are exposed to the sun, they send a chemical signal to the melanocytes, which stimulates them into making more melanin.

The melanocytes move the melanin into small sacs called melanosomes, and these get taken up by newly formed keratinocytes, which will later metabolize the melanin as they migrate into higher layers of the epidermis.

Melanin then acts as a natural sunscreen, because its protein structure dissipates, or scatters, UVB light--which if left unchecked can damage the DNA in the skin cells and lead to skin cancer.

Melanocytes can also be found in the dermis, at the base of the hair follicle, where they transfer melanin to the keratinized cells that make up hair.

Now, a tumor develops if there’s a DNA mutation in any of these cell types that leads to uncontrolled cell division.

Typically these are mutations in proto-oncogenes which result in a promotion of cell division, or mutations in tumor suppressor genes which result in a loss of inhibition of cell division.

You can think of proto-oncogenes as the accelerator or gas pedal and tumor suppressor genes as the brakes. Too much acceleration or an inability to brake can lead to runaway cell division.

As a result, the mutated cells can start piling up on each other and can become a tumor mass.

Some of these tumors are benign and stay well contained or localized. But some become malignant tumors or cancers, and these are the ones that break through their basement membrane and invade nearby tissues.

Malignant tumor cells can get into nearby blood or lymph vessels, and travel from the primary site to establish a secondary site of tumor growth somewhere else in the body - and that’s called metastasis.

Skin cancer is differentiated based upon the type of skin cell that’s involved in the tumor mass.

The most common is basal cell carcinoma, which involves cells in the stratum basale. These tend to be slow growing tumors that can be locally invasive, but rarely metastasize to distant regions of the body.

Nearby blood vessels in the dermis can become dilated to deliver more nutrients as the tumor grows.

Basal cell carcinomas can grow superficially, spreading over several centimeters of the epidermis. And they can break through the basement membrane and invade the dermis, forming islands or cords of tumor cells.

Tumor cells on the periphery of islands typically arrange themselves in a line, like fence-posts, forming a palisading pattern.

The second most common type of skin cancer is squamous cell carcinoma which involves squamous keratinocytes.

Now, a precancerous lesion that can turn into squamous cell carcinoma is called actinic keratosis.

Resumen

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.

Fuentes

  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. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Review: Ultraviolet radiation and skin cancer" International Journal of Dermatology (2010)
  6. "Non-melanoma Skin Cancer: Mini Review" The Cancer Press (2017)
  7. "Visual inspection and dermoscopy, alone or in combination, for diagnosing keratinocyte skin cancers in adults" Cochrane Database of Systematic Reviews (2018)