Skin cancer: Clinical practice

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Skin cancer: Clinical practice

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A 78-year-old woman comes to the clinic because of a growing "bump" on her face for the past year. She says that the bump used to just be flat and dark, but it seems to be growing more quickly, especially over the past couple months. She's spent most of her time gardening since retirement over a decade ago. Her temperature is 37.0°C (98.6°F), pulse is 74/min, respirations are 12/min, and blood pressure is 122/80 mm Hg. Physical examination shows a darkly pigmented nodule with an irregular border surrounded by a patch of irregularly pigmented skin that is 4cm wide.  A biopsy is performed and shows severe cellular atypia of darkly pigmented cells that extend beyond the basement membrane of the epidermis. Which of the following is the most likely diagnosis?

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Content Reviewers:

Rishi Desai, MD, MPH

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

There are three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma - collectively known as non-melanoma skin cancer, and melanoma.

Diagnosis of skin cancer starts with naked-eye skin examination of the characteristics of the lesion, as well as detailed history of the current skin complaint, asking for the time of onset, duration, location, evolution, and symptoms.

This is then followed by dermoscopy. Dermoscopy is a noninvasive, in vivo technique used for the evaluation of skin lesions.

It allows for the visualization of subsurface skin structures in the epidermis, dermoepidermal junction, and upper dermis, which are otherwise not visible to the naked eye.

There are three dermoscopic criteria to predict malignancy of a pigmented lesion - asymmetric distribution of colors and structures within a lesion, blue-white structures, and atypical network.

On the other hand, for nonpigmented lesions, the three criteria are ulceration, white zones, and vascular structures and patterns.

Now, the main purpose of dermoscopy in the evaluation of pigmented and nonpigmented skin lesions to help decide whether or not to monitor the lesion over time with sequential digital dermoscopy imaging to determine its biologic nature, or to perform a skin biopsy, which is needed to confirm diagnosis of skin cancer, showing the type of cells involved.

Biopsy can also serve as the definitive treatment for lesions that haven’t spread elsewhere.

The three main types of skin biopsy are shave biopsies, punch biopsies, and excisional biopsies.

In shave biopsies, a superficial thin piece of skin is removed from the surface using a small sharp blade, so they are typically used for lesions for which sampling of the full thickness of the dermis is not necessary.

On the other hand, punch biopsies involve the removal of a core-shape piece of tissue using a sharp cutting tool, allowing to sample the deep dermis as well.

Finally, excisional biopsies consist in the removal of an entire area of skin, including the entire lesion and the portion of normal skin around it using a scalpel, and are the preferred procedure for pigmented lesions.

The most common type is basal cell carcinoma, which involves cells in the stratum basale.

Basal cell carcinomas can appear as well circumscribed, pearly, waxy, or shiny solid elevation of skin with small blood vessels running over it.

Now, these tend to be slow growing tumors that rarely metastasize to distant regions of the body or result in death, but can be locally invasive, spreading over several centimeters of the epidermis.

And they can break through the basement membrane and invade the dermis. In fact, basal cell carcinomas can frequently become ulcerated.

A skin biopsy shows how tumor cells on the periphery of islands typically arrange themselves in a line, like fence-posts, forming a palisading pattern.

The selection of appropriate therapy depends upon lesion characteristics such as size, location, and pathologic features like aggressiveness.

Whenever possible, the first choice for treatment is surgery, which is typically performed in an outpatient setting.

Surgical excision is the removal of a chunk of tissue using a scalpel, and the surgical defect typically is immediately repaired either by side-side closure or the use of adjacent tissue flaps or skin grafts.

A major disadvantage of surgical excision is that it’s invasive, and variable amounts of healthy tissue must be sacrificed to achieve acceptable cure rates, which may lead to undesirable functional or cosmetic results.

Re-excision is an appropriate option for incompletely excised lesions.

Adjuvant radiotherapy is another option when surgical excision has been done incompletely, as well as for the treatment of basal cell carcinoma in individuals who are poor candidates for surgical intervention.

Now, a specialized surgical technique is called Mohs micrographic surgery, or simply Mohs surgery, in which the tumor is surgically excised and then immediately examined under a microscope to verify sufficient margins before the surgical repair of the site.

If the margins are insufficient, more tissue is removed until the margins are sufficient.

This allows to control the tumor margins while minimizing the amount of normal tissue that must be resected.

Curettage and electrodesiccation may be an alternative treatment for individuals who may not tolerate surgery or prefer not to undergo surgical excision.

First, curettage is performed using a round knife, or curette, to scrape off the cancer down to the dermis.

Electrodesiccation is then performed by burning the exposed dermis with an electric current.

The curette is used again over the surgical ulcer to remove denatured dermis down to living tissue, until achieving reasonable safety margins of curettage of normal skin around the visible tumor.

Finally there’s cryotherapy, which uses liquid nitrogen to freeze and destroy the tumor.

This technique is rarely used for treatment of skin cancer.

Now, some superficial cancers may respond to topical therapy with 5% cream or solution of fluorouracil, a chemotherapy agent, or 5% cream of imiquimod, an immune response modifier.

These agents must be applied for several weeks, and they may cause inflammatory reactions.

Finally, basal cell carcinoma may be treated with photodynamic therapy, which uses photosensitizing porphyrins that are applied topically to the tumor, and the involved area is then exposed to visible light.

The light penetrates the skin and is selectively absorbed by the photosensitizer, leading to tumor destruction.

This technique is not often used, since risk of recurrence is pretty high compared to the other treatment options.

After successful treatment, individuals should be followed up at least once a year.

The second most common type of skin cancer involves squamous keratinocytes, and it can be further divided into three stages - actinic keratosis, Bowen’s disease, and squamous cell carcinoma.

First there’s actinic keratosis, which is a precancerous lesion where keratinocytes are damaged by radiation and begin to over-produce keratin.

Actinic keratosis can appear as dry, rough, almost sandpaper-like patches that are surrounded by tan, brown, red or flesh colored skin.

They tend to commonly form on the lips, face, scalp, arm, ears, and the back of the hands.

Next there’s Bowen’s disease, which is an early stage of squamous cell carcinoma, also called squamous cell carcinoma in situ.

This usually appears as small, well-circumscribed, red elevations of the skin with scaly plaques on top.

At this point, the tumor can be found in the epidermis, but it has not broken through the basement membrane.

If squamous cell carcinoma becomes invasive, it can break through the basement membrane and extend into the dermis, and it may even reach the hypodermis.

As the lesion enlarges, the center becomes necrotic and may eventually turn into an ulcer.

Squamous-cell skin cancer is more likely to spread to regional lymph nodes or distant areas than basal cell cancer.

For that reason, a deeper biopsy including the subcutaneous tissue is necessary for correct diagnosis.

On skin biopsy, the keratinocytes are pleomorphic with hyperchromatic nuclei, and numerous mitoses are present.

Actinic keratoses have partial-thickness epidermal dysplasia, while Bowen’s disease presents keratinocytic dysplasia involving the full thickness of the epidermis without infiltration of atypical cells into the dermis, and finally, invasive squamous cell carcinomas have dysplastic keratinocytes involving the full thickness of the epidermis that penetrate the epidermal basement membrane to involve the dermis or deeper tissues.

The degree of cell differentiation may vary, becoming less and less differentiated with more advanced disease.

Treatment depends on the cancer stage. Actinic keratosis may be treated with cryotherapy, topical therapy with fluorouracil or imiquimod, or photodynamic therapy, to prevent its progression.

On the other hand, standard surgical excision and Mohs surgery are the first line treatment options for Bowen’s disease and invasive squamous cell carcinoma.

Individuals with extensive perineural or large nerve involvement may also benefit from the use of adjuvant radiotherapy, as well as those in which surgical margins are positive, and those with one positive lymph node that’s no larger than 3 centimeters with no extracapsular extension.

On the other hand, more extensive lymph node involvement requires aggressive surgical resection of the nodal basins.

Non surgical treatments may be performed as second line options, including curettage and electrodesiccation, cryotherapy, photodynamic therapy, or radiotherapy alone.

Topical therapy with fluorouracil or imiquimod may be used for the treatment of Bowen's disease, especially for lesions that are larger than 3 centimeters in diameter, and in situations in which healing after the other treatment options would be compromised.

Finally, systemic chemotherapeutic agents, such as cisplatin, capecitabine, methotrexate, cetuximab, bleomycin, doxorubicin, and the monoclonal antibody cemiplimab may be used in individuals with locally advanced squamous cell carcinoma that cannot be adequately managed with surgical excision or radiation therapy, as well as for metastatic squamous cell carcinoma.

And again, after getting successful treatment, individuals should be followed up at least once a year.