melanoma

NON-MELANOMA SKIN CANCERS

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  • - ILYA MUKOVOZOV
  • Non-melanoma skin cancer (NMSC), or keratinocyte carcinoma, is the most common malignancy in Caucasian individuals
  • Keratinocyte carcinomas include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)
  • Keratinocyte carcinomas occurs worldwide in all races
  • Keratinocyte carcinomas are most commonly located on the head and neck, and increasingly on the trunk in Canada
  • Men have a higher incidence rate (new cases per year) of NMSC
  • In both sexes, the rate of basal cell carcinomas to squamous cell carcinoma is >2.5:1 (there are approximately 2.5 BCCs for every 1 SCC)
  • Approximately one in five persons will develop skin cancer during their lifetime (over 95% will be NMSC)
  • The exact incidence of BCCs and SCCs is difficult to determine as these neoplasms are not routinely included in cancer registries
  • The average amount of annual UV radiation exposure (predominantly from exposure to sunlight) correlates with the incidence of skin cancer
  • There is a direct relationship between incidence of skin cancer and latitude, in that the closer individuals are to the equator the greater their exposure to UV radiation and therefore subsequent development of skin cancer
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BASAL CELL CARCINOMA

  • Basal cell carcinoma (BCC) is the most common skin cancer in humans
  • BCC can develop anywhere, although it is commonly found on sun exposed areas of the body
  • It is very rare for BCCs to spread, or metastasize, to other parts of the body. The risk of spread is dependent on the size of the tumor. If the tumor is neglected and grows larger than the size of a palm, the doctor should check for a possible metastasis of a BCC with PET-CT scan imaging.
  • Men generally have higher rates than women (1.5 – 2 times higher)
  • Over the past 30 years, the incidence rates have increased between 20 to 80%
  • Incidence rates of BCC also increase with age and the median age of diagnosis is 68 years
  • Mortality from BCC is very rare and occurs primarily in immunocompromised individuals and in individuals with genetic disorders such as Basal Cell Nevus Syndrome

SQUAMOUS CELL CARCINOMA

  • UV exposure – predominant cause of basal cell carcinoma (BCC)
    • intermittent intense episodes of UV exposure
    • sunburns at any age
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Tanning devices are associated with a 2.5x higher odds for BCC, even after adjustment for history of sunburns and sun exposure
  • Tanning beds
  • photochemotherapy (also known as PUVA therapy)
  • Ionizing radiation
    • Airline pilots are exposed to ionizing radiation at high altitudes and have been shown to be at increased risk for BCC
  • Chemicals (arsenic, mineral oil, coal tar, soot, and many more)
  • Outdoor occupations
    • Persons with outdoor occupations have a higher risk of developing BCC
  • Human papillomavirus
  • Skin type (fair skin, always burns, never tans)
  • Freckling
  • Red hair
  • Certain genetic syndromes
  • Immunosuppression
  • Organ transplantation

SUBTYPES OF BASAL CELL CARCINOMA

  • There are several subtypes of basal cell carcinoma (BCC): nodular, superficial, infiltrative, sclerosing, and pigmented, although additional histologic types exist
  • Nodular BCC is the most common subtype of BCC
    • usually appears as a raised lesion with rolled borders (appearance similar to rolled nature of a pizza crust) and visible blood vessels on its surface
    • Sometimes it can be pigmented and may be mistaken for a melanoma
    • commonly occurs on the face
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  • The second most common subtype is superficial BCC
    • usually appears as a scaly red patch
    • can be confused for eczema or actinic keratoses/Bowen’s disease
  • Infiltrative BCC
    • Can occur in deeper layers of skin
    • Often in the head and neck area
    • May have a similar appearance to scar tissue
    • This term –“infiltrative” -- is used by a pathologist indicating that under a microscope BCC has finger like projections with which it is invading the deeper layers of the skin.
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  • Sclerosing (or morpheaform) BCC
    • usually appears as a flat lesion or a scar like lesions without a defined border
    • commonly occurs on the head and neck region
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DIAGNOSIS OF BASAL CELL CARCINOMA

  • Basal cell carcinoma is often diagnosed clinically and some times with a help of dermoscopy (and treated with electrodesiccation and curettage; with removed tissue sent to pathology to confirm the diagnosis)
  • If signs and symptoms of basal cell carcinoma are present but diagnostic uncertainty remains, a sample of skin may be obtained via a biopsy procedure in order to make a diagnosis (diagnosis requires a pathologist to review the skin specimen under a microscope)
  • Type of biopsies include punch (small cylinder of tissue typically 3-6mm is obtained) or shave biopsy (superficial skin shaved with a blade)

TREATMENT OF BASAL CELL CARCINOMA

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      Standard excision

      • Surgical excision is effective for most primary basal cell carcinomas
      • When maximal preservation of tissue is desired (tumors on the face for example), or when there is a high risk of positive margins (tumour left at the edge after initial excision of the tumour) and recurrence, Mohs micrographic surgery should be considered
      • Surgical excision of basal cell carcinoma requires 4 mm margins of healthy tissue

    • Curettage with electrodesiccation (scraping and burning the tumor)

      • A frequently used treatment modality for basal cell carcinomas
      • Requires local anesthesia
      • Curettage with electrodesiccation achieves cure rates as high as 97-98% for BCC with careful selection of appropriate lesions
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      Mohs micrographic surgery

      • Mohs micrographic surgery provides the best verification for complete removal of the tumour while allowing for maximal preservation of healthy skin
      • Superior to all other treatment modalities in terms of recurrence rate
      • Preferred treatment modality for recurrent BCC
      • Preferred treatment modality for certain forms of BCC (morpheaform)
      • Appropriate for cancers located on the central face, eyelids, eyebrows, periorbital area, nose, lips, chin, mandible, ears, temples and others

    • Radiation therapy

      • Radiation therapy can be used to treat BCC or SCC if surgical removal is impossible or for other reasons
      • Advantage of avoiding an invasive procedure in individuals who may not tolerate surgery
      • Many associated disadvantages including poor cosmetic appearance, prolonged treatment duration, and increased risk of future skin cancers
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      Cryosurgery

      • Liquid nitrogen spray (also known as cryotherapy) is a commonly used treatment modality for actinic keratosis but can also be used to treat BCCs
      • Advantages include speed and ease of treatment and avoidance of invasive procedures (surgical excision); no anesthesia is required; 10 to 14 day healing period
      • Disadvantages include the possibility of scarring, pigmentation changes after healing and the potential for recurrent cancer
      • It can be quite painful as dermatologist will have to freeze the tumor for at least 20 seconds two times.

    • Photodynamic therapy

      • Photodynamic therapy involves the application of a special photosensitizing cream followed by exposure to sunlight or artificial light in order to activate the cream and destroy abnormal cells in the superficial layer of the skin
      • Can be painful; less so with daylight photodynamic therapy
      • This treatment is only used for superficial BCCs
      • It can be quite painful as dermatologist will have to freeze the tumor for at least 20 seconds two times.
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    • • Laser

      • Laser surgery is not a common treatment for BCCs although there are published reports on treatment of small low-risk BCCs
      • Usually requires local anesthesia

    • Medical treatments

      • Topical 5-fluorouracil (5-FU) cream

      • Topical 5-FU cream can be used for treatment of superficial BCCs
      • A variety of creams and solutions available with different dosing regimens (e.g. 5% cream twice daily for 2-4 weeks)
      • Healing usually occurs within 2 weeks of stopping treatment

    • • Imiquimod cream

      • Topical imiquimod cream can be used for treatment of BCC with clearance rates ranging from 53 to 75%
      • May cause flu like symptoms in some individuals
      • Recommended treatment area is 25cm2 or less

    • • Combination therapy

      • Combining more than one therapeutic modality has the advantage of increasing cure rate while lowering the chance of adverse effects and enhancing cosmetic results
      • For example, topical 5-fluorouracil cream or imiquimod cream can be used to pretreat basal cell carcinoma sites prior to Mohs surgery
      • Curettage can be followed by several weeks of topical imiquimod cream

      Several other treatments that are given by infusion (vismodegib or sonidegib) can be used for advanced BCC cancers.

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SQUAMOUS CELL CARCINOMA

  • Squamous cell carcinoma (SCC) is the second most common type of skin cancer (following basal cell carcinoma)
  • SCCs most commonly occur in chronically sun-exposed areas, but can also occur in burn sites, scars and chronic wounds (Marjolin ulcer)
  • The majority of SCCs occur on the head, neck, upper extremities, or shins
  • SCC is found more frequently in men (3:1 male to female ratio)
  • The incidence of SCC increases significantly after age 60 years
  • SCC can spread, or metastasize, from the skin surface to nearby lymph nodes and distant organs
  • SCC mortality is highest in light-skinned, older persons, and men
  • Men have a 3:1 greater mortality rate compared to women
  • SCCs located on the ear, lip and genitalia have a higher risk of death

RISK FACTORS

  • UV exposure – predominant cause of SCC
    • Cumulative long-term UV exposure
    • Sunburns in childhood
  • Tanning beds
  • PUVA therapy
  • Ionizing radiation
  • Chemicals (arsenic, mineral oil, coal tar, soot, and many more)
  • Human papillomavirus
  • Cigarette smoking
  • Skin type (fair skin, always burns, never tans)
  • Freckling
  • Red hair
  • Genetic syndromes
  • Chronic non-healing wounds
  • Longstanding skin inflammatory disease (discoid lupus erythematosus, lichen planus, or lichen sclerosis)
  • Immunosuppression
  • Organ transplantation
  • While lesion characteristics may be highly suggestive of a squamous cell carcinoma, a sample of skin obtained via a biopsy is required in order to make a diagnosis (diagnosis requires a pathologist to review the skin specimen under a microscope)
  • A biopsy may include the whole lesion or a small part of the lesion (in order to establish a diagnosis prior to proceeding with a large excision)
  • Standard excision
    • Surgical excision is effective for most squamous cell carcinomas
    • Surgical excision of squamous cell carcinoma required 6 mm margins of healthy tissue
  • Curettage with electrodesiccation
    • Requires local anesthesia
    • Curettage with electrodesiccation achieves cure rates as high as over 98% for Bowen’s disease and SCCs less than 1 cm in diameter
  • Mohs micrographic surgery
    • Mohs micrographic surgery provides the best verification for complete removal of the tumour while allowing for maximal preservation of healthy skin
    • Superior to all other treatment modalities in terms of recurrence rate
    • Appropriate for cancers located on the central face, eyelids, eyebrows, periorbital area, nose, lips, chin, mandible, ears, temples and others
  • Radiation therapy
    • Radiation therapy can be used to treat SCCs if surgical removal is impossible
    • Advantage of avoiding an invasive procedure in individuals who may not tolerate surgery
    • Many associated disadvantages including poor cosmetic outcome, longer treatment duration, and increased risk of future skin cancers
  • Cryosurgery
    • Liquid nitrogen spray (also known as cryotherapy) is a commonly used treatment modality for actinic keratosis but can also be used to treat SCCs
    • Advantages include speed and ease of treatment and avoidance of invasive procedures (surgical excision); no anesthesia is required; 10 to 14 day healing period
    • Disadvantages include the possibility of scarring, pigmentation changes after healing and the potential for recurrent cancer
  • Photodynamic therapy
    • Photodynamic therapy involves the application of a special photosensitizing cream followed by exposure to sunlight or artificial light in order to activate the cream and destroy abnormal cells in the superficial layer of the skin
    • Can be painful; less so with daylight photodynamic therapy

FREQUENTLY ASKED QUESTIONS

  • Basal cell carcinoma is the most common skin cancer.
  • Individuals with fair skin, who usually burn with sun exposure (often associated with light hair, blue/green eyes, freckles).
  • Sun exposure is the most important modifiable risk factor for the development of all types of skin cancer.
  • Basal cell carcinomas (BCCs) tend to grow slowly and the risk of spread to distant sites is extremely low. In contrast, squamous cell carcinomas (SCCs) have the potential to invade deeper structures and spread to lymph nodes and other organs.
  • The most common treatment modality for actinic keratosis is liquid nitrogen cryotherapy. Basal cell carcinomas (BCCs) are treated via a variety of modalities depending on the type and location on the body. Curettage with electrodesiccation or surgical excision is often utilized for BCCs.
  • Surgical excision is most commonly employed for squamous cell carcinomas once a diagnosis is established.
  • Yes, appropriate use of sunscreen has been shown to decrease the occurrence of skin cancer and prevents photodamage and premature aging.

CASE STUDIES

Jim H is a 75-year-old male living in Victoria, BC. He is of Irish and British heritage and usually burns after exposure to the sun. He is an avid golfer and enjoys spending lots of time outdoors since his retirement a decade earlier.

Jim has noticed the appearance of several rough spots on a pink background on the backs of his hands. He initially thought it was a flare of his eczema, but he has not previously experienced eczema at this location and using gentle soap and moisturizers on this area was of no help.

Pictures of Jim’s hand:

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1. What is the name of the skin changes on the back of Jim’s hand?

  • Actinic keratosis.

2. What will be required to establish a diagnosis?

  • a) Imaging studies (X-ray, CT-scan, or MRI)
  • b) Blood tests
  • c) A sample of skin obtained via biopsy
  • d) None of the above. A skin exam by a qualified physician alone can be used to diagnose actinic keratosis.

3. What is the risk of untreated actinic keratosis?

  • There is a risk of transformation to SCC (1/200 – 1/1000 chance per lesion per year).

4. What is the cause of these lesions?

  • Cumulative sun exposure in fair skinned individuals.

5. What treatment modality should be pursued?

  • This is may vary from person to person. Jim has several spots requiring treatment on his hand, and so either targeted treatment with cryotherapy (liquid nitrogen spray) or field therapy with immunomodulatory cream or photodynamic therapy would be appropriate. Given Jim’s skin phototype (fair skin), his risk of post-inflammatory pigmentation changes following cryotherapy are low, and given the ease of treatment and short recovery time, this treatment modality would be appropriate.

Courtney is a 65-year-old female living in Toronto, ON. She is of Norwegian heritage and usually burns after exposure to the sun. She has spent her career in offices and courtrooms as a corporate lawyer, but enjoys tropical vacations and has experienced sunburns on numerous occasions. She is also taking prednisone (an immunosuppressive medication) for her inflammatory joint disease.
Over the past 6 months, she has noticed an enlarging red scaly plaque on her lower leg. Despite regular moisturization and gentle skin care, this rash has continued to increase in size.

Picture of Courtney’s leg:

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1. What is the likely diagnosis?

  • Bowen’s disease.

2. What will be required to establish a diagnosis?

  • e) Imaging studies (X-ray, CT-scan, or MRI)
  • f) Blood tests
  • g) A sample of skin obtained via biopsy
  • h) Nothing, this diagnosis is clinically obvious

3. What are the treatment options for Bowen’s disease?

The treatment options for Bowen’s disease depend on size and location of the lesion

Liquid nitrogen spray (also known as cryotherapy) is a commonly used treatment modality for small localized lesions

Field therapies can be performed with immune modulating creams; for Bowen’s disease these include:

    • 5-fluorouracil (5-FU), Brand name: Efudex
    • Imiquimod, Brand names: Aldara or Zyclara

Photodynamic therapy

    • Involves the application of a special photosensitizing cream followed by exposure to sunlight or artificial light in order to activate the cream and destroy abnormal cells in the superficial layer of the skin

Surgery

    • Surgical excision
    • Curettage and electrodesiccation

4. What are the risks of untreated Bowen’s disease?

  • Transformation to an invasive squamous cell carcinoma.

5. What additional measures must Courtney take if the biopsy comes back as squamous cell carcinoma?

  • Entire lesion must be removed, safe sun practices (long sleeved cloths, hats, sunscreen, seek shade), annual skin exam.

Caroline is a 58-year-old female living in Hamilton, ON. She has light green eyes and usually burns without proper sun protection. She is an active runner and consistently wears sunscreen. However, she recalls frequent sunburns during her teens and late 20s.
Over the past 9 months, she has noticed a growing red bump on her forehead. The spot has failed to heal despite using polysporin. She also notes that the spot had bled spontaneously on several occasions.

Picture of Caroline’s forehead:

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1. What is the likely diagnosis?

  • Basal cell carcinoma

2. What is a hint to the diagnosis?

  • a) Location on forehead
  • b) History of previous sun burns
  • c) The dark red colour of the growth
  • d) Characteristic rolled border

3. What are the treatment options for basal cell carcinoma?

  • Treatment options include standard surgical excision, curettage with electrodessication, or Mohs surgery.
  • Treatment options are based on the type of basal cell carcinoma and location of tumour.

4. What are the risks of untreated basal cell carcinoma?

  • Infection, bleeding, and destruction of healthy tissue at site of the basal cell carcinoma.

5. What additional measures must be taken if a basal cell carcinoma is confirmed?

  • She should receive a full skin exam to ensure there are no other skin cancers present.

Brian is a 70-year-old male living in Ottawa, ON. He has blonde hair and blue eyes and usually burns after exposure to the sun. He spent many years working on his farm. He first noticed a red scaly plaque on his arm about 6 months ago, and he recalls that it has gradually increased in size. The spot has failed to heal despite regular application of polysporin. He notes that it is tender when he presses on it with his hand. He has extensive actinic keratoses covering his face and scalp.

Picture of Brian’s leg:

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1. What is the likely diagnosis?

  • Squamous cell carcinoma.

2. What will be required to establish a diagnosis?

  • i) Imaging studies (X-ray, CT-scan, or MRI)
  • j) Blood tests
  • k) A sample of skin obtained via biopsy
  • l) Nothing, this diagnosis is clinically obvious

3. What are the treatment options for squamous cell carcinoma?

  • Surgical excision with a small margin of healthy tissue.

4. What are the risks of untreated squamous cell carcinoma?

  • Local destruction of tissue and possible spread to lymph nodes and other organs in the body.

5. What additional measures must Brian take if squamous cell carcinoma is confirmed?

  • Brian should be encouraged to partake in safe sun practices (long sleeved cloths, hats, sunscreen, seek shade), annual skin exam.

REFERENCES

  • Abbas, M., & Kalia, S. (2016). Trends in non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) in Canada: a descriptive analysis of available data. Journal of cutaneous medicine and surgery, 20(2), 166-175.
  • Bolognia, Jean., Jorizzo, Joseph L.Schaffer, Julie V. (Eds.) (2012) Dermatology /[Philadelphia] : Elsevier Saunders.
  • Bridgman, A. C., Fitzmaurice, C., Dellavalle, R. P., Karimkhani Aksut, C., Grada, A., Naghavi, M., ... & Drucker, A. M. (2020). Canadian Burden of Skin Disease From 1990 to 2017: Results From the Global Burden of Disease 2017 Study. Journal of cutaneous medicine and surgery, 24(2), 161-173.
  • Cameron, M. C., Lee, E., Hibler, B. P., Barker, C. A., Mori, S., Cordova, M., ... & Rossi, A. M. (2019). Basal cell carcinoma: Epidemiology; pathophysiology; clinical and histological subtypes; and disease associations. Journal of the American Academy of Dermatology, 80(2), 303-317.
  • Perry, D. M., Barton, V., & Alberg, A. J. (2017). Epidemiology of keratinocyte carcinoma. Current dermatology reports, 6(3), 161-168.
  • While lesion characteristics may be highly suggestive of a squamous cell carcinoma, a sample of skin obtained via a biopsy is required in order to make a diagnosis (diagnosis requires a pathologist to review the skin specimen under a microscope)
  • A biopsy may include the whole lesion or a small part of the lesion (in order to establish a diagnosis prior to proceeding with a large excision)
  • Standard excision
    • Surgical excision is effective for most squamous cell carcinomas
    • Surgical excision of squamous cell carcinoma required 6 mm margins of healthy tissue
  • Curettage with electrodesiccation
    • Requires local anesthesia
    • Curettage with electrodesiccation achieves cure rates as high as over 98% for Bowen’s disease and SCCs less than 1 cm in diameter
  • Mohs micrographic surgery
    • Mohs micrographic surgery provides the best verification for complete removal of the tumour while allowing for maximal preservation of healthy skin
    • Superior to all other treatment modalities in terms of recurrence rate
    • Appropriate for cancers located on the central face, eyelids, eyebrows, periorbital area, nose, lips, chin, mandible, ears, temples and others
  • Radiation therapy
    • Radiation therapy can be used to treat SCCs if surgical removal is impossible
    • Advantage of avoiding an invasive procedure in individuals who may not tolerate surgery
    • Many associated disadvantages including poor cosmetic outcome, longer treatment duration, and increased risk of future skin cancers
  • Cryosurgery
    • Liquid nitrogen spray (also known as cryotherapy) is a commonly used treatment modality for actinic keratosis but can also be used to treat SCCs
    • Advantages include speed and ease of treatment and avoidance of invasive procedures (surgical excision); no anesthesia is required; 10 to 14 day healing period
    • Disadvantages include the possibility of scarring, pigmentation changes after healing and the potential for recurrent cancer
  • Photodynamic therapy
    • Photodynamic therapy involves the application of a special photosensitizing cream followed by exposure to sunlight or artificial light in order to activate the cream and destroy abnormal cells in the superficial layer of the skin
    • Can be painful; less so with daylight photodynamic therapy