Basal Cell Carcinoma (BCC)

Malignant Diseases of The Skin

Basal Cell Carcinoma (BCC)

• Most common form of skin cancer, accounting for approximately 60% of all skin cancers.

Etiologic Factors of BCC

• Chronic sun exposure is a significant cause
• Radiation can induce BCC
• Exposure to arsenic increases the risk
• Burns and scars can lead to BCC development
• Genetic disorders like xeroderma pigmentosa, basal cell nevus syndrome, and albinism predispose individuals to BCC
• Nevus sebaceous present at birth on the scalp or face has approximately a 10% chance of becoming BCC.

Common Clinical Presentations of BCC

• Superficial BCC accounts for 30% of BCC cases and appears as a flush, erythematous, and scaly patch that may show shallow ulceration or crusting, sometimes resembling eczema or a fungal infection.
• Nodular BCC makes up 60% of BCC cases presenting as a flesh-colored nodule with telangiectatic vessels, which may ulcerate and form a rolled border (rodent ulcer).
• Pigmented BCC is a form distinguished by brown pigmentation, otherwise similar to nodular BCC.
• Morpheafrom or sclerosing BCC accounts for 5-10% of BCC cases and appears as a firm white or yellowish plaque with an ill-defined border and induration, without ulceration, described as an enlarging scar, and having aggressive growth.
• Merkel Cell Carcinoma can resemble BCC histologically and may develop as a single tumor in older individuals.
• Adnexal carcinoma can arise from sebaceous sweat glands

Recurrence of BCC

• Lesions are less likely to recur if they are less than 6 mm in diameter in high-risk areas such as the central face, nose, lips, and eyelids
• Low recurrence is also observed when lesions are less than 10 mm in diameter in other areas of the head and neck
• Lower recurrence is seen when lesions are less than 20 mm in diameter in all other areas except the hands and feet
• Nodular or superficial histopathologic growth pattern
• Well-defined clinical borders lesions are less likely to recur
• Approximately 40% of patients who have had one BCC will develop another lesion within 5 years
• Surgical excision with 4 to 5 mm margins demonstrates 5-year cure rates exceeding 95% with this method
• Electrodesiccation and curettage (ED&C) is most appropriate for low-risk superficial or nodular BCCs on the trunk or extremities
• Basal cell carcinomas in low-risk sites (neck, trunk, and extremities) had a 3% recurrence rate
• BCCs less than 6 mm in diameter in high-risk sites (nose, paranasal, nasolabial groove, ear, chin, mandibular, perioral, periocular areas) had a 5% failure rate, larger tumors had a recurrence rate of 18%.

Molecular Pathogenesis of BCC

• PTCH1 is a tumor suppressor gene found on chromosome 9.
• Similar to the retinoblastoma "two-hit" hypothesis, where two somatic hits are required for sporadic cases, and one somatic hit plus inheritance of a defective allele is required for familial cases like basal cell nevus syndrome and xeroderma pigmentosum.
• PTCH proteins, along with the SMO protein, form the receptor for the hedgehog (HH) protein, activating the Sonic Hedgehog signaling pathway.
• PTCH-induced repression of SMO limits the effects of the SHH signal, so inactivating mutations of gene PTCH lead to overexpression of the SHH signal.
• P53 mutations are less frequent in BCCs compared to cutaneous squamous cell cancers.

Squamous Cell Carcinoma (SCC)

• Accounts for roughly 30% of skin cancers.

Etiologic Factors of SCC

• Radiation injury is a cause.
• Chronic sun exposure is a cause
• Chronic chemical exposure, such as to hydrocarbons and arsenic
• Burns can lead to SCC
• Unstable scars, like Marjolin's ulcer, can be a risk
• Conditions can lead to SCC, including actinic keratosis, leukoplakia, chronic ulcers, and chronic draining sinus tracts.

Clinical Presentations of SCC

• Common sites include the ears, lips, temples, upper face, and dorsum of hands.
• Early tumors may look like actinic keratosis but with raised scaling and skin-colored papules.
• Advanced lesions may ulcerate with a horny, crusted appearance.
• Nodular SCC presents as a dome-shaped, skin-colored, ulcerated papule, likely to have outward growth, hemispherical shape, and sharp borders, found on sun-damaged skin, lower lips, ears, and hand dorsum.
• Keratoacanthoma, rapid growth with spontaneous resolution tendency has similar histological and clinical appearances to nodular and squamous cell carcinoma.

Marjolin's Ulcer

• Chronic unstable burn scars or draining osteomyelitis can cause premalignant changes leading to squamous cell carcinoma.
• Ulcers at the margins are present for 5 or more years.
• Is typically slow-growing initially but tends to recur and metastasize rapidly after resection.
• Treatment includes wide local excision followed by regional node dissection 2-4 weeks after the wound has healed primarily.

Radiation-Induced SCC

• Occurs as a firm, poorly marginated ulcer at the site of previously administered radiation therapy, which usually develops 15 years or more after radiation.

Bowen's Disease

• Presents as a slowly enlarging erythematous patch with a sharp, irregular outline.
• Involves superficial scaling and crusting areas.
• Color varies from red to tan, which causes confusion with BCC.
• Surgical excision is the recommended treatment.

The Pathogenesis of SCC

• SCC appears from moderately well-differentiated epithelial cells.
• Low-grade SCC shows considerable evidence of keratinization and a few mitotic figures per high-powered field.
• More aggressive lesions also evidence keratinization but with greatly increased mitotic rates.

Course and Prognosis of SCC

• Untreated SCC will destroy and invade surrounding tissue more aggressively than BCC.
• Actinic-induced SCC: less than 1-2% metastatic rate. Nodular SCC: approximately 10%
• Approximately 10% Keratoacanthomas metastatize.
• The recurrence rate following initial treatment is 10%, but re-treatment leads to a 98% cure rate, with 5-year cure rates between 90-95%.

Treatment for SCC

• For small actinically induced squamous cell carcinomas (less than 2 cm), treatment modalities discussed for basal cell carcinomas are used.
• For aggressive, larger lesions, excision with frozen section pathologic diagnosis is preferred.

New Treatment Concepts for Skin Malignancies

• Imiquimod
• Matristem
• ACell,

Basal Cell Variant: Merkel Cell Cancer

• Interest and incidence of Merkel Cell Cancer is on the rise.
• Journal American Medical Association reported on this in July 3, 2018, volume 320, #1, pages 18-20.
• It's rare, though on the rise, and is associated with a virus, specifically, an unknown polyomavirus.
• 80% of Merkel cell cancers have links to Merkel Polyomavirus, while 20% have links to UV exposure.
• It has proven to be more aggressive than melanoma.
• Merkel Cell Tumors are defined by the acronym AEIOU.
• Significant Acronym
  • A - Asymptomatic
  • E - Expanding rapidly
  • I - Immunosuppressive
  • O - Older patients - typically older than 70 years old
  • U - UV exposure
• 90% of Merkel cell carcinomas have 3 or more of these features

Merkel Cell Cancer Treatment

• Treatment options include excisional surgery, possibly with sentinel node biopsy, and radiotherapy.
• Immunotherapy has proven promising, and AVELUMAB appears to be the standard of care for all metastatic Merkel cell patients.

Melanoma

• Melanoma arises from melanocytes; the pigment-producing cells of the skin.

Suspicious signs of Melanoma

• Look for irregular borders.
• Changes in colors such as red, white, and blue indicate melanoma
• Look for increase in size or change in color.
• Scaliness, erosion, oozing, crusting, bleeding, or development of satellite lesions.

Epidemiology of Melanoma

• Malignant melanomas account for 1% of all cancers
• 20%-30% arise in the head or neck area
• Predominantly occurs in white populations.
• Common in those 30-60 years of age.
• Approximately 50% of malignant melanomas arise from junctional or compound nevi, and 50% arise anew.
• 14,000 new cases are diagnosed in the United States each year.

Clinical Presentations of Melanoma

• Superficial Spreading Melanoma: The most common melanoma type accounts for roughly 70% of cases.
• Superficial spreading melanoma presents as a relatively flat-topped, slow-growing, pigmented papule or plaque with irregular borders and pigmentation in black, red, white, or blue.
• With superficial spreading melanomas, the lesion is almost always wider than tall
• With superficial spreading melanomas, larger lesions may appear "bumpy' and lobulated
• With superficial spreading melanomas, pigment may spread to surrounding normal tissue
• The back is the most common location where, in men; the legs are the most common area, in women.
• Nodular Melanoma: This melanoma type comprises 15% of melanoma cases.
• Nodular melanomas can be dome-shaped and darkly pigmented as papules or nodules.
• Nodular melanomas grow more quickly and have deeper color than the superficial spreading type with more even pigmentation.
• Typically as tall as is wide.
• Lentigo Maligna Melanoma: This is the least common type of melanoma.
• Lentigo Maligna Melanoma is found almost exclusively on the face, arising from pre-existing lentigo
• Appears as numerous small, darkly-pigmented papules superimposed on a flat, light brown patch, or "Hutchinson's freckle."
• Acrolentiginous Melanoma: Comprises 10% of melanomas overall.
• Acrolentiginous Melanoma is most common on the digits, palms, and soles.
• Acrolentiginous Melanoma is most common in African Americans and can appear as smooth papules against a background of gray or black macular, or uneven pigmentation.

Predisposing Factors of Melanoma

• Sun exposure is related to the number and severity of sunburns versus lifetime exposure
• Genetics play a role: 10% of patients have a positive family history
• Congenital nevi: Patients with congenital hairy nevi are at higher risk for transforming to malignancy (15-40% incidence).

Immune Response relating to Melanoma

• Patients who are immunocompromised have an increased risk for melanoma

Staging & Diagnosis for Melanoma

• Clark's classification assesses the level of invasion of Melanoma. - A. Level 1 Tumor is confined to the epidermis - B. Level 2 Tumor invades papillary dermis - C. Level 3 Tumor fills papillary dermis (does not invade reticular dermis) - D. Level 4 Tumor invades reticular dermis - F. Level 5 Tumor invades subcutaneous fat
• Breslow Classification helps measures depth of invasion in millimeters. - A. Melanoma’s regional metastasis correlates with tumor thickness - B. Deep at Up to.75mm deep- 0% - C. Deep at 0.76rnm- 1.5mm – 25% - D. Deep at 1.51mm to 3.99mm – 51% -E. Deep at Greater than 4.0mm- 62%
• Complete staging requires history and physical exam, blood count, SMA -12, urinalysis, and chest x-ray

Metastases and Treatment for Melanoma

• Melanoma can metastasize through both the lymphatic system and the bloodstream and spread to any organ of the body.
• Patients with Clark’s level 1, 2 or 3 lesions and depth of less than 0.76mm is considered to have low risk.
• Patients with Clark's level 4 or 5 lesions and a depth of greater than 1.5 mm are at high risk to metastisize.

Treatment for Melanoma

• Treatment depends on depth of invasion and tumor level.
• Excision is requires with level 1 of Clark's level lesions require excision alone, with a cuff of normal tissue, which typically includes 0.5 to 1 cm margins
• For Clark's level of 2-5 wide margins with underlying fascia may be required but a less than wide margin requirement may apply on the face.
• Node resection is done with clinically involved regional lymph nodes at Clark's level 2-5 should be retreated
• Whether Prophylactic resection of lymph nodes is needed, is controversial.
• Resection is required with a depth greater than 0.75mm or Clark’s level 3 to aid staging and enhance survival.
• Therapies to aid in treatment are, Regional hyperthermic perfusion, involves isolating the blood supply of a limb with a pump/ oxygenator, enabling high doses of chemotherapy, and Chemo, Immuno, and Radiotherapy.

Prognosis for Melanoma

• If confined to primary site has a 5 year survival rate of 80-90%
• If regional lymph nodes are involved 5% year survival drops to 30-50%
• Patients with distant or Visceral Metastases usually do not live more than 12 months

Melanoma TNM staging

• Primary Tumor staging is indicated by it’s tumor thickness, ulceration and mitotic rate -T1 Is up to ≤1 mm -T2 Is 1.01 to 2 mm

  • T3 Is 2.01 to 4 mm -T4 is >4 mm -A or B is based on presence of ulcerations.
  • A 10 year survival decreased progressively with depth and tumor thickness

• Lymphatic Involvement: Includes (N) -No regional lymphatic metastases at No -One involved lymph node is N1, and is subdivided into N1a (micrometastases) and N1b is macrometastases). -N2 and N2a and N2b is the presence of two or three involved nodes. N3 4 for more positive nodes are involved Patients with nodal disease limited to micrometastases the most important impact on prognosis was the number of nodes.

• Five year survival rates with one, two or three positive lymph nodes

• Seventy one, Sixty five, and Sixty one percent.

Patients with macro metastases in the regional nodes the number of nodes can significantly associate with prognosis.

Five your survival rates One two, and Three positive lymph nodes there were 50 43 and 40 percent