PATIENT EDUCATION
excessive childhood sun exposure is the most contributory cause of sun damage in cumulative sun exposure.
2. Ionizing radiation.
3. Scar including thermal injury.
4. Chronic inflammation: nonhealing wounds (e.g., chronic ulcer, burns, and infection) and chronic inflammatory dermatoses such as lichen sclerosus et atrophicus. Cutaneous SCC arising from a chronic wound is also known as Marjolin ulcer.
5. Immunosuppression: solid organ transplant recipients, immunosuppressant medication users, HIV infection, and prolonged use of oral prednisone.
6. Genetic disorders: XP, albinism, epidermolysis bullosa (EB) syndrome, epidermodysplasia verruciformis, Fanconi anemia, Fergus-Smith syndrome, dyskeratosis congenital, Rothmund-Thomson syndrome, Bloom syndrome, and Werner syndrome.
7. Human papillomavirus (HPV) infection: HPV-16, HPV-18, HPV-31, HPV-5, and HPV-8.
Large group of HPV are DNA tumor viruses that affect the mucosa and skin epithelial layer, resulting in hyperproliferative lesions and development of SCCs.
8. Organic hydrocarbons (coal, tar, pitch, crude, paraffin oil, lubricating oil, fuel oil, anthracene oil, and creosote) and inorganic arsenic. Presence of palmoplantar arsenical keratoses is the clue of arsenic exposure.
9. PUVA: risk increases with number of treatments, previous exposure of ionizing radiation, and history of prior skin cancers.
10. Use of photosensitizing medications: voriconazole, oral contraceptives, and BRAF inhibitors (vemurafenib, dabrafenib)
11. Precursor lesions include solar keratoses, arsenical keratoses, thermal keratoses, chronic radiation keratoses, tar keratoses, chronic cicatrix keratoses, Bowen disease, erythroplasia of Queyrat, and EV (Lewandowsky-Lutz syndrome).
D. Pathogenesis:
1. Chronic UV exposure induces several different cellular responses, including the induction of stress protein, DNA damage repair process, and cytokine production.
2. In dose-dependent DNA damage, affected cells first either undergo apoptosis (cell death as sunburn cells) or cease proliferating (cell cycle arrest) in order to undergo genetic repair process. Then, hyperproliferation and epidermal thickening follow the growth arrest.
3. In SCC development, accumulated dose of UV radiation exposure induces DNA damage and manifestation of p53 genetic mutation.
4. Mutated p53 in basal layer becomes resistant to UV-induced apoptosis and continuously increases the number of mutated p53 in clonal expansion.
5. Continuous UV irradiation causes second p53 mutation and gains the growth advantage in squamous cell dysplasia in the epidermal layer.
6. Additional genetic alteration leads to proliferation of neoplastic clone and results in SCC in situ at the epidermal surface.
7. Neoplastic tumor progresses to develop invasive property by additional genetic alteration and acquisition of invasive capability to become invasive SCC.
8. Highly differentiated tumors in invasive SCC form epidermal keratinization and invade to the dermis with a broad tumor margin.
9. Continuous progression in tumorigenesis with genetic alteration allows the acquisition of the metastatic capacity in the metastasis of SCC.
II. CLINICAL VARIANTS
A. Invasive SCC (Figure 16-8): dysplastic or malignant keratinocytes involve the full thickness of the epidermis and infiltrate through the basal layer, dermis, or deeper tissues/organs.
1. Well differentiated: pink, violaceous, or erythematous; firm, indurated papulonodule or plaque, with hyperkeratotic scale
2. Poorly differentiated: erythematous or pale pink, soft granulomatous papule or plaque may have ulceration, necrosis, or hemorrhaging without hyperkeratosis.
B. Nodular SCC (Figure 16-9): often well-differentiated, pink or erythematous nodule with keratotic scale.
C. SCC in situ (Bowen disease) (Figure 16-10): erythematous, crusty, rough, and scaly patch or slightly raised plaque.
D. Oral SCC (Figure 16-11): pink or pale indurated plaque, ulcer, or nodule developed on the floor of the mouth or on the ventral/lateral side of the tongue. SCC may arise from erythroplakia (premalignant erythematous patches) or leukoplakia (persistent white plaques) of the oral mucosa.
E. Erythroplasia of Queyrat (SCC in situ of the glans penis) (Figure 16-12): erythematous, well-demarcated velvety patch or slightly raised plaque.
F. Keratoacanthoma (Figure 16-13): fast-growing (1.5 to 2 cm in 4 to 6 weeks), erythematous, pink, or flesh-colored papule or nodule with central keratotic plug.
G. Verrucous carcinoma (Figure 16-14): indolent form of a well-defined, exophytic, large wart-like papillomatous growth involving oral mucosa (oral florid papillomatosis), anogenital areas (condyloma acuminatum of Buschke-Lowenstein), and plantar foot (epithelioma cuniculatum).
FIGURE 16-8. Invasive squamous cell carcinoma. (From Weisel, S. W. (2013). Operative techniques in orthopaedic surgery. Philadelphia, PA: Wolters Kluwer.)
FIGURE 16-9. Nodular squamous cell carcinoma. (From Craft, N., et al. (2010). VisualDx:
Essential adult dermatology. Philadelphia, PA: Wolters Kluwer.)
FIGURE 16-10. Squamous cell carcinoma in situ. (From Craft, N., et al. (2010). VisualDx:
Essential adult dermatology. Philadelphia, PA: Wolters Kluwer.)
FIGURE 16-11. Oral squamous cell carcinoma. (From DeLong, L., & Burkhart, N. (2007).
General and oral pathology for the dental hygienist. Philadelphia, PA: Lippincott Williams
& Wilkins.)
FIGURE 16-12. Penile squamous cell carcinoma in situ. (From Craft, N., et al. (2010).
VisualDx: Essential adult dermatology. Philadelphia, PA: Wolters Kluwer.)
FIGURE 16-13. Keratoacanthoma. (From Goodheart, H. P. (2003). Goodheart’s photoguide of common skin disorders (2nd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.)
FIGURE 16-14. Verrucous carcinoma. (From Craft, N., et al. (2010). VisualDx: Essential adult dermatology. Philadelphia, PA: Wolters Kluwer.)
III. LABORATORY AND DIAGNOSTIC TESTS
A. Clinical evaluation and skin biopsy for confirmation of diagnosis
B. Computed tomography (CT) scanning evaluation for possible metastasis to nearby bones and soft tissues for aggressively developing invasive-type SCC lesions
C. Magnetic resonance imaging (MRI) evaluation for possible involvement of perineural, orbital, or intracranial nerves for neurologic symptoms (local paresthesia, numbness, pain, visual changes, etc.)
IV. DIFFERENTIAL DIAGNOSIS
A. Amelanotic melanoma B. Basal cell carcinoma
C. Hyperkeratotic actinic keratosis D. Inflamed seborrheic keratosis E. Merkel cell carcinoma
F. Nummular eczema G. Paget disease H. Prurigo nodularis I. Psoriasis
J. Pyogenic granuloma
K. Traumatic ulcer/chronic inflammation L. Viral warts (verruca)
V. TREATMENT MODALITIES
A. Mohs micrographic surgery: a treatment of choice for invasive SCC and high-risk SCC.
Mohs procedure is particularly preferred for cosmetically sensitive areas on the head and neck.
1. Histopathologic evaluations of entire margins and depth of the specimen are performed during the procedure (repeated process of harvesting specimen from the surgical defect until total clearance).
2. Cure rate for tumors smaller than 2 cm is 98%; decreased cure rate to 75% for tumors larger than 2 cm.
B. Conventional excision surgery: a typical treatment method for tumors smaller than 2 cm, low-grade, or well-differentiated type on the trunk and extremities.
C. Electrodessication and curettage: treatment for low-grade, small, superficial, and low-risk tumors, preferred on the trunk and extremities.
1. Less invasive treatment option compared to conventional excision surgery
2. Useful treatment option for patients in advanced age and poor surgical candidates D. Cryotherapy: may be effective in treating very small, low-risk, superficial tumors.
E. 5-Fluorouracil (5-FU) and imiquimod topical treatments (biologic modifiers): effective in treating superficial type and early-stage SCC lesions progressing from AK.
F. PDT using photosensitizing agents with blue light (wavelength 400 nm) is effective in destroying skin cancer cells.
G. Radiation therapy is used in combination with other treatment modalities for large tumors;
aggressive, recurrent, or inoperative cases; and poor candidates for invasive surgeries.
H. Regional control 1. Nonpalpable nodes
a. Close monitoring for lymphadenopathy
b. Sentinel node biopsy for high-risk SCCs, followed by elective lymph node dissection if node is positive
c. Radiation to draining (primary echelon) nodes for high-risk lesions 2. Palpable nodes
a. Radiation b. Surgery
c. Chemotherapy
d. Combination of above
VI. PROGNOSIS
The risk of metastasis and prognosis for SCC depend on the size of the tumor, location, depth, perineural involvement, and immunosuppression. SCC lesions developed from ulcerated wounds, chronic inflammation, and recurrent cutaneous lesions are considered high risk for metastasis.