Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor that represents the second leading cause of skin cancer, and its incidence appears to be rising. Although several factors may contribute to the development of cSCC, increased exposure to solar ultraviolet radiation (UVR) that leads to actinic skin damage is its primary cause. White individuals with fair skin—especially those who spend extensive periods of time in the sun and/or who live in close proximity to the equator—as well as individuals who use artificial tanning beds all have a higher risk of acquiring cSCC. A cSCC appears as a red, rough, scaly skin patch or non-healing ulcer, and it has the potential to metastasize to other organs in the body, including the lymph nodes. Most cases of cSCC are low-risk and can be treated effectively with dermatological procedures such as radiation therapy, chemotherapy, electrodissection and curettage, photodynamic therapy, and cryosurgery.1-3,18 High grade cSCC lesions >2 cm, depth > 2 mm, and growing rapidly require surgical excision. Low grade cSSC can also be treated with surgical excision.18
Pathophysiology
- Although a range of factors—including immunosuppression, burns, and chronic infection—may contribute to the development of cSCC, the majority of cases are associated with actinic skin damage, and its main external cause is solar UVR1
- There is a strong relationship between level of cumulative sun exposure and cSCC risk
- In addition to fair-skinned individuals, albinos and those with xeroderma pigmentosum are at an increased risk for cSCC
- There is significant geographic variation in cSCC occurrence that is primarily explained by ambient UVR light exposure, as incidence rates are higher with closer proximity to the equator3
- Exposure to artificial UVR from indoor tanning facilities like sunbeds is also significantly associated with cSCC development, with the highest risks being found in those exposed before 25 years of age1
- One of the strongest predictors of cSCC development in previously unaffected people is the presence of actinic keratoses (AKs), or solar keratoses, caused by cumulative sun exposure and occur mostly on the head and neck, dorsum of the hands, and forearms in older, pale-skinned individuals; however, only a small proportion of AKs are cSCC precursors, and the rate of their malignant transformation is unclear1
- Immunosuppression is another major risk factor for cSCC, and organ transplant recipients, those diagnosed with HIV/AIDS, non-Hodgkin lymphoma, and chronic lymphocytic leukemia all appear to have increased rates of cSCC
- Use of glucocorticoids has been reported to increase the risk of cSCC by approximately twofold1
- Smoking has also been shown to be an important risk factor for the development of SCC3
- Some cases of cSCC develop de novo, as a result of previous exposure to ionizing radiation or arsenic, within chronic wounds, scars, burns, ulcers or sinus tracts, and from pre-existing lesions such as Bowen's disease2 Unlike conventional cSCCs, which tend to occur on the face, neck, hands, and other sun-damage prone areas, de novo cSCCs are most commonly found on the lower extremities4
While cSCC of hand accounts for as much as 90% of the malignancies of hand, SCCNU squamous cell carcinoma of nail unit can also affect the digits of the hand but is very rare. SCCNU can be difficult to diagnose because it may present as a chronic infection or even a wart of nail bed. SCCNU invades the bone about 50% of the time. With metatasis to the lung fatality rates can approach 40%.
Related Anatomy (cSCC)
- The vast majority of Bowen’s disease cases (~72%) occur on sun-exposed surfaces such as the head, neck, and hands, but mucosal surfaces and the nail bed are also commonly involved4
- In the hand and wrist region, cSCCs are most commonly found on the dorsum of the hand and the forearm, and only develop on the palms of the hand in rare circumstances4
- Each case of conventional cSCC can be categorized into 1 of 3 histologic grades based its degree of nuclear atypia and keratinization:
- Well differentiated: nuclei appear normal with abundant cytoplasm and extracellular keratin pearls
- Moderately differentiated: features are an intermediary between well differentiated and poorly differentiated
- Poorly differentiated: there is a high degree of nuclear atypia with frequent mitoses, a greater nuclear-cytoplasmic ratio, and less keratinization
Related Anatomy
The nail united is comprised of the nail bed, nail folds, hyponychium and fingernail (nail plate). The bed has two parts, the terminal matrix and the sterile matrix. SCCNU involves the nail bed approximately 70% of the time. SCCNU also occurs in the nail fold and rarely in both the fold and the nail bed.21
Incidence and Related Conditions
- After basal cell carcinoma (BCC), cSCC is the second most common malignancy of the skin, but the most common subungual malignancy; it has an estimated annual incidence of 700,000 in the United States, which is a figure that appears to be rising5,6
- The lifetime incidence of cSCC is between 7-11%, and it accounts for 20-25% of all non-melanoma skin cancers7,18
- BCC and cSCC account for >95% of all non-melanoma skin cancers4
- The incidence of cSCC is two times higher in men than women, and it increases markedly with age. About 80% of cases occur in people aged ≥60 years8
- In the general population, <5% of cSCCs will metastasize to lymph nodes;11,12 however, in hospital-referred patients with unfavorable tumor characteristics, the incidence may be >10–15%13,14
- Incidence of cSCC is 65–250 times higher among organ transplant recipients compared with the general population15
Incidence
SCCNU is rare. High, et al found only 14 SCCNU's while doing 250,000 dermatology consults.20
Differential Diagnosis
- AK
- Allergic contact dermatitis
- Atopic dermatitis
- Atypical fibroxanthoma
- BCC
- Benign skin lesions
- Bowen’s disease
- Cancerous and pseudo-cancerous lesions
- Chemical burns
- Clear-cell acanthoma
- Congenital tumors
- Eccrine poroma
- Hypertrophic lichen planus
- Keratoacanthoma
- Melanoma
- Merkel cell carcinoma
- Papillomas
- Prurigo nodularis
- Pyoderma gangrenosum
- Pyogenic granuloma
- Sebaceous neoplasms
- Seborrheic keratosis
- Sporotrichosis
- Trichilemmoma
- Vascular lesions
