By Gary M. White, MD
Squamous cell carcinoma (SCC) is the second most common skin cancer and arises from the squamous cells of the epidermis. Chronic ultraviolet light exposure is the main risk factor, although HPV plays an oncogenic role in some lesions. Other key risk factors include light skin, male gender and age > 65.
A rapidly growing nodule that develops a central keratotic core in the sun-exposed area of an elderly person is classic. However, the SCC comes in many shapes and sizes, e.g., red papule or plaque, ulcer, crusted area, subungual growth, cutaneous horn. Chronic UV exposure is a predisposing factor and the patient should be examined for other non-melanoma skin cancers. Note that the basal cell carcinoma (BCC) is usually pearly, translucent and without any keratotic core. In contrast to BCC and melanoma, SCC often hurts. In very unusual cases, SCC may be pigmented [BJD 1999;141;132].
Various risk factors have been associated with metastasis, recurrence and risk of death with SCC. They include:
In one study of SLNB (sentinel lymph node biopsy), tumors with 2 or 3 of the above 4 risk factors had a SLNB positivity rate of 29%. Tumors with all 4 risk factors had a rate of 50%. SLNB should be considered in high risk SCC [JAMA Derm 2018;154;101].
(Some studies have shown that ear, temple or anogenital location and immunosuppression also increase risk.)
Multiple SCC may occur in association with:
Chronic use of photosensitizing drugs such as hydrochlorothiazide have been linked to an increased risk of SCC and melanoma (but not BCC) [Br J Cancer. 2008 Nov 4;99:1522-8 and Dermatol Surg. 2016 Sep;42(9):1107-9]. The highest risk is for those using hydrochlorothiazide for more than 5 years.
A recent study demonstrated a 97% cure rate of invasive SCC by curettage alone [JAAD 2017;77;582].
C&D of a small SCC on the extremities or trunk in a normal host is adequate and appropriate therapy. The experienced dermatologist will evaluate a lesion prior to biopsy as to 1) the likelihood that it is a SCC and 2) the appropriate treatment if the biopsy is positive. If the lesion is very likely a SCC and C&D is appropriate, both biopsy and treatment may be done at that visit.
Squamous cell carcinomas that are larger, develop in sun-protected areas, are on the lip, in scars or have a more aggressive histology should be excised with adequate margins. Mohs surgery is recommended especially if there is perineural invasion (PNI) as cure rates are significantly higher compared with standard excision.
Radiation therapy is occasionally employed for SCC, but cure rates are relatively lower. For small primary SCCs, cure rates over 90% have been quoted. For recurrent SCC, cure rates are much lower.
Neoadjuvant therapy is any treatment given to shrink a tumor prior to surgery. Examples across multiple specialties include chemo, radiation, and hormone therapy. Methotrexate has been used as neoadjuvant therapy for SCC. In one study of 86 patients (half treated, half not), a single treatment of IL mtx resulted in a 43% decrease in tumor size [JEADV 2016;30;1120]. The best responders were lip lesions and SCC > 2 cm. Methotrexate 25 mg/cc was injected once into the base of the tumor until it developed a whitish color several weeks before surgery.
The patient should be seen routinely to monitor for recurrence and new lesions. Lesions at high risk for recurrence e.g., PNI, aggressive histology, etc., may deserve followup every 3 months initially (recurrence is most likely during the first two years). Daily sunscreen use significantly lowers the risk of developing new primary SCCs. Any patient with a history of SCC should be encouraged to have an annual total body skin examination.
A randomized clinical trial of 932 veterans at high risk for keratinocyte carcinoma showed that a 2-4 week course of 5-fluorouracil 5%, BID to the face and ears reduced the risk for 1 year of squamous cell carcinomas [JAMA Derm online 1;2018]. This suggests that annual treatment with 5-FU is recommended for those at high risk for SCC.
A recent placebo-controlled study of 386 patients who had been diagnosed with at least two skin cancers, i.e., basal cell carcinoma and/or squamous cell carcinoma, in the past five years, showed that taking 500 milligrams twice daily of nicotinamide (not nicotinic acid) reduced the subsequent risk of non-melanoma skin cancers by 23%. When patients stopped taking the supplements, their risk of getting skin cancer rose again about six months later.
Some patients have a history of and continue to develop multiple SCCs. Chemoprevention using oral retinoids has a beneficial effect [Arch Dermatol 2005;141:456-64]. In one study of transplant patients, cyclic PDT treatments at 4- to 8-week intervals for 2 years resulted in a nearly 95% reduction of SCCs at week 24 [Dermatol Surg. 2010;36:652-8].
Large SCCs may exhibit PNI. The portion of SCC excisions with PNI ranges from 3-14%. PNI has been associated with head and neck location, clinically palpable regional lymphadenopathy, painful tumors, recurrent tumors, large tumors (e.g., larger than 2 cm) and poorly differentiated histology. When PNI is present, recommendations have included wider surgical margins, sentinel lymph node biopsy and adjuvant radiation therapy (ART). Certainly if PNI is present on the initial biopsy, Mohs surgery is preferred over standard excision. If the excision, however, has already been done (non Mohs), the recommendations are less clear. For example, one review found there to be no strong evidence for or against the use of ART after surgical excision if perineural invasion is found. Since recurrence is most likely in the first 2 years after excision, skin examination every 3-6 months is recommended for that time.
For high-risk SCC, the removal of the sentinel node may be considered. In one study, all SCCs with positive sentinel node were > 2 cm in diameter [JAMA Dermatol 2014 Jan;150(1):19-24.]. In another, lower lip SCC and local recurrence cases were associated [J Plast Surg Hand Surg. 2013 Jun;47(3):204-8].
An SCC which on biopsy showed perineural invasion. Mohs surgery is the recommended treatment.
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