Squamous cell carcinoma (SCC) is the second most common form of skin cancer, with over 250,000 new cases per year estimated in the United States. Most (96-97%) are localized and if identified early and treated promptly will not be serious. The other 3-4% can be very invasive in nature, can spread to distant organs (metastasize) and become life-threatening. SCC on the lip or ear appear to be the sites most likely to metastasize. These should be taken seriously.
SCC is a malignant tumor that arises in the squamous cells of the upper layer of skin (of epidermal keratinocytes). Most arise from sun-induced precancerous lesions known as actinic keratoses (AKs) and patients with multiple AKs are at increased risk for developing SCC. SCC is capable of locally infiltrative growth, spread to regional lymph nodes, and distant metastasis, most often to the lungs. Once lung metastasis occurs, the disease is incurable.
General risk factors include :
Age 50 yrs or older, Male, Fair Skin (burns easily, very or rarely tans)
Geography–lives closer to the equator (Florida, Australia)
History of prior non-melanoma skin cancer
Exposure to UV light--natural or tanning bed or treatment (psoralen plus UVA (PUVA) for psoriasis
Exposure to chemical carcinogens (arsenic, tar)
Radiation exposure–treatment for other cancers (lymphomas, etc)
Chronic immunosuppression–a history of solid-organ transplantation, hematologic malignancy (CLL), HIV infection or long-term use of immunosuppressive medications for an autoimmune condition
Chronic scarring condition–Marjolin ulcer refers to an SCC that arises from chronically scarred or inflamed skin. Patients may report a change in the skin (induration, ulceration, weeping) at the site of a preexisting scar or ulcer. The latency period is often 20-30 years. Major burn scars. Chronic venous ulcers. Not scars from simple lacerations.
Human Papilloma Virus (HPV) infections–Virally induced SCC most commonly manifests as a new or enlarging warty growth on the penis, vulva, perianal area, or periungual region. Patients often present with a history of "warts" that have been refractory to various treatment modalities in the past.
A wart-like growth that crusts and occasionally bleeds.
A persistent, scaly red patch with irregular borders that sometimes crusts or bleeds
An open sore that bleeds and crusts and persists for weeks.
An elevated growth with a central depression that occasionally bleeds. A growth of this type may rapidly increase in size.
Treatment Modalities are similar to those of BCC (see yesterday's post).
Most SCCs are readily treated with an expectation of cure. The 3-year disease-specific survival rate has recently been estimated to be 85%; this rate approaches 100% for lesions with no high-risk factors (see below), but it decreases to 70% for patients with at least 1 risk factor. Local recurrence following definitive treatment is not uncommon, and metastasis and death may ensue. Most series in the literature quote an across-the-board prevalence rate of metastasis for primary cutaneous SCC of 2-6%.
When SCC does metastasize, it is usually occurs within several years from the time of diagnosis and involves the primary draining lymph nodes. In general, metastasis from SCC of the forehead, the temples, the eyelids, the cheeks, and the ears is to the parotid nodes; metastasis from SCC of the lips and the perioral region is primarily to the submental and submaxillary (upper cervical) nodes. Once nodal metastasis of cutaneous SCC has occurred, the overall 5-year survival rate has historically been in the range of 25-35%. Prognosis is extremely poor for patients who have 1) a compromised immune system, 2) metastasis to multiple lymph nodes, or 3) cervical lymph nodes greater than 3 cm in diameter. Metastasis to distant organs remains incurable. Thus, close surveillance and early detection of nodal metastasis can be life saving and is extremely important.
There is a subset of SCC that is considered high risk because of its aggressive behavior. These SCC have a tendency for rapid local growth, higher rates of recurrence and regional metastasis, and a poor prognosis. SCC can be characterized as high-risk by virtue of tumor-related factors (intrinsic factors), patient-related factors (extrinsic factors), or a combination of both.
Risk factors associated with higher rates of recurrence and metastasis
Tumor-related factors in high-risk SCC:
Tumor location (ie, lips,ears, scar)--The historical rates of metastases for SCC of the external ear and the lip are approximately 11% and 10-14%, respectively. Marjolin ulcer subtype of SCC behaves aggressively, with a metastatic rate of approximately 18-38%.
Tumor size greater than 2 cm –These may have a metastatic rate of up to 30.3%.
Invasion to subcutaneous fat (or deeper) --SCC with a depth of less than 2 mm rarely metastasizes. SCC with a depth of invasion less than 4 mm has a historical recurrence rate of 5.3% and a metastasis rate of 6.7%; these rates increase to 17.2% and 45.7%, respectively, for tumors invading greater than 4 mm.
Poorly differentiated tumor – are generally accepted to behave more aggressively.
Recurrent tumor-- has a site-dependent rate of metastasis of 25-45%.
Perineural involvement --has been estimated to occur in 2.4-14% of persons with cutaneous SCC, most commonly in elderly men with tumors of the head and neck. The prognosis in such cases is extremely poor, with historical rates of local recurrence and metastasis reported to be as high as 47%.
Patient-related factors in high-risk SCC
Organ transplant recipient --SCC in OTRs occurs more frequently, appears at an earlier age, is often multicentric, and may be clinically aggressive. The rate of local recurrence has been reported to be as high as 13.4%, while metastasis occurs in 5-8% of patients. Metastatic SCC in OTRs has a dismal prognosis, with a 3-year disease-specific survival of only 56%.
Hematologic malignancy (eg, CLL) --in patients with CLL, the recurrence rate of SCC treated with MMS was 7-fold higher at 5 years compared with patients without CLL. In addition, a small case-control study found the 5-year cumulative incidence of SCC metastasis to be 17.7% for patients with CLL.
Chronic immunosuppressive therapy or disease state: HIV infection or AIDS--In one small case series, 5 of 10 patients with HIV and aggressive SCC died of metastasis within 7 years of the initial diagnosis.
Patients should be counseled to avoid excessive UV radiation by limiting outdoor activity to early morning and late afternoon, using protective clothing, and wearing a broad-brimmed hat to shade the head and the neck area. Counseling patients regarding treatment of areas of chronic skin inflammation or trauma is important in preventing the future development of SCC at those sites.