Cutaneous Oncology: Part 3

High Risk Squamous Cell Carcinoma

Marc Brown, MD

In this presentation, Dr Brown discusses high risk squamous cell carcinomas. Dr Brown comments that this is the tumor than worries him more than any others.


Squamous cell carcinoma (SCC) is the second most common type of cancer and more than 250,000 new cases are reported every year. The estimated lifetime risk is between 10 to 15 percent. The incidence of SCC increases dramatically with age and in older patients (80+), there are more skin cancer deaths from SCC than melanoma. The ratio of SCC is 2:1 in males versus females.

 Risk Factors

It is important that dermatologists understand the risk factors for SCC development; these include sun exposure, ionizing radiation, HPV infection, immunosuppression, genetic syndrome, chronic inflammation, burns and non-healing ulcers, chemical exposures, older men with fair skin and UV light. In addition, healthcare providers should recognize the risk factors for SCC recurrence and metastasis. This involves assessing the size, depth, histology and clinical features of the tumor as well as the overall immune status of the patient.  CLL patients also represent at “at risk” group for metastasis.

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Dr Brown feels that the size and the depth of the tumor are probably the two biggest risk factors. There is evidence that any tumor greater than 2 cm in size if it is an invasive SCC increases the risk for both recurrence and metastatic disease. Depth is also very important. Literature suggests that tumors in the 4-6mm, Clark IV-V, or a deep subQ/muscle depth of invasion would be considered to be a high risk squamous cell cancer.

Regarding location, areas of high risk include the ear, lip, and genitalia.

Histology is extremely important. Risk factors include:

  • Perineural invasion
  • Poorly differentiated
  • Acantholytic, adenoid squamous
  • Desmoplastic

Clinical features of high risk SCC include rapid growth, pain, paresthesias, and cranial nerve involvement. Any of these clinical features should raise a red flag.

Immunosuppression is another important risk factor for SCC. These consist of:

  • Organ transplant recipients
  • HIV
  • Cancer: CLL
  • Immunosuppressive drugs


Mortality from SCC

A 2005 publication from Clayman et al conducted a prospective analysis of 210 patients for a median of 22 months. The disease specific survival was 85%. The significant risk factors included recurrent SCC, tumor size greater than 4 cm, tumor depth greater than 7mm, subQ invasion and perineural invasion. The patients with no risk factors have 100 percent survival.

A similar article published in the Lancet looked at 615 patients over 12 years. 26 patients (4%) developed metastatic disease. Patients with tumors less than 2 mm in size did not develop metastatic disease. 16 percent of the patients with tumors greater than 6mm in size did develop metastatic cancer. Other prognostic factors included immunosuppression, tumor in the ear and an increased horizontal size.

National Comprehensive Cancer Network (NCCN) Guidelines

The NCCN has recently published guidelines for the treatment of high risk SCC and dermatologists can refer to these guidelines for optimal patient care.

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Treatment of SCC and Metastatic Cancer


High risk SCC accounts for approximately 2500 deaths per year. When clinically detectable nodal metastatic disease has occurred, the prognosis is poor ( 5 year survival less than 30%).

Treatment for these patients can consist of:

  • “Watchful waiting”
  • Adjuvant radiation
  • ELND
  • Role of sentinel role biopsy in high risk SCC


 SCC in Organ Transplant Patients


In the United States, there are approximately 28,000 transplants per year. There are over 110,000 people waiting for transplants and over 170,000 people living with an organ transplant.

What does this mean for dermatologists? This is an area to which we should pay particular attention. Because of the extended long-term survival of organ transplant recipients, dermatologists will be caring for them. Of importance, 70 percent of organ transplant recipients will eventually develop skin cancer and five to seven percent will die of their skin cancers.