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.

Pipeline Psoriatic Arthritis Therapies that Have Efficacy in Psoriasis

Arthur Kavanaugh, MD


There are many potential therapies currently under development for the treatment of psoriatic arthritis (PsA) and appear to fall under two categories: biologic agents and oral agents (kinase/enzyme inhibitors).


Th Cell Development

Th17 cells are elevated in PsA patients. One of the exciting areas of research now is that of additional subsets of Th cells. This is leading to the development of new products in the pipeline for inflammatory diseases such as PsA.

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Ustekinumab in PsA

This data was just presented a few months ago at the American College of Rheumatology looking at ACR scores and PASI scores both of which demonstrated improved response versus placebo.  It is important to keep in mind the effect of weight on therapeutic response as heavier patients experience a lower response in therapy. Obesity seems to be very proinflammatory and it effects how people are responding to their current therapies.

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What do we do with patients who have been on TNF inhibitors already and are not responding?

This group of patients is tough and demonstrates the need for more research.


Emerging Molecules Under Development for Psoriatic Arthritis
  • Secukinumab (IL-17a receptor)
  • Abatacept- (T cell inhibitor)
    • In PsA, you don’t see a great response, particularly in those who have been previously exposed to a TNF inhibitor
    • Tofacitinib
      • Quite effective and lots of data for the RA patients; Safety issues are of concern
    • Apremilast
      • Physicians want patients to do the best that they can on the drug
      • There are rather respectable results with apremilast
      • The skin response was significantly better than placebo, but not robust (about 20% at PASI 75)
      • Few discontinuations due to mild AEs
        • Laboratory parameters appeared rather normally. Lab tests probably won’t have to be done as a part of reevaluation.


 CZP in PsA

Data on certolizumab (CZP) (RAPID-PsA) was presented at ACR and rapid improvements in the signs and symptoms of PsA, as well as skin manifestations and nail disease of psoriasis, were observed among both CZP doses (200mg q2W/400 mg q2W). Similar ACR response rates with CZP were also seen in patients with and without prior anti-TNF exposure.

 Final Thoughts
  • Obesity is a major issue in PsA patients and encouraging patients to lose weight is important to therapeutic response
  • The biosimilar (CT-P13) will be coming soon and it seems to demonstrate similar efficacy, safety, and a PK similar to that of infliximab