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Accurately Assessing Prognosis for High-Risk Squamous Cell Carcinoma

Accurately Assessing Prognosis for High-Risk Squamous Cell Carcinoma

Case authors Danny Zakria, MD, MBA, Ryan Rivera-Oyola, MD, and Darrell Rigel, MD, MS, present a case of a 58-year-old male with a history of sun exposure and a skin lesion showing signs of malignancy.

By Danny Zakria, MD, MBA, Ryan Rivera-Oyola, MD, Darrell Rigel, MD, MS

This case describes a 58-year-old Fitzpatrick II White male with no significant past medical history who presented to the office for a skin check. He grew up in Florida and has had significant sun exposure throughout his life. Additionally, he works outside in construction and only intermittently uses sunscreen. He has had many spots frozen but has never been diagnosed with a skin cancer. His father had many moles removed and he believes he had skin cancer, but he is not sure what kind. 

At the beginning of the exam, he pointed out a new spot that he first noticed 2 years ago. He says the spot occasionally itches and has bled a few times in the past year. He also notes that it has gotten progressively bigger over the last two years. On exam, on the left lateral neck there is 5.1 cm x 3.4 cm erythematous plaque with scale and a 3 cm x 1.5 cm central ulceration. He previously tried using over-the-counter hydrocortisone 1% cream without any improvement. 

Physical Exam, Lab Results and Medical History 

A biopsy was performed which showed a poorly differentiated squamous cell carcinoma (SCC). Given that the tumor had several high-risk features, the specimen was sent to Castle Biosciences for DecisionDx-SCC testing to further assess the tumor’s risk of metastasis. 

Diagnostic Review 

Important considerations when diagnosing this patient included the location of the lesion, the patient’s personal history of sun exposure, and his family history of skin cancer. Additionally, the progression of the lesion over time and its persistence and growth with occasional bleeding raise suspicion for a malignancy. 

Once the biopsy confirmed a diagnosis of SCC, it was critical to assess the patient’s prognosis. While SCC typically has an excellent prognosis and 5-year cure rates greater than 90%, up to 6% of these tumors will metastasize.1,2 Metastasis significantly worsens survival, with the 5-year survival rate dropping to 50% to 83% for regional metastasis and below 40% for distant metastasis.3 

There are 2 commonly used staging systems for SCC, the Brigham and Women’s Hospital (BWH) classification and the American Joint Cancer Committee eighth edition (AJCC8) staging system. These systems use pathologic data to stage SCC but have several limitations that lead to a low sensitivity (23%-46%) and positive predictive value (12%-13%).4 Utilizing genomic testing through the 40-gene expression profile (GEP) test has been shown to be an independent and accurate predictor of metastatic risk. Additionally, using this test in conjunction with the BWH and AJCC8 staging systems has also been shown to further improve prognostic assessment.

Thus, for a very large SCC such as the one seen in this case, or any tumor with at least 1 other high-risk feature, the 40-GEP test (DecisionDx-SCC) is a helpful way to assess a patient’s risk of metastasis and adjust management decisions accordingly.

Which of the following is NOT a National Comprehensive Cancer Network (NCCN) high risk feature for squamous cell carcinoma?

Before Photos
Click to enlarge image
BEFORE: 5.1 cm x 3.4 cm erythematous plaque with scale and a 3 cm x 1.5 cm central ulceration on left lateral neck

Treatment Discussion and Outcome

The result of the DecisionDx-SCC test was a Class 2B. This is the highest-risk group which corresponds to a 3-year metastasis-free survival of just under 50%. As a result of this highest risk designation, the patient was referred to medical oncology to be evaluated for neoadjuvant chemotherapy. He was subsequently started on cemiplimab, which resulted in a 60% reduction in the size of the tumor. At this point, the SCC was successfully excised with Mohs micrographic surgery and the patient is seen every 3 months in clinic to monitor for recurrence or metastasis.


  1. Stratigos AJ, Garbe C, Dessinioti C, et al. European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention. Eur J Cancer. 2020;128:60-82. doi:10.1016/j.ejca.2020.01.007 
  2. Brougham ND, Dennett ER, Cameron R, Tan ST. The incidence of metastasis from cutaneous squamous cell carcinoma and the impact of its risk factors. J Surg Oncol. 2012;106(7):811-815. doi:10.1002/jso.23155 
  3. Dessinioti C, Pitoulias M, Stratigos AJ. Epidemiology of advanced cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol. 2022;36(1):39-50. doi:10.1111/jdv.17709 
  4. Ruiz ES, Karia PS, Besaw R, Schmults CD. Performance of the American Joint Committee on Cancer Staging Manual, 8th Edition vs the Brigham and Women's Hospital Tumor Classification System for Cutaneous Squamous Cell Carcinoma. JAMA Dermatol. 2019;155(7):819-825. doi:10.1001/jamadermatol.2019.0032 
  5. Ibrahim SF, Kasprzak JM, Hall MA, et al. Enhanced metastatic risk assessment in cutaneous squamous cell carcinoma with the 40-gene expression profile test. Future Oncol. 2022;18(7):833-847. doi:10.2217/fon-2021-1277
Case Discussion

Aaron Farberg, MD Bare Dermatology Baylor Scott & White Health System Dallas, TX


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