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Overview of Cutaneous Squamous Cell Carcinoma


An overview of CSCC, including diagnosis, distinguishing CSCC from head and neck cancer, and risk factors for developing advanced disease.


Omid Hamid, MD: Cutaneous squamous cell carcinoma [CSCC] is a malignancy of the skin that starts in the squamous cells of the skin. It is not like your standard skin cancer; most people think of melanoma. This is part of the non-melanoma skin cancers that comprise basal cell carcinoma, Merkel cell carcinoma, and squamous cell carcinoma. It is the second deadliest skin cancer behind melanoma. It has a higher incidence than melanoma. There are about 700,000 cases per year in the United States. This is a 50-fold to 200-fold increase over the last 3 decades, and its incidence is increasing 2% to 4% per year.

The majority of the time squamous cell carcinoma is easily taken care of by radiation or surgical resection. About 2% to 4% of those become metastatic, and another percentage become locally advanced. Those are the ones that we’re concerned about. Those have a significant morbidity because they are locally invasive, and a mortality that can be as high as 70%. So squamous cell carcinoma like that poses a significant problem for the oncologist and his or her patient.

CSCC usually presents as a growing or nonhealing ulcer in the skin. Sometimes it’s misdiagnosed. It can look like basal cell carcinoma. At certain times it is not painful, so patients miss it or don’t bring it up to their physician. The majority of the times when it’s seen it can be easily taken care of surgically, either by a surgical resection or a by Mohs surgeon at a dermatologist’s office.

Morgana Freeman, MD: Let’s talk about how CSCC is diagnosed. Typically, this will present as a pink raised scaly lesion or nonhealing wound that appears most often on the head and neck but can also appear on the extremities, typically in heavily sunburned areas. Oftentimes, these are found in patients near the scalp line. They can be encountered by a patient’s spouse, for example, or even something as routine as getting a haircut. It comes to attention most of the time when it becomes painful or itchy. The itchiness is oftentimes a worrisome symptom that may indicate early perineural invasion. Most of the time patients will present to their primary care physician or dermatologist to have the skin lesion investigated.

I think it’s important for healthcare providers to understand that there are great differences that exist between skin CSCC and head and neck squamous cell cancer. Primarily, cutaneous squamous cell carcinoma is sun damage induced. About 70% of the time, these are UV [ultraviolet] radiation—related cancers. Whereas, head and neck mucosal squamous cell carcinomas are oftentimes related to smoking, tobacco use, or alcohol abuse. In the majority of cases, these are also related to HPV [human papillomavirus]. So there are differences right there in the etiology. The other thing to keep in mind is that these cancers are managed very differently. Where we think of primary head and neck squamous cell carcinomas being treatable either with surgery or chemoradiation, cutaneous squamous cell carcinoma is managed with surgery in many cases, followed by adjuvant radiation. Only in very rare circumstances, it’s followed by chemotherapy.

So there are important risk factors to consider when thinking about CSCC and what might put a patient at further risk for local or distant metastases. Primarily we think about patients who are immunocompromised, either those who have a history of solid organ transplant or prior bone marrow transplant, but also patients who are relatively immunocompromised by a comorbid medical condition. Classically, we think of chronic lymphocytic leukemia but also patients who have HIV and AIDS. Those patients, unfortunately, are at higher risk of more advanced disease because of a compromised immune system.

It’s very important to think about imaging when appropriate for patients who present with advanced CSCC and in particular those who have large lesions that may be involving some in the underlying fascia or muscle, or even symptoms of perineural invasion like local itching. As I mentioned, about 70% of these cases will present on the head and neck, and it’s not uncommon for us in our practice to order an MRI [magnetic resonance imaging] of the head and neck or a CT [computed tomography] scan to rule out either bone invasion or perineural invasion. In some cases, if local lymph node involvement is suspected, then an ultrasound of the draining nodal basin is needed. In some cases, even a PET [positron emission tomography] scan if metastatic disease is suspected is also clinically indicated. Depending upon how long the lesion might be present, and any accompanying symptoms that the patient might be presenting with, the clinician can decide on the appropriate medical imaging. But those are typically the modalities that we use, not only for initial diagnosis but also for subsequent treatment follow-up.

When the AJCC [American Joint Committee on Cancer] version 8 guidelines were updated, there were some important differences between AJCC 8 and AJCC 7. The most important differences were on how we thought about the risk factors of the primary tumor being at risk for local or distant metastasis. We started to look a little bit more at risk factors for more aggressive disease, including perineural invasion and the location of the lesion. We actually found that when we changed to AJCC version 8, we were better able to identify those tumors that were more clinically aggressive. In fact, we captured about 70% of those cases compared to 16% previously. We’re also better able to risk stratify those patients for more aggressive disease. Obviously, those things are important in terms of our treatment considerations when thinking about how and when to involve a multimodality team, including the expertise from a medical oncologist such as myself.

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