Introduction: Who Should Undergo Diagnostics and When

Anyone who notices unusual changes on their skin should consider seeking diagnostic evaluation. Squamous cell carcinoma typically appears on parts of the body that receive the most sun exposure, such as the face, ears, lips, neck, scalp, hands, arms, and legs^[1]. However, this type of cancer can also develop in less expected areas, including the genital region and other locations not regularly exposed to sunlight^[2].

You should arrange to see your doctor if you notice a thick, scaly area on your skin that does not heal over time. This may bleed, form a sore, or gradually grow larger^[3]. Other warning signs include rough-feeling bumps or growths that might crust over like a scab, growths that are raised with a depression in the middle, wounds or sores that won’t heal or that heal and then return, or flat, scaly, red areas of skin that measure about an inch or more across^[1]. Any of these changes warrant medical attention, even if they seem minor at first.

Certain groups of people face a higher risk of developing squamous cell carcinoma and should be especially vigilant about checking their skin and seeking timely diagnostics. This includes individuals over 60 years of age, those with fair skin tones, people who spend a lot of time in the sun such as outdoor workers, individuals with sunspots (also called solar keratoses or actinic keratoses), people with weakened immune systems, those with human papillomavirus (HPV) infections, and men, who are about twice as likely to develop this cancer as women^[3][1].

If you have already been treated for skin cancer in the past, you are at increased risk of developing another skin cancer^[3]. This makes regular skin checks and prompt diagnostic evaluation of any new or changing skin lesions even more important. It is also advisable to check your skin regularly at home, looking for any changes in the shape, color, or size of spots or moles. Being familiar with what your skin normally looks like helps you notice when something is different^[3].

Diagnostic Methods

The process of diagnosing squamous cell carcinoma begins with a thorough examination by a healthcare professional. The first step is typically a physical examination where a member of your healthcare team will ask about your health history and carefully inspect your skin for signs of squamous cell carcinoma^[6]. During this exam, the doctor will look at any unusual areas of skin, paying attention to features such as texture, color, size, and whether the area bleeds or forms a crust.

While a physical exam provides important clues, a definitive diagnosis of squamous cell carcinoma requires laboratory confirmation. This is achieved through a procedure called a biopsy, which involves removing a sample of tissue for testing in a laboratory^[6]. The biopsy is essential because it allows specialists to examine the suspicious cells under a microscope to determine whether cancer is present and, if so, what type it is.

There are several ways a healthcare provider can perform a biopsy. The doctor may use a tool to cut away, shave off, or punch out some or all of the area of skin that looks unusual^[6]. Once the tissue sample is collected, it is sent to a laboratory where trained specialists, called pathologists, analyze the cells. This analysis confirms whether the cells are cancerous and helps identify specific characteristics of the cancer that may influence treatment decisions.

For individuals with a previous history of skin cancer or with multiple risk factors, regular full-body skin examinations by a dermatologist are recommended. These examinations can detect early changes that might otherwise go unnoticed^[4]. Regular screenings are particularly important for high-risk patients, as they facilitate early detection and treatment, improving the chances of a successful outcome.

In cases where the squamous cell carcinoma is more advanced, additional diagnostic procedures may be necessary. If there is concern that the cancer has spread beyond the skin to nearby lymph nodes or other parts of the body, imaging tests or a sentinel lymph node biopsy may be required^[4]. These tests help doctors understand the extent of the disease, which is crucial for planning the most appropriate treatment approach.

The role of dermatopathology, which is the specialized study of skin tissue under a microscope, is central to accurate diagnosis. Dermatopathologists have expertise in identifying subtle differences between various types of skin cancers and other skin conditions. Their analysis of biopsy samples provides detailed information about the cancer, such as its depth, subtype, and whether it has invaded deeper layers of the skin^[14]. This information is vital for determining the stage of the cancer and selecting the best treatment.

It is important to note that not all suspicious skin changes turn out to be cancer. Some may be precancerous lesions, such as actinic keratosis, which are early skin changes that could turn into squamous cell carcinoma if not treated^[3]. Others may be benign growths or other skin conditions. Only a biopsy and laboratory analysis can provide a definitive answer, which is why seeking medical evaluation for any unusual skin changes is so important.

Diagnostics for Clinical Trial Qualification

For patients considering participation in clinical trials, the diagnostic process often involves additional steps beyond the standard procedures used for routine diagnosis. Clinical trials are research studies designed to test new treatments or treatment approaches, and they have specific criteria that participants must meet to be eligible. These criteria, known as inclusion and exclusion criteria, are established to ensure the safety of participants and the validity of the research findings.

To determine whether a patient is eligible for a particular clinical trial, doctors will typically require a confirmed diagnosis of squamous cell carcinoma through a biopsy^[6]. This is the same diagnostic procedure used in standard care, but in the context of a clinical trial, the biopsy results must meet specific requirements. For example, some trials may only accept patients with a certain stage or subtype of squamous cell carcinoma, or those whose cancer has specific biological characteristics.

In addition to a biopsy, patients may need to undergo further testing to assess the extent of their disease. This could include imaging tests to check whether the cancer has spread to nearby lymph nodes or other parts of the body^[4]. In more advanced cases, a sentinel lymph node biopsy might be required to determine if cancer cells have reached the lymphatic system. These tests help researchers understand the stage and aggressiveness of the cancer, which is important for matching patients to appropriate trials.

Clinical trials may also require baseline health assessments to ensure that participants are healthy enough to safely undergo the experimental treatment being tested. This can involve blood tests, kidney and liver function tests, heart function assessments, and other routine laboratory work. The goal is to identify any underlying health issues that could complicate the trial or put the patient at risk.

Some clinical trials are specifically designed for patients with advanced or metastatic squamous cell carcinoma, where the cancer has spread beyond the original site. In these cases, additional diagnostic procedures such as computed tomography (CT) scans, magnetic resonance imaging (MRI), or positron emission tomography (PET) scans may be required to evaluate the location and extent of metastatic disease. These imaging tests provide detailed pictures of the inside of the body and help doctors see where the cancer has spread.

Participation in a clinical trial can offer access to cutting-edge treatments that are not yet widely available, but it is important to understand that eligibility is determined through a rigorous diagnostic and evaluation process. Patients interested in clinical trials should discuss this option with their healthcare provider, who can help them understand what diagnostic tests will be needed and whether they might be a good candidate for a specific study.