Introduction: Who Needs Diagnostic Testing
When a person notices unusual changes on their skin that don’t heal or go away, it’s important to see a doctor for an evaluation. Squamous cell carcinoma typically appears on areas of the body that receive a lot of sun exposure, such as the scalp, backs of hands, ears, or lips. The cancer can show up as rough-feeling bumps or growths that might crust over like a scab and bleed, wounds that won’t heal, or areas of flat, scaly, red skin.[3]
Anyone who finds a lump or experiences pain in the neck or throat that doesn’t go away should check with their doctor, as these could be signs that squamous cell cancer has spread to lymph nodes in the neck. This condition is called metastatic squamous neck cancer, and it requires careful examination to find where the cancer originally started in the body.[2]
People at higher risk for developing squamous cell carcinoma include those with pale complexions, blue or green eyes, blonde or red hair, individuals who are 65 years of age or older, those with weakened immune systems or who have received organ transplants, and people who have had significant chemical exposure such as from cigarettes or arsenic. Men are about two times more likely to develop squamous cell carcinoma than women.[3]
Classic Diagnostic Methods
Physical Examination
The diagnostic process begins with a thorough physical examination. A healthcare provider will ask about your personal and family health history, including any past exposure to sunlight or tanning beds, previous skin cancers, and current symptoms. They will carefully examine your skin looking for any unusual growths, bumps, or areas of concern.[12]
For metastatic squamous neck cancer, the physical exam includes a detailed evaluation of the head and neck region. The doctor checks for swollen lymph nodes in the neck and looks for signs of disease that might indicate where the cancer first began to grow. This examination often includes a fiber optic examination to look at areas that are not easily visible, such as the inside of the throat, nose, and voice box.[7]
Skin Biopsy
If the doctor finds an area that looks suspicious during the physical exam, they will perform a biopsy, which means removing a small sample of tissue for testing in a laboratory. This is the most important step in diagnosing squamous cell carcinoma because it allows doctors to confirm whether cancer cells are present and identify exactly what type of cancer it is.[12]
During a biopsy procedure, the healthcare provider uses a specialized tool to cut away, shave off, or punch out some or all of the area of skin that looks unusual. The tissue sample is then sent to a laboratory where it is examined under a microscope by a specialist called a pathologist. The pathologist looks for cancer cells and determines their characteristics, which helps guide treatment decisions.[12]
Testing for Metastatic Disease
When squamous cell cancer spreads to lymph nodes in the neck or around the collarbone, doctors need to perform additional tests to find the primary tumor—the place where the cancer first started growing. This is important because treatment for metastatic cancer is typically the same as treatment for the primary tumor. For example, if lung cancer spreads to the neck, the cancer cells in the neck are actually lung cancer cells and would be treated accordingly.[2]
The diagnostic workup for metastatic squamous neck cancer includes checking for a primary tumor in several body systems. Doctors examine the respiratory tract, which includes parts of the trachea (windpipe), and the upper digestive tract, including the lips, mouth, tongue, nose, throat, vocal cords, and part of the esophagus (the tube that connects your mouth to your stomach). They also check the genitourinary system. Sometimes, despite thorough testing, doctors cannot find where the cancer originally started. When this happens, it’s called an occult primary tumor, meaning the original tumor remains hidden. In many cases, the primary tumor is never found.[2][7]
Advanced Imaging Tests
Various imaging tests may be used to help diagnose metastatic squamous cell carcinoma and determine how far it has spread. These tests create detailed pictures of the inside of the body without requiring surgery. Common imaging methods include computed tomography (CT) scans, which use X-rays to create detailed cross-sectional images of the body, and magnetic resonance imaging (MRI), which uses powerful magnets and radio waves to produce images of soft tissues.[12]
Positron emission tomography (PET) scans may also be used in some cases. This type of imaging test uses a small amount of radioactive material to help identify areas of cancer in the body. The radioactive substance tends to collect in cancer cells more than in normal cells, making abnormal areas easier to spot on the scan images.[12]
Endoscopic Examination
When doctors suspect that squamous cell cancer may have spread to areas inside the body, they may perform an endoscopy. This procedure involves inserting a thin, flexible tube with a light and camera on the end through the mouth, nose, or another body opening. The camera allows the doctor to see the inside of the respiratory and digestive tracts in detail. During an endoscopy, the doctor can also take small tissue samples from any suspicious areas for further testing.[7]
Diagnostics for Clinical Trial Qualification
Staging and Classification
When patients are being considered for enrollment in clinical trials studying treatments for metastatic squamous cell carcinoma, doctors need to determine the exact stage and characteristics of the cancer. Advanced squamous cell carcinoma is classified into two main categories: locally advanced SCC, which includes tumors that are large or have penetrated deep into underlying tissues, muscles, or nerves, and metastatic SCC, which includes tumors that have spread beyond the original location to other parts of the body.[5][8]
Clinical trials often have specific criteria regarding the size of tumors, where they are located, and whether they have spread to lymph nodes or distant organs. Accurate staging helps determine which clinical trials a patient may be eligible for and ensures that research results are meaningful and can be compared across different studies.[4]
Tumor Biopsy and Tissue Analysis
For many clinical trials, fresh tissue samples from the tumor may be required. This allows researchers to analyze specific characteristics of the cancer cells, such as genetic mutations or the presence of certain proteins on the cell surface. Some trials test treatments that target particular molecular features of cancer cells, so confirming that a patient’s tumor has these features is essential for trial enrollment.[18]
Assessment of Previous Treatments
Clinical trial eligibility often depends on what treatments a patient has already received. For advanced squamous cell carcinoma, doctors need to document whether the cancer has been previously treated with surgery, radiation therapy, or other therapies, and how the tumor responded to those treatments. Some trials are designed specifically for patients whose cancer has come back after initial treatment or has not responded to standard therapies.[4][10]
Performance Status Evaluation
Clinical trials require assessment of a patient’s overall health and ability to carry out daily activities. This is called performance status and it helps determine whether a patient is strong enough to participate in a trial that may involve experimental treatments. Healthcare providers evaluate factors such as energy levels, ability to care for oneself, and time spent in bed or resting during the day.[6]
Laboratory Testing
Before entering a clinical trial, patients typically undergo comprehensive laboratory testing. Blood tests check for proper functioning of organs like the kidneys, liver, and bone marrow. These tests help ensure that patients can safely tolerate experimental treatments and allow doctors to monitor for any concerning changes during the trial.[12]
Imaging for Trial Baseline
Clinical trials require baseline imaging studies to accurately measure the size and location of tumors before treatment begins. These images are then compared to follow-up scans taken during and after treatment to determine whether the experimental therapy is working. Common imaging tests include CT scans, MRI scans, and PET scans. The specific imaging requirements vary depending on the particular clinical trial and what is being studied.[18]
Multidisciplinary Team Evaluation
Patients with advanced squamous cell carcinoma who are being considered for clinical trials may be evaluated by a multidisciplinary team of specialists. This team might include dermatologists, surgical oncologists, medical oncologists, radiation oncologists, and other healthcare professionals. This comprehensive evaluation ensures that all aspects of a patient’s condition are considered when determining trial eligibility and selecting the most appropriate treatment approach.[5][8]
