Introduction: Who Should Undergo Diagnostics

People who experience certain warning signs related to their lungs should seek medical evaluation. Common symptoms that should prompt a visit to a healthcare provider include persistent coughing, shortness of breath, coughing up blood or bloody mucus, and chest discomfort that doesn’t go away. These symptoms can be mild at first and are sometimes mistaken for less serious conditions like asthma or the flu, which is why many cases go unnoticed in early stages.^[1][15]

Stage II lung cancer means the tumor has started to spread within the lung but hasn’t traveled far. At this stage, the tumor may be between 4 and 7 centimeters in size, or it may have reached nearby lymph nodes. The cancer develops in or around the airways and may partially block them, but it remains treatable with good outcomes possible when detected early.^[2][3]

Individuals at higher risk should be especially vigilant about seeking diagnostics. This includes current or former smokers, as smoking is a major risk factor for adenosquamous carcinoma. The average age at diagnosis is about 70 years, and men are affected more often than women. Anyone with a history of lung problems or exposure to harmful substances should discuss screening options with their doctor.^[4]

Diagnostic Methods

The Challenge of Diagnosing Adenosquamous Carcinoma

Diagnosing adenosquamous carcinoma of the lung presents unique challenges compared to other lung cancer types. This is because the disease contains two different types of cancer cells mixed together—adenocarcinoma cells and squamous cell carcinoma cells. According to medical definitions, each type must make up at least 10% of the tumor to be classified as adenosquamous carcinoma. However, this mixed nature makes it extremely difficult to identify the cancer accurately before surgery.^[1][4]

Intratumoral heterogeneity—meaning the tumor has different cell types throughout its structure—often leads to diagnostic confusion. Studies show that adenosquamous carcinoma is misdiagnosed as either pure adenocarcinoma or pure squamous cell carcinoma in at least half of biopsy cases taken before surgery. In one study, nearly all cases (98%) were either misdiagnosed or not diagnosed at all until doctors examined the complete surgical specimen. This happens because small biopsy samples may only capture one component of the tumor, missing the mixed nature entirely.^[4]

Initial Physical Examination and Medical History

The diagnostic journey typically begins with a visit to your primary care doctor or a specialist. During this visit, your healthcare provider will ask detailed questions about your symptoms, how long you’ve had them, and whether they’ve changed over time. They’ll also review your medical history, including any history of smoking, exposure to harmful substances, and family history of cancer.^[3]

A physical examination follows, during which the doctor listens to your breathing with a stethoscope and checks for any abnormal sounds in your lungs. They may also examine your lymph nodes to see if any are swollen, which could indicate cancer has spread. While a physical exam alone cannot diagnose lung cancer, it helps doctors decide which tests to order next.

Imaging Tests

Imaging tests create pictures of the inside of your body and are essential for finding and evaluating lung tumors. A chest X-ray is usually the first imaging test ordered when lung cancer is suspected. This simple test can reveal abnormal masses or spots in the lungs, though it cannot definitively identify cancer or determine its exact type.^[3]

Computed tomography (CT) scans provide much more detailed images than standard X-rays. A CT scan takes multiple X-ray pictures from different angles and combines them using a computer to create cross-sectional images of your chest. These images can show the size and location of tumors, whether they’ve spread to nearby structures, and if lymph nodes are enlarged. CT scans are particularly helpful in staging the cancer—determining how far it has spread.^[3]

Positron emission tomography (PET) scans may also be used, sometimes combined with CT scans in a single procedure called a PET-CT scan. During a PET scan, a small amount of radioactive sugar is injected into your body. Cancer cells absorb more of this sugar than normal cells because they grow faster and need more energy. The scanner then detects where the radioactive sugar has accumulated, helping identify both the primary tumor and any areas where cancer may have spread.^[10]

Biopsy Procedures

A biopsy is the removal of a small sample of tissue for examination under a microscope. It’s the only way to definitively diagnose cancer and determine its specific type. For suspected lung cancer, several biopsy methods may be used depending on the tumor’s location and accessibility.^[3]

Bronchoscopy is a common procedure where a thin, flexible tube with a light and camera (called a bronchoscope) is inserted through your nose or mouth, down your throat, and into your airways. The doctor can see the inside of your airways and use tiny instruments to collect tissue samples from suspicious areas. An advanced technique called endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-GS-TBLB) uses ultrasound to guide the biopsy needle more precisely to the tumor.^[10]

For tumors located in the outer areas of the lung, a needle biopsy may be performed through the chest wall. Using CT scan guidance, a radiologist inserts a thin needle through the skin and into the lung to extract tissue from the tumor. This procedure is also called a percutaneous needle biopsy.

In some cases, samples may be taken from lymph nodes. Mediastinoscopy is a surgical procedure where a small incision is made at the base of the neck, and a thin tube is inserted to examine the area between the lungs (the mediastinum) and take samples from lymph nodes there.^[1]

Pathological Examination

After tissue samples are collected, they’re sent to a pathologist—a doctor who specializes in diagnosing diseases by examining cells and tissues. The pathologist examines the samples under a microscope to identify cancer cells and determine their type. For adenosquamous carcinoma, the pathologist must identify both adenocarcinoma components (gland-forming cancer cells) and squamous cell carcinoma components (flat cancer cells).^[1]

However, because small biopsies may only show one cell type, the definitive diagnosis often requires examining the entire tumor after it’s been surgically removed. This is called examining the surgically resected gross specimen, and it remains the most effective way to properly diagnose adenosquamous carcinoma. One case report described how a patient received three different results from different types of samples—squamous cell carcinoma from bronchial biopsy, adenocarcinoma on immunohistochemistry testing, and undifferentiated non-small cell lung cancer from pleural fluid—before surgery revealed the true adenosquamous nature.^[1][4]

Molecular and Genetic Testing

Modern cancer diagnosis goes beyond simply identifying the cell type. Doctors now also test cancer cells for specific genetic changes or mutations that drive cancer growth. These tests are particularly important because they can identify patients who might benefit from targeted therapies—medications designed to attack cancer cells with specific genetic changes.^[1]

Epidermal growth factor receptor (EGFR) testing looks for mutations in a gene that controls cell growth. EGFR mutations are found in about 30% of adenosquamous carcinomas. Patients whose tumors have EGFR mutations may respond well to medications called EGFR tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, gefitinib, or dacomitinib.^[1][4][10]

ALK rearrangement testing identifies changes in another gene called ALK. About 5% of adenosquamous carcinomas have ALK rearrangements, and patients with these changes may benefit from targeted drugs like crizotinib.^[1][4]

PD-L1 expression testing measures a protein on cancer cells that helps them hide from the immune system. Studies show that PD-L1 is expressed in about 11% of adenocarcinoma components and 28% of squamous cell components in adenosquamous carcinoma. Patients with high PD-L1 expression may respond better to immunotherapy drugs that help the immune system fight cancer.^[4]

Other common mutations include changes in the p53 gene, found in about 25% of adenosquamous carcinomas, though no targeted drugs are currently available for this mutation.^[4]

Laboratory Tests

Blood tests are routinely performed as part of the diagnostic workup. While they cannot diagnose lung cancer by themselves, they provide important information about your overall health and how well your organs are functioning. This information helps doctors plan treatment and assess whether you’re healthy enough for surgery or other therapies.^[3]

Complete blood counts check your red blood cells, white blood cells, and platelets. Liver and kidney function tests ensure these organs can handle cancer treatments. Some patients may also have blood tests to measure tumor markers, though these are less commonly used for lung cancer diagnosis.

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or combinations of treatments. Because adenosquamous carcinoma is rare—accounting for only 2% to 4% of all lung cancers—participating in clinical trials may provide access to innovative therapies not yet widely available.^[4]

Standard Eligibility Testing

To participate in a clinical trial, patients must meet specific criteria established by the researchers. These criteria ensure the trial tests the treatment in the right patient population and maintains safety. Standard diagnostic tests used to determine clinical trial eligibility include all the tests mentioned above—imaging scans, biopsies, and laboratory tests—but with particular attention to specific details.^[3]

Most clinical trials require confirmation of the cancer diagnosis through pathology reports. For adenosquamous carcinoma trials, documentation must clearly show the presence of both adenocarcinoma and squamous cell carcinoma components. Trials may also specify minimum percentages of each component required for enrollment.

Staging Requirements

Clinical trials typically enroll patients at specific cancer stages. For stage II adenosquamous carcinoma, the staging criteria follow the American Joint Committee on Cancer (AJCC) system. Stage II includes several subcategories based on tumor size, lymph node involvement, and spread.^[2]

Stage IIA includes tumors that are larger than 5 cm but not more than 7 cm without lymph node involvement (T2b, N0, M0), or smaller tumors (T1a, T1b, or T2a) that have spread to nearby lymph nodes inside the lung (N1). Stage IIB includes larger tumors (T2b) with lymph node involvement (N1), or tumors larger than 7 cm or invading nearby structures but without lymph node spread (T3, N0, M0).^[2]

The designation M0 means no distant metastasis—the cancer hasn’t spread to other organs. Confirming this requires thorough imaging, often including PET-CT scans to rule out spread to distant sites.

Molecular Profiling Requirements

Many modern clinical trials, especially those testing targeted therapies, require specific molecular test results before enrollment. For adenosquamous carcinoma, trials may specifically recruit patients whose tumors have certain genetic mutations. For example, a trial testing an EGFR inhibitor would require confirmation of an EGFR mutation through genetic testing of the tumor tissue.^[1]

Comprehensive molecular profiling panels test for multiple genetic changes at once. These panels might include testing for EGFR mutations, ALK rearrangements, ROS1 rearrangements, BRAF mutations, and other genetic alterations. Having these results available can help match patients to appropriate clinical trials more quickly.

Performance Status Assessment

Clinical trials also evaluate a patient’s overall health and ability to carry out daily activities using a performance status score. The most common system rates patients from 0 (fully active, no restrictions) to 4 (completely disabled, confined to bed or chair). Most clinical trials require patients to have a performance status of 0, 1, or sometimes 2 to ensure they’re healthy enough to receive experimental treatments and provide meaningful data.^[10]

Additional Specialized Tests

Depending on the specific trial, additional diagnostic tests may be required. These might include pulmonary function tests to measure lung capacity and breathing ability, cardiac evaluations to ensure the heart can handle treatment-related stress, or specialized imaging studies. Trials testing immunotherapy drugs often require PD-L1 expression testing to identify patients most likely to benefit.

Some trials may also require fresh tumor biopsies at specific time points during treatment to monitor how the cancer is responding at a cellular level. While this means undergoing additional procedures, the information gathered helps researchers understand how treatments work and contributes to developing better therapies for future patients.