Adenosquamous carcinoma of the lung is a rare and complex form of cancer that combines features of two different cancer types, making diagnosis particularly challenging. Understanding when and how this condition is diagnosed can help patients and their doctors make informed decisions about care and treatment planning.

Introduction: Who Should Undergo Diagnostics

If you experience certain symptoms or have risk factors for lung cancer, your doctor may recommend diagnostic testing to investigate whether adenosquamous carcinoma or another lung condition is present. This disease is a rare type of non-small cell lung cancer, which means it is a cancer that does not behave like the faster-growing small cell type. Adenosquamous carcinoma accounts for a small percentage of all lung cancers, making up only about 1.6% of non-small cell lung cancer cases.^[1][3]

People who should consider seeking diagnostic evaluation include those with persistent symptoms such as a cough that won’t go away, shortness of breath that interferes with daily activities, chest pain, or coughing up blood. These warning signs should never be ignored, especially if they last for several weeks or get worse over time.^[4]

Other symptoms that may prompt diagnostic testing include unexplained weight loss, constant tiredness or weakness that doesn’t improve with rest, and frequent respiratory infections like bronchitis or pneumonia that keep coming back. While these symptoms can be caused by many conditions less serious than cancer, they warrant medical evaluation to rule out adenosquamous carcinoma and other lung diseases.^[4]

Certain risk factors make diagnostic screening more important. Smoking cigarettes remains the most significant risk factor for adenosquamous carcinoma, as tobacco exposure damages lung tissue and can lead to cancerous changes over time. However, this cancer can also develop in people who have never smoked. Other risk factors include exposure to harmful substances such as asbestos, radon, or certain industrial chemicals, as well as previous radiation therapy to the chest area and a family history of lung cancer.^[4][16]

Classic Diagnostic Methods

Diagnosing adenosquamous carcinoma of the lung is notably difficult, and one of the biggest challenges is that it cannot be reliably identified before surgery. The disease contains components of both adenocarcinoma, which is a cancer that develops in mucus-producing cells, and squamous cell carcinoma, which originates in the flat cells lining the airways. Because of this mixed nature, small tissue samples obtained before surgery often don’t capture both components, leading to incomplete or incorrect initial diagnoses.^[1]

The diagnostic journey typically begins with imaging studies. A chest X-ray is often the first test performed when someone has lung symptoms. This simple procedure uses radiation to create pictures of the lungs and can reveal abnormal masses or nodules that require further investigation. While a chest X-ray can show that something is wrong, it cannot determine what type of cancer is present.^[4][16]

When a chest X-ray shows concerning findings, doctors usually order a computed tomography scan, commonly called a CT scan. This test is more detailed than a regular X-ray because it takes multiple images from different angles and uses a computer to combine them into cross-sectional views of the lungs. CT scans can show the size, shape, and location of tumors more clearly, and they can also reveal whether cancer has spread to nearby lymph nodes or other structures in the chest.^[4][16]

Once imaging studies identify an abnormal area, the next step is obtaining tissue for microscopic examination. Bronchoscopy is a common procedure used for this purpose. During a bronchoscopy, a doctor inserts a thin, flexible tube with a light and camera through the nose or mouth and down into the airways. This allows the doctor to see inside the lungs and collect small tissue samples from suspicious areas. However, because adenosquamous carcinoma contains two different types of cancer cells that may not be evenly distributed throughout the tumor, these small samples might only capture one component and miss the other.^[4][16]

Another method for obtaining tissue is needle aspiration or needle biopsy, where a doctor uses imaging guidance to insert a needle through the chest wall into the lung mass. This technique can reach tumors that are located in the outer parts of the lungs, away from the main airways. Like bronchoscopy samples, needle biopsies collect relatively small amounts of tissue, which may not be representative of the entire tumor in adenosquamous carcinoma cases.^[4][16]

Because of these limitations with pre-surgical diagnosis, pathology examination of surgically removed tissue remains the most effective and reliable way to properly diagnose adenosquamous carcinoma. When a surgeon removes part or all of a lung containing the tumor, pathologists can examine large sections of the mass under a microscope. This comprehensive evaluation allows them to identify both the adenocarcinoma and squamous cell carcinoma components and confirm the diagnosis of adenosquamous carcinoma.^[1]

According to current diagnostic standards, for a lung cancer to be classified as adenosquamous carcinoma, each component (both the adenocarcinoma part and the squamous cell carcinoma part) must make up at least 10% of the tumor by volume. This criterion, established by the World Health Organization, helps distinguish true adenosquamous carcinomas from other lung cancers that might show minor features of different cell types.^[2]

Laboratory and Molecular Testing

Beyond identifying the cancer under the microscope, doctors may perform additional tests on tumor tissue to look for specific genetic changes that could affect treatment decisions. Testing for EGFR mutations (changes in the epidermal growth factor receptor gene), KRAS mutations, and ALK gene rearrangements has become standard practice for many lung cancers. These genetic alterations can make tumor cells respond to targeted therapies designed to block the abnormal proteins they produce.^[1][8]

Another important test that may be performed on tumor tissue is PD-L1 expression testing. PD-L1 is a protein that can appear on the surface of cancer cells and helps them hide from the immune system. Measuring PD-L1 levels through a technique called immunohistochemistry involves using special antibodies that bind to this protein, making it visible under a microscope. Research has shown that PD-L1 expression is often higher in the squamous cell component of adenosquamous carcinoma compared to the adenocarcinoma component, and this information can help predict whether immunotherapy treatments might be beneficial.^[5][8]

Scientists have also used a technique called in situ hybridization to measure PD-L1 at the genetic level, looking at the messenger RNA rather than the protein itself. Studies have found that results from measuring PD-L1 protein and PD-L1 genetic material correlate very closely, meaning either method can reliably assess PD-L1 status. This consistency gives doctors confidence in using these tests to guide treatment planning.^[5]

Diagnostics for Clinical Trial Qualification

When patients with adenosquamous carcinoma consider participating in clinical trials testing new treatments, they often need to undergo additional diagnostic procedures beyond those used for standard diagnosis. Clinical trials have specific entry requirements, called eligibility criteria, that ensure participants are appropriate candidates for the experimental therapies being studied.

Staging is a critical component of clinical trial qualification. The TNM staging system, which stands for Tumor, Node, and Metastasis, provides a standardized way to describe how advanced a cancer is. The T component describes the size and extent of the primary tumor in the lung. The N component indicates whether cancer has spread to nearby lymph nodes. The M component shows whether cancer has metastasized, or spread, to distant organs or other parts of the body. Based on these factors, patients are assigned an overall stage from I (early disease) to IV (advanced disease).^[3][6]

Many clinical trials specifically recruit patients with particular stages of disease. For example, some studies focus on early-stage patients (stage I or II) who have had surgery, while others enroll only those with advanced stage IV disease. Determining the correct stage requires thorough evaluation with imaging studies and sometimes additional procedures to check whether cancer has spread to lymph nodes or distant sites.^[6]

Molecular testing results often determine eligibility for clinical trials testing targeted therapies or immunotherapies. Trials evaluating drugs that target EGFR mutations typically require documented proof that a patient’s tumor carries these genetic changes. Similarly, studies of immunotherapy drugs may require PD-L1 expression testing, and some trials only accept patients whose tumors show PD-L1 levels above a certain threshold.^[8][9]

Performance status assessment is another standard requirement for clinical trial participation. Doctors use scales like the ECOG performance status or Karnofsky performance scale to rate how well patients can perform daily activities and care for themselves. These scores help researchers ensure that trial participants are healthy enough to tolerate the experimental treatments being studied. Patients who are too ill or weak may not be eligible for certain trials, as the treatments could cause more harm than benefit.

Blood tests provide important baseline information before clinical trial enrollment. Standard laboratory work typically includes a complete blood count to measure red blood cells, white blood cells, and platelets, which indicate bone marrow function and immune system health. Liver function tests measure enzymes and other substances that show whether the liver is working properly, and kidney function tests assess the filtering ability of these organs. Many cancer treatments can affect these organs, so normal or near-normal function is often required for trial eligibility.^[6]

Some trials specifically studying adenosquamous carcinoma may require confirmation that both the adenocarcinoma and squamous cell carcinoma components are present in adequate proportions. This verification typically involves having tumor tissue reviewed by specialized pathologists who can accurately identify and measure both components. Because adenosquamous carcinoma is rare, some trials may be specifically designed to study this subtype and will only accept patients with this confirmed diagnosis.^[9]

Imaging studies performed for clinical trial qualification often need to be more recent than those used for initial diagnosis. Many trials require imaging within four weeks before enrollment to establish accurate baseline measurements of tumor size and location. These baseline scans are then compared to follow-up scans taken during the trial to determine whether the experimental treatment is working. Common imaging modalities used include CT scans of the chest, abdomen, and pelvis, as well as brain imaging with either CT or MRI if there is concern about brain metastases.^[6]

For trials evaluating immunotherapy treatments, some studies measure immune system markers beyond PD-L1 expression. This might include assessing tumor mutational burden, which is a measurement of how many genetic mutations are present in the cancer cells. Tumors with high mutational burden sometimes respond better to immunotherapy because they produce more abnormal proteins that the immune system can recognize as foreign. However, these specialized tests are not yet standard for all patients and are mainly used in the research setting.^[5]

Previous treatment history also plays a role in clinical trial eligibility. Some trials specifically recruit patients who have never received treatment, while others only accept patients whose cancer has progressed despite prior therapies. Documenting treatment history, including dates of surgery, types and doses of chemotherapy drugs received, and responses to previous treatments, is essential for determining whether someone qualifies for a particular study.

Throughout the clinical trial screening process, patients should maintain open communication with their medical team and the research coordinators. Understanding which diagnostic tests are required and why they are needed can help reduce anxiety about the evaluation process. If certain tests seem duplicative of ones already performed, asking about the reasons can clarify whether the trial has specific requirements about timing or testing methods that differ from standard clinical practice.