Large Cell Lung Cancer

Large cell lung cancer is a rare and aggressive form of lung cancer that can develop anywhere in the lungs but grows quickly and tends to spread faster than some other types.

Table of contents

• What is Large Cell Lung Cancer?
• How Large Cell Cancer Differs from Other Lung Cancers
• Who Gets Large Cell Lung Cancer?
• Signs and Symptoms
• How is it Diagnosed?
• Stages of Large Cell Lung Cancer
• Treatment Options
• Prognosis and Survival

What is Large Cell Lung Cancer?

Large cell lung cancer is one type of lung cancer that affects the lungs. The disease gets its name from how the cancer cells appear when doctors look at them under a microscope—the cells are larger than normal cancer cells and have an unusual appearance^[1].

This cancer can form anywhere in the lung, though it is more common in the outer edges. Large cell lung cancer is classified as a type of non-small cell lung cancer (NSCLC), which is a term that describes cancers based on how the cells look under a microscope^[3].

Large cell lung cancer is quite rare. It accounts for about 1 in 10 cases of all lung cancers, making it the least common type^[1]. According to research data, it comprises between 3% and 9% of all primary lung cancers^[3].

How Large Cell Cancer Differs from Other Lung Cancers

There are two main categories of lung cancer: small cell lung cancer and non-small cell lung cancer. Non-small cell lung cancer is further divided into three main types^[1]:

• Adenocarcinoma, which begins in glandular cells on the outer part of the lungs and is the most common type, making up about 40% of non-small cell lung cancers
• Squamous cell carcinoma, which begins in the thin, flat cells that line the airways and makes up about one-quarter of non-small cell lung cancers
• Large cell carcinoma, which begins in the cells that make up the outer lining of the lungs and makes up 10% to 15% of non-small cell lung cancers

The key difference between small cell and large cell lung cancer is visible under a microscope. Small cell lung cancer cells appear small and round, while non-small cell lung cancer cells appear larger^[1]. Small cell lung cancer also tends to be more aggressive and more difficult to treat than non-small cell lung cancer^[1].

Large cell carcinoma is actually a “diagnosis of exclusion,” meaning that doctors give this diagnosis when the tumor cells are large but don’t have the specific characteristics that would classify them as adenocarcinoma, squamous cell carcinoma, or other more specific types of lung cancer^[3]. The tumor cells typically have abundant pale-staining cytoplasm (the gel-like substance inside cells) and prominent nucleoli (structures inside the cell’s control center)^[3].

What makes large cell carcinoma particularly concerning is that it tends to grow more quickly and spread more aggressively than some other forms of non-small cell lung cancer^[5].

Who Gets Large Cell Lung Cancer?

Large cell lung cancer is more common in certain groups of people. Research shows that 70.2% of patients are older than 60 years of age, and the disease is found more often in men than in women^[4].

Cigarette smoking is the leading cause of large cell lung cancer. According to research, the risk increases significantly with the duration of smoking. People who have smoked for 30 to 40 years have approximately 2.3 times the risk compared to people who have never smoked. Those who have smoked for more than 40 years have approximately 3.6 times the risk^[3].

Another study found that for people who currently smoke two or more packs per day, the odds ratio is 37.0 in men and 72.9 in women, indicating that cigarette smoking is the predominant cause of large cell lung cancer^[3].

When it comes to where the cancer develops in the lungs, 60.2% of tumors are found in the upper lobe of the lung^[4].

Signs and Symptoms

The symptoms of large cell lung cancer are similar to other types of lung cancer. Many people may not have symptoms in the early stages, but as the disease progresses, various signs can appear^[3]:

• Persistent cough that doesn’t go away
• Coughing up blood or rust-colored phlegm (also called hemoptysis)
• Shortness of breath or pain with breathing
• Chest pain that worsens with deep breathing, laughing, or coughing
• Hoarse voice
• Unintentional weight loss
• General fatigue or tiredness
• Loss of appetite
• Frequent upper respiratory infections like bronchitis or pneumonia
• Difficulty swallowing
• Wheezing

If the cancer has spread to other parts of the body, additional symptoms may appear. For example, cancer that has spread to the liver can cause yellowing of the skin and eyes (jaundice). Cancer in the bones can trigger bone pain, such as back pain or pain in the hips. Cancer that has spread to the brain may cause changes in the nervous system, such as headaches or seizures. Cancer that has spread to the lymphatic system (a network of vessels and nodes that helps fight infection) may cause the lymph nodes to swell^[3].

How is it Diagnosed?

A diagnosis of large cell lung cancer usually begins with imaging tests to look at the lungs. If you have symptoms that worry you, a healthcare professional might start with an X-ray. Other imaging tests that can help identify the size, location, and extent of the tumor include chest X-rays, CT scans (computed tomography scans that create detailed cross-sectional images), PET scans (positron emission tomography that shows how organs and tissues are functioning), or PET-CT scans^[3].

The definitive diagnosis of large cell lung cancer is usually made after a biopsy of the lung tissue. A biopsy is a procedure in which tissue samples are removed from the body so they can be viewed under a microscope^[1]. This is classically done through bronchoscopy (inserting a thin tube with a camera through the airways) or CT-guided needle biopsy (using CT imaging to guide a needle to the tumor)^[3].

A pathologist (a doctor who specializes in diagnosing diseases by examining tissues and cells) will look at the tissue under a microscope and check for cancer cells. The pathologist will also check for certain features that are typical of large cell carcinoma^[1].

Other tests that may be performed include sputum cytology, where mucus coughed up from the lungs is examined under a microscope to look for cancer cells^[3].

Stages of Large Cell Lung Cancer

Once large cell lung cancer is diagnosed, doctors perform additional tests to determine how far the cancer has spread. This process is called staging. The stage tells doctors what kind of treatment you need^[1].

Large cell lung cancer is staged from 0 to IV^[1]:

Stage 0: The cancer is found only in the top lining of the lung and has not spread outside the lung.

Stage I (IA and IB): The cancer has not spread to the lymph nodes or other parts of the body. The difference between each sub-stage is based on the size of the tumor and whether it has spread to the lung lining.

Stage II (IIA and IIB): The cancer is larger than Stage I and has begun to spread to nearby lymph nodes (small bean-shaped organs that help fight infection) or tissues, but not to distant organs. The difference between each sub-stage is based on the size of the tumor, its location, and whether it has spread to the lymph nodes.

Stage III (IIIA, IIIB, and IIIC): The cancer may be difficult to remove with surgery. The difference between each sub-stage is based on the size of the tumor, its location, and how much it has spread.

Stage IV: The cancer has spread (metastasized, meaning it has traveled to other parts of the body) to other parts of the body, such as the other lung, the fluid around the lungs, the fluid around the heart, or distant organs^[1].

Research shows that most patients with large cell lung cancer show poor differentiation (meaning the cancer cells look very different from normal cells) and are diagnosed at stage III or IV^[4].

Treatment Options

Treatment for large cell lung cancer depends on several factors, including the stage of the cancer, the size and location of the tumor, and your overall health. Treatment often requires a team approach involving multiple specialists^[3].

Surgery is a common treatment option, especially if the cancer is in only one lung and you are in good general health. There are three main types of lung cancer surgery^[1]:

• Lobectomy—where one of the large parts of the lung (lobes) is removed. This is suggested if the cancer is in just one section of one lung.
• Pneumonectomy—where the entire lung is removed. This is used when the cancer is located in the middle of the lung or has spread throughout the lung.
• Wedge resection or segmentectomy—where a small piece of the lung is removed. This is only suitable for a small number of patients when the cancer is small and limited to one area of the lung, usually in very early-stage non-small cell lung cancer.

Chemotherapy involves the use of special medicines to shrink or kill the cancer. The drugs can be pills you take or medicines given through your veins, or sometimes both^[10]. Research has shown that the prognosis after surgery combined with chemotherapy is better than surgery alone^[4].

Radiation therapy uses high-energy rays (similar to X-rays) to kill cancer cells. If surgery is not possible because your general health means you have an increased risk of complications, you may be offered radiation therapy to destroy the cancerous cells. In some cases, this may be combined with chemotherapy (known as chemoradiotherapy)^[10].

Targeted therapy involves the use of drugs to block the growth and spread of cancer cells. The drugs can be pills you take or medicines given through your veins. You will get tests to see if targeted therapy is right for your cancer type before this treatment is used. If the cancer has a specific mutation (a change in the genes), biological or targeted therapy may be recommended^[10].

Immunotherapy is another treatment option that can be used alone or in combination with other treatments^[10].

According to research, age, gender, marital status, laterality (which side of the body the cancer is on), tumor size, stage, chemotherapy, and surgery are all factors that influence survival outcomes^[4].

Prognosis and Survival

Large cell lung cancer is described as a rare cancer with a generally poor outcome^[4]. However, the prognosis depends on many factors, including the stage at which the cancer is diagnosed, the patient’s overall health, and the treatment received.

Research has identified several factors that are independently associated with overall survival, including age, gender, marital status, the side of the body where the cancer is located, tumor size, cancer stage, and whether the patient receives chemotherapy and surgery^[4].

The combination of surgery and chemotherapy has been shown to achieve better outcomes than surgery alone^[4].