What Is Large Cell Lung Carcinoma?

A Type of Lung Cancer That Can Often Grow and Spread Rapidly

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Large cell lung carcinoma (LCLC) is one of several forms of non-small cell lung cancer (NSCLC). LCLC often develops in the outer regions of the lungs and tends to grow rapidly and spreads more aggressively than some other forms of lung cancer. Early symptoms of LCLC mainly include shortness of breath and fatigue.

NSCLC accounts for around 85% of all lung cancers, of which roughly 10% are LCLC. Large cell lung carcinomas, also called large cell lung cancers, are so named because of the large size of the cancer cells that can be seen when the tumor is viewed with a microscope (as opposed to the tumor size, which also tends to be quite large).

Large cell carcinoma
PEIR Digital Library / Wikimedia Commons / Public Domain

Large Cell Lung Cancer Symptoms

Early symptoms of LCLC can easily be missed and attributed to other less serious conditions, including age.

Such symptoms include:

Because LCLC typically develops in the outer periphery of the lungs, chronic cough and coughing up blood are not common until later in the disease.

LCLC can cause other effects as the disease progresses. It may lead to pleural effusion, a condition in which fluids accumulate in the pleural cavity (the space between the lungs and the chest wall). The symptoms include dyspnea, and pain in the chest or side that gets worse with a deep breath.

LCLC cells can also secrete hormone-like substances that cause paraneoplastic syndromes. The substances trigger the immune system to attack certain cells of the body.

Paraneoplastic syndromes can cause symptoms like slurred speech, impaired coordination, and difficulty walking or swallowing. In men, it can also cause enlargement of the breasts, known as gynecomastia.

Paraneoplastic syndromes occur in 5% to 10% of all lung cancers and can develop in the early stages of malignancy.

Causes

Risk factors for LCLC are the same as the risk factors for other forms of lung cancer. Smoking is the single greatest risk factor for lung cancer. Even living with someone who smokes increases a nonsmoker's risk of lung cancer by 20% to 30%.

Exposure to radon in the home is the second leading risk factor for lung cancer. Produced by the breakdown of natural uranium in soil, radon is found in excessively high levels in many houses.

Though small cell lung cancer (SCLC) is more commonly linked to radon exposure, radon can contribute to the development of LCLC and other NSCLCs. Radon testing can detect it, and mitigation services can remove it.

Research suggests that certain gene mutations may contribute to the risk of some types of LCLC, including mutations of the RUNX1, ERBB4, BRCA1, and EPHA3 genes.

Diagnosis

Lung cancer is often detected with a chest X-ray. With that said, a normal chest X-ray cannot rule out cancer, as smaller tumors are not usually visible with this type of imaging.

If any symptom of LCLC is present, further testing is usually pursued even if a chest X-ray is normal.

These tests may include:

Blood tests are not used to diagnose lung cancer, although liquid biopsies that detect cancer cells in the bloodstream are increasingly used as an additional tool in the diagnostic process.

If initial imaging findings suggest cancer, your healthcare provider will order a lung biopsy to provide definitive identification of the lesion. This may involve fine needle aspiration (FNA), in which a needle is inserted through the chest wall and into the tumor to extract a small sample of cells. A biopsy may also be performed during bronchoscopy if there are visible signs of possible cancer in the airways.

The definitive diagnosis of LCLC can be made by examination of the biopsied cells under a microscope. With LCLC, the cells will be enlarged and undifferentiated (meaning they have little to no resemblance to normal cells).

Undifferentiated cancer cells like LCLC (also referred to as anaplastic cells) tend to divide and spread rapidly.

Stages

The extent and severity of lung cancer is broken down into four stages.

They range from stage 1, in which the cancer is localized within the lung and has not spread to any lymph nodes, to stage 4, in which cancer has metastasized (spread) to distant parts of the body.

Treatment

Depending on the stage of cancer, treatment options for LCLC include surgery, chemotherapy, radiation therapy, targeted therapy, immunotherapy, or a combination of these. Clinical trials are also available for those who may not be responding to standard therapy.

Surgery

Lung cancer surgery offers the best chance for a cure when LCLC is caught in the early stages.

Surgical options include:

Video-assisted thoracoscopic surgery (VATS) is a minimally invasive procedure that doesn't involve removal or separation of the ribs. This surgery is done with several small incisions in the chest and the use of a tiny camera (thoracoscope) and instruments.

Chemotherapy

Chemotherapy may be used on its own or along with surgery. It may also be used prior to surgery to reduce the size of the tumor (neoadjuvant chemotherapy) or after surgery to ensure that no cancer cells are remaining (adjuvant chemotherapy).

Likewise, chemo may be used with or without radiation therapy. Chemotherapy medications commonly used to treat LCLC include Altima (pemetrexed) and Platinol (cisplatin).

Targeted Therapies

Targeted therapies are medications that are designed to attack cancer cells and, in theory, normal cells should be largely untouched. Targeted therapies have a different side effect spectrum than chemotherapy and, in general, the side effects tend to be less severe than with chemotherapy drugs.

Molecular profiling can be used to identify specific DNA alterations (mutations, translocations, and amplifications) in tumor cells that make them susceptible to treatment with targeted therapy.

Molecular profiling is recommended for everyone with advanced NSCLC, including LCLC.

While targeted drugs do not cure lung cancer, they can keep the malignancy in check. After an initial response, almost universally, resistance develops and the drug no longer works. When that happens, second-generation and, in some cases, third generation drugs can be used.

Radiation Therapy

Radiation therapy may be used to treat lung cancer in a number of different ways. It can be used before surgery to reduce the size of a tumor or after surgery to eradicate any remaining cancer cells.

With small cancers, stereotactic body radiotherapy (SBRT), a specialized form of radiation treatment, can be used as the only treatment. SBRT delivers a very high dose of radiation to a localized area of tissue with the aim of curing the malignancy. SBRT may also be used to treat isolated metastases due to lung cancer, including those in the brain.

Radiation may also be used as a palliative treatment to control symptoms and improve quality of life for people with lung cancer.

Immunotherapy

Immunotherapy can result in long-term control of the disease for some people and can improve the five-year survival for some patients with stage 4 cancer. These drugs work by harnessing the body's own immune system in the fight against cancer.

As of October 2020, immunotherapy drugs approved by the Food and Drug Administration (FDA) for the treatment of lung cancer include:

  • Imfinzi (durvalumab): Approved for treating advanced NSCLC in the adjuvant setting after chemotherapy and radiation
  • Keytruda (pembrolizumab): Approved for treating advanced NSCLC, including use in first-line therapy and in second-line therapy
  • Opdivo (nivolumab): Approved for advanced NSCLC for first-line use in combination with Yervoy. It is also approved for advanced NSCLC after platinum-based chemotherapy and at least one other line of treatment has failed.
  • Yervoy (ipilimumab): Approved for first-line use in combination with Opdivo in NSCLC
  • Tecentriq (atezolizumab): Approved for advanced NSCLC, including use in first-line therapy

Prognosis

The stage of lung cancer can help predict a patient's long-term outcome. The prognosis is typically described by the five-year survival rate, which estimates the percentage of people who will survive for at least five years after the diagnosis.

Because undifferentiated cancers like LCLC can be aggressive, survival rates tend to be worse than with some other types of cancer. With that said, newer therapies have started to improve survival times, even for advanced disease.

According to the American Cancer Society, as of January 2021, the five-year survival rates for people with LCLC and other NSCLCs like adenocarcinoma and squamous cell carcinoma are:

  • Localized (stage 1): 63%
  • Regional (stages 2 to 3): 35%
  • Distant (stage 4): 7%

One variant of LCLC, large cell neuroendocrine carcinoma, generally has a worse prognosis, with a median survival time of roughly six months for people who are diagnosed with stage 4 disease.

Coping

A diagnosis of lung cancer can be frightening and make you feel very alone. Allow your loved ones to support you.

Many people have no idea how to react to someone who has been diagnosed with cancer. Letting people know specific things they can do can help provide you with extra support when you need it.

You can better cope with LCLC by learning as much as you can about the disease and asking questions. Consider joining a lung cancer support group, either through your treatment center or online.

Most importantly, remember that you are the captain of this journey. No matter what others have experienced or recommend, you ultimately know what is best for you.

A Word From Verywell

Although people with lung cancer have historically had less than favorable prognoses, treatments and survival times are improving every year.

If you are uncertain about a recommended treatment plan, do not hesitate to seek a second opinion, such as from a large National Cancer Institute-designated treatment center. Your team of oncologists should be knowledgeable about the latest developments, and can work with you to provide you the most current and effective treatment approaches.

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