What Is Large Cell Lung Carcinoma?

A type lung cancer that can often grow and spread rapidly

Large cell lung carcinoma (LCLC) is one of several forms of non-small cell lung cancer. LCLC often develops in the outer regions of the lungs and tends to grow rapidly and spread more aggressively than some other forms of lung cancer. Unlike some lung cancers that typically present with a cough or lung infections, the early symptoms of large cell lung carcinoma mainly include a vague sense of shortness of breath and fatigue.

Non-small cell lung cancers account for around 85% of all lung cancers, of which roughly 10% are large cell carcinomas. Large cell lung carcinomas, also called large cell lung cancers, are so-named because of the prominent size of the cancer cells (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

Because LCLC typically develops in the outer peripheries of the lungs, well-known symptoms of lung cancer (such as a chronic cough and coughing up blood) are less common until later in the disease.

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

LCLC can cause other symptoms as the disease progresses. A tumor's location on the edge of the lungs can cause fluids to accumulate in the space between the lungs and the chest wall (pleural cavity). This can lead to pleural effusion, a condition characterized by dyspnea and the onset of pain in the chest or sides that worsens with a deep breath.

LCLC can also secrete hormone-like substances that trigger a set of conditions known as paraneoplastic syndromes. These are rare disorders in which the immune system responds abnormally to a cancerous tumor.

A paraneoplastic syndrome can cause symptoms like slurred speech, loss of fine motor skills, and difficulty walking or swallowing. In men, it can also cause the 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. Recognition of the signs of paraneoplastic syndromes may help diagnose lung cancer early while it is still highly treatable.

Causes

Scientists still aren't certain what causes LCLC. Research suggests that certain gene mutations may contribute to the risk of the disease, including mutations of the RUNX1, ERBB4, BRCA1, and EPHA3 genes.

Other risk factors for LCLA are the same as for all other forms of lung cancer. Chief among them is smoking. Smoking remains the single greatest risk factor for lung cancer in general, and LCLC is no exception. Even living with someone who smokes increases a non-smoker's risk of lung cancer by 20% to 30%.

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

Though small cell lung cancers are more commonly linked to radon exposure, radon can still contribute significantly to the development of LCLC and other non-small cell lung cancers. Radon testing can detect it, and mitigation services can remove it.

Diagnosis

Lung cancer is often first suspected when abnormalities are seen on a chest X-ray. With that said, a "normal" chest X-ray cannot rule out cancer as smaller tumors are commonly missed with this type of imaging.

If any symptom of LCLC is present, further testing should be pursued—even if a chest X-ray is normal. This may include:

Blood tests are not used to diagnose lung cancer.

If initial imaging findings suggest cancer, your doctor will order a lung biopsy to provide definitive evidence of the malignancy. 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 in the lab by examining 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 all lung cancers are broken down into four stages, each stage of which represents a progression of the disease.

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 the cancer has spread (metastasized) 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 also offer available for those who may not be responding to therapy.

Surgery

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

A newer, minimally invasive procedure, called video-assisted thoracoscopic surgery (VATS), is now available at some cancer centers. It involves making several small incisions in the chest and using a tiny camera (thoracoscope) and instruments to perform surgery without having to remove or separate ribs.

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 leave normal cells largely untouched. Because of this, the side effects tend to be less severe than with chemotherapy drugs.

Molecular profiling, which identifies specific DNA mutations in tumor cells, can determine if a person has a treatable mutation and is a candidate for therapy.

Molecular profiling is recommended for everyone with advanced non-small cell lung cancer, including LCLC. When a treatable mutation is found, there is a good chance that a targeted drug will be able to control the tumor for a period of time.

While targeted drugs do not cure lung cancer, they can keep the malignancy in check until resistance develops and the drug no longer works. When that happens, there are second-generation and, in some cases, third-generation drugs that can be used.

Radiation Therapy

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

With small cancers, radiation may be used alone using a specialized form of radiation called stereotactic body radiotherapy (SBRT). 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 therapy can also be used as a palliative treatment for people with advanced lung cancer to control symptoms and improve the quality of life.

Immunotherapy

Immunotherapy is an exciting field of lung cancer treatment that has resulted in the long-term control of the disease for some people, even those with stage 4 cancer. These drugs work by harnessing the body's own immune system in the fight against cancer.

As of 2020, there are five immunotherapy drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of lung cancer:

  • Imfinzi (durvalumab): Approved for both advanced non-small cell lung cancer and small cell lung cancer, including use in first-line therapy
  • Keytruda (pembrolizumab): Approved for advanced non-small cell lung cancer, including use in first-line therapy, and for some patients with small cell lung cancer
  • Opdivo (nivolumab): Approved for both advanced non-small cell lung cancer and small cell lung cancer after platinum-based chemotherapy and at least one other line of treatment has failed
  • Tecentriq (atezolizumab): Approved for both advanced non-small cell lung cancer and small cell lung cancer, including use in first-line therapy
  • Tecentriq (atezolizumab): Approved for use with Opdivo for first-line treatment (with or without chemo) in people with advanced non-small cell lung cancer

Prognosis

The stage of lung cancer can help predict a patient's long-term outcome, referred to as the prognosis. 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 poorer than with some other types of cancer. With that said, newer therapies have started to improve survival times even in those with advanced disease.

According to the American Cancer Society, and as of January 2020, the five-year survival rates for people with LCLC and other non-small cell lung cancers like adenocarcinoma and squamous cell carcinoma are:

  • Localized (stage 1): 61%
  • Regional (stages 2 to 3): 35%
  • Distant (stage 4): 6%

One variant of LCLC, called large cell neuroendocrine carcinoma, generally has a poorer prognosis with a median survival time of roughly six months.

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 relieve that anxiety and 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. It is important, therefore, that your oncology team keeps on top of the latest research. With science evolving so rapidly, this can sometimes be difficult.

If you are uncertain about a recommended treatment plan, do not hesitate to seek a second opinion, ideally from a larger National Cancer Institute-designated treatment center. The team of oncologists there are likely to be knowledgeable about the latest developments and can work with your team to provide you the most current and effective treatment approaches.

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