JUL 17, 2018 10:15 PM PDT

New Small Cell Lung Cancer Subtype Identified

WRITTEN BY: Mauri Brueggeman

Lung cancer is a leading cause of cancer death worldwide with annual numbers upwards of one million people.  Nowadays, there are three main types including: Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Lung Carcinoid Tumor (or neuroendocrine tumors).  Treatments differ depending on the category of lung cancer.  A group of researchers from the Cold Spring Harbor Laboratory have published research findings outlining what they are characterizing as a new subtype of lung cancer that does not fit into the other categories and likely comprises of difficult to treat cases that don’t respond like the other known lung cancers.

First type of Lung Cancer

Non-Small Cell Lung Cancer has been determined as the most common type of lung cancer and there are multiple subtypes within this diagnostic category.  According to the American Cancer Society, 80-85% of lung cancers are of the non-small cell type.   The different categories subsumed in this group are differentiated by their lung cell origin type.  The subtypes that fall into this category are grouped because of their similar therapeutic approaches for treatment and their overall survival outcomes are more closely linked.  Non-Small Cell Lung Cancer is often identified in patients with a history of smoking, however of the three lung cancer types, this is also the one most often found in non-smoking patients.  Prognosis is usually better because it is most often found on the outer surface of the lung and is slow growing.  It is more likely to be found prior to metastasis which contributes to the better prognosis.  Specific cancer diagnoses associated with this category are: squamous cell carcinoma, large cell carcinoma, adenosquamous carcinoma, and sarcomatoid carcinoma (rare).

Second type of Lung Cancer

Small Cell Lung Cancer accounts for about 10-15% of all lung cancers and currently consists of two subtypes based on the cells involved: small cell carcinoma and combined small cell carcinoma.  Small cell carcinoma is sometimes called “oat cell carcinoma” because the cells are small and oval shaped; under the microscope, the appear like grains of oat.  This subtype is usually aggressive; often originates in the central bronchi and is associated with protracted use or exposure to tobacco products.  Combined small cell carcinoma is identified by the presence or involvement of both non-small cells and small cells of the lung.  This subgroup, while morphologically straddling two main types of lung cancer, has molecular biomarkers that more strongly associate it with small cell lung cancer.  Both small cell lung carcinoma and combined small cell carcinoma have loss of heterozygosity at 22q13 and expression of both synaptophysin and CD56 which are characteristic for small cell carcinomas and not for non-small cell lung cancer.

Third type of Lung Cancer

The last type of lung cancer is found in less than 5% of patients with lung cancer.  It is known as a Lung Carcinoid Tumor and involve neuroendocrine cells within lung tissue.  These are sometimes described as a combination of nerve and endocrine cells; they make hormones, adrenaline and others, like endocrine cells and send sensory messages similar to nerve cells.  These cells do not form an organ but are distributed diffusely throughout the lungs.  Carcinoid tumors of the lung are a type of neuroendocrine tumor, but these special cells are found throughout the body like in the digestive system organs including stomach, intestine, and pancreas.  These tumors typically grow slowly, and screening is difficult because they are very rare.  Individuals with multiple endocrine neoplasia type 1 have been found to be at increased risk for these tumors and are often screened by CT scan every 3 years.   


The newly identified subtype falls under the second type of lung cancer: small cell lung cancer.  It is estimated to account for nearly 20% of all cases of small cell lung cancer.  This subtype involves a unique and only newly identified group of cells called “tuft cells”.  These are sometimes called “pulmonary brush cells” and are characterized by the presence of blunt squat microvilli attached to the cell membrane and are anchored in the cell cytoplasm.  The function of these cells is, as of yet, still somewhat unclear.  Scientists know that these cells express interleukin 25 (IL-25) and the new findings out at the end of June in the journal Genes & Development, indicate that researchers found that what they termed as “variant small cell lung cancer tumors” lacked expression of neuroendocrine markers and expressed markers associated with pulmonary tuft cells.  The gene POU2F3 was found to regulate tuft cells in this “variant” form of lung cancer and the unique molecular expression in these variant lung tumors does not match the normal neuroendocrine features found in small cell lung cancers previously described.    

Sources: Genes & DevelopmentAmerican Cancer SocietyNational Cancer InstituteToxicological SciencesCancer, Lung, Small Cell (Oat Cell); American Journal of Clinical PathologyAmerican Journal of Respiratory and Critical Care Medicine

About the Author
Master's (MA/MS/Other)
Mauri S. Brueggeman is a Medical Laboratory Scientist and Educator with a background in Cytogenetics and a Masters in Education from the University of Minnesota. She has worked in the clinical laboratory, taught at the University of Minnesota, and been in post secondary healthcare education administration. She is passionate about advances and leadership in science, medicine, and education.
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