Diagnosis of Small cell lung cancer

Small cell lung cancer diagnosis depends on identifying and characterizing the specific symptoms, analyzing the patients’ detailed history by clinical evaluation, and conducting different specialized tests. Small cell lung cancer is the type of aggressive cancer that spreads rapidly among the affected individuals and is later confirmed once the diagnosis is made. Small cell lung cancer is histologically defined as the malignant epithelial tumor consisting of small cells with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin, and absent or inconspicuous nucleoli ​1​. The typical type of small cell lung cancer involves small cells and comprises approximately 90% of the total cases. The rest of the issues are divided into a combined disease where the tumor consists of significant cell components. Some of the diagnostic tests for small cell lung cancer has been discussed below:

Imaging diagnosis:

The imaging tests include the scans considered significant towards showing appropriate care to the individuals suffering from small cell lung cancer. The imaging tests are carried out by determining the samples of biopsy. The chest x-rays and scan results are combined with the individuals’ medical history and other physical examinations, blood tests, and information from the biopsy to get complete details regarding the beginning of the cancer development and its level of spread within the body. Some of the imaging tests are described below:

  • CT scan: In this scanning technique, x-rays have been used to produce three-dimensional, cross-sectional images of the lungs and surrounding tissues on a computer monitor. This technique detects the cells’ suspicious growth, and the diagnosis of the larger size of the lymph nodes and trapping of the foreign invaders such as viruses and bacteria through small immune system glands are diagnosed. Hence, it results in the confirmation of the lymph nodes containing the cancerous cells. Contrast solutions are given to the patients before the scan in liquid or injection into the vein to enhance the images. 
  • Positron emission tomography (PET) scan: It is conducted if the growth of the cell is found to be suspicious to cancer. The CT portion of this type of combined scan utilizes the x-rays for generating detailed, cross-sectional images of the body and the PET scan uses the specialized camera for determining the rapid growth of the cells through injecting a small amount of radioactive glucose into the vein, and this radioactive glucose gets collected within the cancer tissues. The PET scan helps the doctors determine the cancerous growth of the cells and its level of aggressiveness within the lungs. Also, the metastasis of cancerous cells throughout the body are determined. 
  • Magnetic resonance imaging (MRI) scan: It utilizes a magnetic field and radio waves to produce cross-sectional images of particular organs and body tissues. The brain’s MRI is conducted to determine the spread of cancer to the brain. 
  • Bone scan: It utilizes a radioactive tracer to determine the inside features of the bones. The radiation emitted from the tracer is very low to cause any harm to the individuals. This tracer is injected into the suspect’s vein and is then collected in regions of bones detected through the camera. The special camera can see the dye within the bones, which is used to generate the skeleton images for determining whether small cell lung cancer to the other regions of the body. The diagnosis is initiated by the identification of healthy and unhealthy bones. The healthy bones appear lighter to the camera, while the cancerous region within the bones stands out in the image. 

Clinical diagnosis:

The clinical diagnosis for small cell lung cancer is carried out by tissue collection protocols and suggesting appropriate treatment. The doctors need to check the suspicious cells that may develop into lung cancer, for which they need to study the tissue or fluid from and around the lungs. The utilization of different protocols has allowed the doctors to remove cells or use biopsy from the body and determine them under the microscope for cancer determination. Some of the tests have been listed as below:

  • Biopsy: As the imaging test can indicate the occurrence of lung cancer, the confirmation is done by the biopsy. In a biopsy, the tissue examination is done under the microscope to determine the cells’ size and shape and whether they show resemblance to small cell lung cancer. The experts use many techniques for performing biopsies to diagnose small cell lung cancer.
  • CT-guided biopsy: The doctors are using CT-guided biopsy for removing the tumor tissues when the abnormal cell growth is capable of reaching outside the body quickly rather than from within the passageways of the lungs like other biopsy protocols. The skin is numbed with local anesthesia, and later a tiny needle is inserted between the ribs and into the lung tumor to withdraw a small tissue sample. The CT scans produce images for guiding the hand during the process.
  •  Bronchoscopy: It  is carried out by the surgeon or pulmonologist to view or remove the tumor tissue in the airways using a thin, flexible tube with a light towards the end. It is inserted into the mouth or nose that goes down through the main windpipe and then into the breathing passages of the lungs. The pulmonologist is an expert in the diagnosis and treatment of lung disease. This test helps visualize the inside features of the lungs and later helps examine the presence of tumors in the lungs. As the tumor is detected, the experts use surgical instruments such as small forceps or needles to take tissue or liquid samples through the bronchoscope. Also, fluoroscopy, an imaging technique, is used for guiding bronchoscopy using two-dimensional X-rays. 
  • Endobronchial ultrasound (EBUS): The use of small tools inserted through the mouth or nose and later passed out into the windpipe and chest region helps take up the fluid or tissue samples for further examining the specimens. The lymph nodes are most often discussed, and the biopsies are taken through ultrasound to guide the bronchoscopy. It is known as endobronchial ultrasound (EBUS). The patients are provided with mild doses of anesthesia and sedation.
  • Needle aspiration/core biopsy: It is mainly carried out by interventional radiologists evolving numbness to the skin as the sample of the lung cancer cells are removed for testing. This test is initiated with smaller sized needles or large-sized needles, whose size varies as per the sample size. The hand is used for removing the sample for testing. The radiologists utilize a chest CT scan or a particular x-ray machine called a fluoroscope to guide needles in removing pieces. Hence, the use of core biopsy helps prove large tissue samples. 
  • Thoracentesis: It is mainly carried out by numbing the skin on the chest region and then inserting a needle through the space between the chest wall and the lung consisting of a fluid collection region. This fluid is later removed and used for the detection of cancer cells.
  • Thoracoscopy: It is the testing performed in the operating room while providing local anesthesia to the patient. A small cut is made in the chest wall region, and a unique instrument with a video camera is inserted to examine the inside part of the chest. The recovery time among the patients tends to be shorter while using thoracoscopy due to the smaller incisions being used in the testing. Hence, this type of testing is further referred to as video-assisted thoracoscopic surgery or VATS. Robotic-assisted surgery is another type of invasive surgery which has replaced thoracoscopy.
  • Mediastinoscopy: It is another type of diagnostic test performed in an operating room as it involves a surgical procedure where the patient is given local anesthesia. The expertise is responsible for taking up the lymph node samples from beneath the centre of the chest region towards the breastbone by making a small insertion at the top of the breastbone. 
  • Thoracotomy: This diagnostic test is also performed within the operating room as the patients are given local anesthesia. The incision is made within the patient’s chest to examine the lung directly and later take tissue samples for testing. It majorly contributed to removing lung tumors.
  • Sputum cytology: This diagnostic test is carried out by collecting the mucus sample from the patient’s cough, known as sputum or phlegm and later examined under a microscope. It will further help check the presence of tumor cells within the lungs.
  • Electromagnetic Navigation Bronchoscopy: It resembles the global positioning system (GPS) in cars, which helps detect lung tumors among patients. The protocol involves the involvement of sensors being used on the chest and back, producing an electromagnetic field. A probe or catheter threading with another sensor on its end is done into the lungs through a bronchoscope. The doctors are using an electromagnetic field for tracking the probe position and bronchoscope on a detailed, three-dimensional CT scan image of the chest as they move through the lungs. The guidance system is used for performing the biopsies within distant regions of the lungs, which cannot be reached using conventional bronchoscopy. The doctors use this technique for marking small lung tumors with blue color dye for quickly locating during the surgery. The electromagnetic navigation bronchoscopy has been used for placing small fiducial markers and tiny wires, which is detected with imaging scans. These markers are responsible for guiding the targeted radiation therapy or stereotactic body radiation therapy, in which energy beams are used to destroy the cancer cells. 

Pathological diagnosis:

The pathological diagnosis is integrated as per the classification of the World health organization (WHO) using the morphology of the small cell lung cancer, including the small cells ranging in shape from uniform to spindle-shaped, sparse cytoplasm, high mitotic index, necrotic areas. Immunohistochemistry is used to identify the markers involving synaptophysin, chromogranin A, CD56, thyroid transcription factor 1, and MIB-1 that helps in the appropriate confirmation of the diagnosis. Depending upon the tumor’s location within the chest regions, the biopsies are usually done by bronchoscopy, mediastinoscopy, endobronchial ultrasound (EBUS), transthoracic needle aspiration, and thoracoscopy. The preferred approach is the biopsy from a metastatic lesion involving the liver, lymph nodes, and subcutaneous nodules during the extensive-stage disease. It will stage the patients pathologically simultaneously ​2​.  

Clinical research diagnosis:

The research on the biomarkers substances in the blood or tissue has been used to diagnose small cell lung cancer ​3​. The biomarkers have shown efficacy in determining the aggressive condition of tumor cells and integrating appropriate treatment for the same.


  1. 1.
    Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors. Journal of Thoracic Oncology. Published online September 2015:1243-1260. doi:10.1097/jto.0000000000000630
  2. 2.
    Früh M, De Ruysscher D, Popat S, Crinò L, Peters S, Felip E. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. Published online October 2013:vi99-vi105. doi:10.1093/annonc/mdt178
  3. 3.
    Rivera MP, Mehta AC, Wahidi MM. Establishing the Diagnosis of Lung Cancer. Chest. Published online May 2013:e142S-e165S. doi:10.1378/chest.12-2353