The initial step involves a precise biological assessment of abnormal cells. Understanding the tumor’s fundamental nature guides subsequent medical care. This requires examining the physical characteristics of the cancer cells themselves. This detailed analysis guides clinicians in staging the disease and selecting the therapeutic strategy.
The Purpose of Histology in Diagnosis
The specialized study of tissue structure under a microscope is known as histology, and it is a defining step in cancer diagnosis. This analysis is performed by a pathologist, a physician trained to identify disease by examining tissue samples. A related method, cytology, involves the study of individual cells rather than the larger tissue architecture. Both approaches confirm the presence of malignant cells and distinguish them from benign changes.
The microscopic examination confirms the abnormal growth is cancer. The pathologist must also differentiate between primary lung cancer (begun in the lung) and metastatic cancer (spread from elsewhere). This distinction is important because primary lung cancer and metastatic cancers are treated using entirely different protocols. The cellular features provide the essential classification needed for treatment planning.
Obtaining the Tissue Sample
To perform analysis, a small tissue sample must be collected. The collection method depends on the tumor’s location and size. For growths near the central airways, Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) is often used. This minimally invasive technique uses a bronchoscope with an ultrasound probe to visualize and sample tumors or lymph nodes adjacent to the bronchial tubes.
If the tumor is located in the outer, or peripheral, regions of the lung, a Computed Tomography (CT)-guided transthoracic needle biopsy is frequently employed. During this procedure, the patient lies in a CT scanner while a radiologist uses the real-time imaging to guide a thin needle through the chest wall directly into the lung mass. In cases where less invasive procedures do not provide enough tissue or are not feasible, a surgical biopsy may be necessary, often using Video-Assisted Thoracic Surgery (VATS). VATS is a minimally invasive surgical technique where a small camera and instruments are inserted through small incisions between the ribs to remove a piece of tissue.
Major Histological Classifications
Once the tissue is collected, the pathologist classifies the tumor based on the appearance, shape, and size of the cancerous cells. The first and most significant division separates tumors into two major groups: Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC). SCLC accounts for approximately 15% of all lung cancer cases and is characterized by cells that appear small, dark, and round under the microscope, often exhibiting a neuroendocrine differentiation. This type of cancer tends to grow rapidly and is typically found near the center of the chest in the large airways.
NSCLC, which makes up about 85% of cases, is further subdivided into three main types based on cellular morphology. The most common subtype is Adenocarcinoma, which frequently develops in the outer regions of the lungs. It is characterized by the formation of glandular structures that resemble the mucus-producing cells lining the lung’s air sacs. Adenocarcinoma is also the most common form of lung cancer found in non-smokers.
Another main subtype of NSCLC is Squamous Cell Carcinoma, which is strongly associated with smoking and usually arises in the central airways. These tumors are distinguishable by the presence of cells that look flat and scale-like, sometimes forming structures known as keratin pearls. The third subtype is Large Cell Carcinoma, which is often considered a diagnosis of exclusion. This classification is reserved for NSCLC tumors whose cells are large and undifferentiated, meaning they lack the specific glandular or squamous features.
Linking Histology to Treatment
The histological classification dictates the treatment strategy for the patient. Small Cell Lung Cancer is aggressive and tends to spread early in the disease course. Because of this rapid spread, the treatment pathway for SCLC is typically systemic, involving chemotherapy and radiation therapy. Surgery is rarely an option for SCLC unless the cancer is identified at a very early, localized stage.
The treatment plan for Non-Small Cell Lung Cancer is highly varied and depends directly on the specific subtype. An Adenocarcinoma diagnosis, for example, triggers molecular testing to identify specific genetic alterations, such as mutations in the EGFR or rearrangements in the ALK gene. The presence of these markers makes the tumor susceptible to targeted therapies, which are drugs designed to block the activity of these specific cancer-driving proteins.
The distinction between Adenocarcinoma (non-squamous) and Squamous Cell Carcinoma also affects the choice of standard chemotherapy agents. Certain chemotherapies are known to be more effective and safer for patients with non-squamous histology. The cellular type also influences the potential for immunotherapy, which harnesses the body’s own immune system to fight the cancer cells.