Lung cancer histology is the microscopic study of lung tissue to identify the specific type of cancer. After imaging tests reveal a suspicious area in the lungs, a biopsy is performed to obtain a tissue sample. This sample is then examined by a pathologist, a doctor who specializes in diagnosing diseases by analyzing cells and tissues to determine the cancer’s classification.
The Diagnostic Process
A histological diagnosis begins with a biopsy to obtain a tissue sample. Doctors may use different methods, such as a bronchoscopy, which involves passing a thin tube through the airways to sample a tumor. Another method is a needle biopsy, which uses a long needle inserted through the chest wall, while thoracentesis can draw fluid from around the lungs.
Once collected, the tissue or fluid is sent to a pathology laboratory. A pathologist prepares a thin slice of the sample on a glass slide and treats it with special stains. These stains highlight different parts of the cells, making their structures and patterns visible under a microscope.
The pathologist looks for signs of cancer, such as uncontrolled cell growth and abnormal cell structures. This examination allows for the initial classification of the cancer, which is documented in a pathology report.
Major Histological Classifications
The first distinction a pathologist makes is between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), based on the cells’ appearance. SCLC accounts for about 15% of lung cancers and is characterized by very small cells with minimal cytoplasm. These cells have an “oat cell” appearance and tend to grow and spread quickly.
NSCLC represents about 85% of cases and is divided into three main subtypes. Adenocarcinoma is the most common, originating in the gland cells that produce mucus. Pathologists can often identify glandular structures, and this type is frequently found in the outer parts of the lungs.
The second major subtype is squamous cell carcinoma, comprising about 25-30% of lung cancers. This cancer arises from the flat cells lining the airways and is characterized by the production of keratin. Squamous cell carcinomas are often linked to smoking and tend to develop in the central part of the lungs.
Large cell carcinoma is the least common subtype, named for the large, undifferentiated appearance of its cells. These cells lack the specific features of adenocarcinoma or squamous cell carcinoma. As diagnostic techniques have improved, many tumors previously classified as large cell are now re-categorized into other NSCLC subtypes.
Molecular Markers and Immunohistochemistry
Beyond visual classification, pathologists use advanced techniques on the biopsy sample to analyze the tissue on a molecular level. These tests look for specific proteins and genetic changes, known as molecular markers, that are not visible with standard staining. This provides a more detailed profile of the tumor.
One primary technique is immunohistochemistry (IHC), which uses antibodies to detect specific proteins on cancer cells. For example, an IHC test can measure the amount of a protein called PD-L1, which helps determine if the cancer may respond to immunotherapy. IHC also helps confirm a tumor’s subtype by identifying proteins like ALK and ROS1.
Molecular testing focuses on identifying specific mutations or rearrangements within the cancer cells’ genes. This testing analyzes the tumor’s DNA to find alterations that drive its growth. Common gene mutations sought in NSCLC include those in the EGFR, ALK, and ROS1 genes. The results from these tests are combined with the visual classification to create a comprehensive profile of the cancer.
Implications for Treatment and Prognosis
The information from histological and molecular analyses directly shapes a patient’s treatment plan. The distinction between SCLC and NSCLC is important because they are treated differently. SCLC is more aggressive and has often spread by diagnosis, so treatment involves chemotherapy and radiation rather than surgery.
For NSCLC, the specific subtype and molecular profile guide the selection of therapies. For instance, certain chemotherapy drugs are more effective against non-squamous NSCLC, which includes adenocarcinoma and large cell carcinoma. The presence of specific molecular markers opens the door for targeted therapies.
If a tumor has a mutation in the EGFR gene, a patient may receive an EGFR inhibitor, a drug designed to block signals that cause cancer cells to grow. If a tumor has an ALK or ROS1 gene rearrangement, specific inhibitors targeting those alterations can be used.
These targeted therapies are often more effective and have fewer side effects than traditional chemotherapy because they act specifically on the cancer cells. The presence of high PD-L1 levels can also indicate that a patient may benefit from immunotherapy, which helps the body’s own immune system fight the cancer.