Cancer Histology: A Look at Cancer Under the Microscope

At its most fundamental level, cancer is a disease of uncontrolled cell growth. To understand and combat it, medical science turns to histology, the microscopic study of biological tissues. In oncology, this discipline allows specialists to peer directly into the cellular world of a tumor, revealing the architectural and cellular changes that define a malignancy. This microscopic examination forms the basis for cancer diagnosis and guides the subsequent treatment strategy.

Defining Cancer Histology

Histology is the branch of biology concerned with the microscopic anatomy of cells and tissues. When this focus narrows to the study of cancerous tissues, it is called cancer histology. This specialized field is dedicated to examining tissue samples to identify the signs of malignancy at the cellular and tissue levels. Medical doctors known as pathologists are the experts who perform this analysis.

Pathologists differentiate between normal, healthy tissue and abnormal growths, determining whether these abnormalities are benign (non-cancerous) or malignant. This distinction is based on a deep understanding of normal tissue architecture and the specific ways cancer disrupts it. Through their microscopic investigation, pathologists provide the diagnosis that sets the course for a patient’s medical journey.

From Patient to Slide: The Tissue Journey

The journey from a patient’s body to a pathologist’s microscope is a multi-step process designed to preserve tissue for examination. It begins with sample acquisition, where tissue is obtained through a biopsy or surgical procedure. Common methods include needle biopsies, which extract a small core of tissue, or incisional and excisional biopsies, where part or all of a suspicious lump is removed.

Once obtained, the tissue is placed in a chemical solution, usually 10% neutral buffered formalin, for fixation. This step halts natural decomposition and preserves the tissue’s structure. The fixed tissue then undergoes processing, starting with dehydration in alcohol to remove all water. Following dehydration, a clearing agent like xylene is used to remove the alcohol, preparing the tissue for infiltration.

The cleared tissue is then embedded in molten paraffin wax. As the wax solidifies, it forms a supportive block, giving the tissue the rigidity needed for sectioning. A microtome with an extremely sharp blade cuts the paraffin block into thin sections, often just 4 to 5 micrometers thick. These ribbons of tissue are mounted onto glass slides for staining.

Because cells are naturally transparent, the slide must be stained to make components visible. The most common combination is Hematoxylin and Eosin (H&E). Hematoxylin stains cell nuclei a purplish-blue, while eosin stains the cytoplasm and extracellular matrix in shades of pink and red. This creates the contrast needed for detailed microscopic evaluation.

What Pathologists See Under the Microscope

When a pathologist examines a stained tissue slide, they search for specific visual cues that signal cancer. One of the primary observations is cellular atypia, which refers to abnormalities in the appearance of individual cells. Cancer cells vary in size and shape, and their nuclei may be larger, darker, and more irregularly shaped than those of healthy cells.

Pathologists also assess the overall tissue architecture. Normal tissues have an organized, recognizable structure, which cancer disrupts. This loss of normal architecture is a sign of malignancy, as cancer cells multiply without regard for the established boundaries of their host tissue. Pathologists also look for an increased rate of cell division, known as mitotic activity, which indicates the rapid proliferation that drives tumor growth.

A defining feature of malignant tumors is their ability to invade surrounding tissues. Under the microscope, a pathologist will look for evidence that cancer cells have breached their normal confines and are infiltrating adjacent structures. Another aspect is differentiation, which describes how much the cancer cells resemble their normal counterparts. Well-differentiated cancers look more like normal cells and tend to be less aggressive, whereas poorly differentiated cancers bear little resemblance to the original tissue and are often more aggressive.

The Role of Histology in Cancer Care

The information from a histological examination is applied to nearly every aspect of cancer management. Beyond confirming a diagnosis, the analysis identifies the specific type of cancer. For example, it can distinguish between an adenocarcinoma and a squamous cell carcinoma, two types of lung cancer that originate from different cells and respond to different therapies.

Histology is also used for cancer grading, which assesses the aggressiveness of a tumor based on its cellular features. A lower-grade tumor has a better prognosis than a high-grade one. This information, combined with findings about the tumor’s size and spread, contributes to cancer staging, a process that determines the extent of the disease in the body. The histological report helps oncologists select the most appropriate course of action, whether it be surgery, chemotherapy, radiation, or targeted therapies.

Beyond the Basics: Specialized Histological Approaches

While the H&E stain is the workhorse of cancer histology, it is often supplemented by advanced techniques that provide deeper insights. One of these is immunohistochemistry (IHC). This method uses antibodies to detect specific proteins, or markers, on or in cancer cells. The presence or absence of these markers can help classify tumors, identify the origin of metastatic cancers, and find targets for therapies, such as hormone receptors in breast cancer.

For situations requiring rapid diagnosis during surgery, pathologists use a technique called a frozen section. In this procedure, a piece of tissue is rapidly frozen, sectioned with a cryostat, and stained, allowing for a diagnosis in minutes. This allows surgeons to make immediate decisions, such as determining if surgical margins are clear of cancer cells before concluding an operation.

Histology also serves as a bridge to molecular pathology. Pathologists can identify specific areas within a tumor on a slide that are ideal for further molecular testing. These tests analyze the tumor’s DNA and RNA for specific genetic mutations or alterations. While molecular pathology is a distinct field, it often begins with the guidance of a histological map, ensuring the most relevant parts of the tumor are analyzed for information that can guide personalized medicine.