An Overview of Histopathology

Histopathology involves using a microscope to look at human tissue to check for signs of disease. The term is derived from "histology" (meaning the study of tissues), and "pathology" (meaning the study of disease).

A histopathology report describes the findings of a specialist known as a medical pathologist. Examples include the accumulation of white blood cells seen with infections, crystallized deposits that occur with gout, granular lumps characteristic of tuberculosis or sarcoidosis, or abnormal cell formations seen with cancer.

This article explains the purpose of histopathology, what's in a histopathology report, and reasons why a histopathology test may be done. It also details how pathology results are interpreted.

What Is Histopathology?

In clinical practice, histopathology refers to the examination of tissues obtained by biopsy or the surgical removal of an organ. It is a form of anatomical pathology that looks specifically at tissues and organs as opposed to clinical pathology which looks at bodily fluids.

Histopathology is performed by a lab-based pathologist who, with the assistance of a medical technologist, prepares the tissues by sectioning them and placing them on a glass slide. The sample can then be exposed to dyes and other techniques to highlight, segregate, or remove cells so they are better viewed under the microscope.

Histopathology is not the same thing as cytopathology which looks at individual cells. With histopathology, the pathologist not only evaluates cell structure but also how cells are grouped.

Why Is Histopathology Important?

Without histopathology, it would be difficult, if not impossible, to diagnose many diseases. It is essential to the diagnosis of many conditions, chief of which includes cancer.

Along with a biopsy (the extraction of tissues for lab evaluation), histopathology remains the gold standard for diagnosing many solid-tumor cancers. Histopathology can differentiate benign tumors from cancerous ones and is also central to cancer staging (determining how advanced a cancer is) and cancer grading (determining how aggressive a cancer is).

Other diseases for which histopathology is central to the diagnosis include:

• Infectious diseases like disseminated tuberculosis, tropical parasitic infections, H. pylori, and necrotizing fasciitis
• Inflammatory diseases like sarcoidosis, Crohn's disease, ulcerative colitis, and vasculitis
• Autoimmune diseases like celiac disease, psoriasis, scleroderma, autoimmune hepatitis, and lupus nephritis
• Organ-specific diseases like endometriosis, uterine fibroids, and peptic ulcers

Histopathology is also important for the management of diseases. It can help monitor for organ rejection after transplant surgery or check for the response to treatment of inflammatory bowel disease (IBD).

Histopathology also contributes to advances in our understanding of diseases, leading to the development of new treatments. It can also look for new genetic or immunological biomarkers for diseases so that they can diagnosed earlier when they are most treatable.

How Is Histopathology Performed?

Histopathology is performed by pathologists who process and cut tissue into very thin layers, called sections. Then, they stain and examine it with a microscope. Using a microscope, they can observe and document the tissue's details.

Histopathology relies on samples of tissue obtained through procedures such as endoscopy, colonoscopy, and colposcopy, or by doing surgical procedures such as a breast biopsy.

Frozen Section

For some diseases, a sample of the tissue can be interpreted very quickly using frozen sections (also called a cryosection) that are obtained during surgery. Frozen sections are examined immediately in the lab to provide a result within about 20 minutes.

This type of pathology is most commonly used to evaluate tumor margins during surgery so that a surgeon can decide if more tissue should be removed for the full removal of cancer. The use of frozen sections during surgery depends on the type of cancer being removed and other factors.

Lymph and Blood Cancers

Lymph nodes are often biopsied to evaluate for certain types of blood cancer and to identify metastases of solid tumors (such as breast cancer and lung cancer). A bone marrow biopsy may also be required for a definitive diagnosis of many types of blood cancers.​

Components of a Histopathology Report

Histopathology reports on surgical cancer specimens can be complex. They may include:

• A description of the appearance of the involved tissue
• A diagnosis
• A synoptic report detailing the findings of the case
• Pathologist's comments

Interpreting the Results

Many of the pathologist's findings are used to help determine prognosis, especially in cases of cancer. Prognosis is the prediction or estimate of survival or recovery from a disease.

Prognostic indicators may include:

• Size and severity of the disease
• Tumor grade
• Indications that cancer has spread and the extent of spread

Grading systems differ depending on the kind of cancer. In general, the cells are scored based on how abnormal they appear under the microscope. The more abnormal the cells look, the higher the grade.

For example, Grade 1 tumors appear nearly normal, whereas Grade 4 tumors reflect more abnormalities.

Other Sampling Techniques

In addition to histopathology, pathologists may use other techniques to assess the presence of cancer in the tissues.

Molecular Techniques

Molecular techniques refer to the ability to analyze cells and tissues at the molecular level, which is at the level of proteins, receptors, and genes.

Pathologists diagnose cancer, such as leukemia, through a combination of techniques, including:

• Cytochemistry: How the sampled cells take up certain stains
• Immunophenotype: Looks for unique surface proteins
• Karyotype: Chromosomal changes
• Morphology: How the cells look

Immunohistochemistry

Often in lymphomas and other cancers, pathologists use immunohistochemistry to help assess the tumor type, prognosis, and treatment.

Immunohistochemistry involves using antibodies to stick to particular tags or markers outside the cancer cells. These markers that the antibodies attach to often have "CD" in their name, which stands for "cluster of differentiation." CDs identify cell phenotypes, which identify different cancers.

For example, if CD23 and CD5 are present in the cancer cells, it might support the notion that chronic lymphocytic leukemia (CLL) is a possible diagnosis.

However, these same markers are also present in other malignancies. So pathologists use this method in combination with other identifying features.

Chromosomal Studies

Pathologists may perform molecular and chromosomal studies to look at gene rearrangements and specific changes to the chromosomes. Sometimes inserted or deleted genes correlate to prognosis. Genetic changes present in a cancer tissue sample may be hereditary or acquired.

For instance, in CLL, a specific piece of a chromosome (17p) is lost. Along with the missing chromosome, a gene that helps suppress cancer is often lost.

The 17p deletion is found in about 5% to 10% of people with CLL overall. The 17p deletion CLL is a form of CLL that is harder to treat with conventional chemotherapy.

Summary

Histopathology is the study of tissue to look for disease. Pathologists perform histopathology in a lab. They examine tissue under a microscope and develop a report of their findings.

Histopathology reports can include descriptions of the tissue, diagnosis, and prognosis. In addition to evaluating the shape and structure of cells, pathologists may also use other techniques to assess and diagnose cancer.