Intranuclear Inclusions: Definition

Intranuclear inclusions are abnormal collections of material found inside the nucleus of a cell. The nucleus is the control center of the cell where the genetic material (DNA) is stored. Under the microscope, intranuclear inclusions appear as small, round, compact areas within the nucleus that look different from the surrounding material because of their color, texture, or density. These inclusions can be made of proteins, viral particles, or other substances, depending on the cause.

What medical conditions are associated with intranuclear inclusions?

Intranuclear inclusions can be observed in various medical conditions. They are especially common in viral infections but can also occur in other diseases. Examples include:

• Herpesvirus infections: Viruses such as herpes simplex virus (HSV) and varicella-zoster virus (VZV, the virus that causes chickenpox and shingles) often produce inclusions called Cowdry Type A inclusions. These are a classic feature of cells infected by herpesviruses.

• Cytomegalovirus (CMV) infection: CMV creates large, distinctive inclusions that are often described as looking like an “owl’s eye.” These inclusions are especially important in patients with weakened immune systems, such as those with HIV/AIDS or people who have had organ transplants.

• Adenovirus infections: These can produce intranuclear inclusions in cells of the respiratory tract or gastrointestinal tract.

• Measles (subacute sclerosing panencephalitis): A rare complication of measles virus infection affecting the brain can produce inclusions in nerve cells.

• Neurodegenerative diseases: Conditions such as Huntington’s disease and certain types of dementia can lead to the abnormal buildup of proteins inside the nucleus, forming inclusions.

• Liver conditions: Diseases like Wilson’s disease (a genetic disorder that causes copper buildup) and certain types of drug-related liver injury can result in intranuclear inclusions.

What are intranuclear inclusions made of?

The contents of intranuclear inclusions depend on the underlying disease:

• In viral infections, inclusions are composed of viral particles and altered cellular material that result from the virus replicating within the nucleus. These inclusions may contain nucleic acids (DNA or RNA) and proteins.

• In non-infectious conditions, such as neurodegenerative diseases or liver disorders, the inclusions are usually made up of abnormal proteins that have clumped together.

Why is it important to find intranuclear inclusions?

The presence of intranuclear inclusions can provide important information in a pathology report:

• Diagnosis: The appearance and location of inclusions can help pathologists identify the cause of disease. For example, the “owl’s eye” inclusions of CMV are considered a strong clue for that infection. Inclusions in brain cells may suggest a neurodegenerative disease.

• Treatment: Recognizing inclusions in infections may guide the use of antiviral medications. In non-infectious conditions, it may prompt further testing or treatment for the underlying disease.

• Prognosis: The presence and extent of inclusions can sometimes indicate the severity of the disease or its stage of progression, especially in patients with weakened immune systems.

Questions to ask your doctor

• What caused the intranuclear inclusions in my tissue sample?

• Do these inclusions mean I have an infection, a genetic disease, or another condition?

• Are there specific treatments available for the cause of these inclusions?

• Does the presence of inclusions change my prognosis or the way my disease will be managed?

• Will I need further testing to confirm the diagnosis?