Intranuclear inclusions are aggregates of protein or viral particles within the nucleus. Their presence is a key histological finding for several diseases, particularly viral infections.

Viral Inclusions

• Cowdry Type A Inclusions

  • Appearance: Large, eosinophilic (pink), amorphous inclusions that push chromatin to the nuclear membrane ("margination").
  • Associated Conditions:
    • Herpes Simplex Virus (HSV-1, HSV-2): Seen in infected epithelial cells (e.g., Tzanck smear) or neurons (e.g., herpes encephalitis).
    • Varicella-Zoster Virus (VZV): Found in skin lesions of chickenpox or shingles.
    • Cytomegalovirus (CMV): Although CMV is famous for another inclusion type, it can also show Cowdry A inclusions.
  • Buzzwords: "Punched-out" ulcers (HSV esophagitis), multinucleated giant cells.

• "Owl's Eye" Inclusions (Cowdry Type B-like)

  • Appearance: Large, basophilic (purple) central inclusion surrounded by a clear halo, giving the appearance of an owl's eye. Found in greatly enlarged cells (cytomegaly).
  • Associated Condition: Cytomegalovirus (CMV).
  • High-Yield Scenarios: CMV retinitis, esophagitis, or pneumonia in immunocompromised patients (e.g., AIDS, transplant recipients). Congenital CMV infection.

• "Ground-Glass" Nuclei

  • Appearance: Homogenous, opaque appearance of the entire nucleus due to viral particles, obscuring normal chromatin detail.
  • Associated Condition: Herpes Simplex Virus (HSV), particularly in early-stage infection before Cowdry A inclusions form. Can also be seen in liver cells with Hepatitis B virus (though cytoplasmic inclusions are more classic).

• Measles Virus Inclusions

  • Appearance: Eosinophilic intranuclear inclusions.
  • Associated Condition: Subacute Sclerosing Panencephalitis (SSPE), a rare, progressive, fatal brain disorder caused by persistent measles virus infection. Found in both neurons and glial cells.

Non-Viral Inclusions

• Lead Poisoning (Plumbism)

  • Appearance: Eosinophilic intranuclear inclusions.
  • Location: Most prominently seen in the epithelial cells of the renal proximal convoluted tubules.
  • Clinical Context: Patient with microcytic anemia, abdominal pain ("lead colic"), wrist/foot drop, and cognitive deficits (especially in children).

• Papillary Thyroid Carcinoma

  • Appearance:
    • Orphan Annie Eye Nuclei: Large, overlapping nuclei with finely dispersed, pale chromatin, giving a clear or empty appearance.
    • Intranuclear Pseudoinclusions: Invaginations of the cytoplasm into the nucleus that appear as eosinophilic inclusions on H&E stain.
  • Buzzwords: Psammoma bodies (laminated calcifications).

• Neuronal Intranuclear Inclusion Disease (NIID)

  • Appearance: Eosinophilic, hyaline intranuclear inclusions.
  • Associated Condition: A rare, progressive neurodegenerative disorder. Inclusions can be found in neurons and also in somatic cells, like those in skin or renal biopsies.