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Intranuclear Inclusions

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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

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.

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