Cowdry type A inclusion

**Definition/Morphology** - Cowdry type A inclusions: single, large, glassy, eosinophilic (pink) intranuclear inclusions with a clear halo separating them from marginated chromatin along the nuclear membrane. They represent accumulations of viral nucleocapsids and proteins in the nucleus. - Described by Edmund Cowdry (1934), who classified intranuclear inclusions into type A (with the halo and chromatin margination, a "disintegrating" nuclear structure) and type B (multiple small inclusions, e.g., poliovirus and adenovirus in early stages, with nucleolus preserved).

**Associated Infections (high-yield)** - **HSV-1/HSV-2:** Cowdry A inclusions in infected keratinocytes and neurons (e.g., HSV encephalitis in the temporal lobe). Infected cells also show multinucleation, nuclear molding, and ground-glass nuclei (the "3 Ms": multinucleation, margination of chromatin, molding). Tzanck smear shows multinucleated giant cells. - **VZV:** Same findings in vesicular lesions (varicella, zoster). - **CMV:** Typically has a large "owl's eye" intranuclear inclusion (basophilic/amphophilic with halo) plus smaller cytoplasmic inclusions. This is distinct from the classic herpes Cowdry A appearance, although CMV inclusions can be loosely described with this halo morphology. - **Others historically classified as type A:** Yellow fever (Torres bodies in hepatocytes), subacute sclerosing panencephalitis (SSPE; measles) and, in some references, measles/PML-related inclusions.

**Pathophysiology** - Herpesviruses are enveloped dsDNA viruses that replicate in the nucleus. Viral assembly causes nuclear enlargement, a displaced nucleolus, and chromatin margination against the nuclear membrane, producing the halo.

**Clinical Significance** - HSV encephalitis: fever, altered mental status, seizures, temporal lobe involvement. MRI shows temporal lobe hyperintensity, CSF shows lymphocytic pleocytosis with RBCs, PCR for HSV is the diagnostic test of choice. Treat with IV acyclovir. - Tzanck smear is rapid but insensitive and nonspecific (it can't distinguish HSV from VZV); PCR or DFA is preferred.

**Differentiation (board tips)** - Cowdry A = intranuclear, eosinophilic, with halo (herpes group). - Negri bodies = eosinophilic cytoplasmic inclusions in rabies (Purkinje cells, hippocampal pyramidal neurons). - Owl's eye = CMV. - Guarnieri bodies = cytoplasmic, in smallpox/vaccinia. - Councilman bodies = apoptotic hepatocytes in viral hepatitis/yellow fever. - Lewy bodies and Pick bodies are non-viral cytoplasmic neuronal inclusions.