HISTOPATHOLOGY-INDIA.NET

 Pathology of  Cytomegalovirus  Infection

           Dr  Sampurna Roy  MD

Cytomegalovirus is a member of the Herpesviruses and contain double-stranded DNA.

Description of the organism : Image Link(Pathguy)

 Characterized by intra-nuclear inclusion with enlargement of both cell & nucleus. Cytoplasmic inclusions are also seen in the infected cells. 

Nuclear inclusion :  Single, measuring up to 20 µm in diameter, while the cytoplasmic inclusions are much smaller, measuring 1 to 3 µm ; it is usually basophilic but may be eosinophilic ; round to oval, with a peripheral halo and accentuation of the nuclear membrane ;at the edge of the viral inclusion, a rounded clump of peripheral chromatin may be seen extending into the clear region of the halo. Following Ganciclovir therapy, the intranuclear inclusion of CMV has been reported to have a globular and eosinophilic appearance due to loss of viral DNA.

Cytoplasmic inclusions :  Basophilic to amphophilic and indistinct.

Special stain:   Cytoplasmic inclusions  stain with the PAS and GMS stains. The intranuclear inclusions are Feulgen positive and contain viral nuclear, protein, and capsid material. Cases in which the inclusions are not easy to recognize or few in number and it is helpful to perform either immunohistochemical staining  or in situ hybridization as a diagnostic aid  .

Epidemiology:

It is common all over the world. 40-100% adult population is sero- positive.

Transmission:

1. From mother: i) In-uterus (transplacental) ; ii) birth canal secretion-during birth. iii) breast milk

2. From Day-Care-Center through saliva.

3. Commonly from venereal contact, respiratory secretion & fecal-oral route.

4. Iatrogenic- i)Blood transfusion ; ii)Transplant from infected donor.

                     Congenital CMV infection:

Mostly asymptomatic, CMV remains latent in leucocytes (major reservoir). Some produce fatal  syndrome, known as ‘Cytomegalic Inclusion Disease (CID) 

Clinical presentation:

Jaundice, petechiae, microcephaly, thrombocytopenea, diarrhea & CNS disease.

Pathology:

Liver:   Clinicopathological study of liver involvement in cytomegalovirus infection in infant autopsy cases.J Gastroenterol Hepatol. 1991 Nov-Dec;6(6):603-8.
i)Persistence of hepatic hematopoesis. ; ii )Periportal hepatic necrosis iii)Dense mononuclear infiltrate.

                     Adult CMV infection:

Mostly in immunosuppressed individuals.

Eg. i) Organ transplant from seropositive donor associated with immunosuppressive therapy.

ii) Bone marrow transplant-due to immunosuppressive therapy & Graft vs Host reaction.

iii) AIDS patients primarily affect Lungs & Gastrointestinal tract.

Lung:    (Tulane edu)

CMV can infect a variety of cell types and in the lung -

Epithelial cells of the airways and alveoli ;  fibroblasts ; macrophages ;   endothelial cells. The cytopathic effects of CMV include both nuclear and cytoplasmic inclusions. Infected cells show cytomegaly or marked enlargement.

Four major patterns of CMV infection of the lung  :

i) Miliary pattern:  result from hematogenous spread ; shows multicentric lesions ; consist of alveolar exudation by fibrin, inflammatory cells, neutrophils, and chronic inflammatory cells. Centrally - lesions may show necrosis, hemorrhage, alveolar fibrin, and inflammatory cells. CMV inclusions are presentin the nodular lesions.

ii) Diffuse interstitial pneumonitis:  Features range from mild to a pattern of diffuse alveolar damage ; There may be interstitial edema, alveolar fibrin, and hyaline membranes, or interstitial fibroblastic proliferation and type 2 pneumocyte hyperplasia ; Number of CMV inclusions vary from a few to numerous.

iii) Hemorrhagic pneumonia:

iv) CMV inclusions associated with minimal inflammation or lung injury:

CMV pneumonia frequently occurs in immunocompromised patients. Combined infection of lung with CMV, is commonly seen with Pneumocystis carnii, Candida, Aspergillus, Nocardia & M. tuberculosis. Special techniques help to confirm the presence of multiple organisms, especially if more than one virus is present .

Gastrointestinal tract - PubMed link to related abstracts:

In CMV infection of GI tract patient prresents with severe pain, loss of weight, weakness, remitting fever. Gastrointestinal lesions are erosive-ulcerous or ulceronecrotic. Infection & viral replication, mostly occurs in ulcerative disease of intestine. Eg. Crohns’ disease, Ulcerative colitis. Inclusions are seen in endothelial & mucosal cells.

Pathogenesis of CMV infection in the gastrointestinal tract:  Vasculitis - microcirculatory disorders - segmental ischemia - necrosis with inflammatory infiltration and CMV transformation of the cells -fibrosing - cicatricial transformation of the organ wall. Some authors have suggested that developing sclerosis due to CMV involvement of the intestine may promote cancer .

Skin: Few cases of cutaneous involvement have been reported:

Microscopic features: 

i) Non-specific dermal infiltrate ;

ii) Cells involved include - Endothelial cells in small dermal vessels ; fibrocytes ;  macrophages and rarely ductal epithelial cells.

'Blueberry muffin lesions' seen in congenital infections are due to dermal erythropoiesis.

Diagnosis:

1. Demonstration of CMV  ; 2. Antiviral antibody ; 3. PCR- detection of viral genome.