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Lung-nontumor

Infections

CMV pneumonia / pneumonitis


Reviewer: Elliot Weisenberg, M.D. (see Reviewers page)
Revised: 4 September 2011, last major update September 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.

Definition
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● Lung injury caused by infection by CMV, a herpes virus
● Usually immunocompromised patients
● Often associated with pneumocystis and other infections
Xray: 2-4 cm peripheral nodules, miliary pattern, diffuse interstitial process

Epidemiology
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● 70% of Americans in large cities have latent infection
● In immunocompetent individuals, primary infection is generally asymptomatic, but mononucleosis-like illness may occur; rarely, self-limiting CMV pneumonia may occur during mononucleosis-like illness (eMedicine)
● In organ transplant recipients, infection may occur when the donor organ is latently infected with CMV
● When infection occurs in immunosuppressed patients, the risk of organ damage is higher the greater the immunosuppression
● In AIDS patients, CMV disease generally occurs when the CD4+ cell count < 50/mm3
● CMV is the most common life threatening infection in hematopoietic stem cell transplant recipients and is the most common opportunistic viral infection in AIDS
● Prophylactic therapy and preemptive therapy, where CMV DNA levels are monitored by PCR and antiviral therapy against CMV is given prior to end organ damage, has greatly reduced the incidence of CMV induced disease in vulnerable patients
● Highly active anti-retrovirus therapy has reduced the incidence of end organ damage by 80% in HIV positive patients

Sites
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● In addition to lung, CMV causes severe disease in retina, brain, kidneys, GI

Etiology
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● Disease may occur with primary infection or secondarily when latent disease is reactivated
● Virus can be spread transplacentally; neonatal disease can occur through exposure to cervical or vaginal secretions or from breast milk when active infection is present
● In children and adults, infection is spread through saliva, respiratory droplets or sexual activity
● Fecal oral transmission has also been documented
● CMV causes down regulation of expression of MHC class I and II molecules, which helps it elude host immune responses

Clinical features
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● In immunocompetent patients, cough with interstitial infiltrates on chest x-ray
● Immunosuppressed patients present with cough, fever, fatigue, shortness of breath, malaise, night sweats, muscle and joint pain
● Note: positive culture, serology or PCR may not represent evidence of illness
● Diagnosis is based on identification of viral inclusions in biopsy material
● Acute CMV infection leads to transient but severe immunosupression
● Prevention is key as CMV pneumonia has high mortality rate even with aggressive anti-viral therapy

Treatment
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● Ganciclovir, valganciclovir, foscarnet, cidofovir, maribavir

Gross description
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● Lung is firm (similar to interstitial lung disease) with hemorrhagic nodules that may become confluent

Micro description
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● Mononuclear infiltrates, usually mild edema and pneumocyte hyperplasia
● Infected cells are generally large with a prominent basophilic nuclear inclusion, often with a clear halo, and smaller basophilic cytoplasmic inclusions are also present
● Hemorrhagic necrosis may be present
● In lung, usually infects endothelial and epithelial cells and alveolar histiocytes

Micro images
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Contributed by Drs. Michael P. Orejudos and Rosemarie Rodriguez, San Antonio, Texas (USA)

Cytology description
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● Diagnostic inclusions may be seen in brochiolalveolar lavage fluid, but diagnostic yield is very low

Positive stains
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● Immunohistochemical staining for CMV is confirmatory
● PAS and GMS stains highlight the inclusions

EM description
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● Particles are 150-200 nm with round core and double membrane

Differential diagnosis
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● Herpes simplex virus and herpes varicella zoster produce similar lung disease, but characteristic CMV inclusions are not present
● Drug induced injury, particularly in bone marrow transplant recipients, may cause changes similar to CMV; in problematic cases, immunohistochemical studies are useful

Additional references
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● Connor DH, Chandler FW, Schwartz DA, Lack EE, eds. Pathology of Infectious Diseases. Stamford CT: Appleton & Lange;1997:91
● Mandell GL, Bennett JE, Dolin R. Principles and Practice of Infectious Diseases (7th ed). Philadelphia: Churchill Livingstone; 2010:1971

End of Lung-nontumor > Infections > CMV pneumonia


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