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A 53-year-old man comes to the emergency department due to progressively worsening shortness of breath, nonproductive cough, and low-grade fevers over the past 2 weeks.  He has not had a runny nose or sore throat and does not recall any sick contacts.  He received a lung transplant for idiopathic pulmonary fibrosis 4 months ago.  His medications include immunosuppressants and trimethoprim-sulfamethoxazole.  Temperature is 37.8 C (100 F).  Chest x-ray reveals diffuse interstitial infiltrates bilaterally.  A decrease in pulmonary function is noted on testing.  A lung biopsy specimen is shown below.

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Which of the following best characterizes the organism most likely responsible for this patient's current condition?

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Transplant patients are at risk for a variety of unusual infections due to their immunocompromised state.  Cytomegalovirus (CMV) is particularly common in patients with lung transplants (typically occurring within the first few months after transplant).  Most but not all transplant centers practice universal prophylaxis for lung transplant recipients (eg, valganciclovir).

CMV is an enveloped double-stranded DNA virus belonging to the Herpesviridae family.  Major risk groups for infections include transplant patients, patients with HIV, and fetuses (congenital infections).  CMV pneumonitis is the most common form of tissue-invasive CMV following lung transplantation; other organ-specific disease manifestions (eg, esophagitis, colitis, and retinitis) occur more frequently in patients with HIV.

Biopsy findings consistent with CMV include enlarged cells with intranuclear and intracytoplasmic inclusions (viral particles); there is often a surrounding halo (owl's eye).

(Choices B, D, and E)  Influenza viruses are enveloped single-stranded RNA viruses.  Rhinovirus (a cause of the common cold) is a nonenveloped single-stranded RNA virus.  Adenovirus is a nonenveloped double-stranded DNA virus.  Although these viruses can cause respiratory illness, this patient's clinical features (2 weeks of progressive symptoms, impaired pulmonary function, no upper respiratory infection symptoms) and histologic findings make post-transplant CMV pneumonitis a more likely diagnosis, particularly given the lack of CMV prophylaxis.

(Choice C)  Organs affected by Nocardia and Actinomyces show filamentous branching beaded gram-positive rods in Gram stain preparations.  Nocardia is aerobic and positive for modified acid-fast stain; Actinomyces is anaerobic and negative for modified acid-fast stain.

(Choice F)  Histopathologic and cytologic findings in Pneumocystis jirovecii pneumonia (PCP) include eosinophilic foamy alveolar material and cystic and trophic forms that can be stained with Giemsa or silver stain (producing a cup-in-saucer appearance).  In addition, PCP is more common in patients with advanced HIV than in transplant patients and would be unlikely in this patient on PCP prophylaxis with trimethoprim-sulfamethoxazole.

Educational objective:
In a transplant patient, pneumonia with intranuclear and cytoplasmic inclusion bodies histologically points to opportunistic infection with cytomegalovirus, an enveloped virus that contains a double-stranded DNA genome.