Page 139 - AIDSBK23C

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Untreated, or with poor response to therapy, the terminal hospital course with PCP can be as
short as a few days.[208,609]
Pneumocystis is more likely to have a diffuse involvement of lung than other
opportunistic infectious agents or neoplasms with AIDS. Pneumocystis typically involves
alveolar spaces, giving the gross appearance of pneumonic consolidation. P jiroveci (carinii)
pneumonia tends to be more confluent throughout the lungs than bacterial pneumonias. Cut
surfaces of lung with early PCP show a prominent "poached salmon" or pale pink appearance
when in the fresh state, and the markedly consolidated lung is firm to friable with a definable
lobular pattern. There may be scattered areas of hemorrhage or congestion. The weight of each
lung can exceed 1 kg.[602] Laboratory diagnosis is accomplished by staining of the organisms
in fluids and tissues recovered from the patient.[610]
An uncommon gross appearance of PCP is a "granulomatous" pattern resembling
Mycobacterium tuberculosis infection. This pattern is more likely to be present when a chest
radiograph shows parenchymal nodules, but diffuse infiltrates or a solitary nodule may also
occur. The granulomas range from 0.1 to 2.5 cm, averaging 0.5 cm in size. Microscopically
they all contain epithelioid macrophages and lymphocytes, but slightly more than half have giant
cells. Foamy eosinophilic exudate typical for PCP may be present within a granuloma in a
fourth of cases, but associated intra-alveolar foamy exudates in only 5% of cases. Non-
necrotizing granulomas are found in 20% of cases.[611] A "pneumocystoma" pattern with one
or more ill-defined pale pink to tan masses is also uncommonly seen.[612,613] Another pattern
is the appearance of multiple thin-walled bi-apical cystic spaces with a subtle ground-glass
pattern surrounding the cysts.[614]
As PCP progresses, the lung texture becomes rubbery and the cut surfaces are often
slimy, typical of diffuse alveolar damage (clinically defined as adult respiratory distress
syndrome or "shock" lung). Severe infections poorly responsive to therapy may go on to
produce diffuse alveolar damage that can organize to "honeycomb" lung with type II cell
hyperplasia and interstitial fibrosis. Lymphocytic or plasma cell interstitial infiltrates can be
prominent, though this is more common with PCP in children than in adults. A pattern of
bronchiolitis obliterans may be apparent. The greater the degree of organization, the fewer and
smaller the alveolar exudates become, and the harder the organisms are to identify within the
tissue histologically. Concomitant therapy of PCP with intubation and ventilation utilizing high
oxygen tensions may lead to oxygen toxicity that also promotes diffuse alveolar damage.[602]
The inflammatory reaction to P jiroveci (carinii) is primarily mediated by macrophages,
and impairment of macrophage function in immunocompromised hosts leads to risk for
establishment of infection. The diminished CD4 lymphocyte count contributes to development
of PCP, because tumor necrosis factor and interleukin-1 released by macrophages aid in
activation of CD4 cells, and activated CD4 cells release interferon-gamma that stimulates
macrophage function to clear the organisms.[397]
In hematoxylin-eosin-stained transbronchial biopsy specimens, PCP is suggested by the
presence of a characteristic intra-alveolar exudate consisting of refractile, foamy to granular to
honeycomb eosinophilic material composed mainly of the Pneumocystis organisms (both
trophozoites and cysts) held together by intertwined slender membranotubular extensions. The
exudate contains little fibrin, and scanty admixed cellular elements or debris may consist of
lymphocytes, macrophages, pneumonocytes.[401] Early infections may lack the foamy exudate,
though P jiroveci (carinii) cysts and trophozoites can be demonstrated on alveolar septae. An
inflammatory component is not a striking feature in most cases, though in some cases