key: cord-016237-sk1wzghx
authors: Zhang, Chen; Myers, Jeffrey L.
title: Infectious Diseases
date: 2018-09-07
journal: Atlas of Lung Pathology
DOI: 10.1007/978-1-4939-8689-7_4
sha: 
doc_id: 16237
cord_uid: sk1wzghx

Pulmonary infections are caused by a wide range of pathogenic microorganisms, including bacteria, viruses, fungi, and parasites. The most common lung infections in immunocompetent hosts are caused by pyogenic bacteria (e.g., Streptococcus pneumoniae), common respiratory viruses, and mycoplasma. These infections are usually diagnosed by clinical and microbiologic studies, including cultures and serology tests. Lung biopsy is rarely used in these diagnoses. Patients with life-threatening pneumonia, especially those who are immunocompromised, are more likely to undergo lung biopsy to rule out unusual infections not easily diagnosed using conventional microbiologic methods and for which treatment strategies may be different. Pathogens more likely to be diagnosed using lung biopsy for which there are characteristic pathologic changes are highlighted in this chapter and listed in Table 4.1.

Acute bronchopneumonia (Figs. 4.1, 4.2 and 4.3) is caused by various gram-positive or gram-negative bacteria that are sometimes visible on a Gomori methenamine silver (GMS) stain. Bacterial identification using tissue gram stains has low sensitivity and specificity and is neither necessary nor possible in most cases.

Legionnaires' disease ( Fig. 4.4) is an acute bronchopneumonia often characterized by prominent necrosis, karyorrhexis, and histiocyte-rich fibrinous exudates. Special stains are of limited value in identifying the gram-negative bacillus responsible for Legionnaires' disease and have been largely supplanted by a combination of cultures and serology. Nocardiosis ( Fig. 4 .5) occurs almost exclusively in immunocompromised patients and is caused by a gram-positive filamentous organism (Nocardia spp.) common in soil and as normal oral microflora. Nocardia pneumonia may follow a fulminant course, and about half of patients develop disseminated infections, which frequently involve the central nervous system. Actinomycosis (Fig. 4.6) is also caused by gram-positive, anaerobic, filamentous bacteria (Actinomyces spp.) common in the oral cavity and oropharynx. Actinomycosis often occurs in patients with poor oral and dental hygiene. Lung involvement frequently includes fistulous involvement of pleural and chest wall soft tissues. Microscopically, the histologic findings are similar to those described in nocardiosis, but the organisms have a propensity to form larger macroscopic colonies in vivo that are identifiable in routinely stained sections as sulfur granules; these are indistinguishable from those seen more commonly in tonsils.

Rhodococcus equi pneumonia (malakoplakia) (Fig. 4 .7) is caused by a gram-positive bacillus commonly found in soil. Pulmonary infection occurs primarily in immunocompromised patients, most commonly in AIDS patients but also in other immunocompromised populations and occasionally in immunocompetent adults. The histologic findings unique to malakoplakia are the key to establishing the diagnosis in biopsy specimens. Mycobacterial Disease (Figs. 4.8, 4.9, 4.10, 4.11, 4.12 and 4.13) The prevalence of Mycobacterium tuberculosis infection (tuberculosis) is low in the United States. Incident cases have fallen dramatically, and most newly diagnosed cases represent reactivation disease in immigrants who acquired the infection elsewhere. Most cases are diagnosed clinically by means of skin tests, cultures, and other laboratory tests. Occasionally, tuberculosis manifesting as a solitary lung nodule or miliary lesions may be biopsied or resected owing to a preoperative concern for malignancy.

Atypical/nontuberculous mycobacterial infections of the lung (Figs. 4.11, 4.12 and 4.13) commonly resemble tuberculosis in terms of clinical presentations and patterns of disease in both immunocompetent and immunocompromised hosts. Definitive diagnosis relies on culture and molecular techniques. Mycobacterium avium complex (MAC) is the most commonly encountered nontuberculous mycobacterium. In addition to causing patterns of disease resembling those seen in tuberculosis, MAC also causes a hypersensitivity pneumonia-like syndrome resulting from sensitization to contaminated hot tubs ("hot-tub lung"). High-magnification photomicrograph showing acid-fast organisms (arrows) in a section stained using a Ziehl-Neelsen technique. While there are subtle differences between Mycobacterium tuberculosis and nontuberculous mycobacterial organisms, they cannot be reliably separated based on morphology alone; speciation is accomplished more reliably with culture or molecular techniques. The organisms are usually scarce even when necrosis is extensive. Careful examination under high magnification is necessary 

Viral pneumonia is common, especially in immunocompromised patients. Some viral infections cause unique cytopathic changes that can be identified on routinely stained sections (Figs. 4.14, 4.15, 4.16, 4.17, 4.18, 4.19 and 4.20) . Immunohistochemical staining with specific antibodies is helpful in identifying some of the viruses with overlapping histologic features with greater confidence. 

The types of fungal infections encountered in lung biopsies or surgical lung specimens are heavily dependent on whether the patient is immunocompetent or immunocompromised. Fungal infections more commonly seen in immunologically intact hosts may also occur in immunocompromised patients in whom the histologic findings may be more variable. Histoplasmosis, blastomycosis, cryptococcosis, and coccidioidomycosis are the fungal infections likely to be encountered in lung biopsies from immunocompetent hosts living in North America. Other fungal diseases are seen almost exclusively in immunocompromised patients.

Histoplasmosis Histoplasmosis (Figs. 4.21, 4.22, 4.23, 4.24) is endemic in the Mississippi and Ohio River valleys of the United States. The disease is usually asymptomatic and self-limited but may cause a persistent lung nodule that leads to a needle biopsy or excision of the lesion. Necrotizing granulomatous inflammation is the usual finding, except for disseminated histoplasmosis, which is an uncommon form of the disease seen more often in immunocompromised patients. Coccidioidomycosis Coccidioidomycosis (Figs. 4.32, 4.33, 4.34 and 4.35 ) is endemic in the southwestern United States and is caused by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii. It causes disease in both immunocompetent and immunocompromised patients and may be biopsied or excised because of its tendency to form a localized lung nodule. The organism divides by a process of endosporulation, a feature helpful in identifying Coccidioides in routinely and specially stained sections. The mycelial form is much less commonly found in surgical lung specimens. 

Aspergillus infections (Figs. 4.36, 4.37, 4.38, 4.39, 4.40 and 4.41) in the lungs can be noninvasive or invasive. The commonly recognized forms include noninvasive mycetoma or Aspergillus fungus ball, allergic bronchopulmonary aspergillosis (ABPA), invasive Aspergillus pneumonia, and necrotizing tracheobronchitis. Aspergillomas form in immunocompetent patients with underlying cavitary or cystic lung disease. ABPA affects patients with asthma or cystic fibrosis, and invasive forms of the disease occur in immunocompromised patients. Chronic cavitary aspergillosis is a progressive form of disease that has features intermediate between noninvasive and invasive forms of aspergillosis. It is characterized by radiologic progression and tends to occur in patients with underlying comorbidities, particularly chronic lung disease. 

Invasive mucormycosis (Figs. 4.42 and 4.43) is caused by a group of fungi referred to as mucormycetes, also referred to as Mucoromycotina or Zygomycota (zygomycetes).

Mucormycosis occurs almost exclusively in immunocompromised patients and frequently involves the lungs. Given the high mortality rate, frozen sections are sometimes requested in order to make a rapid diagnosis and promptly start antifungal therapy. Candidiasis Candidiasis (Figs. 4.44 and 4.45) is rare and occurs primarily in immunocompromised hosts, usually presenting as angioinvasive disease with necrotizing acute bronchopneumonia and abscess formation. Occasionally, candidiasis is more exquisitely localized to blood vessels (intravascular candidiasis). Rarely, the disease is associated with granulomatous inflammation, mainly in patients with underlying chronic granulomatous disease. 

Pneumocystis pneumonia (Figs. 4.46, 4.47, 4.48, 4.49 and 4 .50) occurs exclusively in immunocompromised patients. The organism Pneumocystis jirovecii was historically considered a protozoon but was reclassified as a fungus on the basis of molecular evidence demonstrating its close relationship to fungi. Pneumocystis pneumonia is affiliated with highly variable histologic features and therefore should always be in the differential diagnosis of infections in immunocompromised patients. In its most classic form, the organisms cluster within a fibrinous air-space exudate, producing a characteristic frothy or bubbly appearance on routinely stained sections. Other relatively common variants include granulomatous inflammation and diffuse alveolar damage. Pneumocystis pneumonia with coexisting HSV infection. As illustrated in this high-magnification photomicrograph, more than one organism may be present in a lung biopsy from an immunocompromised patient. This biopsy shows frothy exudates characteristic of Pneumocystis pneumonia as well as viral cytopathic changes (arrows) and an associated necrotizing exudate typical of HSV infection

Protozoal and parasitic infestations (Figs. 4.51, 4.52, 4.53, 4.54, 4.55 and 4.56) in the lungs are rare. Except for dirofilarial nodules, these typically occur in immunocompromised patients. 

Pathological diagnosis of granulomatous lung disease: a review

Pulmonary pathologic findings of fatal 2009 pandemic influenza A/H1N1 viral infections

Granulomatous reaction to Pneumocystis jirovecii: clinicopathologic review of 20 cases

In: Katzenstein and Askin's surgical pathology of non-neoplastic lung disease

Rhodococcus equi pneumonia and pulmonary malakoplakia in acquired immunodeficiency syndrome. Pathologic features

Actinomycosis and nocardiosis. A morphologic study of 17 cases

Challenges and pitfalls of morphologic identification of fungal infections in histologic and cytologic specimens: a tenyear retrospective review at a single institution

Atypical pathologic manifestations of Pneumocystis carinii pneumonia in the acquired immune deficiency syndrome. Review of 123 lung biopsies from 76 patients with emphasis on cysts, vascular invasion, vasculitis, and granulomas

The pathology of the legionella pneumonias. A review of 74 cases and the literature