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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_182_библиотеки_им_акад_М_И_Перельмана.pdf
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- •Dedications
- •Contributing Authors
- •Preface
- •Acknowledgments
- •Sections
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •IMAGE GALLERY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •VIRUSES
- •VECTORS
- •CLINICAL ISSUES
- •IMAGING FINDINGS
- •MACROSCOPIC FINDINGS
- •MICROSCOPIC FINDINGS
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •KEY POINTS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •INFLUENZA VIRUS
- •OTHER RESPIRATORY VIRUSES
- •DIAGNOSTIC CHECKLIST
- •KEY POINTS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •STAGING
- •SELECTED REFERENCES
- •TERMINOLOGY
- •EBOLA AND MARBURG VIRUSES
- •OTHER HEMORRHAGIC FEVER VIRUSES
- •KEY POINTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •INFECTIOUS AGENTS: EPIDEMIOLOGY, CLINICAL PRESENTATION, AND PATHOGENESIS
- •CLINICAL IMPLICATIONS
- •MICROBIOLOGY
- •BY ORGAN SYSTEM
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •INFECTIOUS AGENTS
- •CLINICAL IMPLICATIONS
- •MICROBIOLOGY
- •DISEASES BY ORGAN SYSTEM
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •INFECTIOUS AGENTS
- •CLINICAL IMPLICATIONS
- •MICROBIOLOGY
- •MACROSCOPIC FINDINGS
- •MICROSCOPIC FINDINGS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •CLINICAL ISSUES
- •PROTOZOA CLASSES
- •DIAGNOSTIC APPROACHES TO PROTOZOA
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •ANCILLARY TESTS
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •IMAGE FINDINGS
- •MICROBIOLOGY
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MICROBIOLOGY
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •TERMINOLOGY
- •ETIOLOGY/PATHOGENESIS
- •CLINICAL ISSUES
- •MACROSCOPIC FEATURES
- •MICROSCOPIC PATHOLOGY
- •DIFFERENTIAL DIAGNOSIS
- •DIAGNOSTIC CHECKLIST
- •SELECTED REFERENCES
- •INDEX

False-positive results for both complement fixation
and immunodiffusion have also been reported in
cases of tuberculosis
Treatment
Most infections in immunocompetent patients are
self-limited and hence no therapy is required
Therapy is needed in patients who are
immunocompromised, and those who are exposed to
large fungal inoculum
Antifungal regimens vary according to patient’s
clinical presentations
In general, itraconazole is preferred for mild to
moderate histoplasmosis, and amphotericin B is
needed in treating disseminated, CNS, or severe
infections
Prognosis
Most infections are asymptomatic and self-limited in
immunocompetent individuals
Immunocompromised patients
Pulmonary disease can progress rapidly to involve
multiple lung lobes; patients can develop acute
Fungal Infections: Morphological Diagnosis of Fungal Infections
respiratory distress syndrome within days if not
treated
More likely to present with disseminated disease
IMAGE FINDINGS
Radiographic Findings
Pulmonary histoplasmosis
Most common: Diffuse reticulonodular pulmonary
infiltrates
Coalescence of nodules can be seen in discrete areas
of lung
Cavitations are mostly seen in chronic cavitary
pulmonary histoplasmosis
Mediastinal or hilar lymphadenopathy are often
present
Extrapulmonary disease
Radiographic findings are highly variable and not
specific
MICROBIOLOGY
Culture
Sabouraud dextrose agar or brain-heart infusion agar
Organisms grow slowly; 4-6 weeks are needed to
determine whether culture is positive or negative
Lysis-centrifugation is needed to release organisms
from phagocytic cells in clinical samples
Yield from culture is generally good when respiratory
samples are taken from patients who have chronic
cavitary pulmonary histoplasmosis, acute pulmonary
histoplasmosis, or disseminated infection following
exposure to a large fungal inoculum
Cultures are usually negative in respiratory samples
taken from cases of mild pulmonary infection,
III
granulomatous mediastinitis, mediastinal fibrosis
HISTOPLASMOSIS
MACROSCOPIC FEATURES
General Features
Heavy infections may cause marked enlargement of
involved organs, e.g., lymph nodes, adrenal glands,
liver, spleen
MICROSCOPIC PATHOLOGY
Histologic Features
Oval small yeast cells (2-4 m in diameter) with
narrow-based budding
Not encapsulated; however, it may appear to be
surrounded by a clear zone/pseudocapsule in tissue
Yeasts tend to cluster and reproduce within
macrophages, monocytes, and occasionally
neutrophils
When yeasts are released from cells into surrounding
tissue such as alveoli in lungs, they often remain in
clusters
Acute histoplasmosis
Nodular areas of parenchymal and vascular necrosis
associated with lymphohistiocytic vasculitis
Scattered small epithelioid and giant-cell
granulomas with small yeasts in parenchyma can be
present
Over time granulomas may turn into fibrocaseous
nodules, which can become calcified
Chronic histoplasmosis
Granulomatous inflammation with central necrosis
and occasionally calcification
Yeasts are usually present in necrotic calcified
material, which can be lost during tissue processing
Disseminated disease: Sheets of macrophages
parasitized with yeast cells can be seen
Organisms may primarily be seen extracellularly,
making it more difficult to make diagnosis
ANCILLARY TESTS
Histochemistry
Histoplasma yeast cells are positive for Gomori
methenamine silver (GMS) and (less so) periodic acidSchiff (PAS) stains
Staining is best on extracellular yeast; intracellular
yeast may not pick up silver staining to the same
degree
Negative for Gram and Fontana-Masson stains
Molecular Diagnostics
Chemiluminescent DNA probe for H. capsulatum
(AccuProbe; GenProbe, Inc., San Diego, CA)
Can be used as confirmatory test for definitive
identification in culture
Highly sensitive (up to 100%) and specific (up to
100%)
False-positive tests have been reported with
Chrysosporium spp. but are rare
PCR-based assays
1
32

HISTOPLASMOSIS
Fungal Infections: Morphological Diagnosis of Fungal Infections
Real-time PCR and semi-nested PCR assays have
been developed for testing blood, bronchoalveolar
lavage, and tissue samples
PCR assay for routine use is not yet commercially
available
DIFFERENTIAL DIAGNOSIS
Candidiasis
Histoplasma spp. can be confused easily with
Candida glabrata, which is similar in size and lacks
pseudohyphae
C. glabrata
Exhibits more size variability than Histoplasma spp.
Predominantly produces neutrophilic inflammation
rather than a granulomatous reaction seen with
histoplasmosis
Lacks a pseudocapsule on H&E stain as would be
seen with histoplasmosis
Positive on Gram stain
Cryptococcosis
Cryptococcal yeast cells
Rounder and exhibit more size variation than
Histoplasma spp.
Have capsules that are positive for mucicarmine;
capsule-deficient cryptococci, however, can be
mistaken for Histoplasma yeast cells
Positive for Fontana-Masson, which stains melanin
in their cell walls, whereas Histoplasma spp. are
negative for melanin stains
Coccidioidomycosis
Coccidioides endospores are about the same size as
Histoplasma spp., but they are usually present within
an intact spherule or associated with a ruptured
spherule in surrounding tissue, while spherules are
absent in histoplasmosis
Coccidioides endospores show no budding, while
Histoplasma spp. exhibit narrow-based budding
Blastomycosis
Blastomyces yeast cells are larger in size and have
broad-based rather than narrow-based budding as
would be seen with histoplasmosis
Pneumocystosis
Pneumocystis jirovecii cysts lacks budding and usually
have focal thickenings in cyst wall, which stain as dark
dots; these features are not seen with Histoplasma spp.
Penicilliosis
Penicillium marneffei yeast-like cells within
macrophages or monocytes may look like Histoplasma
spp., but in contrast to Histoplasma spp., P. marneffei
lacks budding, reproduces by binary fission, and shows
a prominent central septum
Extracellular P. marneffei cells are larger and may
manifest several septa
Protozoan Diseases
Leishmaniasis, toxoplasmosis, Chagas disease
None of the protozoa show halo produced by fungal
cell wall as would be seen with Histoplasma spp. on
H&E stain
None of the protozoa show budding and they are
negative for GMS or PAS stains
Cells infected by these protozoa are generally not
histiocytes as would be seen with histoplasmosis
Paranuclear-bar shaped kinetoplasts should be
observed with amastigotes of Leishmania spp. and
Trypanosoma cruzi, but not with Histoplasma spp.
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
Yield of diagnostic modalities differs depending on
extent of infection and timing following exposure
Pathologic Interpretation Pearls
Oval small yeast cells (2-4 m in diameter) with
narrow-based budding
Yeast cells tend to cluster within macrophages and
monocytes
Morphology of extracellular yeast cells on H&E are
not specific; therefore, utilization of special stains and
correlation with clinical and other laboratory findings
is needed for definitive diagnosis
SELECTED REFERENCES
1. Couturier MR et al: Urine antigen tests for the diagnosis
of respiratory infections: legionellosis, histoplasmosis,
pneumococcal pneumonia. Clin Lab Med. 34(2):219-36,
2014
2. Murthy JM et al: Fungal infections of the central nervous
system. Handb Clin Neurol. 121:1383-401, 2014
3. Sizemore TC: Rheumatologic manifestations of
histoplasmosis: a review. Rheumatol Int. 33(12):2963-5,
2013
4. Gupta AO et al: Immune reconstitution syndrome and
fungal infections. Curr Opin Infect Dis. 24(6):527-33, 2011
5. Mukhopadhyay S: Role of histology in the diagnosis of
infectious causes of granulomatous lung disease. Curr Opin
Pulm Med. 17(3):189-96, 2011
6. Gupta N et al: Histoplasmosis: cytodiagnosis and review of
literature with special emphasis on differential diagnosis
on cytomorphology. Cytopathology. 21(4):240-4, 2010
7. Hage CA et al: Pulmonary histoplasmosis. Semin Respir
Crit Care Med. 29(2):151-65, 2008
8. Assi MA et al: Systemic histoplasmosis: a 15-year
retrospective institutional review of 111 patients. Medicine
(Baltimore). 86(3):162-9, 2007
9. Kauffman CA: Histoplasmosis: a clinical and laboratory
update. Clin Microbiol Rev. 20(1):115-32, 2007
10. Chu JH et al: Hospitalizations for endemic mycoses:
a population-based national study. Clin Infect Dis.
42(6):822-5, 2006
11. Brandt ME et al: False-positive Histoplasma capsulatum
Gen-Probe chemiluminescent test result caused by a
Chrysosporium species. J Clin Microbiol. 43(3):1456-8,
2005
III
1
33

Radiographic and Microscopic Features
g
p
(Left) Chest CT shows a
nodule in right lung raising
concern for neoplastic vs.
infectious diseases. Positron
emission tomography may
be mildly to strongly avid.
Wedge resection of the nodule
revealed a calcified necrotic
mass containing Histoplasma
yeast forms. (Right) Lowmagnification of a lung section
on H&E stain shows confluent
ranulomatous inflammation
with necrosis in a
atient with acute pulmonary
histoplasmosis.
Fungal Infections: Morphological Diagnosis of Fungal Infections
(Left) High magnification
of a lung section shows the
edge of a granuloma
with central necrosis in
a patient with pulmonary
histoplasmosis. Subtle yeast
forms may reside in the
necrotic material. A GMS or
PAS-D stain to evaluate yeast
is needed. (Right) Medium
magnification of a lung nodule
shows a healing granuloma
with a fibrocaseous center .
Giant cells are noted in
the periphery. Follow-up GMS
and PAS stains highlight rare
Histoplasma yeast forms in the
nodule.
HISTOPLASMOSIS
(Left) High magnification of
this lung section on H&E stain
shows multiple macrophages
and monocytes fully packed
with yeast cells in the
alveolar spaces in a patient
with acute histoplasmosis.
(Right) High magnification of
this lung section on Gram stain
shows intracellular and
extracellular round Gramnegative yeast cell clusters,
consistent with histoplasmosis.
III
1
34

Microscopic Features
A
p
p
p
A
Fungal Infections: Morphological Diagnosis of Fungal Infections
HISTOPLASMOSIS
(Left) High magnification
of this tissue section reveals
numerous small yeast forms
highlighted by GMS stain.
few of the yeast cells
appear to exhibit narrowbased budding . (Right)
High magnification of a
skin section shows fungal
dermatitis associated with
PAS-positive small round
yeast forms, both intraand extracellularly . The
findings are consistent with
histoplasmosis. Correlation
with clinical and other
laboratory findings is
needed.
(Left) Medium magnification
of this tenosynovial biopsy
shows scattered minute
clusters of small yeasts
highlighted by PAS stain,
utting histoplasmosis on
the differential. The small
size of the nonpigmented
yeasts makes it challenging
to detect on H&E stain when
the fungal load is small.
(Right) High magnification
of this PAS-stained tissue
section shows scattered dark
blue lymphocytes and
aggregates of pink small
oval yeast cells in a
atient with disseminated
histoplasmosis.
(Left) High magnification
of a lung mass on GMS
stain shows small oval yeast
forms with fairly uniform
size, putting histoplasmosis
on the differential. (Right)
GMS stain shows small,
variably sized yeast forms
with occasional budding
. A pale halo appears
to surround some of the
yeast cells, suggesting a
seudocapsule or a capsule.
The findings raise the
differentials of Cryptococcus
vs. Histoplasma spp.
negative FontanaMasson would exclude
Cryptococcus.
III
1
35

MUCORMYCOSIS
High magnification of a lung lesion on H&E stain shows
numerous broad ribbonous fungal hyphae with rightangle branching consistent with mucormycosis.
Fungal Infections: Morphological Diagnosis of Fungal Infections
TERMINOLOGY
Synonyms
Zygomycosis (former name), phycomycosis (former
name)
Definitions
Latin: "Mucor" (bread mold, wine must)
Greek: "Zygon" (yoke) + "mykes" (mushroom)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Mucorales fungi are ubiquitous in environment in
association with decaying organic matter
Most common genera causing human infections:
Rhizopus spp., Mucor spp., Rhizomucor spp.
Less common genera causing infections:
Cunninghamella, Absidia, Saksenaea, and Apophysomyces
Pathogenesis
Infection presumed to occur after inhalation of spores
In healthy people: Spores are transported by cilia to
pharynx and are cleared through gastrointestinal tract
In immunocompromised individuals: Spores are not
cleared and infection usually begins in nasal sinuses or
pulmonary alveoli
Organisms are angioinvasive, causing tissue infarction
and necrosis
CLINICAL ISSUES
Epidemiology
Risk factors
Immunosuppression, e.g., AIDS, hematological
III
malignancies, solid organ transplant recipients,
hematopoietic stem cell transplant recipients,
glucocorticoid recipients
1
Low magnification of a lung mass on PAS stain shows
angioinvasion of fungal forms. Hyphae are relatively
broad with very few septa, putting mucormycosis in the
differential.
Diabetes mellitus with poor glycemic control
Treatment with deferoxamine
Deferoxamine-iron chelate can act as siderophore
for Rhizopus spp., hence stimulates fungal growth
by increasing their iron uptake
Other iron chelating agents, such as deferasirox
and deferiprone, do not act as siderophores and
therefore do not increase the risk of mucormycosis
Iron overload
Injection drug use
Malnutrition
Severe prematurity
Presentation
Most cases have rapid course; rare cases have indolent
course
Most common primary mucormycosis: Rhinocerebral,
pulmonary, cutaneous infections
Rhinocerebral infection
Most common clinical presentation of
mucormycosis
Most commonly caused by Rhizopus spp.
Contiguous spread to other structures, such as
palate, orbit, and brain; can progress rapidly
Pulmonary infection
Pneumonia with tissue infarction and necrosis,
which may ultimately lead to cavitation &/or
hemoptysis
Clinical course is usually rapidly progressive
Infection can spread to contiguous structures,
such as mediastinum and heart, or disseminate
hematogenously to other organs
Cutaneous infection
Often due to inoculation of spores into dermis; rare
cases are seen with disseminated disease
Can occur in cases of trauma or contaminated
wounds
Deep tissue involvement and dissemination from
cutaneous infection is relatively unusual
36

Terminology
Former names: Zygomycosis, phycomycosis
Etiology
Most common genera found in human infections:
Rhizopus spp., Mucor spp., Rhizomucor spp.
Opportunistic pathogens
Clinical Issues
Most cases have a rapid course
Risk factors
Immunosuppression, diabetes mellitus, injection
drug use, trauma, burns, malnutrition, iron
overload, treatment with deferoxamine
Most frequent primary clinical manifestations:
Rhinocerebral, pulmonary, cutaneous infections
Disseminated infection carries poor prognosis
MUCORMYCOSIS
Key Facts
Microscopic Pathology
Nonpigmented, wide (5-20 m), thin-walled, ribbonlike hyphae with few septations and right-angle
branching
Hyphae are angioinvasive, causing tissue necrosis,
hemorrhage, and blood vessel thrombosis,
particularly in immunocompromised hosts
Ancillary Tests
Hyphae can be highlighted by silver stain and
periodic acidSchiff stain on tissue sections
Top Differential Diagnoses
Aspergillosis
Candidiasis
Hyalohyphomycosis
Concurrent infections with other fungi
Fungal Infections: Morphological Diagnosis of Fungal Infections
Disseminated infection
Most commonly seen in severely
immunocompromised patients, burn patients,
premature infants, and transplant recipients
Any primary manifestations can give rise to
disseminated disease
Brain is the most common site of spread
Other sites of spread: Spleen, heart, kidney, and
other organs
Gastrointestinal infection
Rare
Thought to arise from ingestion of fungal organism
Most common sites: Stomach, colon, and ileum
Mostly occurs in transplant recipients and in
severely malnourished patients
Treatment
Combination of antifungal therapy and surgical
debridement of infected tissues
Predisposing factors should be watched out for and
managed, e.g., metabolic acidosis, hyperglycemia
immunosuppressive drugs
Early initiation of therapy improves outcome
Drugs
Initial therapy
Amphotericin B is usually drug of choice for
mucormycosis, or as empiric treatment for
aspergillosis or mucormycosis before definitive
diagnosis is made
Step-down therapy
Oral posaconazole can be used as a step-down in
patients responding to amphotericin B
Salvage therapy
Intravenous posaconazole can be used in patients
who cannot tolerate or do not respond to
amphotericin B
Studies are needed to establish whether combination
therapy with other antifungals (e.g., echinocandins)
is beneficial
Voriconazole, fluconazole, and flucytosine are not
effective against Mucorales
Surgery
Surgical debridement should be made as soon as
diagnosis of rhinocerebral or orbital mucormycosis
is suspected
Pulmonary mucormycosis often present with
multilobar involvement that precludes surgical
resection
Prognosis
Generally poor for disseminated cases
Early diagnosis and combined surgical and medical
therapy are key to improved prognosis
IMAGE FINDINGS
Chest Radiographs or CT Scans
Focal consolidation, masses, or nodules
Halo sign: Ground-glass attenuation surrounding a
nodule, seen with angioinvasive fungi, mycobacteria,
or in cases of neoplasia causing tissue infarction or
hemorrhage
Reversed halo sign: Focal area of ground-glass
attenuation surrounded by ring of consolidation
Mucormycosis has been reported to be the most
common condition to cause reversed halo sign in
immunocompromised hosts
MICROSCOPIC PATHOLOGY
Histologic Features
Nonpigmented, wide (5-20 m in diameter), thinwalled, ribbon-like hyphae with few septations and
right-angle branching
Fungal elements are often seen invading blood vessel
wall or inside their lumen
Associated with tissue necrosis, hemorrhage, and
blood vessel thrombosis
Hyphae may vary in width, and may appear folded,
fragmented, crinkled or degenerated on tissue or
cytologic specimens
III
1
37

A
Lack of regular septations in hyphae makes them
fragile and prone to damage during tissue processing
ANCILLARY TESTS
Special Stains
Hyphae can be highlighted by silver stain and periodic
acidSchiff stain on tissue sections
Fragmentation and degeneration of the fungal
elements may cause these stains, particularly silver
stain, to be either faintly positive or negative
Hyphae can be highlighted with Papanicolaou and
calcofluor white stains on cytologic specimens
Cultures
Fast-growing (< 3 days)
Yield of cultures can be low
Rarely recovered from blood, even in invasive cases
Airborne spores can cause contamination of laboratory
media, hence positive cultures have to be correlated
with clinical and histologic findings
Serological Tests
Fungal Infections: Morphological Diagnosis of Fungal Infections
Not clinically useful in invasive disease
Serum galactomannan and 1,3-beta-D-glucan are
typically negative in invasive mucormycosis
Molecular Diagnostics
PCR with sequencing using conserved fungal primers
(28S rRNA)
DIFFERENTIAL DIAGNOSIS
spergillosis
Hyphae of Mucorales are pauciseptate, broad with
right-angle branching whereas Aspergillus hyphae are
narrower, septate with acute-angle branching
Poor staining of hyphae with silver stain would
suggest mucormycosis as the pauciseptate hyphae are
prone to degeneration resulting in less pickup of silver
stain
Serum galactomannan and 1,3-beta-D-glucan are
typically positive in cases of invasive aspergillosis and
negative in cases of invasive mucormycosis
Candidiasis
Candida spp. produce yeast forms admixed with
pseudohyphae and true hyphae
Gram stain highlights Candida spp., while hyphae in
cases of mucormycosis are negative with Gram stain
Hyalohyphomycosis
Hyaline molds, such as Fusarium and Scedosporium
spp., are morphologically similar to Aspergillus spp.
and hence can be confused with Mucorales
These molds generally produce abundant septations,
in contrast to cases of mucormycosis, which produce
pauciseptate hyphae
MUCORMYCOSIS
Concurrent Infections With Other Fungi
Concurrent aspergillosis and candidiasis have been
reported
Alternative diagnostic testing of tissues such as
immunohistochemistry, in situ hybridization, or PCR
are needed for definitive identification
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
Infections are mostly opportunistic in nature
Clinical course is usually rapid, with the exception of
isolated cutaneous infection
Yield from culture is usually low; positive cultures
have to be correlated with clinical and histologic
findings for interpretation to rule out culture
contamination
Pathologic Interpretation Pearls
Hyphae are typically nonpigmented, pauciseptate,
broad (5-20 m in diameter) with irregular or rightangle branching
Fungal elements are often angioinvasive, causing
hemorrhage, necrosis, and tissue infarction
Hyphae are positive for silver stains, PAS stains, and
negative for Gram stain
Fragmentation and degeneration of the fungal
elements can make it hard to assess septation and
branching
Correlation with clinical and culture findings is
needed
SELECTED REFERENCES
1. Petrikkos G et al: Epidemiology and clinical manifestations
of mucormycosis. Clin Infect Dis. 54 Suppl 1:S23-34, 2012
2. Spellberg B et al: Combination therapy for mucormycosis:
why, what, and how? Clin Infect Dis. 54 Suppl 1:S73-8,
2012
3. Georgiadou SP et al: The diagnostic value of halo and
reversed halo signs for invasive mold infections in
compromised hosts. Clin Infect Dis. 52(9):1144-55, 2011
4. Guarner J et al: Histopathologic diagnosis of fungal
infections in the 21st century. Clin Microbiol Rev.
24(2):247-80, 2011
5. Spellberg B et al: Recent advances in the management of
mucormycosis: from bench to bedside. Clin Infect Dis.
48(12):1743-51, 2009
6. Roden MM et al: Epidemiology and outcome of
zygomycosis: a review of 929 reported cases. Clin Infect
Dis. 41(5):634-53, 2005
7. Maertens J et al: Mucormycosis in allogeneic bone marrow
transplant recipients: report of five cases and review of the
role of iron overload in the pathogenesis. Bone Marrow
Transplant. 24(3):307-12, 1999
8. Harril WC et al: Chronic rhinocerebral mucormycosis.
Laryngoscope. 106(10):1292-7, 1996
9. Boelaert JR et al: Deferoxamine augments growth and
pathogenicity of Rhizopus, while hydroxypyridinone
chelators have no effect. Kidney Int. 45(3):667-71, 1994
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Radiologic and Gross Features
p
p
p
p
Fungal Infections: Morphological Diagnosis of Fungal Infections
MUCORMYCOSIS
(Left) Chest CT scan
shows right upper lobe
opacification and mass
extending into the
mediastinum in a patient
with acute myeloid leukemia
status post consolidation
chemotherapy. Biopsy
of the mass confirms
ulmonary mucormycosis.
(Right) Photo shows
aggregates of superficial
skin ulcers in a patient
on immunosuppression
after heart transplantation.
Histology and culture
confirms involvement by
mucormycosis.
(Left) Lung section from
a patient with pulmonary
mucormycosis shows
multiple tan/pink centrally
necrotic lesions
containing Mucorales spp.
on histologic examination
and culture. (Right) Gross
hoto of a lung section
shows fungal emboli
and confluent nodular
infarctions caused by
fungal infection in lung
arenchyma. Microscopic
examination confirms
invasive mucormycosis.
(Left) Gross photo shows
meningeal gray-white lesions
consistent with infection
in a patient who died of
disseminated mucormycosis.
Microscopic examination
reveals numerous fungal
forms consistent with
Mucorales. (Right) Gross
hoto shows cerebral
infarction surrounded by
erythema in the right frontal
lobe of a patient who died
of infectious complications.
Histologic examination
shows angioinvasion by
fungal forms consistent with
Mucorales.
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Gross and Microscopic Features
p
(Left) Gross photo shows
multiple dark green nodular
lesions
in a patient who died of
disseminated fungal infection.
Microscopic examination
showed transmural colitis
with fungal forms consistent
with Mucorales. (Right) High
magnification of a fine-needle
aspiration with Diff-Quik stain
shows broad aseptate fungal
hyphae
Mucorales. Branching
appears to be acute-angle due
to folding of the fungal forms.
Fungal Infections: Morphological Diagnosis of Fungal Infections
(Left) Medium magnification
of this fine-needle aspiration
on Pap stain shows long,
ribbonous, broad hyphae
consistent with Mucorales.
Branching is difficult to assess
due to folding of hyphae.
(Right) Brain section on H&E
stain shows fungal forms in
the vessel lumen invading
into surrounding tissue ,
resulting in infarction. Broad
hyphae and right-angle
branching are consistent with
Mucorales.
on cecal mucosa
consistent with
MUCORMYCOSIS
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40
(Left) Tissue section of 2
adjacent blood vessels on
H&E stain shows abundant
thick aseptate hyphae
with occasional branching
consistent with Mucorales.
Numerous fungal forms are
resent inside the vessel
lumen, with some invading
through the vessel wall
. (Right) Section of a
liver embolus on H&E stain
in a case of disseminated
mucormycosis shows
subtle but numerous broad
Mucor hyphae admixed
with fibrin. Silver or PAS
stains would be helpful in
highlighting the organisms.

Microscopic Features
g
A
Fungal Infections: Morphological Diagnosis of Fungal Infections
MUCORMYCOSIS
(Left) Tissue section of a
blood vessel on silver stain
shows numerous broad,
ribbonous, pauciseptate
hyphae with occasional
branching, most consistent
with Mucorales. Transverse
sections of hyphae mimic
yeast forms . (Right) PA S
stain highlights numerous
fungal forms with broad
hyphae admixed with
neutrophilic inflammation
in a patient with known
disseminated mucormycosis.
Hyphae can appear
fragmented and degenerated
on tissue section.
(Left) GMS stain highlights
broad segments of aseptate
hyphae consistent with
Mucorales in this tissue
section. (Right) Calcium
oxalate crystals as well
as ribbonous hyphae with
variable branching and
occasional septa are present
in this biopsy. Differentials
include Aspergillus vs.
Mucorales spp. The presence
of crystals (Aspergillus) and
thick hyphal morphology
(Mucor) make definitive
speciation difficult. Culture
confirms the presence of A.
flavus.
(Left) Differentials of
these fragmented hyphae
highlighted by GMS stain
include Mucorales (favored
iven the hyphal size) vs.
spergillus spp. Correlation
with culture is needed.
(Right) H&E section shows
fungal forms invading into
respiratory mucosa. Thick
hyphae
with round to square forms,
which may represent yeast
vs. arthroconidia . Culture
is required for definitive
speciation.
, some with septa
, are present admixed
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