Definition/General
Introduction:
Fungal infections of the respiratory tract are opportunistic infections commonly seen in immunocompromised patients
They represent a significant diagnostic challenge in cytology
Sputum cytology is a rapid, cost-effective method for diagnosis
Early diagnosis is crucial for appropriate antifungal therapy.
Origin:
Fungal organisms enter the respiratory tract through inhalation of spores
They colonize the bronchopulmonary tree in susceptible hosts
Immunocompromised states facilitate invasive disease
Common predisposing factors include diabetes
HIV infection
Prolonged antibiotic therapy
Corticosteroid use.
Classification:
Classified as superficial or invasive infections
Aspergillus species (most common)
Candida species
Cryptococcus neoformans
Pneumocystis jirovecii
Mucor species
Histoplasma capsulatum
Blastomyces dermatitidis.
Epidemiology:
Increased incidence in immunocompromised patients
Rising prevalence with HIV epidemic
Common in hospitalized patients on broad-spectrum antibiotics
Higher incidence in tropical regions
Seasonal variation noted with environmental spore counts.
Clinical Features
Presentation:
Persistent cough with purulent sputum
Dyspnea and chest discomfort
Hemoptysis (especially Aspergillus)
Fever with night sweats
Weight loss
Allergic symptoms (ABPA)
Chest pain.
Symptoms:
Productive cough (>3 weeks)
Thick, tenacious sputum
Shortness of breath on exertion
Pleuritic chest pain
Constitutional symptoms
Wheezing (allergic component)
Recurrent respiratory infections.
Risk Factors:
Immunocompromised state
Diabetes mellitus
HIV/AIDS
Prolonged antibiotic therapy
Corticosteroid use
Chronic lung diseases
Malignancy
Organ transplantation
Neutropenia.
Screening:
High clinical suspicion in immunocompromised patients
Serial sputum examination
Bronchoscopy with BAL
Imaging studies (CT scan)
Antigen detection tests
Culture confirmation.
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Gross Description
Appearance:
Thick, purulent sputum with varying colors
Yellow-green (Aspergillus)
White, creamy (Candida)
Blood-tinged (invasive disease)
Frothy (Pneumocystis)
Black specks (Aspergillus niger).
Characteristics:
Tenacious consistency
May contain fungal plugs
Mucoid appearance
Foul odor (secondary bacterial infection)
Variable volume
Persistent production.
Size Location:
Volume varies from scanty to copious
Upper respiratory tract colonization
Lower respiratory tract infection
Bilateral involvement common
Focal or diffuse distribution.
Multifocality:
Multiple fungal species may coexist
Mixed bacterial-fungal infections
Different anatomical sites
Progressive disease pattern
Systemic dissemination possible.
Microscopic Description
Histological Features:
Fungal hyphae with characteristic morphology
Spores and conidia
Budding yeasts
Inflammatory cell infiltrate
Neutrophilic exudate
Eosinophils (allergic component)
Macrophages with organisms.
Cellular Characteristics:
Aspergillus: Septate hyphae with acute angle branching
Candida: Budding yeasts with pseudohyphae
Cryptococcus: Encapsulated yeasts
Pneumocystis: Cysts with intracystic bodies
Mucor: Broad, non-septate hyphae.
Architectural Patterns:
Hyphal networks in tissue sections
Conidiophores (Aspergillus)
Fruiting heads
Yeast forms in clusters
Mixed inflammatory pattern
Granulomatous reaction (chronic cases).
Grading Criteria:
Graded by organism burden
Light growth: Few organisms
Moderate growth: Numerous organisms
Heavy growth: Abundant organisms
Tissue invasion assessment
Inflammatory response severity.
Immunohistochemistry
Positive Markers:
PAS stain (highlights fungal wall)
GMS stain (silver stain for fungi)
Calcofluor white (fluorescent stain)
Mucicarmine (Cryptococcus capsule)
Specific fungal antigens
Galactomannan (Aspergillus).
Negative Markers:
Bacterial stains (Gram stain negative)
Acid-fast stains (differentiate from mycobacteria)
Viral inclusions absent
Parasitic forms absent
Normal bacterial flora may be reduced.
Diagnostic Utility:
Essential for species identification
Differentiates from bacteria and parasites
Confirms viability
Guides antifungal therapy
Monitors treatment response
Detects mixed infections.
Molecular Subtypes:
Aspergillus fumigatus (most common)
Aspergillus niger
Candida albicans
Candida tropicalis
Cryptococcus neoformans
Species-specific PCR available
Antifungal susceptibility patterns.
Molecular/Genetic
Genetic Mutations:
Host genetic factors affect susceptibility
Mannose-binding lectin deficiency
Complement deficiencies
Primary immunodeficiencies
Genetic polymorphisms in cytokine production
CFTR mutations (Aspergillus risk).
Molecular Markers:
Fungal DNA detection by PCR
rRNA gene sequencing
ITS region analysis
Galactomannan antigen
Beta-D-glucan
Cryptococcal antigen
Aspergillus antigen.
Prognostic Significance:
Species identification determines prognosis
Antifungal resistance patterns
Host immune status
Early detection improves outcomes
Invasive disease has worse prognosis
Mixed infections complicate treatment.
Therapeutic Targets:
Ergosterol biosynthesis (azole antifungals)
Beta-glucan synthesis (echinocandins)
Cell wall synthesis (polyenes)
Specific enzymes
Membrane integrity
Drug combination therapy.
Differential Diagnosis
Similar Entities:
Bacterial pneumonia (different organism morphology)
Viral infections (inclusion bodies)
Mycobacterial infections (acid-fast positive)
Parasitic infections (different life cycle stages)
Malignancy (atypical cells).
Distinguishing Features:
Fungi: Characteristic morphology
Fungi: PAS/GMS positive
Bacteria: Different staining
Viruses: Inclusion bodies
Mycobacteria: Acid-fast positive
Parasites: Different life stages
Malignancy: Cytological atypia.
Diagnostic Challenges:
Distinguishing colonization from infection
Mixed infections
Contamination during collection
Overgrowth of bacteria
Poor specimen quality
Non-specific inflammatory changes.
Rare Variants:
Zygomycosis (Mucor, Rhizopus)
Paracoccidioidomycosis
Coccidioidomycosis
Sporothrix schenckii
Penicillium marneffei
Fusarium species
Scedosporium.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Sputum specimen, [volume] mL, [appearance], adequate for evaluation
Diagnosis
Fungal respiratory infection - [organism species]
Organism Identification
[Fungal species] identified showing [morphological features]
Microscopic Findings
Shows [organism morphology] with [inflammatory response]
Organism Burden
Organism burden: [light/moderate/heavy growth]
Inflammatory Response
Inflammatory response: [neutrophilic/eosinophilic/mixed]
Special Studies
Special stains: [PAS/GMS/Calcofluor white]: [positive/negative]
Culture: [recommended/pending/results]
Antigen tests: [recommended/results]
Clinical Correlation
Clinical correlation with [symptoms] and [risk factors]
Final Diagnosis
Sputum cytology: Fungal respiratory infection - [organism species]