SCBM341: GENERAL PATHOLOGY

L11 – Fungal Infection

Niwat Kangwanrangsan, Ph.D.

Department of Pathobiology

Faculty of Science, Mahidol University

<niwat.kan@mahidol.ac.th>

Outline

� Introduction

� Pathogenesis of fungal infection

� Pathology of fungal infection

- superficial

- cutaneous

- subcutaneous

- endemic (primary & systemic)

- opportunistic

Fungi

� eukaryotes*

� non-motile

� cell membrane (ergosterol)

� cell wall (glucan & chitin)

� enzyme to degrade organic substrates

� toxin (but not potent to pathogenicity)

Introduction

Site of infection

� skin

� respiratory tract

� GI tract

� Urogenital tract

Laboratory diagnosis

� culture

- Sabouraud’s dextrose agar (SDA)

- Inhibitory mold agar (IMA)

� microscopic examination

- Hematoxylin and Eosin (H&E)

- Periodic acid-Schiff (PAS)

- Gomori-methenamine silver (GMS)

� genetic examination

� serology

Morphologic types of fungi

� Yeast (unicellular, budding/pseudo-hyphae)

� Mold (hypha/mycelial, spore)

� Dimorphic fungi

Pathogenesis

� highly accumulate of fungi

� related to host immunity (e.g. inflammation, hyperimmune,…)

� vary in their virulence

Fungal infection

� term “mycoses”

�most are “opportunists”

� infect to people with impaired immune responses

caused by - corticosteroid drugs

- antineoplastic therapy

- T-cell deficiency (congenital or acquired)

Category of major mycoses

1

2

3

4

5

Superficial Infection

Pityriasis versicolor

� Malassezia species

� highly prevalent, chronic infection of stratum corneum

� usually on chest, upper back, arms, abdomen

� M. restricta - seborrheic dermatitis (ie, dandruff)

� discrete, serpentine hyper-, or hypopigmented maculae, may enlarge and coalesce, but scaling, inflammation, and irritation are minimal

� This common affliction is largely a cosmetic problems

(1)

Tinea nigra

� Hortaea werneckii

� chronic and asymptomatic infection

� more prevalent in warm coastal regions and among young women

� lesions appear as dark discoloration (often on palm)

� skin scrapings will reveal septate hyphae and budding yeast with melanized cell walls

(1)

White/Black piedra

� Piedraia hortae � Black piedra

� nodular infection of hair shaft

� Trichosporon species � White piedra

� present as larger, softer, yellowish nodules on the hairs

� hair of axilla, genitalia, bread, scalp

(1)

Cutaneous Infection

Dermatophytosis

� Microsporum species, Trichophyton species, Epidermophyton floccosum

� superficial infection of keratinized tissue, most prevalent in the world

� fungi proliferate in keratinized tissue and spread centrifugally, producing round, expanding lesions with sharp margins

� thickening of squamous epithelium, increase number of keratinized cells / hyaline, septate and branching hyphae

� severe infection shows a mild lymphocytic inflammation

� hyphae and spore are restricted to the nonviable portion of skin, hair, and nails

� asymptomatic / chronic / fiercely pruritic eruptions

(2)

Cutaneous candidiasis

� Candida albicans and other Candida species

� skin (intertrigo), nails (paronychia), or mucosa (oropharynx&esophagus; esophagitis)

� superficial invasion, associated with acute inflammation

� deep infections are much less common – abscesses (yeast, hyphae, necrotic debris, and neutrophils)

� rarely elicit granulomatous inflammation

� tender / erythrematous papules

(2)

Subcutaneous Infection

Sporotrichosis

� Sporothrix schenckii

� mold form in soil / yeast form in body

� accidental inoculation from trauma (thorns or splinters)

� proliferate locally and elicit inflammation � ulceronodularlesion / periphery of nodules is granulomatous and the center is suppurative / pseudoepitheliomatous hyperplasia

� some yeasts may surrounded by eosinophilic speculated zone, “asteroid bodies” (Ag-Ab complexes)

� can be spread along lymphatic drainage � extracutaneousdisease (joint, bone; ankle, knee, elbow, wrist)

(3)

Asteroid bodies

Chromoblastomycosis

� Phialophora verrucosa, Fonsecaea pedrosoi,…

� slowly develop of granulomatous lesions that in time induce hyperplasia of epidermal tissue

� over months to years, primary lesions become verrucous and wart-like with extension along with lymphatics / clauliflower-like nodules with crusting abscesses eventually cover the area / black dot of hemopurulent

� dissemination, obstruction and fibrosis of lymphatic vessels are very rare

(3)

Mycetoma

� Pheudallescheria boydii, Madurella mycetomatis,…

� chronic subcutaneous infection

� local swelling of local infected tissue

� suppuration, abscesses, granulomata, and draining sinuses containing granules

� mycetoma granules (contain septate hyphae) may range up to 2 mm / the color of granule may provide information of agent

� lesion may persist for years and extend deeper causing organ deformation and loss of function

� actinomycetoma (more invasive) ≠ eumycetoma

(3)

Phaeohyphomycosis

� Exophiala, Bipolaris, Exserohilum,…

� hyphae are large and often distort and may and may be found with yeast form

� melanin in their cell walls can be used for differentiation to other fungi

(3)

Endemic Infection

Histoplasmosis

� Histoplasma capsulatum

� primary infection in lung / resembles to TB /commonly found in people with impaired cell-mediated immunity

� yeast cell has central basophilic body surrounded by a clear zone or halo

� alveolar macrophage phagocytose microconidia / fungi grow in macrophage before spread out to hilar and mediastinal lymph nodes and then throughout the body

� acute self-limited histoplasmosis / necrotizing granuloma (caseousmaterial is surrounded by macrophages, Langhans giant cells, lymphocytes, plasma cells) / granuloma later disappear, the caseous material calcifies and forming “fibrocaseous nodule”

� disseminated histoplasmosis – progressive organ infiltration

with macrophage carrying fungi

(4)

Blastomycosis

� Blastomyces dermatitidis

� chronic granulomatous and suppurative pulmonary disease, often followed by dissemination to other body sites

� infection produce consolidation of fungi in mixed suppurative and granulomatous inflammation

� skin and bone are most common sites of extrapulmonaryinvolvement

� flu-like illness / fever, arthralgias and myalgias, weight loss, cough / skin lesion resemble to squamous cell carcinoma / lung infection may appear to resolve but lesion at skin may appear at months to years later

(4)

Coccidioidomycosis

� Coccidioides posadasii and C.immitis

� begin as local pneumonitis, where the spores are deposit

� mixed inflammatory cells (neutrophils and macrophages) / necrotizing caseous granuloma development

� disseminated coccidioidomycosis by involve almost any body site e.g. skin, bone, meninges, liver, spleen, genital tract

(4)

Paracoccidioidomycosis

� Paracoccidioides brasiliensis

� chronic granulomatous infection (mix with suppurative)

� may involve with lung alone or disseminate to other parts e.g. skin, oropharynx, adrenals, and macrophage of liver, spleen and lymph nodes

� overall lesions are similar to Blastomycosis

(4)

Opportunistic Infection

Systemic candidiasis

� Candida albicans and other Candida species

� most common opportunistic pathogen

� produce polysaccharides, glycoproteins (agglutinin-like sequence; ALS) to facilitate attachment and invasion

� local invasion by yeasts and pseudohyphae

� pyogenic abscess to chronic granuloma containing budding yeast cells and pseudo hyphae

� administration of broad-spectrum antibiotics often promotes large increases in Candida growth in GI tract, oral, and vaginal mucosa

� systemic candidiasis – yeast enters blood stream by crossing the intestinal mucosa / go to kidney, heart valves / later develops arthritis, meningitis, endophthalmitis

(5)

Cryptococcosis

� Cryptococcus neoformans, C. gattii (pigeon droppings)

� proteoglycan capsule important in pathogenicity

� fungal meningoencephalitis (lung, skin, liver may also involved) – the entire brain is swollen and soft, leptomeninges are thicken and gelatinous from infiltration by thickly encapsulated fungi

� poorly stain with H&E (appear as bubbles or holes) / PAS or GMS for demonstrate the yeast clearly

(5)

Aspergillosis

� Aspergillus fuminatus and other Aspergillus species

� pulmonary aspergillosis:

1)allergic bronchopulmonary aspergillosis – bronchi and bronchioles are infiltrated with lymphocytes, plasma cells , eosinophils

2)colonization of pre-existing pulmonary cavity – dense, roundish mass of tangled hyphae with in fibrous cavity / the cavity wall is collagenous fiber with lymphocytes and plasma cells

3)invasive aspergillosis – invasion of blood vessels and produces thrombosis / hyphae are arranged radially around blood vessels and extend to their walls

(5)

Mucormycosis (Zygomycosis)

� Rhizopus, Lichthemia, Cunninghamella, …

� produce severe, necrotizing, invasive opportunistic infection

� Fatal Gastrointestinal Mucormycosis in an Infant

� “rhinocerebral mucormycosis” – proliferate in nasal sinuses, invade surrounding tissues and extend to facial and brain / nasal turbinates are covered by black crust, underlying tissue is friable and hemorrhagic / hyphae grow into arteries, septic infarction, hemorrhagic encephalitis

� “pulmonary mucormycosis” – resemble to aspergillosis

� “subcutaneous mucormycosis” – produce an gradually enlarging, hard inflammatory mass (shoulder, trunk, buttock or thigh)

(5)

Pneumocystis pneumonia

� Pneumocystis jiroveci

� common in AIDS patients or those who treated withcorticosteroids or cytotoxic therapy

� fungi reproduce in associated with alveolar type 1 liningcells, cause progressive consolidation, alveoli contain frothyeosinophilic material (alveolar macrophage, cysts, andtrophozoites), in newborns alveolar septa are thickening bylymphoid cells and macrophages (plasma cell pneumonia)

� fever and progressive shortness of breath, exacerbated byexertion with nonreproductive cough, dyspnea, radiographsshow diffuse pulmonary process

� Diag.: Bronchoscopy, sputum induction

(5)

Penicilliosis

� Penicillium marneffei

� major risk for infection is HIV/AIDS, TB, corticosteroid treatment, or lymphoproloferation diseases

� fungemia, skin lesions, systemic involvement of multiple organs, especially reticuloendothelial system

� can observe papules, pustules or rashes

(5)

References

� Rubin’s Pathology; Clinicopathologic Foundations of Medicine

(2012). 7th Edition. Wolters Kruwer.

� Medical Microbiology (2013). 24th Edition. McGraw-Hill Education.

� https://www.cdc.gov/fungal/diseases/index.html

Laboratory

Station 1 – Skin Infection (superficial, cutaneous, subcutaneous)

Station 2 – Endemic Infection (Histoplasmosis)

Station 3 – Opportunistic. #1 (Candidiasis)

Station 4 – Opportunistic. #2 (Cryptococcosis)

Station 5 – Opportunistic. #3 (Aspergillosis)