Fungal Infections

Slide 1 · Fungal Infections

Fungal forms · mycosis classes · host defenses · tissue patterns

General and systemic pathology

A morphology-led clinicopathologic approach

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Classify mycoses by site, depth, host state, and epidemiologic context.

Explain the distinctions between budding yeast, pseudohyphae, mold hyphae, and dimorphic growth.

Link innate / adaptive immune responses to fungal tissue injury.

Recognize major organism-associated morphology and formulate appropriate differentials.

Slide 3 · Fungi are eukaryotic pathogens

Eukaryotic fungus

Yeast or mold growth

Tissue infection (mycosis)

Fungal pathogens differ structurally from bacteria and are organized as yeast cells or filamentous molds. Cell walls maintain fungal shape; Morphology is a useful first step in tissue recognition.

Slide 4 · Yeast growth: Budding cells

Budding daughter cell attached to yeast

SCHEMATIC

Interpretation

Round-to-oval cells are the typical yeast form.

New daughter cells usually arise by budding.

The budding pattern may help narrow a morphologic differential, but does not always identify species.

Slide 5 · Pseudohyphae: Buds that remain attached

Elongated buds linked at constricted junctions

SCHEMATIC

Interpretation

Some yeasts, including Candida albicans, form elongated daughter buds that fail to separate.

Linked elongated cells create a pseudohyphal chain.

Constricted junctions between cells are an important distinguishing feature.

Slide 6 · Mold architecture: Apically growing hyphae

Continuous branching filaments; Septa indicated schematically

SCHEMATIC

Interpretation

Molds are made of multicellular filaments called hyphae.

Filaments extend and divide at their tips, producing a branching network.

Hyphal configuration becomes especially important in the diagnosis of invasive mold infections.

Slide 7 · Conidia enable airborne dispersal

Mold growth

Conidia released

Airborne exposure

Potential inhalation

Molds can generate rounded reproductive cells called conidia. Conidia can become airborne and disperse widely.

Slide 8 · Dimorphism links environment to tissue form

Environmental mold

Temperature / host transition

Tissue form

Many medically significant fungi alternate between environmental mold and tissue yeast forms. The Robbins overview describes mold at room temperature and yeast at body temperature as the usual pattern.

Slide 9 · Yeast, pseudohyphae, and true hyphae

Yeast

Pseudohyphae

Mold hyphae

Schematic cell forms — topology only; Not a stained preparation

Morphism is a diagnostic clue, but does not independently establish species.

Slide 10 · The central diagnostic question is tissue invasion

Organism detected

Evaluate tissue relation

Colonization or invasion

Finding fungal structures is not equivalent to establishing invasive fungal disease. Noninvasive Aspergillus growth in pre-existing cavities with angioinvasive disease.

Slide 11 · Four major clinicopathologic types of mycosis

Category

Anatomic / clinical boundary

Superficial / cutaneous

Surface and keratinized skin, hair, nails

Subcutaneous

Skin, deeper soft tissue, lymphatics

Endemic

Systemic infection possible in healthy hosts

Opportunistic

Severe disease with impaired defenses or devices

Slide 12 · Superficial and cutaneous mycoses

Surface / keratinized tissues

Viable epidermis / dermis

Subcutaneous tissue

Lymphatic region

Common infections limited to the superficial or keratinized layers of skin, hair, and nails.

The site and depth distinguish this category from deep or systemic infections.

More detailed dermatophyte pathology belongs to the separate skin chapter/topic.

Slide 13 · Subcutaneous mycoses

Surface / keratinized tissues

Viable epidermis / dermis

Subcutaneous tissue

Lymphatic region

Involve the skin, subcutaneous tissue, and lymphatic structures.

The process extends deeper than superficial keratinized sites.

Systemic dissemination is uncommon according to the Robbins overview.

Slide 14 · Endemic mycoses

Environmental exposure

Primary infection

Containment or spread

Caused by dimorphic fungi associated with particular environmental regions. Can produce serious systemic illness even in an immunocompetent host.

Slide 15 · Opportunistic mycoses

Compromised defense / device

Invasive growth

Systemic illness

Severe systemic fungal disease is favored by immunosuppression. Prosthetic devices and vascular catheters provide additional opportunities for infection.

Slide 16 · Classification is not a species list

Axis

Practical question

Anatomic extent

Surface, deep tissue, or systemic?

Host condition

Normal defense or altered immunity?

Pathogen biology

Yeast, mold, or dimorphic fungus?

Evidence

Colonization, inflammation, or invasion?

Slide 17 · Host-pathogen interaction determines severity

Fungal exposure

Innate / adaptive defense

Containment or disease

The same fungal organism may be contained, remain localized, or disseminate. Different fungal strategies include adhesive growth, capsules, environmental transition, and biofilms.

Slide 18 · Macrophages defend initial portals of entry

Inhaled particles

Alveolar macrophage

Clearance or persistence

Alveolar macrophages ingest Aspergillus conidia and Histoplasma propagules after inhalation. Phagocytosis may control exposure, but some fungi survive intracellularly.

Slide 19 · Neutrophils are central in invasive molds

Conidium germinates

Hyphal extension

Neutrophil damage to hyphae

Neutrophils injure and kill growing Aspergillus and mucormycete hyphae. Profound neutropenia is strongly associated with aggressive invasive mold disease.

Slide 20 · Th17 immunity protects against Candida

β-1,3-glucan recognition

IL-6 / IL-23 signaling

Th17 response

Myeloid cell recruitment

Candida yeast β-1,3-glucan is sensed by dectin on dendritic cells. IL-6 and IL-23 promote Th17 responses; These recruit neutrophils and monocytes.

Slide 21 · Th1 immunity restrains Histoplasma

Yeast within macrophage

Th1-derived IFN-γ

Activated macrophage

Intracellular Histoplasma can persist in macrophages until T-cell-mediated immunity develops. Th1-derived IFN-γ activates macrophage fungicidal activity.

Slide 22 · Biofilms alter device-associated infection

Device surface

Adhesion

Structured fungal biofilm

Persistence

C. Albicans can grow as attached microbial communities with extracellular matrix. Yeast and filamentous forms can coexist in these device-associated biofilms.

Slide 23 · Fungal virulence mechanisms vary by organism

Example

Mechanism

Candida

Adhesion, morphologic switching, biofilm

Cryptococcus

Capsule limits phagocytosis; Melanin

Aspergillus

Conidial camouflage; Antioxidant activity

Mucormycetes

Growth favored by increased free iron

Slide 24 · Histology is an initial identification method

Biopsy / specimen

Microscopy + tissue response

Culture / targeted testing when needed

Fungi can often be recognized in tissue sections by their cellular or filamentous forms. Tissue examination allows direct correlation with inflammation and invasion.

Slide 25 · H&E may reveal fungi; Special stains sharpen contrast

Technique

What the source supports

H&E

Fungal forms sometimes visible with tissue context

GMS

Better visualization of many fungi

PAS

Enhances fungal structures; Stains cryptococcal capsule

Mucicarmine

Highlights cryptococcal polysaccharide capsule

Slide 26 · Branching pattern is suggestive, not definitive

Septate / acute-angle

Broad / wide-angle

SCHEMATIC

Interpretation

Septate acute-angle branching raises the possibility of Aspergillus.

Broad, irregular, typically nonseptate hyphae with near-right-angle branching suggest mucormycetes.

Hyphal overlap and other molds mean morphology alone may not yield a species-level diagnosis.

Slide 27 · Tissue reaction can range from absent to florid

Response

Example in Chapter 8

Minimal inflammation

Cryptococcal masses in major immune suppression

Suppurative

Some invasive Candida foci; Blastomycotic lesions

Granulomatous

Controlled Histoplasma or cryptococcal infection

Necrosis and infarction

Angioinvasive Aspergillus or mucormycetes

Slide 28 · Angioinvasion explains hemorrhage and infarction

Hyphae invade vessel

Thrombosis / vascular injury

Hemorrhage + infarction

Invasive Aspergillus and mucormycetes can penetrate blood vessel walls. Vascular thrombosis compromises perfusion and promotes necrosis.

Slide 29 · A fungal differential needs multiple dimensions

Morphology

Tissue response / distribution

Host factors

Definitive test if required

Begin with the organism’s tissue form: Budding yeast, hyphae, or spherules. Then evaluate capsule, budding base, septation, and branching.

Slide 30 · Candida is usually a human commensal

Commensal colonization

Barrier disruption / altered host

Mucosal or invasive candidiasis

C. Albicans is an important human fungal pathogen and may normally reside on skin and mucosal surfaces. The mouth, gastrointestinal tract, and vagina are recognized commensal sites.

Slide 31 · Candida syndromes vary with host context

Context

Common consequence

Intact community host

Mucosal / skin infection

Diabetes or burns

Susceptibility to superficial candidiasis

Vascular access devices

Bloodstream entry / dissemination

Profound neutropenia

Severe invasive or disseminated disease

Slide 32 · Candida morphologic plasticity aids adaptation

Environmental / host change

Phenotypic switching

Changed fungal behavior

C. Albicans can switch among multiple cellular phenotypes. The Robbins section links switching to temperature, nutrient conditions, antibiotic exposure, and immunity.

Slide 33 · Adhesion and enzymes promote Candida invasion

Host adherence

Extracellular matrix degradation

Tissue invasion

Adhesins bind host extracellular matrix components and epithelial/endothelial cells. Secreted aspartyl proteinases may facilitate tissue invasion by degrading matrix proteins.

Slide 34 · Pseudohyphae are a Candida diagnostic clue

Elongated buds linked at constricted junctions

SCHEMATIC

Interpretation

Tissue Candida may display budding yeast, pseudohyphae, and sometimes true hyphae.

Pseudohyphal junctions show constrictions between elongated cells.

Multiple forms in one field favor interpretation of a mixed morphologic population.

Slide 35 · Oral candidiasis produces pseudomembranes

Surface / keratinized tissues

Viable epidermis / dermis

Subcutaneous tissue

Lymphatic region

Fungal overgrowth forms gray-white superficial material with organisms and inflammatory debris.

Inflamed mucosa lies beneath the superficial plaques.

Antibiotics, steroids, debility, and impaired cellular immunity are relevant contexts.

Slide 36 · Esophageal candidiasis causes mucosal plaques

Impaired host defense

Esophageal mucosal overgrowth

Plaques + swallowing symptoms

Candida esophagitis is associated with advanced HIV disease and hematologic malignancy. Patients can develop swallowing symptoms and retrosternal pain.

Slide 37 · Superficial Candida infection has varied sites

Site

Named example

Vagina

Candida vaginitis

Nail fold

Paronychia

Intertriginous skin

Intertrigo

Infant perineum

Diaper candidiasis

Slide 38 · Disseminated Candida follows bloodstream spread

Barrier or device access

Bloodstream dissemination

Multi-organ microfoci

Candidemia can seed multiple distant organs. Renal, myocardial, cerebral, ocular, and hepatic involvement.

Slide 39 · Endocarditis is a device-associated complication

Fungal access to bloodstream

Valve / prosthesis colonization

Endocardial infection

Candida is a major cause of fungal endocarditis in the source discussion. Prosthetic heart valves create a major predisposing setting.

Slide 40 · Candida auris challenges infection control

Clinical aspect

Practical interpretation

Colonization

Not synonymous with invasive disease

Healthcare setting

Device-associated outbreaks described

Environment

Persistence on dry and moist surfaces

Therapy

Resistance can span multiple antifungal classes

Slide 41 · Cryptococcus enters through inhalation

Environmental particles

Inhalation / lung

Potential CNS spread

C. Neoformans and C. Gattii are pathogenic encapsulated yeasts. C. Neoformans may be acquired from soil containing pigeon guano.

Slide 42 · The cryptococcal capsule blocks host defense

Polysaccharide capsule

Encapsulated budding yeast

SCHEMATIC

Interpretation

A thick polysaccharide capsule impedes phagocytosis.

Capsular factors can reduce inflammatory-cell recruitment and dendritic-cell functions.

A weak tissue response may allow organism-rich gelatinous lesions.

Slide 43 · Cryptococcus causes meningoencephalitis

Blood-borne spread

Meninges / gray matter

Perivascular fungal accumulation

The central nervous system is a major disease site. In markedly immunosuppressed hosts, enlarged perivascular spaces may contain gelatinous fungal masses.

Slide 44 · Cryptococcal morphology: Capsule-rich yeast

Polysaccharide capsule

Encapsulated budding yeast

SCHEMATIC

Interpretation

In human tissue, Cryptococcus appears as yeast rather than pseudohyphae or true hyphae.

The capsule is prominently visualized with mucicarmine and periodic acid–Schiff.

Capsular antigen may be detected in cerebrospinal fluid or blood.

Slide 45 · Pneumocystis is a pulmonary opportunist

Impaired immunity

P. Jirovecii lung infection

Bilateral pneumonia

Pneumocystis jirovecii is classified as a yeast-like fungus. It principally causes potentially progressive bilateral pneumonia in immunocompromised hosts.

Slide 46 · Pneumocystis yields foamy alveolar exudate

Schematic alveolar exudate, not tissue microscopy

SCHEMATIC

Interpretation

The Robbins description emphasizes interstitial alveolar thickening.

Alveolar spaces contain eosinophilic, honeycombed or foamy material.

Cysts can be demonstrated with methenamine silver; Trophic forms are not shown by that stain.

Slide 47 · Pneumocystis testing is modality-dependent

Method

Interpretive point

GMS tissue stain

Cyst / ascus wall highlighted

Immunofluorescence

Organism-targeted visualization

PCR

Sensitive organism nucleic-acid detection

β-D-glucan

Supportive but not species-specific

Slide 48 · Aspergillus begins with inhaled conidia

Airborne conidia

Alveolar deposition

Macrophage defense

A. Fumigatus is described as the most common pathogenic Aspergillus species. Small airborne conidia can reach the pulmonary alveoli.

Slide 49 · Aspergillus conidia evade early detection

Masked resting conidium

Hyphal germination

Innate recognition

Surface hydrophobic proteins conceal fungal molecular motifs on resting conidia. Germination exposes microbial cell-wall structures to immune recognition.

Slide 50 · Aspergillus has allergic, colonizing, invasive forms

Syndrome

Dominant mechanism

Allergic bronchopulmonary disease

Hypersensitivity to airway colonization

Aspergilloma

Fungal ball in pre-existing cavity

Invasive aspergillosis

Hyphal invasion and tissue necrosis

Slide 51 · Aspergilloma occupies a pre-existing cavity

Hyphal mass contained within a pre-existing cavity

SCHEMATIC

Interpretation

Previous tuberculosis, bronchiectasis, infarction, or abscess may leave a suitable lung cavity.

Hyphae proliferate within the cavity to form a fungus ball.

Recurrent hemoptysis is a recognized clinical consequence.

Slide 52 · Invasive Aspergillus targets blood vessels

Impaired hyphal killing

Pulmonary invasion

Vascular invasion

Necrotic target lesion

A major risk setting is severe neutropenia or corticosteroid treatment. Angioinvasion causes tissue ischemia, necrosis, and hemorrhage.

Slide 53 · Aspergillus-type hyphae: Septate and acute-angle

Continuous branching filaments; Septa indicated schematically

SCHEMATIC

Interpretation

Septate filaments with branching at approximately acute angles.

This pattern is a useful morphologic clue in necrotic tissue.

Without fruiting bodies, morphologically similar fungi can prevent definitive genus identification.

Slide 54 · Mucormycosis exploits distinctive host risks

Predisposition

Pathogenetic relevance

Neutropenia

Reduced hyphal killing

Diabetic ketoacidosis

Metabolic / iron-related vulnerability

Corticosteroids

Impaired antifungal defenses

Open wounds / burns

Disrupted physical barrier

Slide 55 · Increased free iron favors mucormycete growth

Greater available iron

Enhanced fungal growth

Invasive infection risk

The chapter identifies available free iron as a promoter of mucormycete growth. Ketoacidosis in diabetes is a key clinical setting.

Slide 56 · Rhinocerebral mucormycosis follows tissue planes

Nasal sinus

Orbit / adjacent tissue

Cranial invasion

Vascular infarction

The organism can progress from nasal sinuses into the orbit and cranial compartment. Hyphae can invade arterial walls, leading to thrombosis and necrosis.

Slide 57 · Mucormycete hyphae: Broad and irregular

Broad irregular, typically nonseptate; Wide-angle branching

SCHEMATIC

Interpretation

The source describes nonseptate filaments of variable width.

Branching is often at wide, approximately right angles.

Morphology must be combined with necrosis, vascular invasion, and confirmatory studies.

Slide 58 · Aspergillus and mucormycetes are not equivalent

Feature

Aspergillus-type mold

Mucormycetes

Hyphae

Narrower; Generally septate

Broader; Irregular; Nonseptate

Branching

Typically acute angle

Often near right angle

Shared finding

May invade vessels

May invade vessels

Key clinical context

Neutropenia / steroids

DKA, iron overload, neutropenia

Slide 59 · Endemic dimorphic fungi produce systemic disease

Endemic environment

Inhalation

Pulmonary infection

Containment or dissemination

These organisms exist in specific geographic environments. Exposure to environmental fungal particles may initiate respiratory infection in healthy hosts.

Slide 60 · Histoplasma may reside inside macrophages

Small yeast forms shown within a phagocyte

SCHEMATIC

Interpretation

Histoplasma capsulatum is acquired by inhaling contaminated dust.

Its small yeast forms are often found within macrophages.

Before effective T-cell immunity, organisms can persist and disseminate from the lung.

Slide 61 · Histoplasma lung disease may resemble tuberculosis

Pulmonary infection

Granulomatous response

Necrosis / fibrosis

Possible calcification

Primary pulmonary infection can be self-limited and occasionally produce a radiographic coin lesion. Chronic progressive disease can affect apical lung regions.

Slide 62 · Disseminated histoplasmosis changes morphology

Host state

Dominant pathologic pattern

Relatively intact immunity

Granulomas; Possible necrosis / fibrosis

Depressed cell immunity

Disseminated yeast-laden macrophages

Interpretation

Immune status strongly alters morphology

Slide 63 · Blastomyces produces broad-based budding

Broad contact between parent and daughter buds

SCHEMATIC

Interpretation

Blastomyces dermatitidis is a soil-associated dimorphic fungus.

Tissue forms have thick-walled, round yeast cells with broad-based buds.

Pulmonary lesions may be suppurative granulomas; Epithelial hyperplasia can mimic squamous carcinoma.

Slide 64 · Coccidioides produces endospore-filled spherules

Large nonbudding spherule with endospores

SCHEMATIC

Interpretation

Coccidioides tissue morphology features thick-walled, nonbudding spherules.

Spherules contain endospores and may provoke suppuration when they rupture.

Invasive disease can involve lung, skin, meninges, bones, and other organs.

Slide 65 · Morphologic recognition: Major fungal signatures

Tissue form

Leading consideration

Budding yeast + pseudohyphae

Candida

Encapsulated yeast

Cryptococcus

Intracellular small yeast

Histoplasma

Broad-based budding yeast

Blastomyces

Spherule with endospores

Coccidioides

Septate / acute-angle hyphae

Aspergillus-type mold

Broad / wide-angle hyphae

Mucormycetes

Slide 66 · Diagnostic decisions depend on host context

Clinical clue

Most relevant interpretation

Antibiotic exposure + oral plaque

Superficial candidiasis

Neutropenia + necrotic lung focus

Potential invasive mold disease

CNS disease + encapsulated yeasts

Cryptococcosis

Granulomas + environmental exposure

Consider endemic dimorphic fungi

Slide 67 · Case application: Oral plaques after antibiotics

Teaching scenario: A debilitated patient develops white oral plaques after broad-spectrum antibiotics.

Most likely process: Superficial Candida proliferation with an inflammatory pseudomembrane.

What process explains the plaque?

Surface fungal proliferation plus inflammatory debris

Slide 68 · Case application: Neutropenic pulmonary necrosis

Teaching scenario: Profound neutropenia is followed by a rounded hemorrhagic lung lesion.

The source’s major concern is an angioinvasive mold, particularly Aspergillus.

Why is the border hemorrhagic?

Vascular invasion with thrombosis and infarction

Slide 69 · Case application: Diabetic sinonasal necrosis

Teaching scenario: Diabetes with ketoacidosis accompanies rapidly progressive sinonasal disease extending toward the orbit.

Mucormycosis is strongly suggested by the risk setting and angioinvasive anatomy.

What links the metabolic risk to invasion?

Greater accessible iron and impaired antifungal defense

Slide 70 · Case application: Meningitis with capsulated yeast

Teaching scenario: An immunosuppressed patient develops meningoencephalitis with encapsulated budding yeasts.

Cryptococcus is the major diagnostic consideration.

Which structure aids immune evasion?

Polysaccharide capsule

Slide 71 · Case application: Lung granuloma with tiny yeast

Teaching scenario: Granulomatous pulmonary inflammation contains small yeasts in macrophages.

Histoplasma is a leading possibility in a suitable exposure setting.

Why can granulomas be absent in disseminated disease?

Failure of effective cell-mediated macrophage activation

Slide 72 · Synthesis: Trace the path from fungus to injury

Fungal form / entry

Host interaction

Tissue injury pattern

Etiologic diagnosis

Start with the fungal form and route of entry. Determine the relevant defense failure or hypersensitivity response.

Slide 73 · Reading and source context

Robbins, Cotran & Kumar: Pathologic Basis of Disease, 11th edition (2026), Chapter 8, “Infectious Diseases.”

Primary overview: “Fungal Infections”; adjacent sections cover Candida, Cryptococcus, Pneumocystis, molds, and endemic dimorphic fungi.

All cell-form illustrations in this lecture are original schematics, not histologic micrographs.