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Gross and Microscopic Features
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(Left) Photo shows a skin infection presenting as a firm,
ink nodule with central hemorrhagic crust. Biopsy showed involvement by blastomycosis. (Right) Medium magnification of a skin biopsy on H&E stain shows numerous yeast forms associated with microabscesses. The yeast size and presence of thick cell wall put Blastomycosis on the differentials, confirmed by culture findings.
Fungal Infections: Morphological Diagnosis of Fungal Infections
(Left) Gross photo shows cross section of a nasal mass with pseudoepitheliomatous hyperplasia on microscopic examination. Culture confirms
resence of blastomycosis. (Right) Low magnification of a nasal mass on H&E stain shows massive
seudoepitheliomatous hyperplasia mimicking squamous cell carcinoma. Multifocal microabscesses
are noted. Presence of Blastomyces sp. associated with the microabscesses was revealed by higher magnification, follow-up GMS stain, and culture findings.
BLASTOMYCOSIS
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(Left) Medium magnification o a skin section shows crowding big yeast forms with thick cell wall highlighted by PAS stain. Culture confirms the fungus to be Blastomyces dermatitidis. (Right) High magnification of this tissue section on H&E stain shows a yeast form a neutrophilic abscess. The size of the yeast form and the appearance should warrant the differential of blastomycosis.
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Microscopic Features
Fungal Infections: Morphological Diagnosis of Fungal Infections
BLASTOMYCOSIS
(Left) High magnification of a tissue section on GMS stain shows medium to large yeast forms with characteristic broad-based budding in a case of disseminated blastomycosis. (Right) High magnification of a tissue section on H&E stain shows a subtle fungal form admixed with necrosis and acute neutrophilic inflammation in a patient with history of disseminated blastomycosis. Silver or PAS stain would be helpful to highlight the morphology of the fungal organism.
(Left) Medium magnification of a tissue section on GMS stain shows 2 forms of broad-based budding exhibiting the initial stage of division , and a division that is almost complete . The yeast size and type of budding are consistent with blastomycosis. (Right) High magnification of a fine­needle aspiration of a splenic lesion shows big yeast forms with broad-based budding and a thick cell wall, most consistent with Blastomyces spp.
(Left) High magnification of a fine-needle aspiration specimen on Diff-Quik stain shows a large yeast form with thick cell wall. No budding is detected. The findings raise the differential of blastomycosis, which was confirmed on subsequent biopsy and culture. (Right) High magnification of a fine­needle aspiration of a lesion on ThinPrep shows big yeast forms with thick cell wall and broad-based budding consistent with Blastomyces spp.
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CANDIDIASIS
Section of esophageal mucosa shows abundant Candida yeast forms and hyphal/pseudohyphal forms admixed with bacteria.
Fungal Infections: Morphological Diagnosis of Fungal Infections
TERMINOLOGY
Synonyms
Candidosis
Definitions
Latin: "Candidatus" (a candidate for public office, who dressed in white)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Candida spp. are the most common cause of fungal infections
> 20 different species reported as etiologic agents of invasive candidiasis in humans
Candida albicans is the most common infectious agent, accounting for 1/3-2/3 of invasive cases, followed by Candida glabrata and Candida parapsilosis
Normal flora associated with skin, gastrointestinal and genitourinary tracts of humans
Superficial infections
Minimal to suppurative inflammation
Occur when there are microbial imbalances caused by fluctuations in reproductive hormones, antibiotic use, and immunosuppression
Invasive infections
Various inflammatory responses depending on host immune status
Primarily suppurative inflammation with rare granulomas, invasion of blood vessels, necrotizing vasculitis
Can involve any organ
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Umbilical cord PAS section demonstrates hyphal/ pseudohyphal forms and budding yeast forms consistent with Candida in association with acute funisitis and necrosis.
CLINICAL ISSUES
Epidemiology
Candida are ubiquitous organisms that cause disease worldwide in a range of human hosts
Presentation
Superficial skin infections: Commonly seen in immunosuppressed patients
Oropharyngeal candidiasis (thrush): White plaques on buccal mucosa; commonly seen in patients with immunodeficiency
Esophagitis: Most common in HIV-infected patients and patients with hematologic malignancies
Vulvovaginitis: Most common form of mucosal candidiasis
Mastitis: Lactating women with injured nipples are at increased risk
Urinary tract infection
Renal infection: Often secondary to hematogenous seeding in setting of disseminated candidiasis
Candiduria may represent merely colonization and not infection; microscopic, culture, and clinical correlation need to be made to determine its relevance and need for antifungal therapy
Osteoarticular infections
Hematogenous seeding in cases of candidemia
Inoculation during trauma, intraarticular injection, surgical procedures, or injection drug use
Meningitis
Manifestation of disseminated candidiasis, or in premature neonates as a complication of contaminated ventricular drainage devices
Endocarditis: Most common cause of fungal endocarditis
Seen in intravenous drug users or patients with prosthetic heart valves, indwelling central venous catheters, or fungemia
Peritonitis and intraabdominal infections
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Etiology
Normal flora associated with skin, gastrointestinal and genitourinary tracts of humans
Yeast form is associated with dissemination, and hyphal form with adhesion and tissue invasion
Clinical Issues
Diseases range from superficial, invasive to disseminated infections, depending on host immune status
> 20 different species of Candida reported as etiologic agents of invasive candidiasis in humans
Candida albicans is the most common agent for invasive infections, followed by C. glabrata and C.
parapsilosis
CANDIDIASIS
Key Facts
Microscopic Pathology
Small yeast cells (2-6 m in diameter) intermingled with pseudohyphae and branching septate hyphae
Suppurative inflammation and necrosis is often seen, but inflammation can be minimal
Giant cells and granulomas are sparse
Ancillary Tests
Candida spp. are gram positive
Periodic acid-Schiff and fungal silver stains highlight fungal forms for histologic examination
Top Differential Diagnoses
Aspergillosis
Trichosporon infections
Histoplasmosis
Cryptococcosis
Fungal Infections: Morphological Diagnosis of Fungal Infections
Often exists in polymicrobial infections that occur following gastrointestinal tract perforation, or acute necrotizing pancreatitis
Pneumonia: Rare
Empyema: Most commonly seen in patients with malignancies
Pericarditis: Rare; often a complication of thoracic surgery, contiguous spread from an adjacent focus, or hematogenous spread
Endophthalmitis
Develops following trauma or eye surgery
Hematogenous seeding in cases of candidemia
Chronic disseminated candidiasis
Persistent microabscesses in liver, spleen, and occasionally kidneys
Risk factors: Acute leukemia, neutropenia, intravascular catheters
Chronic mucocutaneous candidiasis: Heterogeneous group of syndromes with autoimmune manifestations associated with chronic noninvasive Candida infections of skin, nails, and mucous membranes
Laboratory Tests
Culture and Gram stain of biopsy tissue
Culture of blood or other body fluids
Non-culture methods
Biopsy for histopathologic examination
KOH preparation on skin scrapings to evaluate for hyphae and pseudohyphae
-D-glucan in serum
Marker of fungemia or disseminated disease
Useful in patients with deep-seated invasive
candidiasis for which blood cultures may be insensitive Sensitivity: 57-90%; specificity: 44-92%
Treatment
Different species have slightly different intrinsic susceptibilities to antifungal agents
Mucocutaneous infections
Therapy is dominated by azole antifungal agents
Invasive infections
Amphotericin Bbased preparations, azole and echinocandin antifungal agents
Prognosis
Successful treatment depends on site of lesion and immune status of host
MICROBIOLOGY
Fungal Features
In tissue and cytologic preparations
Round to oval yeast cells (2-6 m in diameter); size varies according to species
Pseudohyphae and branching septate hyphae
C. glabrata only forms small (2-4 m in diameter) oval yeast cells; no pseudohyphae are formed
Culture
Species identified according to macroscopic colony morphology on agar and microscopic morphology on specific medium
Microscopic morphology on cornmeal-Tween 80 agar
Pseudohyphae and some true hyphae with clusters of round blastoconidia (blastospores) at septa
Terminal chlamydospores are formed
Most are rapid growers that mature in 3-5 days
MICROSCOPIC PATHOLOGY
Histologic Features
Small yeast cells (2-6 m in diameter) intermingled with pseudohyphae and branching septate hyphae
Neutrophilic inflammation with some lymphocytes and macrophages, fibrin, and coagulative necrosis
Giant cells and granulomas can be present but are sparse
Mycotic aneurysms or thrombophlebitis can occur in cases of vascular invasions
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CANDIDIASIS
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Superficial mucosal infections can be associated with enlarged hyperchromatic nuclei with perinuclear halos in gynecologic specimens or pap smears
Changes can be confused with low-grade squamous intraepithelial lesions
ANCILLARY TESTS
Histochemistry
Gram stain: Candida spp. stain purple/blue (gram positive)
Fungal silver stains (Gomori methenamine silver (GMS): Fungal cell wall appears black or dark brown
Periodic acid-Schiff (PAS): Fungal cell wall appears pink to red-purple
In Situ Hybridization
Peptide nucleic acid fluorescent in situ hybridization can identify the most frequent Candida spp. directly from positive blood culture bottles without need for subcultures
Fungal Infections: Morphological Diagnosis of Fungal Infections
Probes used to detect fungi are unique, organism­specific rRNA targets
PCR
Direct PCR using blood samples
Better sensitivity and specificity for diagnosis of invasive candidiasis than blood cultures
Its effects on clinical outcomes are still being investigated
DIFFERENTIAL DIAGNOSIS
spergillosis
Nonpigmented (hyaline), uniform, septate hyphae with dichotomous branching at 45 angles
Aspergillus hyphae may be mistaken for nonbudding yeast cells when the hyphae are cut transversely on sections
Candida spp. form pseudohyphae with distinct constrictions in addition to true hyphae
Fungal hyphae of Aspergillus spp. may be scant or fragmented on histologic or cytologic preparations, making it challenging to assess for septation and type of branching
Trichosporon Infections
Pleomorphic yeast-like cells (3-8 m in diameter) intermingled with pseudohyphae, septate true hyphae without predominant dichotomous branching
Distinguished by the presence of arthroconidia (formed by fragmentation of true hyphae), which can be sparse or absent on tissue sections
Candida spp. lack pseudocapsule and stain better with H&E and Gram stain
Candida spp. generally tend to generate suppurative tissue reaction, while it is more common among Histoplasma spp. to elicit a granulomatous reaction
Cryptococcosis
Narrow-based budding pleomorphic yeast forms (4-10 m in diameter)
Fontana-Masson stain is positive in melanin­producing Cryptococcus and mucicarmine stain highlights capsule of Cryptococcus spp.
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
Generally elicits an acute suppurative inflammation
Coagulative necrosis often seen in neutropenic patients
Granulomas rarely occur; mostly seen in chronic systemic candidiasis
Pathologic Interpretation Pearls
Small round to oval budding yeast cells, pseudohyphae, and branching septate true hyphae
Candida spp. are gram positive
SELECTED REFERENCES
1. Guarner J et al: Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev. 24(2):247-80, 2011
2. Lyon GM et al: Antifungal susceptibility testing of Candida isolates from the Candida surveillance study. J Clin Microbiol. 48(4):1270-5, 2010
3. Concia E et al: Epidemiology, incidence and risk factors for invasive candidiasis in high-risk patients. Drugs. 69 Suppl 1:5-14, 2009
4. Moriarty AT et al: Performance of Candida-fungal-induced atypia and proficiency testing: observations from the College of American Pathologists proficiency testing program. Arch Pathol Lab Med. 133(8):1272-5, 2009
5. Pappas PG et al: Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 48(5):503-35, 2009
6. Wilson DA et al: Multicenter evaluation of a Candida albicans peptide nucleic acid fluorescent in situ hybridization probe for characterization of yeast isolates from blood cultures. J Clin Microbiol. 43(6):2909-12, 2005
7. Kontoyiannis DP et al: Hepatosplenic candidiasis. A manifestation of chronic disseminated candidiasis. Infect Dis Clin North Am. 14(3):721-39, 2000
8. Herrod HG: Chronic mucocutaneous candidiasis in childhood and complications of non-Candida infection: a report of the Pediatric Immunodeficiency Collaborative Study Group. J Pediatr. 116(3):377-82, 1990
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Histoplasmosis
Small yeast forms (2-4 m in diameter) with narrow­based budding
Often intracellular in macrophages but extracellular Histoplasma spp. can be easily confused with yeast forms of Candida spp., particularly C. glabrata, which lacks pseudohyphae production
Gross and Microscopic Features
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Fungal Infections: Morphological Diagnosis of Fungal Infections
CANDIDIASIS
(Left) Liver section from a patient who died of disseminated multiorgan fungal disease shows multiple nodular abscesses
, which are PCR-
confirmed to be caused by Candida albicans. (Right) Fungal hyphal/pseudohyphal forms consistent with Candida are present in ectocervix with acute and chronic inflammation.
(Left) PAS stain highlights rare hyphal/pseudohyphal forms and yeast forms consistent with Candida in vulvar epithelium . Minimal inflammation is present. (Right) Skin section with central necrosis and hemorrhage shows abundant Candida organisms secondary to hematogenous spread of systemic infection. In areas of extensive necrosis, hyphal
seudohyphal forms may assume a more swollen and distorted appearance.
(Left) GMS stain of esophageal mucosa shows numerous yeast forms,
seudohyphae, and true hyphae with septa consistent with Candida. Germinating Candida blastospores can appear to be branching. (Right) Gram-stained section of gastric pylorus shows multiple yeast forms and hyphae positive for Gram stain, consistent with Candida spp.
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CHROMOBLASTOMYCOSIS
High magnification of a skin section on H&E stain shows thick-walled, brown sclerotic bodies in association with microabscess and a multinucleated giant cell , consistent with chromoblastomycosis.
Fungal Infections: Morphological Diagnosis of Fungal Infections
TERMINOLOGY
Definitions
Greek: "khroma" (color) + "blastos" (sprout, germ) + "mykes" (fungus, mushroom)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Black yeast or dematiaceous fungi: Infectious species produce dematiaceous mycelium
Common agents
Fonsecaea pedrosoi: Most common agent;
less sensitive to antifungal therapy than
Cladophialophora carrionii or Pocillopora verrucosa C. carrionii
Phialophora verrucosa
Less common agents
Fonsecaea compacta
Rhinocladiella aquaspersa
Exophiala dermatitidis
Exophiala jeanselmei complex
Fungi causing chromoblastomycosis are present in environment as part of the microbiota, which decompose organic matter in soil and water
Fungi cause skin and subcutaneous infection via direct inoculation of fungi through contact with contaminated soil, plants, or rotting wood
CLINICAL ISSUES
Epidemiology
Occurs worldwide but most cases are found in tropical and subtropical areas of Americas, Asia, and Africa
Species causing chromoblastomycosis vary by region
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and climate
e.g., F. pedrosoi is associated with humid areas with a tropical and subtropical climate, and causes most
Medium-power H&E stain of a skin section shows brown, thick-walled fungal forms in a granuloma in a patient with known chromoblastomycosis. Small neutrophilic foci are present.
cases in Brazil, Mexico, northern Madagascar, and Japan
e.g., C. carrionii is associated with a semi-arid climate, and causes most cases in Australia, southern Madagascar, South Africa, and Cuba
In tropical and subtropical countries, infection more commonly affects male agricultural workers in rural regions, possibly due to increased chance of injury with parts of plants affected by fungi responsible for chromoblastomycosis
Presentation
Fungi gain entry into human body through cutaneous wounds and can affect virtually any skin site
Most common sites of infection are distal limbs, especially feet
Skin lesions on other sites have also been reported, e.g., cornea, face, trunk
Primary lesion can enlarge and develop into various forms and sizes
Nodular type
Small pale pink or purple nodules, which may
gradually grow into bigger tumoral lesions
Tumoral type
Papillomatous, tumor-like masses with
cauliflower-like appearance; most common on feet and lower parts of shin
Verrucous type
Resembles verruca vulgaris (common warts);
frequently seen along edges of feet Raises differentials of verrucous variants of
leishmaniasis and tuberculosis, sporotrichosis, and verrucous carcinoma
Cicatricial type
Annular lesions that extend radially, leaving
central areas of scarring
Plaque type
Planoconvex lesions of various shapes and sizes
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CHROMOBLASTOMYCOSIS
Etiology
Most common agents: Fonsecaea pedrosoi, Cladophialophora carrionii, Phialophora verrucosa
Agents are dematiaceous fungi
Cause skin and subcutaneous infections via direct fungal inoculation
Clinical Issues
Occurs worldwide, but most cases are reported in tropical and subtropical areas of Americas, Asia, and Africa
Most common sites of infection: Distal limbs
Infection mostly confined to skin and subcutaneous fat and does not invade into underlying muscle or bone
Low cure rates and high relapse rates, especially in chronic and extensive disease
Infection mostly confined to skin and subcutaneous fat and does not invade into underlying muscle or bone
Disease dissemination in form of satellite lesions may occur via scratching autoinoculation, resulting in fungal spread by lymphatic system
Complications
Secondary bacterial infections and ulcerations are common
Lymphedema and elephantiasis in severe cases have been reported
Development of squamous cell carcinoma has been reported in association with chromoblastomycosis in case studies
Rare reports of invasive infections to other organs such as lung and brain had been made
Controversy exists, as some of those cases were
believed to be phaeohyphomycosis instead of chromoblastomycosis
Laboratory Tests
Serological tests
Serological tests have been developed to detect chromoblastomycosis caused by F. pedrosoi and C.
carrionii
Sensitivities of these assays range from 78-100%, and specificities range from 83-99%
Not routinely or widely used in diagnosis
Treatment
Treatment choice and outcome depend on etiological agent, clinical presentation, and presence of complications
Common antifungal drugs for treatment: Itraconazole, terbinafine, posaconazole, 5-fluorocytosine
Antifungal drugs have also been used in conjunction with other methods such as cryosurgery and thermotherapy to eradicate skin lesions
Combination of laser vaporization and thermotherapy has been reported to eradicate lesions successfully in patients with relapses
Key Facts
Macroscopic Pathology
Characteristic "black dots" can form in skin lesion due to migration of fungi to skin surface and keratin scales
Microscopic Pathology
Brown, thick-walled Medlar bodies (5-12 m in diameter) with horizontal &/or vertical septations
Branched septate hyphae (3-5 m in diameter)
Fungi multiply by septation (binary fission) rather than budding
Associated with granulomatous inflammation, accompanied by suppurative reaction and pseudoepitheliomatous hyperplasia
Top Differential Diagnoses
Phaeohyphomycosis
Prognosis
Low cure rates and high relapse rates, especially in chronic and extensive disease
Mortality: Rare
MICROBIOLOGY
Culture
Routine fungal cultures (Sabouraud dextrose agar)
Allows species identification
Yield from tissue can be low
Fungal species are slow growing and require > 2 weeks to mature
MACROSCOPIC FEATURES
General Features
Characteristic "black dots" can form in skin lesion due to migration of fungi to skin surface and keratin scales
MICROSCOPIC PATHOLOGY
Histologic Features
Brown-pigmented fungi
Characteristic Medlar bodies/muriform cells/"copper pennies"
Fungi multiply by septation (binary fission) rather than budding
Branched septate hyphae (3-5 m in diameter) may also be seen
Features of tissue reaction
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Round to polyhedral thick-walled sclerotic bodies (5-12 m in diameter) with horizontal &/or vertical septations
Pseudoepitheliomatous hyperplasia, hyperkeratosis, parakeratosis Associated with granulomatous inflammation Neutrophilic inflammation and microabscesses may also be present
Fungal Infections: Morphological Diagnosis of Fungal Infections
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CHROMOBLASTOMYCOSIS
ANCILLARY TESTS
Histochemistry
Fungal organisms are positive for Gomori methenamine silver (GMS) and periodic acid-Schiff (PAS) stains
Direct Examination of Clinical Specimens
Skin scrapings from lesion can be treated with 10% potassium hydroxide for direct microscopy
Diagnosis is made when brown Medlar bodies are seen
Molecular Diagnostics
PCR-based assays targeting ribosomal DNA for Fonsecaea spp. and C. carrionii have been developed
Not widely available in endemic areas
DIFFERENTIAL DIAGNOSIS
Phaeohyphomycosis
Skin and/or subcutaneous infection caused by brown-
Fungal Infections: Morphological Diagnosis of Fungal Infections
pigmented fungi producing hyphal forms in tissue
Fontana-Masson stains cell walls of agents of both phaeohyphomycosis and chromoblastomycosis
Common genera: Bipolaris, Cladophialophora, Coniothyrium, Curvularia, Exophiala, Exserohilum, Lasiodiplodia, Phialophora, Ochroconis, and Wangiella
In contrast to fungal species causing chromoblastomycosis, Medlar bodies are absent in phaeohyphomycosis, which often presents with yeast­like cells as well as brown-pigmented hyphae with constricted septations and large vesicular swellings
In phaeohyphomycosis, an encapsulated cystic granulomatous reaction associated with suppurative exudate is often present in dermis and subcutaneous tissue; epidermis is often spared
Blastomycosis
Distinguished by lack of pigmentation in yeast forms
Coccidioidomycosis
Distinguished by lack of pigmentation in yeast forms and may have large spherules with endospores
Hemosiderosis
Excessive iron in macrophages may produce round to oval collections mimicking pigmented yeast
Pathologic Interpretation Pearls
Characteristic brown thick-walled Medlar bodies (5-12 m in diameter) with horizontal &/or vertical septations
Branched septate hyphae (3-5 m in diameter) may also be seen
Associated with granulomatous inflammation as well as pseudoepitheliomatous hyperplasia
SELECTED REFERENCES
1. Queiroz-Telles F et al: Challenges in the therapy of chromoblastomycosis. Mycopathologia. 175(5-6):477-88, 2013
2. Jamil A et al: Invasive squamous cell carcinoma arising from chromoblastomycosis. Med Mycol. 50(1):99-102, 2012
3. Torres E et al: Chromoblastomycosis associated with a lethal squamous cell carcinoma. An Bras Dermatol. 85(2):267-70, 2010
4. Ameen M: Chromoblastomycosis: clinical presentation and management. Clin Exp Dermatol. 34(8):849-54, 2009
5. de Andrade TS et al: Rapid identification of Fonsecaea by duplex polymerase chain reaction in isolates from patients with chromoblastomycosis. Diagn Microbiol Infect Dis. 57(3):267-72, 2007
6.
Lpez Martnez R et al: Chromoblastomycosis. Clin Dermatol. 25(2):188-94, 2007
7.
Oberto-Perdign L et al: [An ELISA test for the study of the therapeutic evolution of chromoblastomycosis by Cladophialophora carrionii in the endemic area of Falcon State, Venezuela.] Rev Iberoam Micol. 22(1):39-43, 2005
8. Abliz P et al: Specific oligonucleotide primers for identification of Cladophialophora carrionii, a causative agent of chromoblastomycosis. J Clin Microbiol. 42(1):404-7, 2004
9. Bonifaz A et al: Treating chromoblastomycosis with systemic antifungals. Expert Opin Pharmacother. 5(2):247-54, 2004
10. Vidal MS et al: Highly specific and sensitive, immunoblot­detected 54 kDa antigen from Fonsecaea pedrosoi. Med Mycol. 42(6):511-5, 2004
11. Vidal MS et al: Immunoprecipitation techniques and Elisa in the detection of anti-Fonsecaea pedrosoi antibodies in chromoblastomycosis. Rev Inst Med Trop Sao Paulo. 45(6):315-8, 2003
12. Rubin HA et al: Evidence for percutaneous inoculation as the mode of transmission for chromoblastomycosis. J Am Acad Dermatol. 25(5 Pt 2):951-4, 1991
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Foreign Body
Fragments of wood or plant matter may have pigment and morphology suggestive of yeast and produce similar lesions after traumatic introduction
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
To confirm diagnosis, presence of muriform/Medlar bodies and identification of an etiological agent in culture are necessary
Relapse of disease is common
Microscopic Features
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Fungal Infections: Morphological Diagnosis of Fungal Infections
CHROMOBLASTOMYCOSIS
(Left) Low magnification of a skin section on H&E stain shows
seudoepitheliomatous
hyperplasia and focal
ranulomatous reaction in a patient with known chromoblastomycosis. (Right) High magnification of this skin section on H&E stain shows multifocal microabscesses in the epidermis and dermis. A small cluster of brown-
igmented fungi is
resent. The findings put chromoblastomycosis on the top differentials.
(Left) High magnification of this skin section on PAS stain highlights a characteristic thick-walled sclerotic body with septation in a patient with chromoblastomycosis. The other fungal form
may represent a short segment of septate hyphae or daughter cells that are undergoing binary fission. (Right) High magnification of this skin section on GMS stain shows thick-walled sclerotic bodies with septations, consistent with chromoblastomycosis.
(Left) Medium magnification of this biopsy on H&E stain shows necrotizing
ranulomatous inflammation with large round pigmented fungal forms , which may represent an agent of chromoblastomycosis or phaeohyphomycosis. Correlation with culture is needed for diagnosis. (Right) High magnification of this tissue section on H&E stain shows large, pigmented, yeast-like cells and septate hyphae. Culture is needed to differentiate between
haeohyphomycosis or chromoblastomycosis.
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