In gynecologic Pap smears, superficial Candida infections are associated with enlarged, hyperchromatic nuclei with perinuclear halos; these changes can be confused with low-grade, squamous intraepithelial lesions (104).

Histopathologic examination of biopsy specimens, surgical resection specimens, and autopsy material should always start with H&E staining of the tissue. Hyphae and aleurioconidia can be visualized and are particularly prominent in hair follicles. The majority of acute pulmonary infections known as “valley fever” resolve; however, in a minority of patients the infection may become chronic progressive, showing either a cavity or nodule.

An international consensus defining proven, probable, and possible invasive fungal infections for research purposes was published in 2002 and revised in 2008 (7, 43).



Although histoplasmosis can occur in outbreaks when old buildings are renovated/demolished or groups of tourists visit caves, most cases are sporadic. The presence of microabscesses with hyphae could represent an early stage of invasive aspergillosis.
(iii) Pitfalls in morphological diagnosis.A study of 122 specimens showed concordance in 83% of cases with septated, acute-angle-branching hyphae in histology and the presence of Aspergillus spp. Immunosuppressed patients show an anergic necrotizing host response with abundant infected macrophages accompanied by various degrees of necrosis; however, in patients where immunity is less compromised, granulomatous and abscess formation have been described. Staining for Fungi. Diseases Where Hyphae Are Usually Seen in Tissue. In addition, Fusarium has the ability to produce toxins, and mycotoxicosis can occur in animals and humans when they ingest food contaminated with a toxin-producing species (113).

Fusarium spp. The tissue can be fresh frozen or FFPE and can be stained with H&E or by other methods that permit visualization of the desired cells in a bright-field microscope. 4. Examples include tinea unguium or onychomycosis (in nails), tinea cruris (in the groin), tinea corporis, tinea circinata, or tinea glabrosa (in the extremities), tinea pedis (athlete's foot), tinea capitis or tonsurans (in the scalp) and tinea barbae (in the beard).

The advantages of obtaining these specimens have created a series of diagnostic challenges because of the limited amount of tissue obtained and the architectural distortion produced by these new procedures. duboisii infections in HIV-infected patients, Direct and specific identification of Cryptococcus neoformans in biological samples using fluorescently labelled DNA probes, Pulmonary blastomycosis: an appraisal of diagnostic techniques, Invasive mould infections: a multi-disciplinary update, Blastomycosis: new insights into diagnosis, prevention, and treatment, Pathogenesis of dermatophytosis and tinea versicolor, The interaction between piperacillin/tazobactam and assays for, Posttransplantation disseminated coccidioidomycosis acquired from donor lungs, Biopsy findings in acute pulmonary histoplasmosis: unusual histologic features in 4 cases mimicking lymphomatoid granulomatosis, Improving molecular detection of fungal DNA in formalin-fixed, paraffin-embedded tissues: comparison of five DNA extraction methods using panfungal PCR, An overview of laser microdissection technologies, Molds: hyalohyphomycosis, phaeohyphomycosis, and zygomycosis, Histopathological study of candidal infection in the central nervous system, Gastrointestinal basidiobolomycosis an unusual fungal infection mimicking colon cancer, Fusarium infections in immunocompromised patients, Fungal species identification from avian lung specimens by single hypha laser microdissection and PCR product sequencing, Diagnosis of blastomycosis in surgical pathology and cytopathology: correlation with microbiologic culture, Allergic bronchopulmonary aspergillosis: staging as an aid to management, Unusual fungal and pseudofungal infections of humans, Invasive aspergillosis diagnosed by immunohistochemistry with monoclonal and polyclonal reagents, Chromoblastomycosis: an overview of clinical manifestations, diagnosis and treatment, Superficial mycoses in immunodepressed patients (AIDS), Splendore-Hoeppli phenomenon in the conjunctiva: immunohistochemical analysis, Immunomycology: rapid and specific immunocytochemical identification of fungi in formalin-fixed, paraffin-embedded material, Bone marrow necrosis related to paracoccidioidomycosis: the first eight cases identified at autopsy, Primary central nervous system phaeohyphomycosis: a review of 101 cases, Diagnosis of invasive aspergillosis and mucormycosis in immunocompromised patients by seminested PCR assay of tissue samples, Comparison of histopathological analysis, culture, and polymerase chain reaction assays to detect invasive mold infections from biopsy specimens, Epidemiology and outcome of zygomycosis: a review of 929 reported cases, Inhibition by estrogens of conidium-to-yeast conversion in the fungus, Challenges and pitfalls of morphologic identification of fungal infections in histologic and cytologic specimens: a ten-year retrospective review at a single institution, Laboratory aspects in the diagnosis of coccidioidomycosis, Correlation of culture with histopathology in fungal burn wound colonization and infection, Allergic fungal sinusitis: pathophysiology, diagnosis and management, Pulmonary fungal infections in kidney transplant recipients: an 8-year study, Pulmonary aspergillosis: clinical presentation, diagnostic tests, management and complications, The critical role of pathology in the investigation of bioterrorism-related cutaneous anthrax, Paediatric cutaneous blastomycosis: a rare case diagnosed on FNAC, Underlying conditions in chronic pulmonary aspergillosis, including simple aspergilloma, Host-dependent patterns of tissue injury in invasive pulmonary aspergillosis, Pathophysiological study of chronic necrotizing pulmonary aspergillosis, Coelomycetous fungi in human disease. Stains.

The frequency of branching will depend on the fungus. Thus, the presence of nonpigmented, septate hyphae with acute-angle branching in tissue should not be signed out as “compatible or suggestive of Aspergillus,” since there are important treatment implications (67). Coelomycetes cause superficial skin infections, onychomycosis, and keratitis/endophthalmitis and can occasionally become systemic in immunocompromised hosts (51).

In this section, we provide information about the commonly used histopathologic staining methods and the usual appearances of the frequently encountered fungi in infected tissues [415, 602, 654, 1173, 2041, 2064].

However, Pneumocystis may be difficult to differentiate from Histoplasma when present inside granulomas or when there is extrapulmonary disease.

This could also happen if the patient has received antifungal medications.

ABPA is an exaggerated hypersensitivity reaction to a variety of fungi, most frequently A. fumigatus, in cystic fibrosis and steroid-dependent asthma patients. When coccidioidomycosis is suspected, it is important to look for spherules; endospores outside spherules or young spherules without endospores can be confused with Blastomyces, Histoplasma, Emmonsia, Candida, Pneumocystis, and other yeasts (142). Exposure to P. brasiliensis does not guarantee the development of active disease.

• CE Marking Policy, © 2020  Merck KGaA, Darmstadt, Germany and/or its affiliates. Fusarium spp. in culture, while Scedosporium spp., Fusarium spp., Pseudallescheria spp., Phialophora verrucosa, and Trichophyton spp. Most fungi are fairly large and their walls are rich in polysaccharides (1,2-glycol groups), which can be demonstrated with Schiff's reagent or hexamine (methenamine) silver solutions.

The majority of the published assays target specific rRNA genes (18S, 28S, and 5.8S), the intervening internal transcribed spacer (ITS1 and ITS2), or particular portions of the fungal genome and use nested or seminested PCR methods. Emmonsia pasteuriana has also been reported in a patient with AIDS (47); this species does not produce adiaspores in tissue. Bauer (1933) is credited with the earliest report that the oxidation of sugars (1,2-glycols) with chromic acid creates aldehydes that will bind the Schiff molecule.

but would lack activity against C. krusei, C. glabrata, or the other septated hyaline molds. In any of these instances it is indispensable to correlate the laboratory findings (pathology and microbiology) with the clinical presentation of the patient and determine if alternative testing is required.

(B) Collagen fibers, with one even showing a “pseudoseptum” (arrow). If a second fungus is not mentioned but grows in the culture, the results may appear to be discrepant. Jeannette Guarner was brought up in Mexico City, where she obtained her medical degree from LaSalle University.
From the lung, cryptococci can disseminate to the central nervous system (producing meningitis or cryptococcomas), skin, bones, or other tissues. Hormonal, genetic, immunologic, and nutritional statuses appear to determine if the patient will present with acute or chronic or with localized or disseminated disease.

The GMS stain is more sensitive than the PAS stain, but has a signal to noise issue in that it stains inflammatory cells (lysosomes) and tissue reticulin, in addition to fungi.

Background pale green. In situ hybridization offers the highest degree of specificity compared to histochemical stains and immunohistochemistry (the other morphology-based techniques). Diabetic ketoacidosis causes dysfunction of macrophages and is the most frequent risk factor for sinusitis and rhinocerebral infection. In order to stain the fungal wall, GMS and PAS stains can be used in cytologic specimens. 3) (64). While some of these are special fungal stains, others are of more general use but still help to observe the tissue reactions and/or the infecting fungus. ; thus, analysis of other regions should be considered (37, 84). In addition, these fungi thrive when iron is present in the host, and those patients receiving iron-chelating agents such as deferoxamine to reduce iron overload are also at risk.

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