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False-positive results for both complement fixation and immunodiffusion have also been reported in cases of tuberculosis
Treatment
Most infections in immunocompetent patients are self-limited and hence no therapy is required
Therapy is needed in patients who are immunocompromised, and those who are exposed to large fungal inoculum
Antifungal regimens vary according to patient’s clinical presentations
In general, itraconazole is preferred for mild to moderate histoplasmosis, and amphotericin B is needed in treating disseminated, CNS, or severe infections
Prognosis
Most infections are asymptomatic and self-limited in immunocompetent individuals
Immunocompromised patients
Pulmonary disease can progress rapidly to involve multiple lung lobes; patients can develop acute
Fungal Infections: Morphological Diagnosis of Fungal Infections
respiratory distress syndrome within days if not treated
More likely to present with disseminated disease
IMAGE FINDINGS
Radiographic Findings
Pulmonary histoplasmosis
Most common: Diffuse reticulonodular pulmonary infiltrates
Coalescence of nodules can be seen in discrete areas of lung
Cavitations are mostly seen in chronic cavitary pulmonary histoplasmosis
Mediastinal or hilar lymphadenopathy are often present
Extrapulmonary disease
Radiographic findings are highly variable and not specific
MICROBIOLOGY
Culture
Sabouraud dextrose agar or brain-heart infusion agar
Organisms grow slowly; 4-6 weeks are needed to determine whether culture is positive or negative
Lysis-centrifugation is needed to release organisms from phagocytic cells in clinical samples
Yield from culture is generally good when respiratory samples are taken from patients who have chronic cavitary pulmonary histoplasmosis, acute pulmonary histoplasmosis, or disseminated infection following exposure to a large fungal inoculum
Cultures are usually negative in respiratory samples taken from cases of mild pulmonary infection,
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granulomatous mediastinitis, mediastinal fibrosis
HISTOPLASMOSIS
MACROSCOPIC FEATURES
General Features
Heavy infections may cause marked enlargement of involved organs, e.g., lymph nodes, adrenal glands, liver, spleen
MICROSCOPIC PATHOLOGY
Histologic Features
Oval small yeast cells (2-4 m in diameter) with narrow-based budding
Not encapsulated; however, it may appear to be surrounded by a clear zone/pseudocapsule in tissue
Yeasts tend to cluster and reproduce within macrophages, monocytes, and occasionally neutrophils
When yeasts are released from cells into surrounding tissue such as alveoli in lungs, they often remain in clusters
Acute histoplasmosis
Nodular areas of parenchymal and vascular necrosis associated with lymphohistiocytic vasculitis
Scattered small epithelioid and giant-cell granulomas with small yeasts in parenchyma can be present
Over time granulomas may turn into fibrocaseous nodules, which can become calcified
Chronic histoplasmosis
Granulomatous inflammation with central necrosis and occasionally calcification
Yeasts are usually present in necrotic calcified material, which can be lost during tissue processing
Disseminated disease: Sheets of macrophages parasitized with yeast cells can be seen
Organisms may primarily be seen extracellularly, making it more difficult to make diagnosis
ANCILLARY TESTS
Histochemistry
Histoplasma yeast cells are positive for Gomori methenamine silver (GMS) and (less so) periodic acid­Schiff (PAS) stains
Staining is best on extracellular yeast; intracellular yeast may not pick up silver staining to the same degree
Negative for Gram and Fontana-Masson stains
Molecular Diagnostics
Chemiluminescent DNA probe for H. capsulatum (AccuProbe; GenProbe, Inc., San Diego, CA)
Can be used as confirmatory test for definitive identification in culture
Highly sensitive (up to 100%) and specific (up to 100%)
False-positive tests have been reported with Chrysosporium spp. but are rare
PCR-based assays
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HISTOPLASMOSIS
Fungal Infections: Morphological Diagnosis of Fungal Infections
Real-time PCR and semi-nested PCR assays have been developed for testing blood, bronchoalveolar lavage, and tissue samples
PCR assay for routine use is not yet commercially available
DIFFERENTIAL DIAGNOSIS
Candidiasis
Histoplasma spp. can be confused easily with Candida glabrata, which is similar in size and lacks
pseudohyphae
C. glabrata
Exhibits more size variability than Histoplasma spp.
Predominantly produces neutrophilic inflammation rather than a granulomatous reaction seen with histoplasmosis
Lacks a pseudocapsule on H&E stain as would be seen with histoplasmosis
Positive on Gram stain
Cryptococcosis
Cryptococcal yeast cells
Rounder and exhibit more size variation than Histoplasma spp.
Have capsules that are positive for mucicarmine; capsule-deficient cryptococci, however, can be mistaken for Histoplasma yeast cells
Positive for Fontana-Masson, which stains melanin in their cell walls, whereas Histoplasma spp. are negative for melanin stains
Coccidioidomycosis
Coccidioides endospores are about the same size as Histoplasma spp., but they are usually present within
an intact spherule or associated with a ruptured spherule in surrounding tissue, while spherules are absent in histoplasmosis
Coccidioides endospores show no budding, while Histoplasma spp. exhibit narrow-based budding
Blastomycosis
Blastomyces yeast cells are larger in size and have broad-based rather than narrow-based budding as would be seen with histoplasmosis
Pneumocystosis
Pneumocystis jirovecii cysts lacks budding and usually have focal thickenings in cyst wall, which stain as dark dots; these features are not seen with Histoplasma spp.
Penicilliosis
Penicillium marneffei yeast-like cells within macrophages or monocytes may look like Histoplasma spp., but in contrast to Histoplasma spp., P. marneffei lacks budding, reproduces by binary fission, and shows a prominent central septum
Extracellular P. marneffei cells are larger and may manifest several septa
Protozoan Diseases
Leishmaniasis, toxoplasmosis, Chagas disease
None of the protozoa show halo produced by fungal cell wall as would be seen with Histoplasma spp. on H&E stain
None of the protozoa show budding and they are negative for GMS or PAS stains
Cells infected by these protozoa are generally not histiocytes as would be seen with histoplasmosis
Paranuclear-bar shaped kinetoplasts should be observed with amastigotes of Leishmania spp. and Trypanosoma cruzi, but not with Histoplasma spp.
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
Yield of diagnostic modalities differs depending on extent of infection and timing following exposure
Pathologic Interpretation Pearls
Oval small yeast cells (2-4 m in diameter) with narrow-based budding
Yeast cells tend to cluster within macrophages and monocytes
Morphology of extracellular yeast cells on H&E are not specific; therefore, utilization of special stains and correlation with clinical and other laboratory findings is needed for definitive diagnosis
SELECTED REFERENCES
1. Couturier MR et al: Urine antigen tests for the diagnosis of respiratory infections: legionellosis, histoplasmosis, pneumococcal pneumonia. Clin Lab Med. 34(2):219-36, 2014
2. Murthy JM et al: Fungal infections of the central nervous system. Handb Clin Neurol. 121:1383-401, 2014
3. Sizemore TC: Rheumatologic manifestations of histoplasmosis: a review. Rheumatol Int. 33(12):2963-5, 2013
4. Gupta AO et al: Immune reconstitution syndrome and fungal infections. Curr Opin Infect Dis. 24(6):527-33, 2011
5. Mukhopadhyay S: Role of histology in the diagnosis of infectious causes of granulomatous lung disease. Curr Opin Pulm Med. 17(3):189-96, 2011
6. Gupta N et al: Histoplasmosis: cytodiagnosis and review of literature with special emphasis on differential diagnosis on cytomorphology. Cytopathology. 21(4):240-4, 2010
7. Hage CA et al: Pulmonary histoplasmosis. Semin Respir Crit Care Med. 29(2):151-65, 2008
8. Assi MA et al: Systemic histoplasmosis: a 15-year retrospective institutional review of 111 patients. Medicine (Baltimore). 86(3):162-9, 2007
9. Kauffman CA: Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev. 20(1):115-32, 2007
10. Chu JH et al: Hospitalizations for endemic mycoses: a population-based national study. Clin Infect Dis. 42(6):822-5, 2006
11. Brandt ME et al: False-positive Histoplasma capsulatum Gen-Probe chemiluminescent test result caused by a Chrysosporium species. J Clin Microbiol. 43(3):1456-8, 2005
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Radiographic and Microscopic Features
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(Left) Chest CT shows a nodule in right lung raising concern for neoplastic vs. infectious diseases. Positron emission tomography may be mildly to strongly avid. Wedge resection of the nodule revealed a calcified necrotic mass containing Histoplasma yeast forms. (Right) Low­magnification of a lung section on H&E stain shows confluent
ranulomatous inflammation
with necrosis in a
atient with acute pulmonary
histoplasmosis.
Fungal Infections: Morphological Diagnosis of Fungal Infections
(Left) High magnification of a lung section shows the edge of a granuloma with central necrosis in a patient with pulmonary histoplasmosis. Subtle yeast forms may reside in the necrotic material. A GMS or PAS-D stain to evaluate yeast is needed. (Right) Medium magnification of a lung nodule shows a healing granuloma with a fibrocaseous center . Giant cells are noted in the periphery. Follow-up GMS and PAS stains highlight rare Histoplasma yeast forms in the nodule.
HISTOPLASMOSIS
(Left) High magnification of this lung section on H&E stain shows multiple macrophages and monocytes fully packed with yeast cells in the alveolar spaces in a patient with acute histoplasmosis. (Right) High magnification of this lung section on Gram stain shows intracellular and extracellular round Gram­negative yeast cell clusters, consistent with histoplasmosis.
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Microscopic Features
A p
p
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A
Fungal Infections: Morphological Diagnosis of Fungal Infections
HISTOPLASMOSIS
(Left) High magnification of this tissue section reveals numerous small yeast forms highlighted by GMS stain.
few of the yeast cells
appear to exhibit narrow­based budding . (Right) High magnification of a skin section shows fungal dermatitis associated with PAS-positive small round yeast forms, both intra­and extracellularly . The findings are consistent with histoplasmosis. Correlation with clinical and other laboratory findings is needed.
(Left) Medium magnification of this tenosynovial biopsy shows scattered minute clusters of small yeasts highlighted by PAS stain,
utting histoplasmosis on the differential. The small size of the nonpigmented yeasts makes it challenging to detect on H&E stain when the fungal load is small. (Right) High magnification of this PAS-stained tissue section shows scattered dark blue lymphocytes and aggregates of pink small oval yeast cells in a
atient with disseminated histoplasmosis.
(Left) High magnification of a lung mass on GMS stain shows small oval yeast forms with fairly uniform size, putting histoplasmosis on the differential. (Right) GMS stain shows small, variably sized yeast forms with occasional budding
. A pale halo appears to surround some of the yeast cells, suggesting a
seudocapsule or a capsule. The findings raise the differentials of Cryptococcus vs. Histoplasma spp.
negative Fontana­Masson would exclude Cryptococcus.
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MUCORMYCOSIS
High magnification of a lung lesion on H&E stain shows numerous broad ribbonous fungal hyphae with right­angle branching consistent with mucormycosis.
Fungal Infections: Morphological Diagnosis of Fungal Infections
TERMINOLOGY
Synonyms
Zygomycosis (former name), phycomycosis (former name)
Definitions
Latin: "Mucor" (bread mold, wine must)
Greek: "Zygon" (yoke) + "mykes" (mushroom)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Mucorales fungi are ubiquitous in environment in association with decaying organic matter
Most common genera causing human infections: Rhizopus spp., Mucor spp., Rhizomucor spp.
Less common genera causing infections: Cunninghamella, Absidia, Saksenaea, and Apophysomyces
Pathogenesis
Infection presumed to occur after inhalation of spores
In healthy people: Spores are transported by cilia to pharynx and are cleared through gastrointestinal tract
In immunocompromised individuals: Spores are not cleared and infection usually begins in nasal sinuses or pulmonary alveoli
Organisms are angioinvasive, causing tissue infarction and necrosis
CLINICAL ISSUES
Epidemiology
Risk factors
Immunosuppression, e.g., AIDS, hematological
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malignancies, solid organ transplant recipients, hematopoietic stem cell transplant recipients, glucocorticoid recipients
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Low magnification of a lung mass on PAS stain shows angioinvasion of fungal forms. Hyphae are relatively broad with very few septa, putting mucormycosis in the differential.
Diabetes mellitus with poor glycemic control
Treatment with deferoxamine
Deferoxamine-iron chelate can act as siderophore
for Rhizopus spp., hence stimulates fungal growth by increasing their iron uptake Other iron chelating agents, such as deferasirox
and deferiprone, do not act as siderophores and therefore do not increase the risk of mucormycosis
Iron overload
Injection drug use
Malnutrition
Severe prematurity
Presentation
Most cases have rapid course; rare cases have indolent course
Most common primary mucormycosis: Rhinocerebral, pulmonary, cutaneous infections
Rhinocerebral infection
Most common clinical presentation of mucormycosis
Most commonly caused by Rhizopus spp.
Contiguous spread to other structures, such as palate, orbit, and brain; can progress rapidly
Pulmonary infection
Pneumonia with tissue infarction and necrosis, which may ultimately lead to cavitation &/or hemoptysis
Clinical course is usually rapidly progressive
Infection can spread to contiguous structures, such as mediastinum and heart, or disseminate hematogenously to other organs
Cutaneous infection
Often due to inoculation of spores into dermis; rare cases are seen with disseminated disease
Can occur in cases of trauma or contaminated wounds
Deep tissue involvement and dissemination from cutaneous infection is relatively unusual
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Terminology
Former names: Zygomycosis, phycomycosis
Etiology
Most common genera found in human infections: Rhizopus spp., Mucor spp., Rhizomucor spp.
Opportunistic pathogens
Clinical Issues
Most cases have a rapid course
Risk factors
Immunosuppression, diabetes mellitus, injection drug use, trauma, burns, malnutrition, iron overload, treatment with deferoxamine
Most frequent primary clinical manifestations: Rhinocerebral, pulmonary, cutaneous infections
Disseminated infection carries poor prognosis
MUCORMYCOSIS
Key Facts
Microscopic Pathology
Nonpigmented, wide (5-20 m), thin-walled, ribbon­like hyphae with few septations and right-angle branching
Hyphae are angioinvasive, causing tissue necrosis, hemorrhage, and blood vessel thrombosis, particularly in immunocompromised hosts
Ancillary Tests
Hyphae can be highlighted by silver stain and periodic acidSchiff stain on tissue sections
Top Differential Diagnoses
Aspergillosis
Candidiasis
Hyalohyphomycosis
Concurrent infections with other fungi
Fungal Infections: Morphological Diagnosis of Fungal Infections
Disseminated infection
Most commonly seen in severely immunocompromised patients, burn patients, premature infants, and transplant recipients
Any primary manifestations can give rise to disseminated disease
Brain is the most common site of spread
Other sites of spread: Spleen, heart, kidney, and other organs
Gastrointestinal infection
Rare
Thought to arise from ingestion of fungal organism
Most common sites: Stomach, colon, and ileum
Mostly occurs in transplant recipients and in severely malnourished patients
Treatment
Combination of antifungal therapy and surgical debridement of infected tissues
Predisposing factors should be watched out for and managed, e.g., metabolic acidosis, hyperglycemia immunosuppressive drugs
Early initiation of therapy improves outcome
Drugs
Initial therapy
Amphotericin B is usually drug of choice for
mucormycosis, or as empiric treatment for aspergillosis or mucormycosis before definitive diagnosis is made
Step-down therapy
Oral posaconazole can be used as a step-down in
patients responding to amphotericin B
Salvage therapy
Intravenous posaconazole can be used in patients
who cannot tolerate or do not respond to amphotericin B
Studies are needed to establish whether combination therapy with other antifungals (e.g., echinocandins) is beneficial
Voriconazole, fluconazole, and flucytosine are not effective against Mucorales
Surgery
Surgical debridement should be made as soon as diagnosis of rhinocerebral or orbital mucormycosis is suspected
Pulmonary mucormycosis often present with multilobar involvement that precludes surgical resection
Prognosis
Generally poor for disseminated cases
Early diagnosis and combined surgical and medical therapy are key to improved prognosis
IMAGE FINDINGS
Chest Radiographs or CT Scans
Focal consolidation, masses, or nodules
Halo sign: Ground-glass attenuation surrounding a nodule, seen with angioinvasive fungi, mycobacteria, or in cases of neoplasia causing tissue infarction or hemorrhage
Reversed halo sign: Focal area of ground-glass attenuation surrounded by ring of consolidation
Mucormycosis has been reported to be the most common condition to cause reversed halo sign in immunocompromised hosts
MICROSCOPIC PATHOLOGY
Histologic Features
Nonpigmented, wide (5-20 m in diameter), thin­walled, ribbon-like hyphae with few septations and right-angle branching
Fungal elements are often seen invading blood vessel wall or inside their lumen
Associated with tissue necrosis, hemorrhage, and blood vessel thrombosis
Hyphae may vary in width, and may appear folded, fragmented, crinkled or degenerated on tissue or cytologic specimens
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A
Lack of regular septations in hyphae makes them fragile and prone to damage during tissue processing
ANCILLARY TESTS
Special Stains
Hyphae can be highlighted by silver stain and periodic acidSchiff stain on tissue sections
Fragmentation and degeneration of the fungal elements may cause these stains, particularly silver stain, to be either faintly positive or negative
Hyphae can be highlighted with Papanicolaou and calcofluor white stains on cytologic specimens
Cultures
Fast-growing (< 3 days)
Yield of cultures can be low
Rarely recovered from blood, even in invasive cases
Airborne spores can cause contamination of laboratory media, hence positive cultures have to be correlated with clinical and histologic findings
Serological Tests
Fungal Infections: Morphological Diagnosis of Fungal Infections
Not clinically useful in invasive disease
Serum galactomannan and 1,3-beta-D-glucan are typically negative in invasive mucormycosis
Molecular Diagnostics
PCR with sequencing using conserved fungal primers (28S rRNA)
DIFFERENTIAL DIAGNOSIS
spergillosis
Hyphae of Mucorales are pauciseptate, broad with right-angle branching whereas Aspergillus hyphae are narrower, septate with acute-angle branching
Poor staining of hyphae with silver stain would suggest mucormycosis as the pauciseptate hyphae are prone to degeneration resulting in less pickup of silver stain
Serum galactomannan and 1,3-beta-D-glucan are typically positive in cases of invasive aspergillosis and negative in cases of invasive mucormycosis
Candidiasis
Candida spp. produce yeast forms admixed with pseudohyphae and true hyphae
Gram stain highlights Candida spp., while hyphae in cases of mucormycosis are negative with Gram stain
Hyalohyphomycosis
Hyaline molds, such as Fusarium and Scedosporium spp., are morphologically similar to Aspergillus spp. and hence can be confused with Mucorales
These molds generally produce abundant septations, in contrast to cases of mucormycosis, which produce pauciseptate hyphae
MUCORMYCOSIS
Concurrent Infections With Other Fungi
Concurrent aspergillosis and candidiasis have been reported
Alternative diagnostic testing of tissues such as immunohistochemistry, in situ hybridization, or PCR are needed for definitive identification
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
Infections are mostly opportunistic in nature
Clinical course is usually rapid, with the exception of isolated cutaneous infection
Yield from culture is usually low; positive cultures have to be correlated with clinical and histologic findings for interpretation to rule out culture contamination
Pathologic Interpretation Pearls
Hyphae are typically nonpigmented, pauciseptate, broad (5-20 m in diameter) with irregular or right­angle branching
Fungal elements are often angioinvasive, causing hemorrhage, necrosis, and tissue infarction
Hyphae are positive for silver stains, PAS stains, and negative for Gram stain
Fragmentation and degeneration of the fungal elements can make it hard to assess septation and branching
Correlation with clinical and culture findings is needed
SELECTED REFERENCES
1. Petrikkos G et al: Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis. 54 Suppl 1:S23-34, 2012
2. Spellberg B et al: Combination therapy for mucormycosis: why, what, and how? Clin Infect Dis. 54 Suppl 1:S73-8, 2012
3. Georgiadou SP et al: The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts. Clin Infect Dis. 52(9):1144-55, 2011
4. Guarner J et al: Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev. 24(2):247-80, 2011
5. Spellberg B et al: Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis. 48(12):1743-51, 2009
6. Roden MM et al: Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 41(5):634-53, 2005
7. Maertens J et al: Mucormycosis in allogeneic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis. Bone Marrow Transplant. 24(3):307-12, 1999
8. Harril WC et al: Chronic rhinocerebral mucormycosis. Laryngoscope. 106(10):1292-7, 1996
9. Boelaert JR et al: Deferoxamine augments growth and pathogenicity of Rhizopus, while hydroxypyridinone chelators have no effect. Kidney Int. 45(3):667-71, 1994
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Radiologic and Gross Features
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p
Fungal Infections: Morphological Diagnosis of Fungal Infections
MUCORMYCOSIS
(Left) Chest CT scan shows right upper lobe opacification and mass
extending into the mediastinum in a patient with acute myeloid leukemia status post consolidation chemotherapy. Biopsy of the mass confirms
ulmonary mucormycosis.
(Right) Photo shows aggregates of superficial skin ulcers in a patient on immunosuppression after heart transplantation. Histology and culture confirms involvement by mucormycosis.
(Left) Lung section from a patient with pulmonary mucormycosis shows multiple tan/pink centrally necrotic lesions containing Mucorales spp. on histologic examination and culture. (Right) Gross
hoto of a lung section shows fungal emboli and confluent nodular infarctions caused by fungal infection in lung
arenchyma. Microscopic examination confirms invasive mucormycosis.
(Left) Gross photo shows meningeal gray-white lesions
consistent with infection in a patient who died of disseminated mucormycosis. Microscopic examination reveals numerous fungal forms consistent with Mucorales. (Right) Gross
hoto shows cerebral infarction surrounded by erythema in the right frontal lobe of a patient who died of infectious complications. Histologic examination shows angioinvasion by fungal forms consistent with Mucorales.
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Gross and Microscopic Features
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(Left) Gross photo shows multiple dark green nodular lesions in a patient who died of disseminated fungal infection. Microscopic examination showed transmural colitis with fungal forms consistent with Mucorales. (Right) High magnification of a fine-needle aspiration with Diff-Quik stain shows broad aseptate fungal hyphae Mucorales. Branching appears to be acute-angle due to folding of the fungal forms.
Fungal Infections: Morphological Diagnosis of Fungal Infections
(Left) Medium magnification of this fine-needle aspiration on Pap stain shows long, ribbonous, broad hyphae consistent with Mucorales. Branching is difficult to assess due to folding of hyphae. (Right) Brain section on H&E stain shows fungal forms in the vessel lumen invading into surrounding tissue , resulting in infarction. Broad hyphae and right-angle branching are consistent with Mucorales.
on cecal mucosa
consistent with
MUCORMYCOSIS
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(Left) Tissue section of 2 adjacent blood vessels on H&E stain shows abundant thick aseptate hyphae with occasional branching consistent with Mucorales. Numerous fungal forms are
resent inside the vessel lumen, with some invading through the vessel wall
. (Right) Section of a
liver embolus on H&E stain in a case of disseminated mucormycosis shows subtle but numerous broad Mucor hyphae admixed with fibrin. Silver or PAS stains would be helpful in highlighting the organisms.
Microscopic Features
g A
Fungal Infections: Morphological Diagnosis of Fungal Infections
MUCORMYCOSIS
(Left) Tissue section of a blood vessel on silver stain shows numerous broad, ribbonous, pauciseptate hyphae with occasional branching, most consistent with Mucorales. Transverse sections of hyphae mimic yeast forms . (Right) PA S stain highlights numerous fungal forms with broad hyphae admixed with neutrophilic inflammation in a patient with known disseminated mucormycosis. Hyphae can appear fragmented and degenerated on tissue section.
(Left) GMS stain highlights broad segments of aseptate hyphae consistent with Mucorales in this tissue section. (Right) Calcium oxalate crystals as well as ribbonous hyphae with variable branching and occasional septa are present in this biopsy. Differentials include Aspergillus vs. Mucorales spp. The presence of crystals (Aspergillus) and thick hyphal morphology (Mucor) make definitive speciation difficult. Culture confirms the presence of A. flavus.
(Left) Differentials of these fragmented hyphae highlighted by GMS stain include Mucorales (favored
iven the hyphal size) vs.
spergillus spp. Correlation
with culture is needed. (Right) H&E section shows fungal forms invading into respiratory mucosa. Thick hyphae
with round to square forms, which may represent yeast vs. arthroconidia . Culture is required for definitive speciation.
, some with septa
, are present admixed
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