Background

This fungal infection is most commonly found as a lung infection. It is an opportunistic infection usually affecting immunocompromised patients.

OUTLINE

Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
Laboratory Markers
Culture	Sabouraud glucose agar, Inhibitory Mould Agar (IMA) or other proper medium with antibiotics (gentamicin or chlorampenicol) and incubate at 30° Sensitive to cycloheximide
A. flavus	Slow to rapid growing, woolly to cottony, occasionally radially furrowed, initially yellow, quickly becoming bright to dark yellow green or jade green, with an uncolored to pinkish drab reverse color Sclerotia are often present Conidiophores are thick walled, hyaline, coarsely roughened with a subglobose or globose vesicle Phialides are flask shaped, either uniseriate or biseriate, covering the majority of the vesicle Conidia are 1-celled, globose to subglobose, echinulate, 3-6 µm. Conidial heads radiate, typically splitting into several poorly formed columns

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
CNS
Central nervous system aspergillosis: A 20-year retrospective series B. K. Kleinschmidt-DeMasters, MD	Hum Pathol 2002;33:116-124. Abstract quote Over the past 20 years at my institution, 71 patients with invasive necrotizing aspergillosis have been encountered; 42 have shown central nervous system (CNS) involvement by autopsy (40) or surgical biopsy (2). Most non-CNS aspergillosis patients had invasive disease confined to the lung, and only 2 with dissemination to 3 or more organs did not have spread to the CNS. In addition to the expected post-transplantation and hematologic malignancy cases, other risk groups identified included those with chronic asthma and steroid use, acquired immunodeficiency syndrome, thermal burn, hepatic failure, and postoperative infection. Unusual cases manifested with basilar meningitis, myelitis, proptosis caused by sino-orbital disease, or epidural and subdural Aspergillus abscesses. The extent of gross neuropathologic disease ranged from subtle abscesses to massive hemorrhagic necrosis causing herniation and death. In addition to the expected hemorrhagic necrosis, extensive hemorrhage, focal purulent meningitis, and subtle bland infarctions were also seen. Distinctive microscopic findings encountered included 1 case with numerous meningeal granulomas and multinucleated giant cells and 4 cases showing the Splendore-Hoeppli phenomenon. During the same period, single cases of cerebritis caused by morphologically similar fungi (Pseudoallescheria boydii [Scedosporium apiospermum], Scedosporium inflatum, Chaetomium sp) were identified and were indistinguishable from CNS aspergillosis clinically and pathologically.
HEART
Cardiac aspergillosis in patients with acquired immunodeficiency syndrome: a case report and review of the literature. Xie L, Gebre W, Szabo K, Lin JH. Department of Pathology, Nassau University Medical Center, East Meadow, NY 11554, USA.	Arch Pathol Lab Med. 2005 Apr;129(4):511-5. Abstract quote   Cardiac aspergillosis is uncommon in patients with acquired immunodeficiency syndrome (AIDS) in the absence of open heart surgery. We report a unique case of a 62-year-old man with AIDS who developed Aspergillus pancarditis with Aspergillus vegetations on mitral valve without evidence of pulmonary aspergillosis. There was extensive embolization to the brain and multiple foci of Aspergillus infection in kidneys and adrenal glands. There are only 10 documented cases of cardiac aspergillosis in the literature (1966-2003) in severely immunocompromised AIDS patients with CD4 T-lymphocyte counts ranging from 10 to 121 cells/muL. The cardiac aspergillosis could result from invasive pulmonary aspergillosis, either by hematogenous dissemination or by direct invasion, and skin Aspergillus infection can be carried through the bloodstream to the right heart in intravenous drug abusers. Most of the reported cases of cardiac aspergillosis were diagnosed at autopsy. Mortality among AIDS patients with cardiac aspergillosis is 100%, despite appropriate therapy.
SKIN	Br J Dermatol 1998;139:522-526 A. flavus most common species causing skin disease Primary disease may occur with trauma Secondary disease from hematogenous spread after colonization of lower and upper respiratory tracts-lesions may occur on extremities and head Multiple violaceous papules or plaques that progress to necrotic ulcers with eschars
LUNG
ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS	Sinuses, lungs
Pulmonary aspergilloma	Pre-existing lung cavity
Pulmonary aspergillosis	Invasive Disease
Endophthalmitis
Osteomyelitis
Renal abscesses

 

HISTOLOGICAL TYPES	CHARACTERIZATION
General	Distinct dichomotous, right angle branching Blood vessel invasion, thrombosis, infarction, and dissemination
VARIANTS
LUNG
Allergic bronchopulmonary aspergillosis: an overview. Zander DS. Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston Medical School, Houston, TX 77030, USA.	Arch Pathol Lab Med. 2005 Jul;129(7):924-8. Abstract quote   This article provides an overview of the major pathologic manifestations of allergic bronchopulmonary aspergillosis; patient characteristics; clinical, radiographic, and laboratory features of the disease; and current knowledge about its pathogenesis. Although allergic bronchopulmonary aspergillosis is an infrequent complication of asthma or cystic fibrosis, recognition of this disorder is important to avoid progression of bronchiectasis and lung parenchymal damage. Clinical, laboratory, and radiographic criteria allow for diagnosis of most cases, but the pathologist may encounter clinically unsuspected or atypical cases that require morphologic confirmation.
SKIN	Vary from granulomatous lesions with few organisms to large suppurative necrotic areas with numerous organisms
Pseudoepitheliomatous Hyperplasia Secondary to Cutaneous Aspergillus Rajat Goel, M.D.; Michael L. Wallace, M.D. From the Department of Pathology, Medical College of Virginia, Richmond, Virginia.	Am J Dermatopathol 2001;23:224-226 Abstract quote Cutaneous aspergillosis commonly occurs in immunocompromised hosts and may also complicate burn wounds. Pseudoepitheliomatous hyperplasia (PH) is a histologic reaction secondary to a wide range of stimuli, including fungal infection. We describe a case of an 18-year-old man, status-post burns over 70% of his total body surface area, with cutaneous aspergillosis of the axilla and secondary PH. A single case of PH secondary to primary aspergillosis has been described in the larynx but, to our knowledge, has never been described cutaneously. Histologic examination of the lesion reveals an irregularly acanthotic epidermis with deep invaginations within the dermis. There is an intense inflammatory reaction within the superficial and deep dermis. Numerous fungal forms are identified within the dermis. Special stains demonstrate septate hyphae with dichotomous branching, which is morphologically consistent with Aspergillus. Therefore, we conclude that cutaneous aspergillosis should be included in the differential diagnosis of causes of PH, especially in a patient population at risk for this infection.

 

SPECIAL STAINS/ IMMUNO- PEROXIDASE/ OTHER	CHARACTERIZATION
Special stains	GMS and PAS positive
IMMUNO-HISTOCHEMISTRY
Immunohistochemical Detection of Aspergillus Species in Pediatric Tissue Samples John K. Choi, MD, PhD, Joanne Mauger, and Karin L. McGowan, PhD	Am J Clin Pathol 2004;121:18-25 Abstract quote Definitive diagnosis of invasive aspergillosis often requires tissue samples for histologic evidence of fungal infection and culture confirmation of Aspergillus species. However, the culture frequently fails to isolate Aspergillus species. Alternative approaches to confirm Aspergillus infection use polymerase chain reaction, in situ hybridization, and immunohistochemical analysis on paraffin-embedded sections. These approaches are well characterized in animals and adult patients but not pediatric patients. We studied the immunoreactivity of a commercially available monoclonal antibody, Mab-WF-AF-1 ( DAKO , Carpinteria, CA), on paraffin-embedded sections from 16 pediatric cases with invasive aspergillosis, of which 12 were proven by culture. Optimal immunoreactivity required microwave antigen retrieval using high pH; 5 other antigen retrieval approaches were unsuccessful. With optimization, the monoclonal antibody was strongly immunoreactive in all cases with staining of the Aspergillus cell wall, septa, and cytoplasm. Background was minimal with no cross-reactivity to Candida albicans. These findings demonstrate the usefulness of the Mab-WF-AF-1 antibody in pediatric tissues suspected of invasive aspergillosis.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors	Invasive forms of aspergillosis are associated with significant morbidity and mortality, regardless of therapy
Treatment
Invasive disease	Amphotericin B and itraconazole
Aspergillomas	Surgical resection may cause significant morbidity and mortality-reserved for patients at high risk to develop severe hemoptysis
Allergic Aspergillosis	Corticosteroids, and intraconazole Prolonged use of steroids in cases of chronic aspergillosis should be approached with caution
Experimental Therapies	Voriconazole, posaconazole, ravuconazole, caspofungin, FK463, and V-echinocandin (LY303366)

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Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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Last Updated July 15, 2005

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