Approach Considerations
Timely diagnosis is paramount in cases of mucormycosis. Persons with suspected rhinocerebral disease should undergo an emergent CT scanning of the paranasal sinuses and an endoscopic examination of their nasal passages with biopsies of any suggestive lesions. The diagnosis of mucormycosis is established by obtaining a biopsy specimen of the involved tissue, and frozen tissue samples should be immediately evaluated for signs of infection. Tissue should also be sent for routine pathology examination and cultures. Swabs of tissue or discharge are unreliable.
For pulmonary disease, a bronchoalveolar lavage (BAL), biopsy, or both may assist in the diagnosis.
Laboratory Tests
A complete blood cell (CBC) count should be obtained to assess for neutropenia. A chemistry panel that includes blood glucose, bicarbonate, and electrolytes is useful to monitor homeostasis and direct correction of acidosis. An arterial blood gases (ABG) study can help determine the degree of acidosis and direct corrective treatments.
Iron studies may be indicated to assess the presence of iron overload as shown by high ferritin levels and a low total iron-binding capacity.
In cases of central nervous system (CNS) involvement, cerebrospinal fluid (CSF) findings may include elevated protein levels and a modest mononuclear pleocytosis. CSF cultures are typically sterile. A computed tomography (CT) scan should precede a lumbar puncture to ensure that this procedure is safe.
Blood cultures can be obtained; however, they are usually negative despite the angioinvasive nature of the organism. Antigen tests (beta-D-glucan or galactomannan) are not useful for detecting this infection.
Radiologic Studies
Rhinocerebral infections
Plain films may show sinus involvement with mucosal thickening, air-fluid levels, and/or bony erosions.
Head and facial computed tomographic (CT) scanning should be used as the initial investigation in rhinocerebral infections. CT scans may show sinusitis of the ethmoid and sphenoid sinuses, as well as orbital and intracranial extension. As the disease progresses, bony erosion may occur and the infection may spread into the brain or orbits. In addition, because mucormycosis organisms have a predilection for vascular involvement, thromboses of the cavernous sinus or internal carotid artery may occur.[10] All of the areas of involvement must be understood in order to plan the extent of surgical debridement.
Magnetic resonance imaging (MRI) of the facial sinuses and brain is superior to a CT scan in assessing the need for ongoing surgery.
Pulmonary disease
Obtain chest radiography and chest high-resolution CT scanning. The most common finding is consolidation, usually unilobar; with disease progression, multilobar involvement may develop. Cavitation, especially producing an air crescent or halo sign, is highly suggestive of fungal infection but does not distinguish it from aspergillosis. Nodular lesions (especially multiple nodules) and pleural effusions may be present. See the images below.
Chest computed tomography (CT) scan showing pulmonary mucormycosis with left basal consolidation and widespread nodules due to Rhizopus oryzae infection. The patient was receiving cytotoxic chemotherapy for myelodysplastic syndrome and had iron overload from numerous blood transfusions.
Chest computed tomography (CT) scan showing pulmonary mucormycosis with left basal consolidation and widespread nodules due to Rhizopus oryzae infection. The patient was receiving cytotoxic chemotherapy for myelodysplastic syndrome and had iron overload from numerous blood transfusions. This CT scan of the patient shows resolution of pulmonary mucormycosis after 5 months of antifungal treatment. Gastrointestinal disease
In gastrointestinal (GI) disease, abdominal CT scans may show a mass associated with the GI tract.
Central nervous system
CT scanning or MRI of the central nervous system may reveal abscesses (especially in the setting of intravenous drug use) or extension of rhinocerebral disease into the brain. Additionally, cavernous and, less commonly, sagittal sinus thrombosis may be seen.
Biopsy and Histologic Features
The critical test procedure for diagnosing mucormycosis is obtaining a biopsy specimen of the involved tissue. A rapid histologic assessment of a frozen tissue section should be performed in order to promptly institute surgical and medical management for the infection.
Biopsy of necrotic tissue
Biopsy of necrotic tissue may be obtained from nasal, palatine, lung, cutaneous, gastrointestinal (GI), or abscess wall site.
Stains of fixed tissues with hematoxylin and eosin (H&E) or specialized fungal stains, such as Grocott methenamine-silver (see the following image) or periodic acid-Schiff (PAS) stains, show pathognomonic changes of broad-based (typically 10- to 20-µm diameter), irregular, ribbonlike, nonseptate hyphae with irregular branching that may occur at right angles. Vascular invasion and necrosis are the characteristic consequences of the infective process. Thus, neutrophil infiltration, vessel invasion, and tissue infarction are often observed. A granulomatous reaction may also be observed.
Histologic findings from an immunocompetent man who sustained a high-pressure water jet injury, resulting in rhinocerebral mucormycosis. Traumatic inoculation of Apophysomyces elegans was the pathogenetic mechanism. Findings show the typical Mucorales hyphae on Grocott methenamine-silver staining. The hyphae are the dark structures with budlike, right-angle hyphae. (Courtesy of A. Allworth, MD, Brisbane, Australia.) Culture of biopsy samples is required to determine the species of Mucorales. Do not crush or grind the specimen, because the nonseptate hyphae are prone to damage. Growth usually occurs in 2-3 days. The genus and species are determined via examination of the fungal morphology (eg, the presence and location of the rhizoids).
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