Invasive Aspergillosis Presenting as a Neck Mass in a Person With HIV/AIDS

A 38-year-old HIV-infected man with a CD4+ cell count of 4/?L and an HIV RNA level of more than 750,000 copies/mL was admitted to the hospital after 1 month of painful right neck swelling and 1 week of dysphagia. His history was also notable for methicillinresistant Staphylococcusaureus (MRSA) bacteremia, which occurred 2 months earlier; adrenal insufficiency; chronic hepatitis C; remote Cytomegalovirus retinitis; and recurrent bacterial pneumonia.

The patient had started antiretroviral treatment with efavirenz and coformulated abacavir/lamivudine/zidovudine 10 months before admission but discontinued therapy on his own after 7 months. At the time of admission, his medications were daily valganciclovir, dapsone, and prednisone and weekly azithromycin.

On physical examination, the patient had a fever (temperature, 37.5C [99.5F]) and a swelling in the right side of his neck. Findings from the remainder of his physical examination were unremarkable. ACT scan of the neck demonstrated multiple low-density masses with rim enhancement in the right side (Figure 1). A CT scan of the orbits demonstrated abnormal soft tissue involving the right pterygopalatine fossa with destruction of the posterosuperior right maxillary sinus wall (Figure 2, area marked by arrow).

Figure 1

Figure 2

CT-guided aspiration of the neck fluids yielded pus. Gram stains suggested the presence of fungal elements. Calcofluor white stain demonstrated a mould with septate hyphae that was morphologically consistent with Aspergillus (Figure 3). Culture confirmed the presence of Aspergillus fumigatus, characterized by short conidiophores with conidia forming long chains (Figure 4; lactophenol cotton blue stain, original magnification X 100).

Figure 3

Figure 4

The right maxillary sinus was the likely site of the primary infection, with subsequent spread of the infection to the neck. Otolaryngologists were consulted; they decided not to operate because of the unacceptably high morbidity of any procedure in this patient.

The patient was treated with voriconazole. Caspofungin was added when his health did not improve. The patient's antiretroviral therapy was not restarted. After 1 month of antifungal therapy, the patient died as a result of invasive aspergillosis and nosocomial MRSA bacteremia.

DISCUSSION
Surprisingly, invasive aspergillosis is uncommon in HIV-infected patients, and the diagnosis is commonly not made until autopsy.^1,2 Most patients described in the literature have CD4+ cell counts that are less than 50/?L and are vulnerable to immunosuppression because of hematological malignancy, neutropenia, corticosteroid use, or prolonged antibacterial use.^1-5

The most common pathogen isolated among HIV-infected patients is A fumigatus followed by Aspergillus flavus^1-3 and Aspergillus niger.⁴ The respiratory tract is the most common site of the disease, with the brain as the next most common site. Other sites include the sinuses, kidneys, thyroid, liver, pancreas, spleen, and skin.^1-3 We were unable to identify any previous report in the literature of invasive aspergillosis presenting as a neck mass in an HIV-infected patient.

The diagnosis of invasive aspergillosis requires a high index of suspicion and appropriate staining to visualize the pathogen. On Gram stain, the hyphae of Aspergillus can appear as unstained negative images or they can be invisible. Aspergillus is best visualized by using calcofluor, Gomori methenamine-silver, or periodic acid-Schiff stain. Aspergillus appears in tissue as septate hyphae with acute-angle branching. Because Aspergillus is indistinguishable from Scedosporium and Fusarium species, cultures using Sabouraud dextrose with brain-heart infusion agar, usually with 5% sheep blood, are needed to make a definitive diagnosis. If specimens are obtained from nonsterile sites, chloramphenicol and gentamicin should be added to the media. Immunohistochemical identification of Aspergillus species using monoclonal antibodies can also be used on tissue sections.

Persons with HIV/AIDS are routinely treated with surgery and amphotericin B or itraconazole.^1-3 Median survival in these patients has been only 3 months after diagnosis. ^1,5 The role of newer azole and echinocandin antifungal agents needs further evaluation.

Acknowledgment: We thank Dr Gabriel Caponetti for his assistance with the pathology slides.

References:

• Lortholary O, Meyohas MC, Dupont B, et al. Invasive aspergillosis in patients with acquired immunodeficiency syndrome: report of 33 cases. Am J Med. 1993;95:177-187.

• Khoo SH, Denning DW. Invasive aspergillosis in patients with AIDS. Clin Infect Dis. 1994;19(suppl 1):S41-S48.

• Minamoto GY, Barlam TF, Vander Els NJ. Invasive aspergillosis in patients with AIDS. Clin Infect Dis. 1992;14:66-74.

• Pursell KJ, Telzak EE, Armstrong D. Aspergillus species colonization and invasive disease in patients with AIDS. Clin Infect Dis. 1992;14:141-148.

• Holding KJ, Dworkin MS, Wan PC, et al. Aspergillosis among people infected with human immunodeficiency virus: incidence and survival. Clin Infect Dis. 2000;31:1253-1257.