A case of skull base mucormycosis with osteomyelitis secondary to temporal bone squamous cell carcinoma.

Abstract

We describe an unusual case in which a 35-year-old man presented with skull base mucormycosis with osteomyelitis secondary to squamous cell carcinoma of the temporal bone. We also review the literature on the clinical characteristics, diagnosis, and treatment of mucormycosis.

Introduction

Skull base osteomyelitis is a complication of fungal infection that may be seen in immunocompromised patients. The most common causative pathogens are Aspergillus, Candida, and Cryptococcus spp. We encountered an unusual case of skull base osteomyelitis secondary to mucormycosis. The fungal infection was diagnosed only after the patient had been diagnosed with squamous cell carcinoma of the temporal bone.

Case report

A 35-year-old man initially presented to our outpatient clinic with a 10-year history of left ear discharge that would subside with medication. Six months earlier, he had developed left-sided facial paralysis with associated left-sided facial pain and severe headache. He underwent a left mastoid exploration under general anesthesia. Intraoperatively, a large cholesteatoma sac was found filling the antrum and extending to the mesotympanic and epitympanic areas. Also, the vertical part of the facial nerve had been exposed by the disease process.

Postoperatively, the patient continued to complain of severe facial and periauricular pain. The facial paralysis diminished initially, but it returned 3 months after surgery. It was with these complaints that the patient presented to us and was subsequently admitted.

In addition to the aforementioned symptoms, the patient reported the onset of vertigo and a blood-stained aural discharge. He had also experienced one episode of double vision, which resolved spontaneously.

Upon further questioning, the patient related no history of tuberculosis, diabetes, or any condition that would suggest an immunocompromised state. Our physical examination revealed the presence of torticollis and neck rigidity associated with grade II trismus. The patient reported fullness in the area of the left sternocleidomastoid muscle and a soft, tender swelling in the left postauricular area. His left ear was discharging purulent, blood-stained fluid, and granulations were seen protruding through the meatoplasty. In addition to the left facial nerve palsy, a deficit was noted in the ipsilateral VIIIth nerve. Findings on the remainder of the neurologic examination were normal.

Routine laboratory tests revealed an elevated alkaline phosphatase level (168 IU; normal: <90) and elevated erythrocyte sedimentation rate (36 mm for the first hour; normal: 0 to 20); the blood glucose level and the results of kidney function tests were normal, and the enzyme-linked immunosorbent assay for human immunodeficiency virus was negative. An ear swab culture yielded Staphylococcus aureus, which was sensitive to lincomycin and vancomycin. A biopsy of the granulation tissue in the left ear was sent for histopathology and microbiology. Histopathologic analysis revealed the presence of a moderately differentiated squamous cell carcinoma. Microbiologic examination on a 10% potassium hydroxide mount identified epithelial cells invaded by broad aseptate hyphae. Hematoxylin and eosin staining of tissue identified broad, ribbon-like aseptate hyphae (figure 1). The granulation tissue biopsy was positive on periodic acid-Schiff staining. Incubation in Sabouraud's dextrose agar (at 25[degrees]C) and brain-heart infusion agar (at 37[degrees]C) for 6 days yielded a grayish growth with aerial mycelia. The lactophenol cotton blue mount from the growth revealed Mucor spp. A culture for Mycobacterium tuberculosis was sterile after 10 weeks of incubation.

[FIGURE 1 OMITTED]

Contrast-enhanced computed tomography (CT) of the temporal bone (3-mm serial cuts) demonstrated (1) heterogenously enhancing densities with loculated collections in the left middle ear and mastoid cavities, (2) gross destruction of the mastoid portion of the left temporal bone, left occipital bone, and adjacent basisphenoid bone, and (3) destruction of the carotid canal, jugular foramen, and styloid process (figure 2). Erosion of the left lateral mass of the atlas (C1) was seen with extradural and subdural extension into the epidural spinal canal.

[FIGURE 2 OMITTED]

On the basis of these findings, we made a diagnosis of skull base osteomyelitis and mucormycosis secondary to squamous cell carcinoma of the temporal bone. The patient was treated with intravenous amphotericin B at a dose of 0.2 mg/kg/day and with IV ceftazidime, amoxicillin/clavulanate, and metronidazole. He was also administered full-dose radiotherapy for the malignancy.

The patient returned to the hospital's outpatient unit for 3 weeks following treatment but was subsequently lost to follow-up.

Discussion

Most invasive fungal infections occur in patients with prolonged neutropenia, in critically ill patients in intensive care, in patients undergoing chemotherapy for solid tumors, in patients with acquired immunodeficiency syndrome, and in patients who have received an organ transplant. (1) A secondary infection by an opportunistic fungus in an already-immunocompromised patient is not easy to diagnose or treat, and the prognosis for patients with this life-threatening complication is poor. Improvements in the management of bacterial infections in cancer patients have resulted in a decrease in the incidence of invasive fungal infections in this group.

Proven invasive fungal infections are divided into three categories: deep-tissue infections, fungemias, and endemic fungal infections. The diagnosis requires a positive blood culture, histopathologic analysis, or cytopathologic evidence of fungus and damage to tissue.

Mucormycosis is caused by fungi of the order of Mucorales and Entomophthorales; among the genera are Absidia, Mucor, and Rhizopus. Mucormycosis includes diseases caused by all members of the class Zygomycetes, hence it is also known as zygomycosis. The fungi are generally saprophytic and rarely cause disease in an immunocompetent host. Histologic differentiation of Mucor and Aspergillus fungi is based on the appearance of the hyphae; Mucor spp. feature aseptate, ribbon-like, haphazardly branching hyphae, while Aspergillus spp. are characterized by septate hyphae with uniform diameters and dichotomous branching. (2)

Mucormycosis is the third most common opportunistic fungal infection in immunocompromised and diabetic patients. In these patients, the infection is acute and rapidly fatal, even when it is diagnosed early and treated promptly. The infection has no predilection for either sex or for any specific age group, race, or geographic area. It may present in a rhinocerebral, pulmonary, abdominal, pelvic, or gastrointestinal site; it may even affect the skin before disseminating. Regional involvement determines morbidity and mortality. For example, the rhinocerebral form is associated with an 85% mortality; the overall mortality is 50%. (3) The primary determinant of survival is the length of time between the onset of infection and its treatment. In most cases, by the time mucormycosis is diagnosed, fungal invasion is so widespread and diffuse that therapy is unable to halt the progress of the disease. (3)

Treatment involves a combination of surgical (debridement) and medical modalities. Amphotericin B exerts broad-spectrum coverage and remains the drug of choice for life-threatening invasive fungal infections. (4) Since the 1990s, the number of available oral and parenteral antifungal agents has increased significantly. The use of phospholipid carriers for amphotericin B or cyclodextrine carriers for the triazoles (e.g., itraconazole and fluconazole) has improved safety profiles and/or pharmacokinetics. Three investigational agents under study are voriconazole, posaconazole, and ravuconazole. (5,6) Other new antifungals (e.g., echinocandins) that have a novel mechanism of action have been introduced into clinical practice, but studies have yet to determine their exact role in the management of different mycoses.

The occurrence of concomitant rhinocerebral mucormycosis and skull base osteomyelitis is not an altogether unusual phenomenon today, considering the increasing number of immunocompromised patients. (2) What was unusual in our case is that the infection was secondary to a squamous cell carcinoma of the temporal bone. Most cases of mucormycosis with skull base osteomyelitis that have been reported thus far have been sinonasal, orbital, or deep facial soft-tissue infections. Most cases of skull base osteomyelitis secondary to ear infections result from malignant otitis externa and are pseudomonal or candidal in origin. (7) Therefore, the unusual presentation in the case described herein posed a bit of a diagnostic puzzle. The persistent pain and ear discharge, coupled with the positive culture report for the fungus, is what clinched the diagnosis. Our patient was immunocompromised by his existing squamous cell carcinoma. We must emphasize that a search for a primary malignancy in the temporal bone should be actively undertaken in similar cases of skull base osteomyelitis with mucormycosis if all other causes of immunocompromise have been ruled out.

Recognition of mucormycosis, a potentially fatal infection, requires a high index of suspicion and knowledge of its atypical clinical and radiologic features.

References

(1.) De Pauw BE, Meunier F. The challenge of invasive fungal infection. Chemotherapy 1999;45(suppl 1):1-14.

(2.) Chan LL, Singh S, Jones D, et al. Imaging of mucormycosis skull base osteomyelitis. AJNR Am J Neuroradiol 2000;21:828-31.

(3.) Alleyne CH Jr., Vishteh AG, Spetzler RF, Detwiler PW. Long-term survival of a patient with invasive cranial base rhinocerebral mucormycosis treated with combined endovascular, surgical, and medical therapies: Case report. Neurosurgery 1999;45:1461-3.

(4.) Dupont B. [Choice and use of antifungal drugs]. Rev Prat 2001;51:752-7.

(5.) Hoffman HL, Ernst EJ, Klepser ME. Novel triazole antifungal agents. Expert Opin Investig Drugs 2000;9:593-605.

(6.) Kontoyiannis DP, Mantadakis E, Samonis G. Systemic mycoses in the immunocompromised host: An update in antifungal therapy. J Hosp Infect 2003;53:243-58.

(7.) Magliulo G, Varacalli S, Ciofalo A. Osteomyelitis of the skull base with atypical onset and evolution. Ann Otol Rhinol Laryngol 2000;109:326-30.

From the Department of ENT (Dr. Safaya and Dr. Batra) and the Department of Microbiology (Dr. Capoor), Safdarjung Hospital, New Delhi.

Reprint requests: Dr. Anil Safaya, PO Box 391, PC 516 Ibri, Sultanate of Oman. Fax: [phone]; e-mail: [e-mail]

Anil Safaya, MS; Kadambari Batra, DLO, DNB; Malini Capoor, MD