Unenhanced T1 coronal image (Fig. 3A) again shows the poorly defined and diffuse orbital mass. There has been interval worsening of the maxillary sinus opacification since the CT. This image is an excellent example of the value of the precontrast images, as the orbital mass is clearly seen against the high signal intensity of intraconal fat. After intravenous contrast, the T1 image with fat saturation shows robust enhancement in the mass (Fig. 3B). Note that the inferior and lateral rectus muscles cannot be differentiated from the lesion, implying invasion and probable inflammation of the muscle. The lacrimal gland remains normal and symmetric compared with the contralateral gland. Enhancement in the superior ophthalmic vein is normal. The maxillary sinus contents do not enhance, which likely implies that the sinus is filled with benign fluid. Figure 3C, obtained slightly posterior to Figure 3B, shows enhancement in the pterygomaxillary fissure. The process is diffuse, not discrete, and is now extra-orbital.
The MRI report described a “large, enhancing, ill-defined mass arising from the inferior rectus muscle … invades right maxillary and right ethmoid sinuses … abuts posterior wall the globe and inferior optical nerve sheath … most likely represents rhabdomyosarcoma.” Because of concern for a malignancy, we performed a right anterior orbitotomy at which time we identified a firm, white orbital mass that appeared to extend through the orbital floor. A biopsy of the lesion was performed, with frozen sections interpreted as a “moderately cellular spindle cell lesion with mixed inflammatory infiltrate.”
The images do not show a discrete mass but rather a process, that is diffuse, both intraconal and extraconal, and now in the extra-orbital pterygomaxillary fissure. The maxillary sinus disease is likely related, but because it does not enhance, it probably is fluid and not part of the mass.
The patient recovered uneventfully and was discharged home. The pediatric oncology service was contacted about meeting the patient once final pathology was known.
On postoperative day 3, the patient's parents reported increased swelling and chemosis around the child's right eye. On the same day, we received the pathology report from the initial biopsy.
Histologic sections show an active inflammatory process with extensive necrosis and a reactive spindle cell response (Figs. 4A, 4B). Pockets of chronic inflammatory cells are intermingled with necrobiotic material and a dense fibroblastic and collagenous response. The inflammatory infiltrate is composed predominantly of lymphocytes and plasma cells with only a vague granulomatous appearance. There are no well-formed granulomas. Special stains for fungus (Gomori methenamine silver) reveal fungal hyphae intermixed within the inflammatory infiltrates (Figs. 4C, 4D). The morphology is most consistent with Aspergillus species. or zygomycosis, but definitive speciation is not possible based on histologic examination.
Permanent sections were read as showing a fungal process. Accordingly, we contacted the family and had them bring the patient back to the hospital immediately so that she could be admitted for surgical debulking. At the time of surgery, the bulk of the mass was removed. The floor of the maxillary sinus was intact except for a focal area of dehiscence.
Histologic sections and special stains obtained on the specimen from the debulking procedure showed findings identical with those from the first specimen and were consistent with an active, necrobiotic fungal infectious disease.
At surgery, a catheter was placed in the orbit for direct orbital and sinus irrigation with antifungal medication. Amphotericin B was given intravenously and intraorbitally until catheter was dislodged on postoperative day 2. Immunologic evaluation was performed that revealed no evidence of systemic immune compromise. Posaconazole was added, and the patient was discharged home 10 days after the surgery, once it was clear that her disease was not clinically progressing. She subsequently received intravenous amphotericin B as an outpatient for 3 months and oral posaconazole for 15 months, during which time her examination normalized and imaging evidence of disease resolved (Fig. 5). Cultures from the surgical specimens never grew any organism. The patient's examination normalized and follow-up MRI showed gradual resolution of her orbital infection.
Contrast-enhanced T1 coronal MRI shows that the infectious process has decreased in extent but is still present (Fig. 5). Imaging findings, especially in the setting of infection, often lag behind the clinical examination. In light of the improvement in the patient's physical examination, persistent disease should not be interpreted as treatment failure.
Final Pathologic Diagnosis:
Invasive fungal orbital cellulitis in an immunocompetent child.
Orbital zygomycosis in immunocompetent patients, especially children, is a rare cause of an orbital mass mimicking cellulitis (1,2). Management usually includes surgical debulking, long-term antifungal medication, and evaluation for immune suppression dysfunction (1,3). Emerging organisms, such as Apophysomyces elegans, may make these presentations more common in the future. These cases typically are associated with some form of traumatic inoculation. In others, the mechanism of disease may not be evident, as in our case (4,5). Although our patient's family noted that she enjoyed playing outside and particularly in the dirt, they could not recall an episode where she had any sort of injury that could have caused her infection.
Invasive fungal disease was one of our diagnostic considerations but so were other orbital inflammatory disorders, including Langerhans cell histiocytosis and idiopathic orbital inflammatory disease, (orbital pseudotumor). Our patient's family had been told that she had an orbital malignancy by the first orbital surgeon; the first MRI report stated that she likely had rhabdomyosarcoma, and the intraoperative frozen section pathology was inconclusive. The child had no signs or symptoms of systemic infection and the orbital mass appeared solid with no evidence of purulence or tissue necrosis. Therefore, treatment for fungal disease was not initiated after the first surgery and cultures were not obtained. Once the final pathologic diagnosis was known, we chose to debulk the lesion and institute intraorbital irrigation and systemic treatment with antifungal medication. Duration of treatment was determined in consultation with the infectious disease specialists whose recommendations were guided by clinical and imaging findings in her orbit. Once she showed no evidence of residual disease, all antifungal medications were discontinued and she was discharged from ongoing care.
The patient's fungal cultures never grew any organism. The spectrum of invasive fungi typically includes zygomycoses, such as Mucor and Rhizopus species as well as Aspergillus species. It has been suggested that the incidence of these infections in immunocompetent patients may be increasing (4). Such infections have drawn the attention of the National Institute of Allergy and Infectious Disease, and a clinical trial (NCT01386437) currently is under way to identify genetic factors that may predispose patients to these types of infections even when no primary immune deficiency has been identified with conventional testing (6). The study proposes to use information gathered from patients to help gain new insights into the pathogenesis of these infections in immunocompetent hosts and to identify potential targets for novel therapies. It is critical that the clinician consider the possibility of fungal disease in any patient who develops an orbital process, regardless of their immune status.
1. Margo C, Rabinowicz I, Kwon-Chung KJ, Zimmerman LE. Subacute zygomycosis of the orbit. Arch Ophthalmol. 1983;101:1580–1585.
2. Seiff SR, Choo PH, Carter SR. Role of local amphotericin B therapy for sino-orbital fungal infections. Ophthal Plast Reconstr Surg. 1999;15:28–31.
3. Rutar T, Cockerham KP. Periorbital zygomycosis (mucormycosis) treated with posaconazole. Am J Ophthalmol. 2006;142:187–188.
4. Fairley C, Sullivan TJ, Bartley P, Allworth T, Lewandowski R. Survival after rhino-orbital-cerebral mucormycosis in an immunocompetent patient. Ophthalmology. 2000;107:555–558.
© 2014 by North American Neuro-Ophthalmology Society
5. Liang KP, Tleyjeh IM, Wilson WR, Roberts GD, Temesgen Z. Rhino-orbitocerebral mucormycosis caused by apophysomyces elegans. J Clin Microbiol. 2006;44:892–898.