Abstract
Continuous therapy with cytotoxic drugs suppresses humoral immune function and may result in local infection. We present a case of orbital apex syndrome caused by Aspergillus infection during chemotherapy for metastatic colorectal cancer. A 74-year-old man with colorectal liver metastases under long-term continuous systemic chemotherapy presented with painful, progressive orbital apex syndrome. Magnetic resonance imaging disclosed a small enhancing lesion around the right ethmoid sinus. We initially diagnosed colorectal cancer metastasis and he underwent biopsy via the endoscopic endonasal transethmoid approach. However, pathological examination of the cultured specimen revealed Aspergillus fumigatus. The patient was treated with voriconazole and the orbital apex syndrome resolved after 1 month. Orbital aspergillosis is a life-threatening disease and should be listed as a differential diagnosis of uncommon local infections during continuous chemotherapy.
Dramatic improvements have been made in the treatment of metastatic colorectal cancer (mCRC) over the past decade (1). Long-term survival can be achieved in a minority of patients with mCRC by adopting a multimodal treatment approach, which can increase the median overall survival to approximately 30 months, compared to 4-6 months with best supportive care alone (2, 3). However, long-term systemic chemotherapy can cause adverse events. Continuous therapy with cytotoxic drugs appears to suppress humoral immune function, while leaving cell-mediated immunity relatively intact. The resulting immunocompromised state means that febrile neutropenia remains a common life-threatening complication of cancer chemotherapy. In addition, local infections such as abscesses or pneumonia may also occur uncommonly during continuous cytotoxic chemotherapy.
Orbital apex syndrome has been described as a collection of cranial nerve deficits associated with a mass lesion near the apex of the orbit of the eye (4). It may be caused by inflammatory, infectious, neoplastic, iatrogenic, or vascular processes. Herein, we report a rare case of orbital apex syndrome caused by invasive aspergillosis during systemic chemotherapy for mCRC. This case was considered in the differential diagnosis of orbital metastasis from colorectal cancer.
Case Report
A 74-year-old man who had undergone systemic chemotherapy for mCRC for 4 years at our Hospital experienced a sudden onset of reduced vision and right-sided periorbital pain in June 2011. The periorbital pain worsened and he presented to his home doctor. On examination, his eye movements were normal. However, orbit magnetic resonance imaging (MRI) disclosed a small enhancing lesion near the right orbital apex. He was diagnosed with ischemic optic neuropathy and prescribed anti-histamine eye drops. After a few days, the periorbital pain worsened and he visited our hospital. On examination, he had ocular motility disorder and ptosis of his right eye, with abnormal findings of cerebral nerve of II-IV. MRI revealed an orbital mass about 2 cm in diameter, with an enhanced lining (Figure 1A and B). Brain computed tomographic (CT) scan revealed bony erosion around the right ethmoid sinus (Figure 1C). We made a diagnosis of orbital apex syndrome caused by invasive aspergillosis or metastasis of CRC. We performed a biopsy using a transnasal approach. Histology of the biopsy specimen showed no malignancy, but culture revealed Aspergillus fumigatus (Figure 2). Following a definitive diagnosis of invasive aspergillosis, the patient was treated with voriconazole. His symptoms improved immediately, and subsequent MRI showed that the orbital mass had disappeared. However, he was unable to resume treatment for mCRC due to poor performance status and died 2 months later.
Magnetic resonance imaging (MRI) and computed tomography of the orbit before treatment. A: T1-weighted axial MRI showing a right-sided orbital apex mass (arrow). B: T1-weighted coronal MRI post-gadolinium enhancement. C: Coronal computed tomographic scan of the orbits demonstrating a mass in the right orbit that obliterates medial structures of the orbit with bony erosion.
Histology of the lesion. The image shows many fungal septate hyphae. Periodic acid-Schiff stain, ×200.
Discussion
We present a patient with orbital apex syndrome caused by invasive aspergillosis as an adverse effect of systemic chemotherapy for mCRC. This case highlights two important clinical issues: continuous cytotoxic chemotherapy for mCRC can lead to orbital apex syndrome associated with Aspergillus infection, and this may resemble a metastatic lesion of colonic cancer on MRI, necessitating careful differential diagnosis.
Patients receiving systemic chemotherapy for cancer sufficient to have an adverse effect on myelopoiesis are at risk of invasive infection by colonizing bacteria or fungi. Fungal tissue invasion usually occurs in the setting of immunosuppression associated with therapy for hematological malignancies, hematopoietic cell transplantation, or solid organ transplantation. However, this case demonstrates the potential for invasive infection during long-term chemotherapy for colonic cancer. The inflammatory response to the infection may be blunted because of neutropenia (5), and therefore diagnosis of invasive infections may be significantly delayed. Localized disease often starts in the sinuses and spreads to adjacent structures through vessel walls, causing stroke and death. The prognosis of invasive sino-orbital aspergillosis in immunocompetent patients is significantly poorer than that of other forms of sinus aspergillosis (6). It is therefore necessary to remain aware of the possibility of this rare infectious disease during continuous chemotherapy.
Invasive sino-orbital aspergillosis presents like a metastatic lesion of colonic cancer on MRI and should thus be considered as a differential diagnosis (7). Orbital apex syndrome can be caused by tumors, and should thus be considered as a possible symptom of metastasis in the case of malignancy. Although biopsy is the best means of establishing a diagnosis, this may not be feasible because of the risk of bleeding complications. Noninvasive modalities, such as imaging and serum biomarkers (galactomannan and beta-D-glucan assays) are therefore suitable first steps for diagnosing invasive aspergillosis. CT and MRI are useful for diagnosing orbital invasive aspergillosis and its complications. However, imaging findings may be subtle and can include focal soft-tissue lesions, subtle focal bony erosions, focal enhancement of the sinus lining on MRI, or focal hypodense areas on CT scans (8).
Conclusion
Orbital apex syndrome caused by invasive aspergillosis can present as an adverse effect of systemic chemotherapy for mCRC, and should be considered in the differential diagnosis of CRC metastasis. It is necessary to be aware of the possibility of this rare infectious disease during continuous chemotherapy.
Footnotes
Consent
Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Competing Interests
The Authors declare that they have no competing interests.
- Received November 23, 2015.
- Revision received December 17, 2015.
- Accepted December 23, 2015.
- Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
