Unilateral Proptosis FREE

A 40-year-old man presents with left periorbital swelling and pain,which developed gradually over 2 months with no history of trauma, fever, or recent sinusitis. He has no previous medical illness and is not taking any medications. The patient denies diplopia and exposure to allergic or contact irritants. Physical examination confirms chemosis and left proptosis (Figure 1) without pulsation or bruit. The patient is neurologically intact, including normal pupillary response and extraocular movements. Laboratory studies are unremarkable, including normal complete blood cell count findings, negative blood cultures, and normal thyroid-stimulating hormone values.

See www.jama.com for online Clinical Challenge.

High-grade neuroendocrine carcinoma involving the left ethmoid and frontal sinuses.

B. Request computed tomography of the head, with contrast.

The key feature in this case is to recognize that malignancy is part of the differential diagnosis of unilateral proptosis. The first priority, after obtaining thyroid function studies, is to perform imaging to rule out a retro-orbital infiltrative process.

Although the terms proptosis and exophthalmos are generally used interchangeably, it has been suggested that exophthalmos is an endocrine-related ocular protrusion and proptosis is a nonendocrine-related condition.¹ The differential diagnosis for proptosis includes Graves disease, Wegener granulomatosis, sarcoidosis, idiopathic orbital inflammation, orbital myositis, infection, and malignancy.² Treatment for most of those conditions entails systemic immunosuppression; hence, neoplastic and infectious etiologies must first be ruled out. Thyroid ophthalmopathy, an autoimmune inflammatory orbital disease, is the most common cause of exophthalmos in adults.³ Most patients with thyroid ophthalmopathy do not require any particular treatment; nevertheless, steroids, radiation, and surgical decompression may be used in severely refractory cases to avoid potential sight-threatening complications.

Orbital soft tissues are divided into anterior and posterior compartments by the orbital septum. Orbital cellulitis is a deep soft tissue infection posterior to the orbital septum, whereas preseptal cellulitis is a superficial soft tissue infection anterior to the septum. Most cases of orbital cellulitis are secondary to direct extension of bacterial sinusitis and usually present with acute onset of blurred vision, diplopia, fever, and exophthalmos. Although patients with orbital and preseptal cellulitis may have a similar appearance, patients with preseptal cellulitis do not develop exophthalmos. Mucormycosis is an aggressive and potentially life-threatening fungal infection that must be ruled out in any immunocompromised patient presenting with orbital cellulitis.⁴ Neuroendocrine tumors are a heterogeneous group of malignancies generally divided into high-grade, intermediate-grade, and low-grade based on cytologic and histologic features, such as the Ki-67 marker of proliferative activity.⁵ According to data from the Surveillance, Epidemiology, and End Results program, the incidence of neuroendocrine tumors was 5.25 cases per 100 000 persons per year in 2004, with the most common locations being the gastrointestinal tract and lungs. Other primary locations, such as the paranasal sinuses, are rare.⁶ Systemic chemotherapy is recommended for unresectable or advanced high-grade neuroendocrine carcinomas, although response rates are modest.⁵

Computed tomography is useful for assessing the integrity of osseous structures; nevertheless, magnetic resonance imaging is a superior modality for delineating soft tissue tumors and the extent of neoplastic or infectious conditions affecting the paranasal sinuses.⁶ Imaging using contrast-enhanced computed tomography, which is superior to computed tomography without contrast for confirming intracranial pathology, would show enhancing tumor and rule out the presence of metastatic disease to the brain. Invasive orbital arteriography and venography are low-yield imaging studies in this setting but are nevertheless an essential part of the workup of orbital arteriovenous malformations.⁷ Arteriovenous malformation is a rare cause of proptosis and is usually accompanied by pulsation or bruit, which typically develops gradually, sometimes over a period of years, after history of previous trauma.⁸

In this patient, computed tomography and magnetic resonance imaging of the head showed a mass extending into the left ethmoid and frontal sinuses (Figure 2). The patient underwent sinus exploration confirming high-grade neuroendocrine carcinoma; he received chemotherapy, radiotherapy, and frontal craniotomy but later developed recurrence and is currently receiving palliative chemotherapy.