Woman presents with unilateral lid redness and swelling

Lateral displacement of the right globe and 3 mm of proptosis in the right eye were seen on examination. Sinusitis and nasal congestion were also present.

Priti Batta

Namrata Nandakumar

A 48-year-old woman with a history of developmental delay and chronic hearing loss was referred by a general ophthalmologist for progressive periorbital erythema and edema with concurrent sinusitis.

Six weeks prior, the patient presented to her primary care physician with conjunctival chemosis and mild eyelid edema, and she was given a presumptive diagnosis of conjunctivitis. Her symptoms resolved within 5 days. Three weeks later, the patient returned to her primary care physician with progressive periorbital erythema in the right eye and was diagnosed with acute preseptal cellulitis. This episode resolved following a 7-day course of oral linezolid. However, she developed fluctuating symptoms of nasal congestion, and about 3 weeks later, the patient suffered another episode of periorbital erythema and edema with right facial swelling, accompanied by nasal congestion and sinusitis with malodorous rhinorrhea. Despite 4 days of oral clindamycin, the patient’s symptoms continued to worsen, and she was referred to our institution for evaluation.

On examination, the patient demonstrated moderate swelling in the right malar region lateral to the nasal bone (Figure 1). Marked, tender periorbital edema in the right upper and lower lids was present without palpable masses or fluctuance. Lateral displacement of the right globe and 3 mm of proptosis in the right eye were observed on Hertel exophthalmometry. Ocular motility was full, without resistance or pain on retropulsion of the globes. Visual acuity testing was limited secondary to the patient’s developmental delay, but she was able to fixate and follow with each eye. Diplopia and color vision could not be assessed. IOPs were normal. Slit lamp examination was unremarkable, including normal-appearing optic nerve heads without swelling or pallor.

Figure 1. External photograph revealing periorbital erythema and edema in the right eye. Images: Monson BK, Kapadia M

What is your diagnosis?

Erythema, edema and proptosis with concurrent sinusitis

The differential diagnosis in this patient includes inflammatory, infectious and neoplastic processes. Inflammatory processes include idiopathic orbital inflammation, Wegener’s granulomatosis and sarcoidosis. Infectious processes include sinusitis with orbital cellulitis. Neoplastic processes include rhabdomyosarcoma, nasopharyngeal carcinoma, lymphoma and mucocele.

Differential diagnosis

Orbital cellulitis is a sight-threatening emergency, and serious orbital signs may include unilateral proptosis, anesthesia of the area innervated by the ophthalmic and maxillary branches of the trigeminal nerve, impaired ocular rotations, ocular pain aggravated by ocular rotation, increased IOP, decreased visual acuity and afferent pupillary defect. Sinusitis is an important cause of orbital cellulitis, with Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus pyogenes as the most common inciting organisms. Recurring orbital cellulitis may be associated with recurrent sinusitis.

Idiopathic orbital inflammation typically presents as recurrent episodes of unilateral acute orbital swelling, chemosis and proptosis, often with ophthalmoplegia and diplopia. Inflammation within the orbit may include myositis, scleritis, tendonitis and associated dacryoadenitis. However, painful onset is characteristic, and the paranasal sinuses are typically normal.

Sarcoidosis is a disease that causes noncaseating granulomatous inflammation. Orbital sarcoidosis can present with proptosis and an orbital mass, and it may also involve the eyelid, eye or lacrimal gland. Patients often have systemic involvement with respiratory symptoms due to hilar and mediastinal lymphadenopathy.

Wegener’s granulomatosis most often presents with respiratory symptoms such as rhinitis, nosebleeds and sinus pain. Systemic manifestations can be fatal if left untreated. Like sarcoidosis, orbital manifestations include proptosis and an orbital mass.

Orbital lymphomas that originate in the orbit comprise the most common malignant orbital tumor, representing 55% of cases in adults. Most are low-grade mucosa-associated lymphoid tissue lymphomas that tend to exhibit an indolent course and remain localized to the mucosal tissues of the orbit. They typically do not cause bony destruction or invade the sinuses. Natural killer T-cell (NK/T-cell) lymphoma is a rare extranodal lymphoma comprising only 3% of all the primary ocular lymphoproliferative lesions in reported cases. It typically originates in the upper respiratory and digestive tracts, including the sinuses. This disease behaves aggressively and may cause bony destruction with invasion into the orbit.

Diagnosis and work-up

A CT scan of the orbits and paranasal sinuses showed a 9-cm soft-tissue mass completely occluding the right nasal cavity, causing septal deviation to the left. The mass extended through the medial wall of the right orbit and anteriorly behind the infraorbital rim, displacing the globe laterally (Figure 2).

Figure 2. Coronal CT image demonstrating a large nasal mass with septal deviation, bony destruction of the medial orbital wall and medial invasion of the right orbit.

The patient was tested for classical antineutrophil cytoplasmic antibodies (C-ANCA); results were negative, making the diagnosis of Wegener’s granulomatosis less likely. Multiple tissue biopsies were taken from both the nasal cavity and orbit. Morphologic analysis revealed atypical lymphoid infiltrate in association with extensive necrosis, with lymphocytes of intermediate size, with irregular nuclear contour and ample pale cytoplasm, and admixed histiocytes and eosinophils.

Flow cytometric analysis demonstrated DC2-positive T-cells constituting 90% of the mass, with aberrant CD5 and CD7, as well as CD138 positive plasma cells polytypic for kappa and lambda. This confirmed a diagnosis of NK/T-cell lymphoma. Epstein-Barr virus DNA was positive.

Bone marrow biopsy did not reveal evidence of lymphoma infiltration. The patient underwent six cycles of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) alternating with methotrexate and Ara-C (cytarabine) chemotherapy, as well as 20 sessions of radiation therapy. Repeat CT scans demonstrated a marked reduction in the size and degree of enhancement of the primary nasopharyngeal lesion, and the patient has been without recurrence of sino-orbital symptoms for 9 months.

Discussion

NK/T-cell lymphoma frequently originates in the sinonasal cavity and may invade into the orbits. It accounts for less than 2% of all lymphomas and has a median age at presentation of 50 years. It is more common in men and in residents of Asia, Mexico, and Central and South America. There is a strong association with Epstein-Barr virus infection.

NK/T-cell lymphoma is an example of a rare, potentially fatal condition that can mimic common benign disorders, and an early diagnosis is often a challenge. Sinusitis and allergic rhinitis symptoms are some of the most common presenting complaints to physicians. NK/T-cell lymphoma should be considered in cases of orbital cellulitis or sinusitis that fail to respond to traditional management.

Differentiating NK/T-cell lymphoma from Wegener’s granulomatosis can be a particular challenge as both entities can present with sino-orbital lesions. Histopathologically, NK/T-cell lymphoma is typified by atypical pleomorphic lymphoid infiltrate with immunophenotyping consistent with NK/T-cell lymphoma. A characteristic admixture of these cells with widespread coagulative necrosis, heavy inflammatory cells including small lymphocytes, plasma cells, histiocytes and eosinophils can mimic an inflammatory process like Wegener’s, making the diagnosis difficult.

Further, while C-ANCA has 98% specificity by enzyme-linked immunosorbent assay in the diagnosis of Wegner’s granulomatosis, the sensitivity ranges from 96% in active generalized disease to 67% in patients with only regional disease, underscoring the importance of tissue biopsies.

Our patient was initially presumed to have orbital cellulitis secondary to pansinusitis. Improvement of periorbital erythema and edema after antibiotic treatment further suggested sino-orbital infection. However, recurrence of her symptoms and development of proptosis implied a concomitant underlying disease process and warranted further work-up.

This case describes a patient with paranasal NK/T-cell lymphoma invading into the orbit, mimicking orbital cellulitis. The case underscores the importance of considering alternative diagnoses when patients with orbital cellulitis do not respond to antibiotic treatment.

References:

• Abu-Zeitoon RG, Abu-Shahin F, Smalligan RD, Hamati A. Sometimes it’s not just sinusitis: nasal type natural killer/T-cell lymphoma. South Med J. 2009;102(8):873-874.
• Ayadi L, Makni S, Toumi N, et al. Aggressive nasal-type natural killer/T-cell lymphoma associated with Epstein Barr virus presenting as testicular tumor. Tunis Med. 2010;88(3):196-198.
• Charton J, Witherspoon SR, Itani K, Jones FR, Marple B, Morse B. Natural killer/T-cell lymphoma masquerading as orbital cellulitis. Ophthal Plast Reconstr Surg. 2008;24(2):143-145.
• Cimino L, Chan CC, Shen D, et al. Ocular involvement in nasal natural killer T-cell lymphoma. Int Ophthalmol. 2009;29(4):275-279.
• Hayek BR, Sitole S, Andreoli M, Banich A, Ahmad AZ. Bilateral eyelid edema and orbital cellulitis associated with Pott’s puffy tumor. Ophthal Plast Reconstr Surg. 2007;23(2):163-165.
• Isobe Y, Aritaka N, Sasaki M, Oshimi K, Sugimoto K. Spontaneous regression of natural killer cell lymphoma. J Clin Pathol. 2009;62(7):647-650.
• Nakajima A, Abe T, Takagi T, et al. Two cases of malignant lymphoma complicated by hemophagocytosis resembling orbital cellulitis. Jpn J Ophthalmol. 1997;41(3):186-191.
• Qin W, Yin Z, Madge SN. Acute presentation of nasal-type natural killer/T-cell lymphoma of the orbit. Eur J Ophthalmol. 2009;19(4):679-682.
• Rootman J, Roth AM, Crawford JB, Fox LP, Patel S. Extensive squamous cell carcinoma of the conjunctiva presenting as orbital cellulitis: the hermit syndrome. Can J Ophthalmol. 1987;22(1):40-44.
• Salam A, Saldana M, Zaman N. Orbital cellulitis or lymphoma? A diagnostic challenge. J Laryngol Otol. 2005;119(9):740-742.
• Suzuki R, Suzumiya J, Yamaguchi M, et al; NK-cell Tumor Study Group. Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type. Ann Oncol. 2010;21(5):1032-1040.

• Bryan K. Monson, MD, and Mitesh Kapadia, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.

• Edited by Priti Batta, MD, and Namrata Nandakumar, MD. Drs. Batta and Nandakumar can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.