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Arch Ophthalmol. 2004;122:290-293.

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon malignancy of the nasal and paranasal sinuses. First recognized by Frierson et al¹ in 1986 as a distinct clinical and pathologic entity, it was recently classified as a large cell subtype of poorly differentiated neuroendocrine carcinoma by Mills.² Common initial symptoms include nasal obstruction, epistaxis, and facial pain.³ Late-stage SNUC may exhibit an orbital mass, causing proptosis, diplopia, and visual loss. Orbital invasion occurs in 59% of nasal and paranasal malignant tumors, occasionally demonstrating dental symptoms.⁴ We report a case of SNUC in a patient with recurrent dacryocystitis and epiphora.

Report of a Case.
A 71-year-old Chinese woman was first seen in April 1999. Her chief complaints were sudden onset of swelling and pain over the right medial canthal area for 1 week. Her medical history was remarkable for recurrent dacryocystitis with tearing and discharge. The problem had been waxing and waning for 1 year. There was no nasal bleeding or congestion. Her symptoms were resolved with oral antibiotics each time. An examination revealed a tender swelling at the right medial canthal region. There was no regurgitation from the punctum on massaging. The clinical diagnosis was dacryocystitis secondary to lacrimal drainage obstruction. Incision and drainage were offered for infection control and specimen culture, but she preferred treatment with antibiotics. Within 1 week, the inflammation subsided. Plain x-ray films of the skull and sinuses were unremarkable. A distal block was confirmed during syringing and probing of the lower canaliculus.

An endoscopic examination revealed no intranasal mass. Endonasal dacryocystorhinostomy was performed, and the osteotomy was created by bone punch. No lesions were found in the lacrimal sac. To minimize postoperative fibrosis, 0.4 mg/mL of mitomycin C was applied around the osteotomy for 5 minutes. A silicone tube was inserted, linking the sac to the nasal cavity.

Two weeks after the operation, extensive granulation tissue was found in the right nasal cavity and immediately removed. The patient was instructed to clean the nasal cavity daily with isotonic sodium chloride solution. Nine weeks after the operation, a 2 x 1-cm mass was noticed at the medial canthal area (Figure 1). The dacryocystorhinostomy site was blocked. Computed tomography revealed a large mass in the lacrimal sac, extending from the medial orbit and the nasal cavity through the osteotomy (Figure 2). An incisional biopsy from the right nasal mass was performed, and a 3 x 5 x 2-mm specimen of firm, reddish tissue was submitted for histopathologic evaluation. Microscopic examination revealed 2 large, well-defined, irregular round lobules surrounded by fibroinflammatory connective tissue. The tumor was composed of solid sheets of large round and polygonal cells with hyperchromatic nuclei and prominent nucleoli (Figure 3). Many cells had vacuolated cytoplasm and periodic acid-Schiff–positive cytoplasmic granules. A central area of necrosis was present in one of the lobules (Figure 4). One mitotic figure was present in 40 high-power fields. There was moderate polymorphonuclear infiltration. No vascular invasion was observed. Special stains for mucin were negative. Immunohistochemical staining showed a positive epithelial marker for cytokeratin (AE1/ AE3) (Figure 5), but negative markers for leukocyte common antigen (lymphoid), S100 protein (melanocytic), desmin (muscle), and neuron-specific enolase (neuroendocrine). The section stained for HMB45 had no tumor present. In situ hybridization for Epstein-Barr virus–encoded RNAs was negative. The pathologic diagnosis of SNUC was confirmed through consultation with William R. Green, Eye Pathology Laboratory, Johns Hopkins Hospital (Baltimore, Md).

View larger version (97K): [in this window] [in a new window] Figure 1. A firm mass in the right medial canthal area.

View larger version (53K): [in this window] [in a new window] Figure 2. Coronal computed tomographic scan shows a large mass in the area of the right lacrimal sac, displacing the globe laterally. The mass extends from the nasal cavity through the osteotomy site.

View larger version (200K): [in this window] [in a new window] Figure 3. Two well-defined irregular round tumor lobules contain solid sheets of large round and polygonal cells with hyperchromatic nuclei and prominent nucleoli (hematoxylin-eosin, original magnification x10).

View larger version (175K): [in this window] [in a new window] Figure 4. Central necrosis and tumor cells with vacuolated cytoplasm (hematoxylin-eosin, original magnification x40).

View larger version (123K): [in this window] [in a new window] Figure 5. Positive immunohistochemical stain for cytokeratin AE1/AE3 epithelial marker (original magnification x40).

Both systemic workup for disseminated malignancy and the serum immunoglobulin A titer for Epstein-Barr virus viral capsid antigen yielded negative results. The patient refused radical surgery. She was treated with palliative radiotherapy and chemotherapy. At the 9-month follow-up, the size of the tumor appeared to be stable, with no evidence of distant metastasis.

Comment.
Sinonasal undifferentiated carcinoma is a distinctive and highly aggressive tumor, arising from the schneiderian epithelium of the nasal and paranasal sinuses.^{1, 3} The tumor is often undiagnosed, owing to the limitation of the exact clinical course and histologic features. Sinonasal undifferentiated carcinoma is not well documented.² Common symptoms are facial pain, nasal obstruction, and epistaxis. Sharara et al⁴ reported an orbital invasion in 3 patients with SNUC; 2 of these patients were initially evaluated for dental symptoms. The correct diagnosis is usually made at a late stage, when the orbital mass begins causing proptosis, diplopia, and visual loss.

Microscopically, the tumor cells are small, with high nuclear-cytoplasmic ratios and numerous mitoses. These cells form nests, trabeculae, or sheets, and show no rosette formation. Vascular invasion and necrosis are commonly found.^{1, 4} In our case, the tumor was composed of large round and polygonal cells that appeared to belong in the large cell subtype of the poorly differentiated neuroendocrine carcinoma group I neuroectodermal tumor described by Mills.² Both SNUC and sinonasal neuroendocrine carcinoma can exhibit histologic features similar to blue round cell tumors.⁵ Immunohistochemical staining differentiates SNUC from sinonasal neuroendocrine carcinoma and esthesioneuroblastoma. Sinonasal undifferentiated carcinoma usually expresses cytokeratins and epithelial membrane antigens. S100 and neuron-specific enolase stains are usually negative.⁴ The positive staining for cytokeratins in our case suggests the epithelial origin.

The treatment requires a combination of radical surgery, irradiation, and chemotherapy.⁶ Computed tomography is indicated to rule out tumor invasion into the skull base, orbit, and pterygo-palatine fossa. Magnetic resonance imaging is useful to delineate between tumor and normal tissue and to indicate areas of residual or recurrent disease at follow-up.⁷

Malignant tumors that cause nasolacrimal duct obstruction (NLDO) are rare. No malignancies were found in a recent report of 166 patients with primary acquired NLDO.⁸ Preoperative computed tomographic imaging was not performed because our case appeared to be a typical NLDO with secondary infection. Postoperative computed tomographic imaging revealed no lesion in the maxillary and paranasal sinuses except for a mass in the lacrimal sac (Figure 2). This case could represent early SNUC arising in the anterior nasal cavity without extensive nasal or sinus extensions. Given the lack of bloody tears and the presence of a distal nasolacrimal block, a lacrimal sac tumor is unlikely. The correct diagnosis was made after dacryocystorhinostomy, when the tumor extended into the lacrimal sac from the nasal cavity through the osteotomy site. This case illustrates that malignancy should always be considered in NLDO.

The authors have no relevant financial interest in this article.

AUTHOR INFORMATION

Benedict C. C. Liang, FRCS; Yuk-Ping Chau, MB, BS; Dennis S. C. Lam, FRCS, FRCOphth; Nongnart R. Chan, MD
Hong Kong

Corresponding author and reprints: Nongnart R. Chan, MD, Eye Pathology Laboratory, Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong Eye Hospital, 147K Argyle St, Kowloon, Hong Kong (e-mail: nongnart28{at}hotmail.com).

REFERENCES
1. Frierson HF, Mills SE, Fechner RE, et al. Sinonasal undifferentiated carcinoma: an aggressive neoplasm derived from schneiderian epithelium and distinct from olfactory neuroblastoma. Am J Surg Pathol. 1986;10:771-779. FULL TEXT | PUBMED 2. Mills SE. Neuroectodermal neoplasms of the head and neck with emphasis on neuroendocrine carcinomas. Mod Pathol. 2002;15:264-278. 3. Levine PA, Frierson HF Jr, Stewart FM, Mills SE, Fechner RE, Cantrell RW. Sinonasal undifferentiated carcinoma: a distinctive and highly aggressive neoplasm. Laryngoscope. 1987;97:905-908. PUBMED 4. Sharara N, Muller S, Olson J, Grist WJ, Grossniklaus HE. Sinonasal undifferentiated carcinoma with orbital invasion. Ophthal Plast Reconstr Surg. 2001;17:288-292. PUBMED 5. Smith SR, Som P, Fahmy A, et al. A clinicopathological study of sinonasal neuroendocrine carcinoma and sinonasal undifferentiated carcinoma. Laryngoscope. 2000;110:1617-1622. FULL TEXT | PUBMED 6. Righi PD, Francis F, Bernard S, et al. Sinonasal undifferentiated carcinoma: a 10-year experience. Am J Otolaryngol. 1996;17:167-171. PUBMED 7. Lloyd G, Lund VJ, Howard D, et al. Optimum imaging for sinonasal malignancy. J Laryngol Otol. 2000;114:557-562. FULL TEXT | PUBMED 8. Lee-Wing MW, Ashenhurst ME. Clinicopathologic analysis of 166 patients with primary acquired nasolacrimal duct obstruction. Ophthalmology. 2001;108:2038-2040. FULL TEXT | ISI | PUBMED

SECTION EDITOR: W. RICHARD GREEN, MD

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