Sinonasal undifferentiated carcinoma (SNUC) is an uncommon malignancyof 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 differentiatedneuroendocrine carcinoma by Mills.2 Commoninitial symptoms include nasal obstruction, epistaxis, and facial pain.3 Late-stage SNUC may exhibit an orbital mass, causingproptosis, diplopia, and visual loss. Orbital invasion occurs in 59% of nasaland paranasal malignant tumors, occasionally demonstrating dental symptoms.4 We report a case of SNUC in a patient with recurrentdacryocystitis and epiphora.
A 71-year-old Chinese woman was first seen in April 1999. Her chiefcomplaints were sudden onset of swelling and pain over the right medial canthalarea for 1 week. Her medical history was remarkable for recurrent dacryocystitiswith tearing and discharge. The problem had been waxing and waning for 1 year.There was no nasal bleeding or congestion. Her symptoms were resolved withoral antibiotics each time. An examination revealed a tender swelling at theright medial canthal region. There was no regurgitation from the punctum onmassaging. The clinical diagnosis was dacryocystitis secondary to lacrimaldrainage obstruction. Incision and drainage were offered for infection controland specimen culture, but she preferred treatment with antibiotics. Within1 week, the inflammation subsided. Plain x-ray films of the skull and sinuseswere unremarkable. A distal block was confirmed during syringing and probingof the lower canaliculus.
An endoscopic examination revealed no intranasal mass. Endonasal dacryocystorhinostomywas performed, and the osteotomy was created by bone punch. No lesions werefound in the lacrimal sac. To minimize postoperative fibrosis, 0.4 mg/mL ofmitomycin C was applied around the osteotomy for 5 minutes. A silicone tubewas inserted, linking the sac to the nasal cavity.
Two weeks after the operation, extensive granulation tissue was foundin the right nasal cavity and immediately removed. The patient was instructedto clean the nasal cavity daily with isotonic sodium chloride solution. Nineweeks after the operation, a 2 × 1-cm mass was noticed at the medialcanthal area (Figure 1). The dacryocystorhinostomysite was blocked. Computed tomography revealed a large mass in the lacrimalsac, extending from the medial orbit and the nasal cavity through the osteotomy(Figure 2). An incisional biopsyfrom the right nasal mass was performed, and a 3 × 5 × 2-mm specimenof firm, reddish tissue was submitted for histopathologic evaluation. Microscopicexamination revealed 2 large, well-defined, irregular round lobules surroundedby fibroinflammatory connective tissue. The tumor was composed of solid sheetsof large round and polygonal cells with hyperchromatic nuclei and prominentnucleoli (Figure 3). Many cellshad vacuolated cytoplasm and periodic acid-Schiff–positive cytoplasmicgranules. A central area of necrosis was present in one of the lobules (Figure 4). One mitotic figure was presentin 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 negativemarkers for leukocyte common antigen (lymphoid), S100 protein (melanocytic),desmin (muscle), and neuron-specific enolase (neuroendocrine). The sectionstained for HMB45 had no tumor present. In situ hybridization for Epstein-Barrvirus–encoded RNAs was negative. The pathologic diagnosis of SNUC wasconfirmed through consultation with William R. Green, Eye Pathology Laboratory,Johns Hopkins Hospital (Baltimore, Md).
A firm mass in the right medialcanthal area.
Coronal computed tomographic scanshows a large mass in the area of the right lacrimal sac, displacing the globelaterally. The mass extends from the nasal cavity through the osteotomy site.
Two well-defined irregular roundtumor lobules contain solid sheets of large round and polygonal cells withhyperchromatic nuclei and prominent nucleoli (hematoxylin-eosin, originalmagnification ×10).
Central necrosis and tumor cellswith vacuolated cytoplasm (hematoxylin-eosin, original magnification ×40).
Positive immunohistochemical stainfor cytokeratin AE1/AE3 epithelial marker (original magnification ×40).
Both systemic workup for disseminated malignancy and the serum immunoglobulinA titer for Epstein-Barr virus viral capsid antigen yielded negative results.The patient refused radical surgery. She was treated with palliative radiotherapyand chemotherapy. At the 9-month follow-up, the size of the tumor appearedto be stable, with no evidence of distant metastasis.
Sinonasal undifferentiated carcinoma is a distinctive and highly aggressivetumor, arising from the schneiderian epithelium of the nasal and paranasalsinuses.1,3 The tumor isoften undiagnosed, owing to the limitation of the exact clinical course andhistologic features. Sinonasal undifferentiated carcinoma is not well documented.2 Common symptoms are facial pain, nasal obstruction,and epistaxis. Sharara et al4 reported anorbital invasion in 3 patients with SNUC; 2 of these patients were initiallyevaluated for dental symptoms. The correct diagnosis is usually made at alate stage, when the orbital mass begins causing proptosis, diplopia, andvisual loss.
Microscopically, the tumor cells are small, with high nuclear-cytoplasmicratios and numerous mitoses. These cells form nests, trabeculae, or sheets,and show no rosette formation. Vascular invasion and necrosis are commonlyfound.1,4 In our case, thetumor was composed of large round and polygonal cells that appeared to belongin the large cell subtype of the poorly differentiated neuroendocrine carcinomagroup I neuroectodermal tumor described by Mills.2 BothSNUC and sinonasal neuroendocrine carcinoma can exhibit histologic featuressimilar to blue round cell tumors.5 Immunohistochemicalstaining differentiates SNUC from sinonasal neuroendocrine carcinoma and esthesioneuroblastoma.Sinonasal undifferentiated carcinoma usually expresses cytokeratins and epithelialmembrane antigens. S100 and neuron-specific enolase stains are usually negative.4 The positive staining for cytokeratins in our casesuggests the epithelial origin.
The treatment requires a combination of radical surgery, irradiation,and chemotherapy.6 Computed tomography isindicated to rule out tumor invasion into the skull base, orbit, and pterygo-palatinefossa. Magnetic resonance imaging is useful to delineate between tumor andnormal tissue and to indicate areas of residual or recurrent disease at follow-up.7
Malignant tumors that cause nasolacrimal duct obstruction (NLDO) arerare. No malignancies were found in a recent report of 166 patients with primaryacquired NLDO.8 Preoperative computed tomographicimaging was not performed because our case appeared to be a typical NLDO withsecondary infection. Postoperative computed tomographic imaging revealed nolesion in the maxillary and paranasal sinuses except for a mass in the lacrimalsac (Figure 2). This case couldrepresent early SNUC arising in the anterior nasal cavity without extensivenasal or sinus extensions. Given the lack of bloody tears and the presenceof a distal nasolacrimal block, a lacrimal sac tumor is unlikely. The correctdiagnosis was made after dacryocystorhinostomy, when the tumor extended intothe lacrimal sac from the nasal cavity through the osteotomy site. This caseillustrates that malignancy should always be considered in NLDO.
The authors have no relevant financial interest in this article.
Corresponding author and reprints: Nongnart R. Chan, MD, Eye PathologyLaboratory, Department of Ophthalmology and Visual Sciences, Chinese Universityof Hong Kong, Hong Kong Eye Hospital, 147K Argyle St, Kowloon, Hong Kong (e-mail:firstname.lastname@example.org).
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