Low-grade adenocarcinoma of nasal passages

CASE REPORTS SERGE A. MARTINEZ, MD Case Report Editor

Low-grade adenocarcinoma of nasal passages THOMAS CAWTE, MD, METIN TASKIN, MD, ASHUTOSH KACKER, MD, and SAMUEL WAHL, MD, New York, New York

| t o w - g r a d e adenocarcinoma (LGA) of the sinonasal tract has been described relatively recently. It is an important tumor despite its comparative rarity, especially because it appears to be eminently curable. Successful treatment, however, requires that neither the pathologist nor the surgeon underestimates the lesion. The classification and nomenclature of this tumor are not universally agreed on. In this case report we present an L G A with unique histology, and we review the current literature and address controversies surrounding the nomenclature and histogenesis of nasal adenocarcinomas. eASE REPORT

An 83-year-old woman sought treatment for a blockage of the right nasal passage that had been present for the preceding 6 months. Examination showed a lobulated 2 x 2 cm mass arising from the septum. The mass was firm and did not bleed when touched. The overlying mncosa was intact. A biopsy was performed, and a diagnosis of LGA was made. One month later, the mass was completely excised and submitted for pathologic analysis. Tissue from the posterior margin was submitted separately. The patient's postoperative course was unremarkable. The most recent follow-up visit was 12 months after surgery, at which time she was free of recurrence. MICROSCOPY AND IMMUNOHISTOCHEMISTRY

The tumor was received in multiple fragments. Microscopically, it showed a relatively regular border and was not encapsulated. The surgical margins of resection were free of tumor. The surface epithelium was focally ulcerated, but where intact, it was of unre-

From the Departments of Pathology, (Drs. Cawte, Taskin, and Wahl) and Otolaryngology(Dr. Kacker), Lenox Hill Hospital. Reprint requests: Metin Taskin, MD, Department of Pathology, Lenox Hill Hospital, 100 East 77th St., New York, NY 10021. Otolaryngol Head Neck Surg 1997;117:116-9. Copyright © 1997 by the American Academy of OtolaryngologyHead and Neck Surgery Foundation, Inc. 0194-5998/97/$5.00 + 0 23/4/72851 i16

markable respiratory type. At one point the tumor appeared to be contiguous with this epithelium. It showed crowded small, round glands and more elongated tubular structures, both with very little intervening stroma (Fig. 1). Often the glands had a back-to-back configuration. Some glands had only a single layer of lining cells, whereas others showed what appeared to be myoepithelial cells as well. In some areas the glands were fused, giving a more solid pattern. Occasionally there were larger cystic spaces, with some papillary info!dings. Cytologically, the tumor cells showed relatively abundant, pink, nongranular cytoplasm and a low nuclear-cytoplasmic ratio. The nuclei were basally located, uniform, and bland, lacking frequent mitoses or cellular anaplasia (Fig. 2). Occasional inconspicuous eosinophilic nucleoli were seen. Immunostains for smooth muscle actin, S-100 protein (Fig. 3), and glial fibrillary acidic protein were all strongly positive in a significant proportion of cells, confirming their myoepithelial nature. The tumor cells were also uniformly positive for cytokeratin. DISCUSSION

Glandular neoplasms of the sinonasal tract as a group are far less frequent than squamous neoplasms, comprising approximately 6% of all nasal neoplasms. 1 They can be divided into "salivary-type" tumors and socalled "surface," or nonsalivary, tumors, of which latter group includes L G A and high-grade adenocarcinoma (HGA). Both L G A and H G A are to be distinguished from tumors that have the phenotype of salivary neoplasms (i.e., adenoid cystic carcinoma and pleomorphic adenoma, to name the two most commonly occurring types, plus the less c o m m o n varieties, including mucoepidermoid carcinoma and acinic cell carcinoma). For this reason we believe it is confusing to use the word salivary or salivary-type in connection with LGA. The nasal passages are predominantly lined by a respiratory type of epithelium that contains numerous seromucinous glands in the lamina propria. These seromucinous glands are direct invaginations of surface epithelium and are morphologically similar to minor

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Fig. 1. Tumor with crowded, small, round glands and more elongated tubular structures with very little intervening stroma shows continuity with the surface epithelium. (Hematoxylinphloxine-saffron stain; low power.)

Fig. 2. Nuclei of neoplastic cells are basally located, uniform, and bland, lacking frequent mitoses or cellular anaplasia. (Hematoxylin-phloxine-saffron; high power.)

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Fig. 3. Immunostain for 8-100 protein is strongly positive in a significant proportion of neoplastic cells, confirming their myoepithelial nature.

salivary glands of the oral cavity. They are not, however, considered true salivary glands, 2 because the structural subdivision of major salivary glands into acinus, intercalated, and striated ducts is not observed in nasal glands. Thus it may not be correct to make a complete analogy between salivary gland tumors and glandular tumors arising in the nasal passages. In addition to morphologic grounds, some have defended the division of glandular neoplasms into salivary-type and surface (non-salivary) on the grounds of presumed cell of origin. Thus Heffner et al. 3 in their series of LGA have cited the lack of immunostaining for actin, S-100, and glial fibrillary acidic protein and the contiguity with surface epitheliu m , which they observed in some of their cases, as evidence of surface origin. Kleinsasser, 2 on the other hand, coined the term terminal tubulus adenocarcinoma for his series of LGA on the basis of its origin (in his view) from the terminal tubulus (i.e., the seromucous gland). However, in the case that we are presenting, there was both contiguity with the surface and a prominent, immunohistochemically proven myoepithelial component. In other reports of these tumors, there is a diversity of histologic and immunohistochemical features in the sense that they may or may not show contiguity with the surface and they may or may not show a double cell layer and/or myoepithelial staining. This finding is in accordance

with the statement by Manning and Batsakis 4 that the cell of origin for glandular neoplasms is the reverse cell from either the surface epithelium, the seromucous gland, or the junction between the two. In our view, calling LGA a salivary-type tumor is unjustified because some of the tumors may genuinely arise from the surface. The basic objection to calling LGA salivary-type, however, is the one we outlined at the beginning of this discussion (i.e., that use of the term salivary-type inevitably conjures up in the pathologist's mind the traditional salivary tumors such as adenoid cystic carcinoma. Tumors of the oral cavity known as polymorphous LGA 5 and similar tumors of the bronchi 6 probably represent an identical lesion to the LGA of the sinonasal tract. The largest series of LGA was compiled by Heffner et al. 3 in which 23 cases of LGA were contrasted with 27 HGAs. The typical patient with LGA has nasal obstruction and/or epistaxis at presentation. The median duration of symptoms is 5.5 months. The average age at diagnosis is 53 years, and there is no sex predilection. The patient with HGA is also likely to have epistaxis and/or nasal obstruction at presentation but in addition may have pain and deformity, neither of which is encountered in LGA. 7,8 The average age of the patient with HGA was reported to be higher, and the sex

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distribution is strongly in favor of men. Many of the high-grade tumors were of intestinal-type histology and were associated with wood-dust exposure. No epidemiologic association has yet been discovered for LGA. L G A has a markedly better prognosis than HGA. During a mean follow-up period of 6.4 years, 30% of the patients had one or more recurrences, ~md 9% died of disease. By contrast, 78% of patients with H G A died of their disease, usually within 3 years of the date of initial diagnosis. 3 LGAs are sometimes diagnosed as adenoma because of the strikingly b e n i g n appearance of the cells. However, there is a definite potential for recurrence, metastasis, and even death (usually from local effects of the tumor). In the study by Heffner et al. 3 7 of 23 patients had recurrences, including 2 who subsequently died. Significantly, of these seven, four had only a localized procedure, such as polypectomy or excisional biopsy. Radiation therapy was used too infrequently to be assessed. However, as one could see by analogy with other well-differentiated tumors, radiation treatment might not be effective because the tumor is low grade and well differentiated. Surgery seems to be the choice

of treatment, but it should not be as extensive and radical for LGA as for HGA. Nevertheless, it should be tailored to allow complete removal of the tumor. 3

REFERENCES 1. Ramsay AD. Ear, nose throat. In: McGee ODJ, Isaacson PG, Wright NA, eds. Oxford textbook of pathology. New "fork. Oxford UniversityPress 1992:1112-20. 2. Kleinsasser O. Terminal tubulus adenocarcinomaof the nasal seromucous glands, a specific entity. Arch Otorhinolaryngol 1985;241:183-93. 3. Heffner DK, Hyams VJ, Hanck KW, Lingeman C. Low-grade adenocarcinoma of the nasal cavity and paranasal sinuses. Cancer 1982;50:312-22. 4. Manning JT, Batsakis JG. Salivary-type neoplasms of the sinonasat tract. Ann Otol Rhinol Laryngol 1991;100:69t-4. 5. EvansHL, Batsalds JG. Polymorphouslow-grade adenocarcinoma of minor salivaryglands.A study of 14 cases of a distinctive neoplasm. Cancer 1984;53:935-42. 6. Evans RW. Histological appearances of tumours. 2nd ed. Edinburgh: Livingstone,1968. 7. MoranCA, WenigBM, MullickFG. Primaryadenocarcinomaof the nasal cavity and paranasal sinuses, Ear Nose Throat J 1991;70:821-8. 8. FranquemontDW, Fechner RE, Mills SE. Histologicclassification of sinonasal intestinal-type adenocarcinoma. Am J Surg Pathol 1991;15:368-75.

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