Case Reports
Sinonasal Clear Cell Adenocarcinoma A Case Report
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Background
ost adenocarcinomas affecting the head and neck region arise from major or minor salivary glands or closely related seromucinous glands. However, sinonasal adenocarcinomas are grouped under the category of nonsalivary tumors, which is divided into high grade (intestinal type) and low grade adenocarcinoma. Diagnosing low grade sinonasal adenocarcinoma (LGSNA) is important because it has a markedly better prognosis and, not rarely, is histologically misdiagnosed as one of the salivary gland tumors. LGSNA with clear cell change is very rare.1-4 The cytologic findings of this tumor are not documented. We present cytologic, immunohistologic and ultrastructural findings of a case of LGSNA with pure clear cells arising from surface epithelium, together with pitfalls in diagnosis.
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Case
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Cytologic findings of this rare tumor overlap with those of salivary gland–type tumors with clear cell change and should be added to the list of head and neck tumors with clear cell change. (Acta Cytol 2009;53:597– 600)
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A 52-year-old woman presented with a facial mass of the left cheek of 3–4 years’ duration, with progressive enlargement, nasal discharge and discoloration of the lateral side of the left eye. Computed tomography was performed in the coronal plain, with bone window, revealing extensive destruction of the bony septa in the left side of the nasal cavity involving the left maxillary sinus and ethmoid sinuses. The lesion was expansile and caused erosion of the alveolar process of the maxillary bone. Extension to the sphenoid sinus and left side of the oral cavity was also demonstrated. Extension to the inferior aspect of the left orbit and destruction of the left zygomatic bone was also found (Figure 1). Fine needle aspiration was performed through the upper buccogingival canine fossa, which lead to the report of a clear cell neoplasm. Excision of the whole mass was performed.
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Conclusion
Case Report
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We believe that collecting cytology, radiology, immunohistochemistry and electron microscopy data is helpful for diagnosing sinonasal tumors, especially LGSNA.
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Nonsalivary adenocarcinomas are the most interesting tumors found in the sinonasal area. They are rare tumors arising from surface epithelium. The clear cell type of this tumor is even more rare. We present cytologic findings of clear cell sinonasal adenocarcinoma and related pitfalls.
A 52-year-old woman presented with a left-cheek facial mass of 3–4 years’ duration, with progressive enlargement, nasal discharge and discoloration of the lateral side of her left eye. Computed tomography was performed, revealing an expansile mass involving the nasal cavity, left maxillary sinus, ethmoid sinus with extension to sphenoid sinus, left side of oral cavity and left orbit. Fine needle aspiration performed through the upper buccogingival canine fossa showed clusters of epithelial cells with clear cytoplasm, round nuclei, inconspicuous nucleoli and slight pleomorphism. Some normal ciliated columnar epithelial cells are identified in the vicinity of neoplastic cells. The mass was reported to be a clear cell neoplasm, and excision of the whole mass was performed.
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Shahrzad Negahban, M.D., Yahya Daneshbod, M.D., M.I.A.C., Bijan Khademi, M.D., Ali-Reza Rasekhi, M.D., and Hossein Soleimanpour, M.D.
Keywords: adenocarcinoma; aspiration, fine-needle; clear cell carcinoma; cytology; sinus.
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Cytologic Findings The smears were cellular, consisting clusters of epithelial cells with a moderate amount of clear cytoplasm, distinct borders and slight pleomorphism (Figure 2). The nuclei were round, with inconspicuous nucleoli. They formed glands, trabeculae (Figure 3) and occasional papillary-like structures. In the vicinity of the neoplastic cells,
From the Department of Cytopathology, Dr. Daneshbod Pathology Laboratory, and Departments of Head and Neck Surgery and of Radiology and Interventional Study, Shiraz School of Medicine, Shiraz, Iran. Drs. Negahban, Daneshbod and Soleimanpour are Assistant Professors, Department of Cytopathology, Dr. Daneshbod Pathology Laboratory. Dr. Khademi is Professor of Otolaryngology, Department of Head and Neck Surgery, Shiraz School of Medicine. Dr. Rasekhi is Associate Professor, Department of Radiology and Interventional Study, Shiraz School of Medicine. Address correspondence to: Shahrzad Negahban, M.D., Department of Pathology and Cytopathology, Dr. Daneshbod Pathology Laboratory, Ordibehesht Avenue, No. 23, P.O. Box 71345-1588, Shiraz, Iran (
[email protected]). Financial Disclosure: The authors have no connection to any companies or products mentioned in this article. Received for publication July 19, 2007. Accepted for publication August 28, 2007.
0001-5547/09/5305-0597/$21.00/0 © The International Academy of Cytology
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Figure 1 Computed tomography reveals a large mass involving the left maxillary, ethmoid and sphenoid sinuses and inferior aspect of left orbit, which destructs bony septa in the left side of the nasal cavity and left zygomatic bone.
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Figure 2 Clusters of epithelial cells with a moderate amount of clear cytoplasm, distinct borders and slight pleomorphism (Papanicolaou stain, × 200).
Immunohistochemical Findings
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Electron Microscopy Findings
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Electron microscopy performed on formalin-fixed tissue samples that were poorly preserved demonstrated a round, clear nucleus, with cytoplasm containing multiple different-sized vacuoles, scanty mitochondria and few tonofilaments. The cell membrane shows
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The gross specimen was fragmented gray-white, soft-to-rubbery tissue measuring 5 × 4 × 4 cm and consisting of a partial hemimaxillectomy specimen. Histologic examination revealed a solid area of neoplastic cells with clear cytoplasm, distinct cell borders and minimal pleomorphism with focal dilated or cystic gland formation (Figure 6). The nuclei were uniform, with inconspicuous nucleoli and regular borders. They were adjacent to normal respiratory sinus epithelium (Figure 7). In transition, the ciliated cells showed clearing of the cytoplasm (Figure 7, inset). Mitosis and necrosis were absent. The glands were empty or, rarely, showed thin secretion. No salivary gland tissue was identified.
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Pathologic Findings
Formalin-fixed, paraffin-embedded sections were used for immunohistochemistry using the labeled streptavidin-biotin technique (Novocastra, Newcastle upon Tyne, U.K.), following a standard protocol. Immunohistochemical findings included diffuse reactivity for cytokeratin (CK) (34βE12, predilute, Novocastra), epithelial membrane antigen (EMA) (GP1.4, predilute, Novocastra) and CK7 (OV-TL 12/30, predilute, Novocastra) (Figure 8). CK20 (K 20.8, predilute, Novocastra), carcinoembryonic antigen (12-140-10, predilute, Novocastra), S100 (S1/61/69, predilute, Novocastra) and glial fibrillary acidic protein (GFAP) (GA5, predilute, Novocastra) were all negative in neoplastic cells.
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some normal ciliated columnar cells were identified (Figures 3B and 4). Structures resembling hyalin globules (Figure 5), such as seen in adenoid cystic carcinoma, also were noted, but psammoma bodies were absent.
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Figure 3 The neoplastic cells form (A) trabeculae and (B) glands (thick arrows) in the vicinity of ciliated respiratory epithelium (thin arrow) (A, Papanicolaou stain, × 200; B, Wright stain, × 300).
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Sinonasal Adenocarcinoma
Figure 6 Solid area of neoplastic cells with clear cytoplasm, distinct cell borders and minimal pleomorphism with focal dilated or cystic gland formation. The nuclei are uniform, with inconspicuous nucleoli and regular borders (hematoxylin-eosin, × 200).
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Glandular neoplasms arising within the sinonasal tract are uncommon. They can be divided into high grade (intestinal type) and low grade adenocarcinomas. The high grade adenocarcinoma histologically and immunohistochemically resembles colonic adenocarcinoma.1-3 No systematic examination of the low grade group of tumors has previously been performed.4 The distinction between high grade sinonasal adenocarcinoma (HGSNA) and LGSNA, as well as differentiating salivary gland adenocarcinoma from LGSNA, are important because prognosis for LGSNA is much better than HGSNA and salivary gland adenocarcinoma.1,2,4 LGSNA, as defined by the Armed Forces Institute of Pathology, is a microscopically somewhat heterogenous group of well-differentiated, often papillary adenocarcinomas arising in the sinonasal and naso-
pharyngeal region and lacking intestinal-like features.1 Risk factors have not been identified for the low grade neoplasm, and there is no association with tobacco use or alcohol consumption.1 Clear cell carcinoma may be seen in salivary glands (mainly in minor salivary glands); it is composed of a monomorphic population of clear cells. It lacks features of other salivary gland neoplasms that may show clear cell change, such as pleomorphic adenoma, mucoepidermoid carcinoma, epithelial-myoepithelial carcinoma, acinic cell carcinoma and clear cell change in oncocytic tumors.5 Sinonasal tumor mainly composed of clear cells is reported in a few articles, not as a subgroup, but as a variety of features that may be seen in LGSNA.2,4 The case presented is interesting because histologically it shares features of both acinic cell carcinoma and clear cell carcinoma of salivary origin. The tumor cells show some acinar and glandular structures and on first look may resemble acinic cell carcinoma. Absence of granular basophilic cytoplasm without any relation to salivary glands separates it from acinic cell carcinoma with salivary gland origin.6-8 On the other hand, focal clearing of
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Discussion
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many short, irregular microvilli projecting into adjacent lumen (Figure 9). Specific features of myoepithelial differentiation, including arrays of fine filaments with focal dense bodies and pinocytic vesicles, were absent.
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Figure 4 Ciliated respiratory epithelium (arrow) seen in continuity with and close to tumor cells (Papanicolaou stain, × 200).
Figure 5 Structures resembling hyalin globules, such as seen in adenoid cystic carcinoma, are noted (Papanicolaou stain, × 200).
Figure 7 The tumor is adjacent to normal respiratory epithelium of sinus. Inset: in transition, the ciliated cells show clearing of cytoplasm (hematoxylin-eosin, × 300; inset, × 200).
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Figure 8 Tumor cells and sinus mucosa (arrow) show diffuse reactivity for CK7.
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We would like to thank Stacy Mills, M.D. (University of Virginia Health System, Charlottesville, Virginia) for reviewing this case.
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References
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1. Ellis GL, Auclair PL: Tumors of the salivary glands. In Atlas of Tumor Pathology. Third series, fascicle 17. Washington, DC, Armed Forces Institute of Pathology, 1996
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2. Cathro HP, Mills SE: Immunophenotypic differences between intestinaltype and low-grade papillary sinonasal adenocarcinomas: An immunohistochemical study of 22 cases utilizing CDX2 and MUC2. Am J Surg Pathol 2004;28:1026–1032
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Acknowledgments
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favor sinus origin of the tumor. We believe that collecting cytology, radiology, immunohistochemistry and electron microscopy data is helpful for diagnosing sinonasal tumors, especially LGSNA.
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respiratory epithelium suggests that a sinus area other than the salivary gland is the primary origin of the tumor. To our knowledge, this is the only report to discuss cytologic findings of LGSNA with a clear cell feature. Monomorphic cells with clear, foamy cytoplasm forming trabeculae; glandular and acinar structures; papillary-like features; and hyaline globule material are not typical for diagnosing a specific tumor and may be seen in many salivary and nonsalivary or even metastatic tumors.1,5 However, the presence of ciliated columnar cells in the vicinity of or the transition of the structures listed supports the sinus origin. Only a few cases of LGSNA have been subjected to immunohistochemical study, with a limited panel of antibodies.1-4,6 Strong staining for CK and EMA, and focal or no staining for S100, GFAP and thyroglobulin are immunohistochemical findings that are common in almost all previous studies.1-4,6,9 Most studies show expression of CK20 and no staining for CK7 in intestinal-type SNA. This is not surprising, considering the expression profile of colorectal adenocarcinoma. On the other hand, LGSNA shows CK20 negativity, and most show focal or diffuse staining for CK7.1-3 Thus, although intestinal-type SNA and LGSNA may simply be differentiated according to histologic features, immunohistochemistry also can help in separating cases in which there is doubt. The finding of diffuse S100 protein staining would help differentiate tumors of minor salivary glands, such as differentiating polymorphous low grade adenocarcinoma and acinic cell tumor from LGSNA.6,7,9 GFAP has been identified in the myoepithelial component of salivary tumors.6,10 As expected, GFAP was negative in this case. This finding further substantiates a nonmucoserous gland origin for these tumors. Electron microscopy findings of LGSNA have not been documented in the literature. The absence of numerous mitochondria or electron-dense granules suggests against the diagnosis of oncocytoma and acinic cell carcinoma, respectively. On the other hand, many mucous granules or desmosomes containing tonofilaments are seen in mucoepidermoid carcinoma but not in LGSNA. LGSNA, especially the clear cell type, is a rare tumor, and so far, limited data exist about this tumor in the literature. It should be differentiated from salivary gland tumors and also from HGSNA because it has a markedly better prognosis. Salivary gland tumors with clear cell change are common, and sometimes it is not easy to separate them from the clear cell type of LGSNA according to cytologic or even histologic findings. Absence of any connection between tumor and salivary glands or presence of transition between sinus lining and tumor
Figure 9 Ultrastructural study shows a round, clear nucleus with a cytoplasm containing multiple different-sized vacuoles, scanty mitochondria and few tonofilaments. The cell membrane shows many short, irregular microvilli projecting into the adjacent lumen.
3. Franchi A, Palomba A, Massi D, Biancalani M, Sardi I, Gallo O, Santucci M: Low-grade salivary type tubulo-papillary adenocarcinoma of the sinonasal tract. Histopathology 2006;48:881– 884 4. Heffner DK, Hyams VJ, Hauck KW, Lingeman C: Low-grade adenocarcinoma of the nasal cavity and paranasal sinuses. Cancer 1982;15:312– 322 5. Negahban S, Daneshbod Y, Shishegar M: Clear cell carcinoma arising from pleomorphic adenoma of a minor salivary gland: Report of a case with fine needle aspiration, histologic and immunohistochemical findings. Acta Cytol 2006;50:687–690 6. Wenig BM, Hyams VJ, Heffner DK: Nasopharyngeal papillary adenocarcinoma: A clinicopathologic study of low-grade carcinoma. Am J Surg Pathol 1988;12:946–953 7. Ellis GL, Corio RL: Acinic cell adenocarcinoma: A clinicopathologic analysis of 294 cases. Cancer 1983;52:542–549 8. Ellis GL, Gnepp DR: Unusual salivary gland tumors. In Pathology of the Head and Neck. Edited by DR Gnepp. New York, Churchill Livingstone, 1988, pp 585–661 9. Gnepp DR, Chen JC, Warren C: Polymorphous low-grade adenocarcinoma of minor salivary gland: An immunohistochemical and clinicopathologic study. Am J Surg Pathol 1988;12:461–468 10. Nakazato Y, Ishida Y, Takahashi K, Suzuki K: Immunohistochemical distribution of S-100 protein and glial fibrillary acidic protein in normal and neoplastic salivary glands. Virchows Arch 1985;405:299–310
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