Endoscopic management of low-grade papillary adenocarcinoma of the ethmoid sinus: Case report and review of the literature

Endoscopic Management of Low-Grade Papillary Adenocarcinoma of the Ethmoid Sinus: Case Report and Review of the Literature Udayan K. Shah, MD, Roger L. Hybels, MD, and John Dugan, MD

(Editorial Comment: This report expands our understanding of the application of minimally invasive technique for management of low-grade malignancies in the sinonasal tract.)

The management of ethmoid adenocarcidepends on the extent of disease at presentation and the histopathological characterization of the tumor. We present one patient with the papillary variant of low-grade adenocarcinoma of the ethmoid sinus (LGPAE) to discuss the clinical presentation, pathological features, and treatment options for this lesion. We focus on our endoscopic removal of this indolent neoplasm to explore the rationale for and dangers of endoscopic tumor removal of low-grade sinonasal malignancy. noma

CASEREPORT A 65-year-old woman presented with several years of intermittent right nasal obstruction that was occasionally improved by oral antibiotics. She denied epistaxis, dysosmia, pain, rhinorrea, or visual changes. Her past medical history was significant for left breast lumpectomy 19 years prior that showed fatty tissue and a motor vehicle accident in which she fractured a left rib. Her external facial appearance was normal. Nasal endoscopy in the office showed a pink, mucosally covered right posterior ethmoid mass measuring 1.5 X 2.0 cm that was well circumscribed, smooth, and soft to palpation (Fig 1). Computerized tomographic (CT) scan showed a mass of soft tissue density filling the right posterior From the Division of Pediatric Otolaryngology, The Children’s Hospital of Philadelphia; University of Pennsylvania School of Medicine. Philadelohia. PA: and the Departments of Otolaryngoiogy-Head and Nedk Surgery and Pathology, Lahey Hitchcock Medical Center, Burlington, MA. Address reprint reauests to Udavan K. Shah, MD, Pediatric Otdlaryngolbgy, The Chiidren’s Hospital of Philadelphia, Wood Center, 1st Floor, 34ti St and Civic Center Blvd, Philadelphia, PA 19104-4399. Copyright 8 1999 by W.B. Saunders Company 0196-0709/99/2003-0012$10.0010 190

American Journal of Otolalyngology,

ethmoid region without bony invasion of the orbit or skull base. Magnetic resonance imaging (MRI) showed the limitation of this lesion to the posterior ethmoid cells (Fig 2). A biopsy specimen obtained under local anesthesia showed a well-organized papillary architecture with rare mitoses (Fig 3). The pathological diagnosis was low-grade papillary adenocarcinoma. The lesion was removed piecemeal through an intranasal endoscopic complete sphenoethmoidectomy. The patient did well postoperatively and reported relief of nasal obstruction. Final pathological evaluation showed well-differentiated adenocarcinoma similar in appearance to the initial biopsy. At 1 year of follow-up, she remained asymptomatic and free of local disease (Fig 4).

DISCUSSION Ethmoid cancer accounts for 5% to 50% of the 0.5 per 100,000 paranasal sinus (PNS) cancers that occur in the United States annually,lJ with adenocarcinoma accounting for 40% to 68% of these cases. Persons exposed to both hardwood and softwood dust have increased rates of PNS adenocarcinoma, as do bootmakers and manufacturers of mustard gas and isopropanol. 3s4Carcinogenesis is believed to be caused by biologically active compounds in wood dust, which also impairs mucociliary clearance.1*3s5 The prognosis of PNS adenocarcinema for woodworkers is better than that for other occupations. 6 Smoking is prevalent in patients with PNS cancer and ethmoid adenocarcinoma7 and may act synergistically with softwood dust in the pathogenesis of PNS adenocarcinoma.8 Viral9 and geneticlO causes have also been implicated. Metastatic adenocarcinoma to the ethmoid region is rare. Adenocarcinoma is recognized by its glandular histopathological appearance using hematoxylin and eosin stains. Periodic acid-Schiff with diastase differentiation and mucicarmine stains allow identification of mucopolysaccharide production in poorly differentiated cases

Vol20, No 3 (May-June), 1999: pp 190-194

ENDOSCOPIC

MANAGEMENT

191

ETHMOID ADENOCARCINOMA

Fig 1. Nasal endoscopy on presentation performed with 0” telescope. (Arrow) identifies posterior ethmoid tumor.

Fig 3. Biopsy specimen. (Hematoxylin stain, original magnification x40.)

and eosin

of adenocarcinoma.7J1 Electron microscopy is unlikely to add useful information. Immunohistochemistry may be helpful in poorly differentiated malignancies. The variation in clinical behavior among adenocarcinomas is explained by attention to (1) histoarchitecture, (2) degree of differentiation, and (3) grade of tumor. Architectural distinction is made between papillary, sessile, mucoid, and special forms, the latter including neuroendocrine adenocarcinoma, colonic forms, and undifferentiated adenocarcinoma.12 Whereas Citelli and Calamida reported an intestinal-type adenocarcinoma of the paranasal sinuses in 1903,” Ringertz13 is credited with being the first to refer to the papillary variant of ethmoid adenocarcinoma as a distinct histopathological entity.7 Papillary tu-

mars are the best localized and are most often associated with woodworkers.4 Sessile tumors show a greater invasive tendency than papillary tumors and thus portend a worse prognosis. Mucoid tumors, also referred to as alveolarmucoid or colloid subtypes, have a poorer prognosis than papillary or sessile.5*6 Because tumor architecture does not always explain tumor behavior and tumors can show several features of different architectural subtypes within the same specimen, histological differentiation may be a better predictor of tumor aggressiveness. l4 Well-differentiated tumors have the best prognosis7 and histologically have regularly patterned glands or papillae, rare mitoses, and uniform cell shape. Well-differentiated ethmoid tumors tend to grow by expansion of smooth borders. Moderately differentiated adenocarcinomas have

Fig 2. MRI scan with lesion limited to right posterior ethmoid region.

Fig 4. Postoperative nasal endoscopy with 0” telescope 1 year after resection. There is no evidence of recurrent disease in the well-mucosalized posterior ethmoid region.

192

complex gland formation with solid foci, some nuclear atypia, and three to five mitoses per high power field. Poorly differentiated tumors have solid nests of cells with inconspicuous lumens or signet-ring cells. The clinical behavior of ethmoid adenocarcinema may also be predicted by histopathological grading, which combines architectural and nuclear features with mitotic index. Lowgrade tumors show well-developed glandular patterns with uniform nuclei and minimal mitotic activity. I1 High-grade tumors show a less uniform glandular pattern with solid or sheet-like areas, nuclear pleomorphism, and a higher mitotic rate. I1 Some high-grade tumors are architecturally similar to colonic adenocarcinema, with villous, papillary, and tubular growth patterns. 3~11Architecture and grade can move together; the predominantly less aggressive papillary and tubular forms of ethmoid adenocarcinoma are often low-grade, whereas the solid tumors are more often classified as high-grade.15 Low-grade tumors, in contrast to high-grade lesions, generally permit a longer symptom duration before presentation, cause minimal pain, and are not cosmetically deforming. Low-grade tumors show their indolent behavior by an anatomically limited presentation, usually ethmoidal or nasoethmoid (36%). Only 17.5% of low-grade tumors present in multiple sinuses, compared with 30% of highgrade tumors. In contrast, only 11% of highgrade tumors are restricted to the ethmoid or nasoethmoid region on presentation.l* In the review of Heffner et al,ll 78% of the patients diagnosed with low-grade ethmoid adenocarcinoma were alive with no evidence of disease (NED) at a mean of 6.3 years of follow-up. Thirteen percent were alive with disease and 9% were dead of disease (DOD) after multiple recurrences. Patients with highgrade lesions fared poorly, with 78% of 27 patients DOD, 87% of these within 3 years of initial treatment, and only 7% NED. The extent of disease at presentation has been regarded as the most useful predictor of tumor aggressiveness and prognosis.7J4 Various staging systems account for the extent of disease at presentation. Tumor size, osteolysis, and extension beyond the sinuses divide tumors in the schema suggested by the Union Internationale Contre le Cancer? The ana-

SHAH, HYBELS, AND DUGAN

tomic site of presentation is the basis for the systems reported by Schwab et all7 and Ellingwood and Million.2J6J8Jg For Ellingwood and Million,18 stage I PNS cancers are free of orbital involvement, whereas stage II tumors involve the orbit. Stage III tumors have broken beyond the sinonasal vault, with involvement of cranial contents, the skull base, and/or the nasopharynx. Staging may be accomplished by using both CT and MRI scanning. CT scanning at present provides better information regarding bony invasion, whereas MRI allows assessment of dural and soft tissue involvement. MRI may allow differentiation of mutinous and cystic from solid components of the tumor. Local recurrence remains the bane of patients with ethmoid adenocarcinoma. Death from local recurrence has been blamed on persistent or recurrent tumor at the skull base, infratemporal fossa invasion, and dural involvement.1~7J0 Nodal metastasis at presentation of ethmoid adenocarcinoma is considered so rare that elective treatment of occult neck disease, by radiotherapy (XRT) or surgery, is not recommended.1,7 Metastatic disease, usually pulmonary or osseous, is seen in one third of the patients with high-grade tumors.7~8~20~2~ Despite occasional aggressive tumors, ethmoid adenocarcinomas as a whole are not relentless, destructive neoplasms. Sisson et alz2 refer to the ethmoid as a favored site because of their finding of a 5-year survival rate of 68% for all pathological types of ethmoid cancer versus the 48% 5-year survival rate for all maxillary cancers. In addition, they found that patients with the salivary-type of PNS malignancies fared much better than patients with squamous cell carcinoma.z2 Adenocarcinoma of the ethmoid in particular is regarded to have a better overall survival rate than other histologies, with 40% of the patients with high-grade adenocarcinomas reported as NED by Goepfert et alI5 compared with a 12.5% NED status of those with highgrade adenoid cystic carcinomas. The management of ethmoid adenocarcinoma aims for complete excision to achieve local control. Radiotherapy has had a limited role in achieving primary cure of adenocarcinoma because of the danger of ocular injury and, as Ringertz13 noted in 1938, the “relative radioresistance” of PNS adenocarcinoma.lJIJo

ENDOSCOPIC

MANAGEMENT

ETHMOID

ADENOCARCINOMA

XRT is recommended for high-grade lesions with dural or “minimal cribriform plate invasion,“3 positive margins after resection, and tumors with large volumes or aggressive histological types1 The recently available delivery of proton-beam radiation may offer localized, curative treatment (A. Zeitman, personal communication, April, 1997). The option of implanting radioactive seeds and/or catheters in resection beds remains to be studied. Chemotherapy as currently available has no role in the initial treatment of primary PNS carcinoma presenting without regional or distant metastases. Because of the inherent structure of the paranasal sinuses and skull base, open surgical approaches do not guarantee en bloc specimens or negative margins.23 Piecemeal delivery is not to be rejected on oncologic grounds because biopsy specimens of patient margins may provide useful information for further resection and/or treatment.l Our patient’s tumor was of the most favorable histological subtype (papillary, low grade), of the most favorable histological characterization (adenocarcinoma), and limited to a favored site (the ethmoid). To achieve local control of this early indolent tumor, we used the endoscopic endonasal approach.24 This technique allowed exenteration of the ethmoid vault and assessment of the integrity of the skull base and medial orbital wall. Nasal endoscopy may be used for diagnosis, screening [particularly in high-risk populations14), and tumor surveillance after resectionz5 Lifelong endoscopic examination will be required for our patient because of reported late recurrences (A. Zeitman, personal communication, April, 1997). No bridges are burnt by the initial endoscopic removal of LGPAE. There is no inherent limitation to other treatment modalities. Wider resection, radiotherapy, or chemotherapy may be offered if incomplete tumor removal is suspected, tumor aggressiveness underestimated, or if the final histopathological analysis differs from the initial evaluation. Should intraoperative examination show orbital or cranial vault involvement, further surgical or adjuvant therapy can be offered. It is for this reason that preoperative discussion should encompass such exigencies. Prior investigators have not studied the clini-

193

cal outcome of LGPAE after endoscopic resection of limited lesions, despite favorable results from local resection or polypectomy in prior series.ll The role of radiotherapy in limited presentations of low-grade lesions has also not been prospectively studied. We, therefore, do not advocate routine endoscopic excision of ethmoid adenocarcinoma of limited presentations until patients are studied through well-controlled multiinstitutional clinical analyses with follow-up periods beyond 5 years (A. Zeitman, personal communication, April, 1997).

CONCLUSION The limited aggressiveness of LGPAE allows anatomically confined presentations of this malignancy to be treated with curative intent by endoscopic sinus surgery. Endoscopic management is supported by the ability to offer single-modality treatment without significant morbidity, examine the exenterated ethmoid vault postoperatively for local recurrence, and preserve future treatment options. Wider experience is necessary to judge the oncologic wisdom of endoscopic removal of this uncommon low-grade paranasal sinus malignancy.

ACKNOWLEDGMENT The authors thank Dr John J. Batsakis for his pathological consultation.

REFERENCES 1. Kraus DH, Sterman BM, Levine HL, et al: Factors influencing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 188:367-372,199Z 2. Lampe HB, St Pierre S, Baker SR: Carcinoma of the ethmoid sinus. Am J Otolaryngol7:209-212,1986 3. Wax MK, Yun KJ, Wetmore SJ, et al: Adenocarcinoma of the ethmoid sinus. Head Neck 17:303-311,1995 4. Batsakis JG, Rice DH, Soloman AR: The pathology of head and neck tumors: Squamous and mucus gland carcinomas of the nasal cavity, paranasal sinuses, and larynx, part 6. Head Neck Surg 2:497-508,198O 5. Kraus DH, Roberts JK, Mendendopr SV, et al: Nonsquamous cell malignancies of the paranasal sinuses. Ann Otol Rhino1 Laryngol99:5-11, 1990 6. Barnes L: Intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses. Am J Surg Path 10:192-202, 1986 7. Alessi DM, Trapp TK, Fu YS, et al: Nonsalivary sinonasal adenocarcinoma. Arch Otolaryngol Head Neck Surg 114:996-999, 1988 8. Leung SY, Yuen ST, Chung LP, et al: Epstein-Barr virus is present in a wide histological spectrum of sinonasal carcinomas. Am J Surg Path01 19:994-1001,1995

194

9. Myers EN, Carrau RL: Neoplasms of the nose and paranasal sinuses, in Bailey BJ (ed): Head and Neck Surgery-Otolaryngology, ~012. Philadelphia, PA, Lippincott, 1993, pp 1091-1109 10. Jin Y, Mertens F, Arheden K, et al: Karyotypic features of malignant tumors of the nasal cavity and paranasal sinuses. Int J Cancer 60:637-641,1995 11. Heffner DK, Hyams VJ, Hauck KW, et al: Low-grade adenocarcinoma of the nasal cavity and paranasal sinuses. Cancer 50:312-322,1982 12. Bats&is JG, Mackay B, Ordonez NG: Enteric-type adenocarcinoma of the nasal cavity. Cancer 54855-860, 1984 13. Ringertz N: Pathology of malignant tumours arising in the nasal and paranasal cavities and maxilla. Acta Otolaryngol27:117-123,1938 (suppl) 14. Nunez F, Suarez C, Alvarez I, et al: Sino-nasal adenocarcinoma: Epidemiological and clinico-pathological study of 34 cases. J Otolaryngol22:86-90,1993 15. Goepfert H, Luna MA, Lundberg RD, et al: Malignant salivary gland tumors of the paranasal sinuses and nasal cavity. Arch Otolaryngol109:662-668,1983 16. Perrin C, Marie1 P, Czorny A: Les tumeurs malignes de l’ethmoide. Encyclopedic Medico-Chirurgicale OtoRhino-laryngologie (Paris, France) 20405c1a, 2-1987 17. Schwab W, Schmeisser KJ, Steinhoff HJ, et al:

SHAH, HYBELS, AND DUGAN

Anleitungen zur Dokumentation von Malignomen im Kopf-Hals-Bereich nach dem TNM-System. HNO 33:337348,1985 18. Ellingwood KE, Million RR: Cancer of the nasal cavity and ethmoid/sphenoid sinuses. Cancer 43:15171526,1979 19. Parsons JT, Kimsey FC, Mendenhall WM, et al: Radiation therapy for sinus maligancies. Otolaryngol Clin North Am 28:1259-1268,1995 20. Alvarez I, Suarez C, Rodrigo JP, et al: Prognostic factors in paranasal sinus cancer. Am J Otolaryngol16:109114,1995 21. Weber AL, Stanton AC: Malignant tumors of the paranasal sinuses: Radiologic, clinical and histopathologic evaluation of 200 cases. Head Neck Surg 6:761-776, 1984 22. Sisson GA Sr, Toriumi DM, Atiyah RA: Paranasal sinus malignancy: A comprehensive update. Laryngoscope 99:143-150,1989 23. Spiro JD, Soo KC, Spiro RH: Nonsquamous cell malignant neoplasms of the nasal cavities and paranasal sinuses. Head Neck 17:114-118,1995 24. Stammberger H: Functional Endoscopic Sinus Surgery. Philadelphia, PA, Decker, 1991 25. Rice DH: Endonasal surgery for nasal wall tumors. Otolaryngol Clin North Am 28:1117-1125,1995