Abstract
Ectopic sphenoid sinus pituitary adenoma (ESSPA) may arise from a remnant of Rathke’s pouch. These tumors are frequently misdiagnosed as other neuroendocrine or epithelial neoplasms which may develop in this site (olfactory neuroblastoma, neuroendocrine carcinoma, sinonasal undifferentiated carcinoma, paraganglioma, melanoma). Thirty-two patients with ESSPA identified in patients with normal pituitary glands (intact sella turcica) were retrospectively retrieved from the consultation files of the authors’ institutions. Clinical records were reviewed with follow-up obtained. An immunohistochemical panel was performed on available material. Sixteen males and 16 females, aged 2–84 years (mean, 57.1 years), presented with chronic sinusitis, headache, obstructive symptoms, and visual field defects, although several were asymptomatic (n = 6). By definition, the tumors were centered within the sphenoid sinus and demonstrated, by imaging studies or intraoperative examination, a normal sella turcica without a concurrent pituitary adenoma. A subset of tumors showed extension into the nasal cavity (n = 5) or nasopharynx (n = 9). Mean tumor size was 3.4 cm. The majority of tumors were beneath an intact respiratory epithelium (n = 22), arranged in many different patterns (solid, packets, organoid, pseudorosette-rosette, pseudopapillary, single file, glandular, trabecular, insular). Bone involvement was frequently seen (n = 21). Secretions were present (n = 16). Necrosis was noted in 8 tumors. The tumors showed a variable cellularity, with polygonal, plasmacytoid, granular, and oncocytic tumor cells. Severe pleomorphism was uncommon (n = 5). A delicate, salt-and-pepper chromatin distribution was seen. In addition, there were intranuclear cytoplasmic inclusions (n = 25) and multinucleated tumor cells (n = 18). Mitotic figures were infrequent, with a mean of 1 per 10 HPFs and a <1% proliferation index (Ki-67). There was a vascularized to sclerotic or calcified stroma. Immunohistochemistry highlighted the endocrine nature of the tumors, with synaptophysin (97%), CD56 (91%), NSE (76%) and chromogranin (71%); while pan-cytokeratin was positive in 79%, frequently with a dot-like Golgi accentuation (50%). Reactivity with pituitary hormones included 48% reactive for 2 or more hormones (plurihormonal), and 33% reactive for a single hormone, with prolactin seen most frequently (59%); 19% of cases were non-reactive. The principle differential diagnosis includes olfactory neuroblastoma, neuroendocrine carcinoma, melanoma, and meningioma. All patients were treated with surgery. No patients died from disease, although one patient died with persistent disease (0.8 months). Surgery is curative in the majority of cases, although recurrence/persistence was seen in 4 patients (13.8%). In conclusion, ESSPAs are rare, affecting middle aged patients with non-specific symptoms, showing characteristic light microscopy and immunohistochemical features of their intrasellar counterparts. When encountering a tumor within the sphenoid sinus, ectopic pituitary adenoma must be considered, and pertinent imaging, clinical, and immunohistochemical evaluation undertaken to exclude tumors within the differential diagnosis. This will result in accurate classification, helping to prevent the potentially untoward side effects or complications of incorrect therapy.
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References
Luna MA, Cardesa A, Barnes L, et al. Benign epithelial tumours. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. Pathology and genetics head and neck tumours. Lyon: IARC Press; 2005. p. 99–101.
Asa SL, Ezzat S. The pathogenesis of pituitary tumors. Annu Rev Pathol. 2009;4:97–126.
Asa SL. The pathology of pituitary tumors. Endocrinol Metab Clin North Am. 1999;28:13–vi.
Langford L, Batsakis JG. Pituitary gland involvement of the sinonasal tract. Ann Otol Rhinol Laryngol. 1995;104:167–9.
Hori A, Schmidt D, Rickels E. Pharyngeal pituitary: development, malformation, and tumorigenesis. Acta Neuropathol. 1999;98:262–72.
Hori A, Schmidt D, Kuebber S. Immunohistochemical survey of migration of human anterior pituitary cells in developmental, pathological, and clinical aspects: a review. Microsc Res Tech. 1999;46:59–68.
Rasmussen P, Lindholm J. Ectopic pituitary adenomas. Clin Endocrinol (Oxf). 1979;11:69–74.
Wenig BM, Heffess CS, Adair CF, et al. Ectopic pituitary adenomas (EPA): a clinicopathologic study of 15 cases. Mod Pathol. 1995;8:56A.
Appel JG, Bergsneider M, Vinters H, Salamon N, Wang MB, Heaney AP. Acromegaly due to an ectopic pituitary adenoma in the clivus: case report and review of literature. Pituitary. 2011: PMID: 21960210.
Anand VK, Osborne CM, Harkey HL III. Infiltrative clival pituitary adenoma of ectopic origin. Otolaryngol Head Neck Surg. 1993;108:178–83.
Bethge H, Arlt W, Zimmermann U, Klingelhoffer G, Wittenberg G, Saeger W, et al. Cushing’s syndrome due to an ectopic ACTH-secreting pituitary tumour mimicking occult paraneoplastic ectopic ACTH production. Clin Endocrinol (Oxf). 1999;51:809–14.
Borit A, Blanshard TP. Sphenoidal pituitary adenoma. Hum Pathol. 1979;10:93–6.
Burch WM, Kramer RS, Kenan PD, Hammond CB. Cushing’s disease caused by an ectopic pituitary adenoma within the sphenoid sinus. N Engl J Med. 1985;312:587–8.
Chan MR, Ziebert M, Maas DL, Chan PS. “My rings won’t fit anymore”. Ectopic growth hormone-secreting tumor. Am Fam Physician. 2005;71:1766–7.
Chessin H, Urdaneta N, Smith H, Van Gilder J. Chromophobe adenoma manifesting as a nasopharyngeal mass. Arch Otolaryngol. 1976;102:631–3.
Coire CI, Horvath E, Kovacs K, Smyth HS, Ezzat S. Cushing’s syndrome from an ectopic pituitary adenoma with peliosis: a histological, immunohistochemical, and ultrastructural study and review of the literature. Endocr Pathol. 1997;8:65–74.
Corenblum B, LeBlanc FE, Watanabe M. Acromegaly with an adenomatous pharyngeal pituitary. JAMA. 1980;243:1456–7.
Erdheim J. Uber einen hypophysintumor von Ungewohnlichen. Sitz Beitr Path Anat. 1909;46:233–40.
Gondim JA, Schops M, Ferreira E, Bulcao T, Mota JI, Silveira C. Acromegaly due to an ectopic pituitary adenoma in the sphenoid sinus. Acta Radiol. 2004;45:689–91.
Hattori N, Ishihara T, Saiwai S, Moridera K, Hino M, Ikekubo K, et al. Ectopic prolactinoma on MRI. J Comput Assist Tomogr. 1994;18:936–8.
Heitzmann A, Jan M, Lecomte P, Ruchoux MM, Lhuintre Y, Tillet Y. Ectopic prolactinoma within the sphenoid sinus. Neurosurgery. 1989;24:279–82.
Hori E, Akai T, Kurimoto M, Hirashima Y, Endo S. Growth hormone-secreting pituitary adenoma confined to the sphenoid sinus associated with a normal-sized empty sella. J Clin Neurosci. 2002;9:196–9.
Horiuchi T, Tanaka Y, Kobayashi S, Unoki T, Yokoh A. Rapidly-growing ectopic pituitary adenoma within the sphenoid sinus–case report. Neurol Med Chir (Tokyo). 1997;37:399–402.
Kammer H, George R. Cushing’s disease in a patient with an ectopic pituitary adenoma. JAMA. 1981;246:2722–4.
Kepes JJ, Fritzlen TJ. Large invasive chromophobe adenoma with well-preserved pituitary gland. Neurology. 1964;14:537–41.
Kikuchi K, Kowada M, Sasaki J, Sageshima M. Large pituitary adenoma of the sphenoid sinus and the nasopharynx: report of a case with ultrastructural evaluations. Surg Neurol. 1994;42:330–4.
Kurowska M, Tarach JS, Zgliczynski W, Malicka J, Zielinski G, Janczarek M. Acromegaly in a patient with normal pituitary gland and somatotropic adenoma located in the sphenoid sinus. Endokrynol Pol. 2008;59:348–51.
Lloyd RV, Chandler WF, Kovacs K, Ryan N. Ectopic pituitary adenomas with normal anterior pituitary glands. Am J Surg Pathol. 1986;10:546–52.
Luk IS, Chan JK, Chow SM, Leung S. Pituitary adenoma presenting as sinonasal tumor: pitfalls in diagnosis. Hum Pathol. 1996;27:605–9.
Madonna D, Kendler A, Soliman AM. Ectopic growth hormone-secreting pituitary adenoma in the sphenoid sinus. Ann Otol Rhinol Laryngol. 2001;110:99–101.
Matsuno A, Katayama H, Okazaki R, Toriumi M, Tanaka H, Akashi M, et al. Ectopic pituitary adenoma in the sphenoid sinus causing acromegaly associated with empty sella. ANZ J Surg. 2001;71:495–8.
Matsushita H, Matsuya S, Endo Y, Hara M, Shishiba Y, Yamaguchi H, et al. A prolactin producing tumor originated in the sphenoid sinus. Acta Pathol Jpn. 1984;34:103–9.
Siegert B, vz Mühlen A, Brabant G, Saeger W, Vogt-Hohenlinde C. Ectopic nonfunctioning pituitary adenoma in the sphenoid sinus. J Clin Endocrinol Metab. 1996;81:430–1.
Slonim SM, Haykal HA, Cushing GW, Freidberg SR, Lee AK. MRI appearances of an ectopic pituitary adenoma: case report and review of the literature. Neuroradiology. 1993;35:546–8.
Suzuki J, Otsuka F, Ogura T, Kishida M, Takeda M, Tamiya T, et al. An aberrant ACTH-producing ectopic pituitary adenoma in the sphenoid sinus. Endocr J. 2004;51:97–103.
Tovi F, Hirsch M, Sacks M, Leiberman A. Ectopic pituitary adenoma of the sphenoid sinus: report of a case and review of the literature. Head Neck. 1990;12:264–8.
Trulea M, Patey M, Chaufour-Higel B, Bouquigny F, Longuebray A, Rousseaux P, et al. An unusual case of ectopic adrenocorticotropin secretion. J Clin Endocrinol Metab. 2009;94:384–5.
Wang H, Yu W, Zhang Z, Xu W, Zhang F, Bao W. Ectopic pituitary adenoma in the spheno-orbital region. J Neuroophthalmol. 2010;30:135–7.
Warner BA, Santen RJ, Page RB. Growth of hormone and prolactin secretion by a tumor of the pharyngeal pituitary. Ann Intern Med. 1982;96:65–6.
Yang BT, Chong VF, Wang ZC, Xian JF, Chen QH. Sphenoid sinus ectopic pituitary adenomas: CT and MRI findings. Br J Radiol. 2010;83:218–24.
Zerikly RK, Eray E, Faiman C, Prayson R, Lorenz RR, Weil RJ, et al. Cyclic cushing syndrome due to an ectopic pituitary adenoma. Nat Clin Pract Endocrinol Metab. 2009;5:174–9.
Arita K, Uozumi T, Yano T, Sumida M, Muttaqin Z, Hibino H, et al. MRI visualization of complete bilateral optic nerve involvement by pituitary adenoma: a case report. Neuroradiology. 1993;35:549–50.
Esteban F, Ruiz-Avila I, Vilchez R, Gamero C, Gomez M, Mochon A. Ectopic pituitary adenoma in the sphenoid causing Nelson’s syndrome. J Laryngol Otol. 1997;111:565–7.
Ali R, Noma U, Jansen M, Smyth D. Ectopic pituitary adenoma presenting as midline nasopharyngeal mass. Ir J Med Sci. 2010;179:593–5.
Shenker Y, Lloyd RV, Weatherbee L, Port FK, Grekin RJ, Barkan AL. Ectopic prolactinoma in a patient with hyperparathyroidism and abnormal sellar radiography. J Clin Endocrinol Metab. 1986;62:1065–9.
Daly AF, Tichomirowa MA, Beckers A. The epidemiology and genetics of pituitary adenomas. Best Pract Res Clin Endocrinol Metab. 2009;23:543–54.
Sanno N, Teramoto A, Osamura RY, Horvath E, Kovacs K, Lloyd RV et al. Pathology of pituitary tumors. Neurosurg Clin N Am. 2003;14:25–39, vi.
Clayton RN. Sporadic pituitary tumours: from epidemiology to use of databases. Baillieres Best Pract Res Clin Endocrinol Metab. 1999;13:451–60.
Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, et al. The prevalence of pituitary adenomas: a systematic review. Cancer. 2004;101:613–9.
Oruckaptan HH, Senmevsim O, Ozcan OE, Ozgen T. Pituitary adenomas: results of 684 surgically treated patients and review of the literature. Surg Neurol. 2000;53:211–9.
van der Mey AG, van Seters AP, van Krieken JH, Vielvoye J, van DH, Hulshof JH. Large pituitary adenomas with extension into the nasopharynx. Report of three cases with a review of the literature. Ann Otol Rhinol Laryngol. 1989;98:618–624.
Kovacs K, Scheithauer BW, Horvath E, Lloyd RV. The World Health Organization classification of adenohypophysial neoplasms. A proposed five-tier scheme. Cancer. 1996;78:502–10.
El-Naggar AK, Batsakis JG, Vassilopoulou-Sellin R, Ordonez NG, Luna MA. Medullary (thyroid) carcinoma-like carcinoids of the larynx. J Laryngol Otol. 1991;105:683–6.
Yamashita M, Qian ZR, Sano T, Horvath E, Kovacs K. Immunohistochemical study on so-called follicular cells and folliculostellate cells in the human adenohypophysis. Pathol Int. 2005;55:244–7.
Thompson LDR. Olfactory neuroblastoma. Ear Nose Throat J. 2006;85:569–70.
Thompson LDR. Olfactory neuroblastoma. Head Neck Pathol. 2009;3:252–9.
Cohen ZR, Marmor E, Fuller GN, DeMonte F. Misdiagnosis of olfactory neuroblastoma. Neurosurg Focus. 2002;12:e3.
Devaney K, Wenig BM, Abbondanzo SL. Olfactory neuroblastoma and other round cell lesions of the sinonasal region. Mod Pathol. 1996;9:658–63.
Wick MR, Nappi O. Ectopic neural and neuroendocrine neoplasms. Semin Diagn Pathol. 2003;20:305–23.
Pellitteri PK, Rinaldo A, Myssiorek D, Gary JC, Bradley PJ, Devaney KO, et al. Paragangliomas of the head and neck. Oral Oncol. 2004;40:563–75.
Myssiorek D, Halaas Y, Silver C. Laryngeal and sinonasal paragangliomas. Otolaryngol Clin North Am. 2001;34:971–982, vii.
Iwase K, Nagasaka A, Nagatsu I, Kiuchi K, Nagatsu T, Funahashi H, et al. Tyrosine hydroxylase indicates cell differentiation of catecholamine biosynthesis in neuroendocrine tumors. J Endocrinol Invest. 1994;17:235–9.
Menon S, Pai P, Sengar M, Aggarwal JP, Kane SV. Sinonasal malignancies with neuroendocrine differentiation: case series and review of literature. Indian J Pathol Microbiol. 2010;53:28–34.
Cordes B, Williams MD, Tirado Y, Bell D, Rosenthal DI, Al-Dhahri SF, et al. Molecular and phenotypic analysis of poorly differentiated sinonasal neoplasms: an integrated approach for early diagnosis and classification. Hum Pathol. 2009;40:283–92.
Schmidt ER, Berry RL. Diagnosis and treatment of sinonasal undifferentiated carcinoma: report of a case and review of the literature. J Oral Maxillofac Surg. 2008;66:1505–10.
Ejaz A, Wenig BM. Sinonasal undifferentiated carcinoma: clinical and pathologic features and a discussion on classification, cellular differentiation, and differential diagnosis. Adv Anat Pathol. 2005;12:134–43.
Thompson LDR, Wieneke JA, Miettinen M. Sinonasal tract and nasopharyngeal melanomas: a clinicopathologic study of 115 cases with a proposed staging system. Am J Surg Pathol. 2003;27:594–611.
Rushing EJ, Bouffard JP, McCall S, Olsen C, Mena H, Sandberg GD, et al. Primary extracranial meningiomas: an analysis of 146 cases. Head Neck Pathol. 2009;3:116–30.
Thompson LDR, Gyure KA. Extracranial sinonasal tract meningiomas: a clinicopathologic study of 30 cases with a review of the literature. Am J Surg Pathol. 2000;24:640–50.
Thompson LDR. Update on nasopharyngeal carcinoma. Head Neck Pathol. 2007;1:81–6.
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A special thanks to Ms. Hannah Herrera for her research assistance. Supported in part by Southern California Permanente Medical Group.
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Thompson, L.D.R., Seethala, R.R. & Müller, S. Ectopic Sphenoid Sinus Pituitary Adenoma (ESSPA) with Normal Anterior Pituitary Gland: A Clinicopathologic and Immunophenotypic Study of 32 Cases with a Comprehensive Review of the English Literature. Head and Neck Pathol 6, 75–100 (2012). https://doi.org/10.1007/s12105-012-0336-9
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DOI: https://doi.org/10.1007/s12105-012-0336-9