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Ectopic Sphenoid Sinus Pituitary Adenoma (ESSPA)

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Ectopic Sphenoid Sinus Pituitary Adenoma (ESSPA) Head and Neck Pathol (2012) 6:75–100 DOI 10.1007/s12105-012-0336-9 NORTH AMERICAN SOCIETY OF HEAD AND NECK PATHOLOGY COMPANION MEETING, MARCH 18, 2012, VANCOUVER, BRITISH COLUMBIA 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 Lester D. R. Thompson • Raja R. Seethala • Susan Mu¨ller Received: 29 November 2011 / Accepted: 25 January 2012 / Published online: 20 March 2012 Ó Springer Science+Business Media, LLC (outside the USA) 2012 Abstract Ectopic sphenoid sinus pituitary adenoma different patterns (solid, packets, organoid, pseudorosette- (ESSPA) may arise from a remnant of Rathke’s pouch. rosette, pseudopapillary, single file, glandular, trabecular, These tumors are frequently misdiagnosed as other neu- insular). Bone involvement was frequently seen (n = 21). roendocrine or epithelial neoplasms which may develop in Secretions were present (n = 16). Necrosis was noted in 8 this site (olfactory neuroblastoma, neuroendocrine carci- tumors. The tumors showed a variable cellularity, with noma, sinonasal undifferentiated carcinoma, paragangli- polygonal, plasmacytoid, granular, and oncocytic tumor oma, melanoma). Thirty-two patients with ESSPA cells. Severe pleomorphism was uncommon (n = 5). A identified in patients with normal pituitary glands (intact delicate, salt-and-pepper chromatin distribution was seen. sella turcica) were retrospectively retrieved from the con- In addition, there were intranuclear cytoplasmic inclusions sultation files of the authors’ institutions. Clinical records (n = 25) and multinucleated tumor cells (n = 18). Mitotic were reviewed with follow-up obtained. An immunohis- figures were infrequent, with a mean of 1 per 10 HPFs and tochemical panel was performed on available material. a\1% proliferation index (Ki-67). There was a vascularized Sixteen males and 16 females, aged 2–84 years (mean, to sclerotic or calcified stroma. Immunohistochemistry 57.1 years), presented with chronic sinusitis, headache, highlighted the endocrine nature of the tumors, with synap- obstructive symptoms, and visual field defects, although tophysin (97%), CD56 (91%), NSE (76%) and chromogranin several were asymptomatic (n = 6). By definition, the (71%); while pan-cytokeratin was positive in 79%, fre- tumors were centered within the sphenoid sinus and dem- quently with a dot-like Golgi accentuation (50%). Reactivity onstrated, by imaging studies or intraoperative examina- with pituitary hormones included 48% reactive for 2 or more tion, a normal sella turcica without a concurrent pituitary hormones (plurihormonal), and 33% reactive for a single adenoma. A subset of tumors showed extension into the hormone, with prolactin seen most frequently (59%); 19% of nasal cavity (n = 5) or nasopharynx (n = 9). Mean tumor cases were non-reactive. The principle differential diagnosis size was 3.4 cm. The majority of tumors were beneath an includes olfactory neuroblastoma, neuroendocrine carci- intact respiratory epithelium (n = 22), arranged in many noma, 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 L. D. R. Thompson (&) curative in the majority of cases, although recurrence/per- Woodland Hills Medical Center, Department of Pathology, sistence was seen in 4 patients (13.8%). In conclusion, Southern California Kaiser Permanente Group, 5601 De Soto ESSPAs are rare, affecting middle aged patients with non- Avenue, Woodland Hills, CA 91365, USA specific symptoms, showing characteristic light microscopy e-mail: [email protected] and immunohistochemical features of their intrasellar R. R. Seethala counterparts. When encountering a tumor within the sphe- Department of Pathology, University of Pittsburgh, Pittsburgh, noid sinus, ectopic pituitary adenoma must be considered, PA, USA and pertinent imaging, clinical, and immunohistochemical S. Mu¨ller evaluation undertaken to exclude tumors within the differ- Department of Pathology, Emory University, Atlanta, GA, USA ential diagnosis. This will result in accurate classification, 123 76 Head and Neck Pathol (2012) 6:75–100 helping to prevent the potentially untoward side effects or By definition of the World Health Organization, ectopic complications of incorrect therapy. pituitary adenoma is a benign pituitary gland neoplasm occurring separate from, and without involvement of, the Keywords Sphenoid sinus Á Ectopic pituitary adenoma Á sella turcica (i.e., with normal anterior pituitary gland) [1]. Neuroectodermal tumor Á Neuroendocrine tumor Á The pituitary gland is housed within the sella just above the Adenoma Á Pituitary neoplasm Á Nasal cavity Á Pituitary sphenoid sinuses. Immediately surrounding the pituitary hormones Á Sphenoid sinus pathology Á gland are the paired, septated cavernous sinuses, which Immunohistochemistry Á Prognosis Á Survival Á Imaging Á also envelop the internal carotid artery, and contain or Differential diagnosis surround branches of several cranial nerves. The vast majority of pituitary adenomas are within the sella. Thus, careful imaging evaluation of these structures is required, Introduction along with intraoperative assessment to make certain that the sella is intact. The relevant anatomy for imaging Neuroectodermal and neuroendocrine tumors of the sino- evaluation of the sphenoid sinus at the level of the naso- nasal tract encompass a selected tumor group, comprising pharynx is shown in Fig. 1. \2% of all sinonasal tract tumors. These tumors include The anterior pituitary primordium appears at about the 4th typical carcinoid (neuroendocrine tumor, grade 1), atypical week of embryogenesis. During the 8th developmental week, carcinoid (neuroendocrine tumor, grade 2), small cell car- the pituitary divides into sellar and pharyngeal parts. There is a cinoma (neuroendocrine tumor, grade 3), paraganglioma, supradiaphragmatic attachment to the pituitary stalk, while Ewing sarcoma/primitive neuroectodermal tumor, olfactory there is an infrasellar invagination referred to as Rathke’s neuroblastoma, melanotic neuroectodermal tumor of pouch. The craniopharyngeal canal allows for migration of the infancy, mucosal melanoma, and ectopic pituitary adenoma. pituitary tissue into the sphenoid or nasopharynx. Therefore, it Fig. 1 A diagrammatic representation of the anatomy around the sphenoid sinus (S), immediately above the nasopharynx (N), and immediately below the sella turcica containing the pituitary gland (P). The cavernous sinus (blue), internal carotid arteries (red) and cranial nerve branches (yellow) all have an intimate relationship with the pituitary fossa and sphenoid sinus (Used by special permission of Amirsys, Inc., Salt Lake City, UT, USA) 123 Head and Neck Pathol (2012) 6:75–100 77 is thought that ‘‘ectopic’’pituitary adenomas are derived from Table 1 Clinicopathologic data on patients with ectopic sphenoid these embryologic remnants along the path of migration of sinus pituitary adenomas from a review of the English literature [7, Rathke’s pouch [2–4]. Nasopharyngeal and sphenoid sinus or 10–41] sphenoid bone ectopic pituitary tissue can be fully functional, Characteristics Sphenoid sinus since pharyngeal pituitary tissue begins to produce hormones pituitary adenoma total: n = 43 around the 17–18th week of gestation, about 8 weeks later than sellar pituitary function begins [5, 6]. Knowledge of Gender pituitary embryonic development should result in the con- Women 27 sideration of a pituitary adenoma in the assessment of a Men 16 sphenoid sinus tumor. Age (in years) Within the upper aerodigestive tract, ectopic pituitary Range 17–76 adenomas are most frequent in the sphenoid sinus and the Mean 51.8 nasopharynx, although also identified in the nasal cavity, Women (mean) 50.1 ethmoid sinus, temporal bone, and nasal bridge [7, 8]. Men (mean) 52.2 Intracranial, extrasellar ectopic pituitary adenomas are also Symptom duration (in months)a recognized (suprasellar, Meckel’s cave, cavernous sinus, Range 1–360 thalamus) [9], but these, along with tumors found exclu- Mean 62.1 sively in the nasopharynx and nasal cavity, are excluded Women (mean) 68.0 from further consideration in this report. Men (mean) 49.9 Ectopic sphenoid sinus pituitary adenoma (ESSPA) with- a, b Symptoms at presentation out sella turcica involvement is rare, with few cases reported in Obstruction, sinusitis, rhinorrhea, 14 the English literature [7, 10–41](Table 1). The infrequency of drainage, discharge these tumors may result in misclassification and subsequent Headache or pain, nerve changes 13 inappropriate management. While there have been two series Cushing symptoms (bruising, 10 [20, 40] the information focused on imaging findings with hypertension, acne, facial hair, only limited information about the histologic findings. weakness) Therefore, there is no large comprehensive evaluation of Acromegaly 8 ESSPA when there is a normal sella turcica. This study Visual disturbances (diplopia, 8 focused on the clinical presentation, histologic features and acuity loss, blurring) immunohistochemical profiles of these tumors in relation to Amenorrhea, galactorrhea 7 or impotency the differential diagnosis and patient management. It is Epistaxis 3 important to state at the outset, however, that subclassification Hormone production clinicallya of these tumors by current methods, using pituitary tran- scription factors (Pit-1, T-pit, SF-1,
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