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Folia Neuropathologica
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vol. 55
Case report

Three cases of ectopic sphenoid sinus pituitary adenoma

Ernest Jan Bobeff
Karol Wiśniewski
Wielisław Papierz
Ludomir Stefańczyk
Dariusz Jan Jaskólski

Folia Neuropathol 2017; 55 (1): 60-66
Online publish date: 2017/03/27
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Pituitary adenoma (PA) is a common entity in the sellar region, it accounts for approximately 12% of primary brain tumours [16]. Its ectopic localization in sphenoid sinus is seen in 0.48% of cases [17]. Although ectopic sphenoid sinus pituitary adenomas (ESSPAs) are benign neoplasms, necrosis is encountered in 25% of them [17]. They are either characterized by well-defined radiological margins [17,19] or described as bone invading expansile lesions [4,15]. They originate from embryolo­gic remnants of Rathke’s pouch, which prematurely terminated their migration to the pituitary fossa [2,4,10,15,17,19].

Material and methods

In order to reveal clinical, radiological and histopathological features of ESSPA, we analysed three cases: two females and one male, aged 61-70.


Patient 1, a 64-year-old-female, presented with a unilateral left-sided insidious hearing loss of one year’s duration. Her medical history was notable for mild hypertension (HT) and type 2 diabetes mellitus (DM II). Additionally she had a past medical history of hypothyroidism, glau­coma, and menopause at the age of 25. The radio­logical imaging showed a spaceoccupying soft-tissue lesion within the sphenoid sinus protruding into the left choana (Fig. 1). It had irregular enhancement after gadolinium administration. Empty sella and bone erosion were observed (Fig. 2). The sella turcica was slightly deepened, lined with a 2 mm thick strand of the pituitary gland and the narrowed pituitary stalk. We performed a subtotal resection of the tumour via the transnasal approach. It presented as a necrotic mass, tender in consistency and with blurred margins. Despite the erosion of adjacent bone structures including sellar floor, it was possible to recognise the intact sellar dura. She was discharged home in good condition with no neurological deficits.
Patient 2, a 70-year-old woman, was referred for evaluation of a 2-cm heterogeneous sphenoid sinus mass discovered when a magnetic resonance scan was obtained to evaluate H/A and vertigo. She offered no other complaints. She had a past medical history of DM II and HT treated medically. On magnetic resonance (MR) images after administration of gadolinium enhancement, we observed an irregular soft-tissue lesion within the sphenoid sinus, with a liquid cyst located interiorly (Fig. 1). It had welldefined margins and there was a normal pituitary gland located inside the sella turcica. She was operated on via the transnasal approach and the lesion was totally removed. The bone borders of the sphenoid sinus were confirmed intact. She was discharged home in good con­dition with no neurological deficits.
Patient 3, a 61-year-old man, was referred to the neurology clinic for evaluation of chronic H/A and episodes of vertigo. He had modest comorbidities such as mild HT and DM II, well-controlled with medi­cations. Radiological studies revealed a space-occupying soft-tissue lesion within the sphenoid sinus with increased bone turnover, and suspected empty sella (Fig. 1). After gadolinium administration it had regular enhancement. The patient was operated on via the transnasal approach; we performed a sub­total resection of the lesion. The intact sellar dura was confirmed. He was discharged home in good condition with no neurological deficits.
The initial histopathological examination show­ed small fragments of tissue with alternating mucoid and fibrous, hyalinized stroma in all cases (Fig. 3). The tumours consisted of small, monomorphic cells with hyperchromatic nuclei and scant cytoplasm. In the first case, necrosis was found in the central zone. The neoplastic cells were arranged in nests and separated by thin-walled vessels and poorly vascularized connective tissue. Haemorrhage was focally observed. All tumours showed no cytologic features of malignancy, with the Ki-67 labelling index of less than 2% and no mitotic figures. Immunohistochemical staining for the transcription termination factor and CD68 were negative in all cases, while cytokeratin was positive in the second and third case. Immunoreactivity for neuroendocrine markers including synaptophysin, neuron-specific enolase, chromogranin A and CD56 was observed. In the first case, the tumour demonstrated some S100-positive cells. The above immunophenotypes indicated a neuroendocrine tumour without cytologic features of malignancy and suggested a differential diagnosis between pituitary adenoma and paraganglioma. We performed immunohistochemical staining for pitui­tary hormones, which demonstrated growth hormone (GH) cells in all cases whereas prolactin (PRL) and adrenocorticotropic hormone (ACTH) in two. Hence, the final diagnoses of pituitary adenoma were established.
In the first case, hormone tests revealed a slightly increased prolactin level. The patients remain under surveillance for further growth symptoms by MRI and were referred to an endocrinologist for medical treatment.


The pathogenesis of ectopic pituitary adenoma (EPA) is not fully understood. It is hypothesized that neoplastic transformation occurs within the ectopic pituitary tissue located along the path of migration of Rathke’s pouch, that is in the craniopharyngeal canal, or in the adjacent area [2,4,10,15,17,19]. Most frequently this tissue may be found in the sphenoid sinus, and then is called ‘ectopic intrasphenoid hypophysis’ [7,18]. Consequently, the coexistence with the primary empty sella in such cases results from premature termination of migration of Rathke’s pouch, before reaching the pituitary fossa [4,10,15,19]. As it was shown in a recent review by Liang et al. [10] (Table I), to date only 15 cases of ESSPA associated with an empty sella have been reported in the literature [2,4-6,9-12,19].
The largest series of ESSPA in the literature by Thompson et al. included 32 cases [17] (Table I). The authors revealed that the mean age of diagnosis was greater than in typical pituitary adenoma by approximately 10 years. They indicated most sensitive neuroendocrine markers that are synaptophysin and CD56, which were also positive in our study.
Ectopic sphenoid sinus pituitary adenomas en­com­passes a wide range of symptomatology: acromegaly, Cushing’s syndrome, sexual dysfunction, amenorrhea, MEN-1 syndrome (multiple endocrine neoplasia type 1), nasal obstruction, rhinorrhoea and epistaxis, H/A, vertigo, and ear symptoms such as hearing loss. All those although mentioned in the literature, can hardly be related to a lesion limited to the sphenoid sinus. We are of the opinion that also in our series the tumours were incidental findings.
Regarding the differential diagnosis, invasive pituitary adenoma is an important consideration. Initial intrasellar localization of a pituitary adenoma with a following localized or diffuse destruction of sellar floor and extension into the sphenoid sinus – grade 3 and 4 in modified Hardy’s system – is expected in 35% and 10% of cases, respectively [13]. Although MRI may help to confirm the integrity of sellar dura and sellar floor [4,10,12,19], the gold standard is an intraoperative verification [2,5,6,9-11,15]. In case of bone erosion of sphenoid, the evidence of ESSPA seems less justifiable. In our series, computed tomography (CT) scans demonstrated erosion of the sellar floor in two patients, with preserved integrity of dural lining on MRI which was later confirmed on surgery. In one case (patient 2), the sphenoid bone was intact.
In the first case, a slightly increased prolactin concentration was observed, possibly related to the empty sella, rather than to the secreting nature of the tumour. Hyperprolactinaemia is seen in 21% of ESSPA [17] and in 15% of the empty sella syndromes [1]. Some authors suggest it is due to the stalk effect observed in the intrasellar hypertension and consists of impaired dopamine delivery [1,3]. Continuity of the pituitary stalk is essential for adequate development and well-functioning of the pituitary gland [8]. We inferred that the process of developing adenoma in the ectopic pituitary gland may be a direct corollary of lack of the hypothalamic regulation of pituitary development during embryogenesis and subsequent impaired dopamine delivery.
A significant proportion of PA is plurihormonal. Plurimorphous PA, however, defined as showing more than one cell type, is a very rare entity [14]. In our study, we observed 2 cases (patient 1 and 3) of non-functioning PA, which were simultaneously locally positive for both ACTH and GH (Fig. 4).
Currently, there is no established treatment for ESSPA [2]. Thompson et al. postulated that surgical removal is a treatment of choice independently of hormone test results [17]. Preoperative medical therapy may be considered in prolactin-secreting pituitary adenomas as it can effectively reduce the size of the tumour. Additional characteristics that might support the conservative treatment are lack of symptoms (incidental finding) and elderly age of a patient.
Ectopic sphenoid sinus pituitary adenoma is a rare tumour that should always be considered in differential diagnosis of a sphenoid sinus lesion in the elderly, especially in coexistence with empty sella, DM II and HT. It can be commonly characterised by radiological and histopathological features of invasiveness – bone erosion and necrosis – despite its clinically benign nature. Surgical confirmation of the intact sellar floor or sellar dura is required to differentiate ESSPA from invasive PA. Surgical removal is an effective treatment.


Authors report no conflict of interest.


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Copyright: © 2017 Mossakowski Medical Research Centre Polish Academy of Sciences and the Polish Association of Neuropathologists. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
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