Ectopic pituitary adenoma: a rare and unexpected diagnosis, clinical presentation and review of the literature

INTRODUCTION

Ectopic pituitary tumors are rare tumors exclusively found outside the sella turcica.¹ Embryologically, the anterior pituitary is derived from an outpouching of the roof of the primordial oral cavity, Rathke’s pouch.¹ These rare tumors seem to derive from cells of the Rathke pouch during its migration in embryogenesis.¹ In the literature are present only 8 cases of ectopic pituitary tumor located in the nasopharynx. Current report is a case of ectopic pituitary adenoma found in the nasopharynx with extension to the clivus, parasellar regions and infratemporal fossa, bilaterally. The description of the pathological findings, radiologic studies and the surgical management are described.

CASE REPORT

History and examination

A 45 year old woman presented with an occasional nasal bleeding for 10 years and progressive bilateral nasal obstruction for 2 years. Regarding the past medical history, she underwent a percutaneous transvenous mitral commissurotomy in 2006, so she was taking anticoagulant therapy (nicoumalone).

She was evaluated at the ENT department, and a nasopharynx mass was rule out during nasal endoscopy. The mass was covered by pinkish smooth mucosa covered and filled the rinopharinx, with posterior choana obstruction bilaterally (Figure 1). Therefore, the patient was taken for biopsy of the mass, under general anesthesia, following a radiological study with a non-contrast computed tomography (NCCT) of paranasal sinuses and a brain MRI with gadolinium contrast.

Radiology

Contrast enhanced magnetic resonance imaging (Figure 2 and Figure 3) and a non-contrast computed tomography (NCCT) scan (Figure 4) of the paranasal sinuses demonstrated the presence of large lobulated well defined homogeneous soft tissue mass lesion measuring 4.6x5.5x3.4 cm (APxMLxCC) in the base of skull extending superiorly involving bilaterally the sphenoid sinus, posteriorly causing destruction of the clivus, anteriorly entering into choanae bilaterally and inferiorly abutting the hard palate, entering bilaterally parasellar regions eroding pterygoid roots and medial part of basi sphenoid bone (Figure 2, Figure 3, and Figure 4). Thinning of the sella was seen, however pituitary glands appeared normal. At the MRI the mass lesion appeared almost isointense to gray matter on T1/FLAIR/T2 weighted images and on post contrast scans, it showed diffuse homogeneous enhancement.

Pathological findings

Unexpectedly, the histological result of the biopsy tissue showed presence of tumor comprising monomorphic tumor cells arranged in organoid, solid and trabecular growth patterns. The individual tumor cells were plasmocytoid and are relatively monomorphic having round to oval nuclei with dispersed chromatin, inconspicuous nucleoli and abundant eosinophilic granular plasmacytoid cytoplasm. Mitosis is infrequent. No necrosis was noted. Morphologic features were pituitary adenoma. Tumor cells were positive for ACTH expression on immunohistochemistry, while negative for GH and PRL (Figure 5).

Surgery and post-operative course

The patient was scheduled for surgical excision of the nasopharynx ectopic pituitary adenoma, through a transnasal transethmoidal endoscopic approach. Using a zero degree endoscope an antero-posterior ethmoidectomy was performed and the mucosa of the posterior portion of the septum was removed. The tumor arised from the posterior nasal septum and extended towards the nasopharynx and the pterygopalatine fossa bilaterally. The tumor was removed endoscopically along with the posterior portion of the nasal septum. The rostrum and the intersphenoid sinus septum were drilled, opening the sphenoid sinus, which was free from disease. The medial pterygoid plates were also removed in order to obtain a good surgical removal laterally, then the tumor was dissected posteriorly. Intraoperatively, erosion of the clivus posteriorly was noted, without any interruption of the bone.

The post-operative course was regular and no intra- and post-operative complications were observed. The final histologic exam confirms the diagnosis of pituitary adenoma. The patient after 8 months of follow up presents regular result of surgery, no recurrence of disease at the endoscopic examination. An MRI is planned to rule out any residual disease.

DISCUSSION

Ectopic pituitary adenoma is defined as a pituitary adenoma occurring outside of the sella turcica, without any direct connection to either the intrasellar gland or the pituitary stalk.¹ The most common locations are the sphenoid sinus, clivus, suprasellar space, nasopharynx, and cavernous sinus.²

The majority of ectopic pituitary tumors are reported as being functional secretory tumors. Nowadays, in total 85 cases of ectopic pituitary tumors are described in literature.² Out of these 85, 6 were classified as malignant or as having undergone a malignant transformation. In the majority of the cases (59% of total) are functional tumors (featured hormonal expression on immunohistochemistry staining and were found to be clinically active (caused hormonal symptoms in the patient), and ACTH producing tumors were the most common subtype (46%).¹

The origin of ectopic pituitary tumors is not clear; nowadays, the accepted hypothesis suggests that the tumors are derived from cells of the Rathke’s pouch during its migration in embryogenesis.^3,4

The anterior pituitary is derived from an outpouching of the roof of the primordial oral cavity, Rathke’s pouch. The pouch during embryogenesis, ascends from the pharyngeal roof to join the neurohypophysis. It then loses its attachment to pharyngeal roof when its stalk ruptures. While the posterior pituitary is derived from an outpouching of the diencephalon. The deposition of residual adenohypophysis cells in the infrasellar region, occurs by partial persistence of the pouch in the wall of the buccal cavity, craniopharyngeal canal, or sphenold sinus.

On the other hand, aberrant suprasellar adenohypophysis may originate later when the pars tuberalis develops from the pars anterior of the pituitary. The adenohypophysis originates extracranially and only later becomes attached to the neurohypophysis, so the pituitary cells may easily be displaced in the leptomeninges of the peri-infundibular region. Hori analyzed the routine autopsy examination of all fetal brains older than the 16th gestational and "normal" adult brains and he found that pharyngeal location of pituitary cells is a constant finding and almost always present in the leptomeninges of the suprasellar region. Therefore, it seems that the origin of extracranial ectopic tumor, might arise from extracranial pre-existent normal aberrant pituitary tissue while intracranial ectopic tumor might arise from suprasellar normal aberrant pituitary tissue.⁵ Anyway, the criteria for diagnosing ectopic adenoma require detailed histopathological examinations including immunocytochemical and ultrastructural studies.⁶

We presented a case of ectopic giant pituitary adenoma with positive staining for ACTH, located into the nasopharynx extending to the clivus, the sphenoid sinuses and parasellar regions. Nasopharinx and clivus are the rarest locations for an ectopic pituitary adenoma, only 14 cases in the clivus are described in literature and 8 cases in the nasopharynx. Moreover, in our case, because of the dimensions of the mass, it may be considered as a giant ectopic pituitary adenoma. Giant pituitary adenoma is defined as tumors 4 cm or greater in maximum diameter, are very rare, account for 5%-14% of adenomas in surgical series.^7-9

The clinical presentation of this lesion was related to the location and size of the mass, since the patient presented with bilateral nasal obstruction and occasionally epistaxis, without hormonal signs and/or symptoms. Radiologically, ectopic pituitary adenomas can mimic other skull base lesions. MRI is useful in evaluating the extension of the extrasellar mass, the integrity of the sellar dura and the presence of normal pituitary gland.¹⁰

Radiologically and intraoperatively, in the reviewed case, the mass presented bony erosion, as described in the literature that the common ectopic pituitary adenoma locations with bone involvement are the clivus and nasopharynx. Because of these radiological characteristics, in our case the differential diagnosis at the MRI and the CT scan were chordoma, chondrosarcoma, plasmocytoma, nasopharyngeal carcinoma or methastasis. The mass was isointense to gray matter on T1/FLAIR/T2 weighted images and on post contrast scans, it showed diffuse homogeneous enhancement. Chondrosarcoma typically shows at the MRI heterogeneously enhanced mass with high signal intensity on T2 and at the CT scan show a chondroid mineralization.

Plasmacytoma is a lytic lesion iso-hypointense to gray matter on T1, homogeneous, isointense on T2, homogeneous, iso or hyperintense to gray matter on FLAIR. While chordoma is a midline mass originating from the clivus hyperintense on T2WI and intermediate to low signal on T1 with a mixed density with areas of cystic necrosis mixed with enhancing soft tissue at the contrasted enhanced CT scan.

The main management of the ectopic pituitary adenomas are the surgical removal, because in the literature malignant ectopic pituitary adenoma or as having undergone a malignant transformation are described, although in very rare cases. The surgical procedures varied according to the location and the extensions. We choose to remove the ectopic pituitary adenoma with a gross total resection, through an endoscopic transnasal transethmoidal approach because of the location and extension of the tumor that no contraindicated the exclusive endoscopic procedure. In our case, since the giant adenoma was ectopic, the main goal of the surgery was a maximal safe tumor resection to relief the symptoms avoiding residual disease.

CONCLUSION

Ectopic pituitary tumors are rare tumors that can present as nasal mass. These should also be kept as differential diagnosis while evaluating nasal masses.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

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