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The pituitary develops as a result of complex, intricate, and precise neuro-embryological events in the sixth to eighth weeks of gestation. Some ectopic cell rests can become adenomatous. Rarely, these cell rests in the clivus can be the site of formation of adenoma. Our patient, a 35-year-old parous woman, was being treated for acromegaly, and imaging studies revealed a clival mass lesion. Trans-sphenoidal excision was done and immunohistochemistry revealed the tumor to be a growth hormone-secreting tumor.
Pituitary adenomas are common intracranial tumors, accounting for nearly 10% of all neuro-oncological workload. Diagnosis is usually obvious in the presence of overt endocrinopathy. However, there may be situations where the hormone-secreting adenoma is ectopic in location, making the diagnosis and management difficult. Clivus is an unusual location for occurrence of a pituitary adenoma, and all previous reported cases of endocrinologically active adenomas involving the clivus have been prolactinomas. We report one case of growth hormone (GH)-producing tumor, occurring in the clivus, with an apparently normal-sized sella. Relevant literature is briefly reviewed.
A 35-year-old parous woman was admitted in January 2005 with a 1-year history of dull, generalized headache, acral enlargement, weight gain, and coarsening and enlargement of facial features. She was amenorrheic for nearly 12 months. There was no visual impairment, nasal discharge, or any limb weakness. Clinical examination revealed a normotensive female patient with acromegalic facies. Fundus examination and visual evaluation were unremarkable. Skull radiograph (lateral projection) revealed an apparently normal-sized sella with erosion of the sellar floor (Fig. 1). MRI of the skull base revealed an isointense mass lesion occupying the clivus below the sellar floor and connected to an intrasellar lesion by a narrow stalk (Fig. 2). Her basal GH level was 30.6 ng/mL (normal 0.0 to 5.0 ng/mL), and other hormone levels in the blood were within normal limits. Glucose tolerance test with 100 g revealed plasma GH levels to be 19.5, 17, 18.8, and 17.8 ng/mL at 30, 60, 90, and 120 minutes (with plasma glucose levels at 96, 194, 182, and 132 mg/dL, respectively).
The patient was prepared for surgery by parenteral steroids on the night prior to surgery. The tumor was approached by the trans-septal–trans-sphenoidal route. After removal of the perpendicular plate of vomer and the keel of the sphenoid, the sphenoid mucosa was removed. The bony covering of the tumor caudal to the sella was entered and pale pink and soft tumor was curetted out, leaving a clean bony cavity. The tumor had attachment to the intrasellar component through the sellar floor. However, on opening the sella and incising the dura, pale, normal-looking pituitary tissue was seen and biopsied from the sellar floor. The nasal cavity was packed after packing the sphenoid sinus with adipose tissue. Postoperatively, patient was given parenteral steroids for 48 hours together with antibiotics. There was no diabetes insipidus postoperatively, and she was discharged after 6 days.
Microsections from the intrasellar portion revealed normal-looking pituitary. Sections from the tumor showed a cellular tumor composed of round to oval cells disposed in a sinusoidal pattern exhibiting delicate fibrovascular septae. The tumor cells showed moderate eosinophilic cytoplasm, uniform-appearing nuclei displaying hyperchromatic evenly dispersed chromatin and small inconspicuous nucleoli. Occasional mitoses were seen (Fig. 3). The immunohistochemistry performed using streptavidin-biotin (Dako) exhibited strong diffuse cytoplasmic positivity of tumor cells for GH and prolactin. The follicle-stimulating hormone and luteinizing hormone showed weak patchy positivity in fewer than 5% of tumor cells. A diagnosis of pituitary adenoma coexpressing GH and prolactin was offered. The patient has been followed up for nearly 12 months. Oral glucose tolerance test with 100 g oral glucose after 3 months revealed plasma GH levels to be 0.5, 1.6, 1.2, and 1 ng/mL at 30, 60, 90, and 120 minutes (with glucose levels at 84, 138, 126, and 124 mg/dL, respectively).
A giant pituitary adenoma invading the sphenoid sinus, cavernous sinus, hypothalamus, posterior fossa, and temporal fossa is well known, and invasion of the clivus by a pituitary adenoma has also been documented. However, a pure ectopic location of pituitary adenoma is rare, and since its first description in 1909,1 only approximately 30 such cases of ectopic pituitary tumors have been reported.2,3 The location of ectopic pituitary tissue is explained on the embryological basis of formation and involution of the craniopharyngeal duct.3 The sellar region is a site of an intricate but precise sequence of neuroembryological development, with formation of pathological entities with an embryonic basis. During organogenesis of the pituitary gland, the separation of the primitive pituitary gland into pharyngeal and distal parts takes place at the eighth week of gestation. Ectopic pituitary tissue is commonly present in the pharyngeal mucosa in the midline over posterior vomerosphenoidal articulation (“pharyngeal pituitary”).3,4 While pharyngeal pituitary is a normal physiological entity in every human being, these cell rests can become the sites of origin of ectopic pituitary adenomas.
The majority of ectopic pituitary tumors have been in the sphenoid sinus5 or cavernous sinus or have presented as a nasopharyngeal mass. The variable location of the pharyngeal pituitary may explain the location of extracranial adenomas, in the nasopharynx, middle meatus of the nose, or the sphenoid sinus. Primary clival pituitary adenoma is rare, and has been reported only seven times so far (Table 1). Considering the fact that ectopic pituitary tissue is normally present in the pharyngeal mucosa, most often on the posterior vomerosphenoidal articulation of the median plane,4 the incidence is surprisingly rare. The location of the adenoma in the clivus corresponds to the posterior location of the pharyngeal pituitary.3 Clival pituitary adenomas have been explained on the basis of the presence of pituitary tissue in the persistent craniopharyngeal canal, which also explains the intraosseous location of the adenoma, an explanation offered for occurrence of clival craniopharyngioma also.6 Erosion of the sella in these cases does not indicate an invasive tumor; pituitary in these cases is usually normal.7 Most of the reported cases of clival pituitary adenomas have been prolactinomas (Table 1).2,4,5,8,9,10,11 In an ultrastructural study on an ectopic pituitary adenoma, Mount et al also found it to be prolactinoma.8 Hori and colleagues found normal pituitary tissue within the adenoma occupying the sella-clivus region, confirming the concept of ectopic pituitary tissue.3 Immunohistochemistry of their reported tumor showed positivity to follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, and thyroid-stimulating hormone. The present case is probably the only reported case yet of a GH-secreting tumor in this location. All reported patients were in their fifth to seventh decades, while the patient reported is the youngest reported so far. Treatment of these cases is surgical excision—by the trans-sphenoidal route. Anand and associates operated their patient by a maxillotomy approach.5 None of the reported cases suffered from postoperative diabetes insipidus, since the pituitary stalk is neither involved by the tumor nor it is affected by surgery.
Ectopic pituitary adenomas are rare. Those occurring within the clivus are distinctly rare, and their occurrence can be explained on the basis of embryology of the pituitary gland. Symptoms are in the form of endocrinopathy and headache. Imaging studies show a mass lesion occupying the clivus, with an apparently normal-sized sella. Surgery by the trans-sphenoidal route is curative.