Pituitary infundibular epidermoid cyst: a rare cause of hypopituitarism

Abstract

A 53-year-old man presented with 6 months history of weight loss associated with nausea, fatigue, dizziness and headache. On arrival he was in adrenal crisis. Biochemistry revealed anterior hypopituitarism with low cortisol, thyroxine, testosterone and a slightly raised prolactin. He was commenced on steroids, thyroxine and testosterone. MRI pituitary gland was reported to have a 9.4 mm microadenoma. Cabergoline was started for a possible microprolactinoma. Follow-up MRI showed increase in the size of complex cystic lesion causing chiasmal compression raising a possibility of craniopharyngioma. Visual fields assessment was normal. In view of the rapid enlargement, to protect vision and obtain a tissue diagnosis he underwent endoscopic trans-sphenoidal surgery. A cystic lesion was noted intraoperatively originating from pituitary stalk with intrasellar and suprasellar extension. It was filled with white caseous material and fluid. Histology revealed epidermoid cyst. His headache resolved postoperatively.

Background

Intracranial epidermoid cysts (ECs) are rare and constitute about 1% of all brain tumours. They are commonly located in the subarachnoid space of the cerebello-pontine angle and less frequently in the parasellar region. EC in the pituitary stalk is extremely rare with only five cases reported in the literature. We describe the sixth case of EC arising from the pituitary infundibulum and the first case to present with anterior hypopituitarism. Radiological diagnosis is challenging as it mimics other cystic conditions. Our case was initially thought to be microprolactinoma and then craniopharyngioma, but the diagnosis was only established on biopsy after trans-sphenoidal surgery. We aim to review literature to look further into the clinical behaviour of pituitary stalk ECs.

Case presentation

A 53-year-old man presented with 6 months history of weight loss, tiredness, nausea, intermittent severe headaches and dizziness which got worse over the preceding 2 weeks. He did not have any visual disturbances. His past medical history included chronic back pain. He was not taking any regular medications. On arrival he was drowsy and hypotensive. A random cortisol level of 34 nmol/L was suggestive of adrenal insufficiency. He was immediately resuscitated with intravenous fluid and hydrocortisone. Further pituitary function tests revealed hypogonadism, hypothyroidism and low adrenocorticotrophic hormone (ACTH) consistent with anterior hypopituitarism.

Initial MRI of the pituitary was reported to have a 9.4 mm hypointense lesion in the posterior aspect of the pituitary consistent with microadenoma with no evidence of chiasmal compression (figure 1A, B). In view of the prolactin being moderately raised at 735 μ/L (normal range: 73–407) this was initially thought to be a possible microprolactinoma and was therefore commenced on cabergoline.

Figure 1.

Sagittal (A) and coronal (B) T1-weighted initial MRI showing a cystic lesion in the pituitary gland (arrows).

Subsequent short synacthen test showed a 30 min response of 100 nmol/L (cut-off >450) and low ACTH confirming secondary adrenal insufficiency. His symptoms improved after hormonal replacements and was discharged home.

Interval MRI 10 months later surprisingly revealed an increase in the size of the cystic lesion from 8.6 mm to 10 mm in the transverse plane with a new rim enhancing component measuring 12.3×9.7×11.1 mm causing compression of the optic chiasma and extending to the third ventricle floor (figure 2A–C). The lesion was thought be a possible craniopharyngioma as the features were atypical for pituitary adenoma. Prolactin levels were undetectable on cabergoline and this was therefore stopped. Formal visual field testing did not show any visual field deficit.

Figure 2.

T1-weighted sagittal (A), T1-coronal (B) and T2-weighted coronal (C) sections of the MR pituitary gland showing complex infundibular cystic lesion (arrows) which has enlarged further with new rim-enhancing components pressing on the optic chiasma, on a follow-up scan 10 months later.

It was decided in pituitary neurosurgical mutidisciplinary team (MDT) to proceed with surgery, with the aim to decompress chiasmal apparatus and obtain a tissue diagnosis. CT pituitary prior to surgery showed further enlargement of the lesion and a tiny focus of calcification was noted, supporting the presumed diagnosis of craniopharyngioma.

He underwent surgery through an expanded endonasal trans-sphenoidal and transtubercular approach. The pituitary gland was transposed inferiorly to expose the lesion between the gland and chiasm. The chiasm and third ventricular floor were exposed and were separate to the lesion. A thin-walled partly cystic lesion containing white caseous material and fluid was resected. The infundibulum was preserved. There were no postoperative complications. He noticed marked symptomatic improvement of his headache.

Biopsy of the specimen showed mostly squamous epithelium with a few keratohyaline granules resting on fibrous connective tissue. There was flaky lamellated keratin. These appearances were consistent with an EC (figure 3).

Figure 3.

Histology of the resected specimen showing squamous epithelium with a few keratohyaline granules resting on fibrous connective tissue. There is flaky lamellated keratin. The appearances are consistent with an epidermoid cyst.

Two scans postoperatively have shown stable appearances of the minor residual tissue posterior to the chiasm and he is currently under endocrine and neurosurgical surveillance. Postoperative hormonal assessment was consistent with anterior hypopituitarism and therefore he remains on hormonal replacement therapy with hydrocortisone, levothyroxine and Ttestosterone.

Investigations

Initial investigations on first presentations showed the following:

• Testosterone: <0.7 nmol/L(normal range (NR): 8.0–30)

• Prolactin: 735 mU/L (NR: 73–407)

• Luteinising hormone (LH): 0.9 IU/L IU/L (NR: 1.0–12.0)

• Follicle-stimulating hormone (FSH): 1.5 IU/L IU/L (NR: 1.0–12.0)

• Cortisol: 34 nmol/L nmol/L

• Free T4: 6.3 pmol/L pmol/L (NR: 9.0–19.1)

• Thyroid-stimulating hormone (TSH): 0.87 mU/L (NR: 0.30–4.40)

• Insulin-like growth factor (IGF-1): 10.6 nmol/L (7.0–29.0)

• Adrenocorticotrophic hormone (ACTH): 2.2 ng/L ng/L (NR: 7.0–63)

• Short synacthen test: 0 minute min cortisol—<28

• 30 minute min cortisol—100

Discussion

ECs are benign slow growing tumours characterised by desquamation of epithelial cells, consisting of keratin and cholesterol-forming pearly white tissue on gross examination.¹ They arise from ectodermal tissue during congenital development.²

Intracranial ECs are rare and accounts for roughly 1% of all intracranial tumours.³ They are commonly located within the cerebellopontine angle cistern and less frequently in the parasellar region.⁴

EC originating from the pituitary stalk are extremely rare and to our knowledge only five cases have been reported in the literature which are summarised in table 1.

Table 1.

Previous and current reported cases of pituitary infundibular epidermoid cyst

Paper	Age	Sex	Presentation	Imaging characteristics	Preoperative hormone status	Postop status
Costa et al, 20135	27	F	Amenorrhoea, galactorrhoea, polyuria, polydipsia	Mixed signal, bilobed rim enhancing cystic lesion	Hyperprolactinaemia (150–200 ng/mL)	Not reported
Nakassa et al, 20176	54	F	Headache, visual disturbance, polyuria, polydipsia	Mixed signal, non-enhancing cystic lesion	Not reported	Persistent DI, subjective visual fields improvement
McCormack et al, 20187	36	F	Headache, visual disturbance	Multilocular T1 hypointense, T2 hyperintense, rim-enhancing lesion	Diabetes insipidus	Transient DI
Khan et al, 20198	55	M	Decreased visual acuity	Mixed signal, rim-enhancing cystic lesion	Normal	Panhypopituitarism, subjective visual fields improvement
Lee et al, 20209	63	M	Polydipsia, polyuria	T2 hyperintense, rim-enhancing cystic lesion	Diabetes insipidus	Persistent DI
Current case	53	M	Weight loss, tiredness, nausea, intermittent headache and dizziness	Mixed signal, rim-enhancing lesion	Anterior hypopituitarism	Persistent hypopituitarism, developed recurrent VTE

DI, Diabetes insipidus; VTE, Venous thromboembolism.

Our case was unique in that it presented with adrenal crisis. Interestingly there was no evidence of diabetes insipidus which has been commonly reported with previous cases.

The main differential diagnosis of a cystic lesion in the parasellar region particularly the infundibulum include craniopharyngioma, Rathke’s cleft cyst and EC.⁵

EC are typically slow-growing tumours which are mainly asymptomatic until it becomes large enough to cause compression of the surrounding structures causing headache, visual symptoms and/or pituitary hormonal disturbance. We observed a rapid enlargement on interval scans in our case causing compression of the optic chiasm but visual fields remained intact. These lesions mainly enlarge by desquamation and accumulation of keratin in the cyst cavity.

The first case of infundibular epidermoid cyst (IEC) was reported by Costa et al in 2013. They reported a 27-year-old female who presented with amenorrhoea, galactorrhoea and osmotic symptoms and was found to have hyperprolactinaemia and diabetes insipidus. Her visual disturbance improved following surgery. Postoperative hormonal status was not included in the report.⁵

Nekassa et al reported the second case of IEC of a 54-year-old woman with presenting symptoms of headache, visual disturbance and diabetes insipidus. She also had mild hyperprolactinaemia. Postoperatively she continued to take desmopressin.⁶

The mild hyperprolactinaemia is likely due to the stalk compression leading to cessation of the inhibitory effect of dopamine on prolactin. This can be confused with prolactinoma as in our case the initial pituitary imaging was reported as microadenoma. This not only delays the diagnosis but also leads to inappropriate treatment with dopamine agonists. Our patient’s symptoms did not improve with cabergoline in spite of prolactin in the undetectable range. The tumour size also increased on interval scan unlike prolactinoma which responds very well to dopamine agonists.

McCormack et al reported a 36-year-old woman presented with headache and visual symptoms and develop a transient diabetes insipidus postoperatively which recovered completely.⁷

The fourth case was reported by Khan et al of a 55-year-old man who presented with bitemporal haemianopsia but no pituitary hormonal deficits. Postoperatively he developed panhypopituitarism which was appropriately treated.⁸

The last and the fifth case of IEC was reported by Paul Lee et al. This was a 63-year-old man presented with osmotic symptoms and was found to have diabetes insipidus. He underwent pretemporal craniotomy unlike the other cases which were treated with endoscopic extended trans-sphenoidal approach. Diabetes insipidus remained persistent post operatively.⁹

There was a remarkable improvement in our patient’s headache postoperatively. Headache was commonly noted in the previous case reports. Current teaching suggests that the stretch of the sellar region and medial wall of the cavernous sinus are influenced by intrasellar hypertension. While many brain tumours present with headache, the headache associated with epidermoid tumours has not demonstrated correlation with the size of the tumour.¹⁰

Arafah et al demonstrated that patients with pituitary adenomas presenting with headache had higher mean intrasellar pressure than those who did not have headache regardless of their pituitary function or tumour size. Therefore they postulated that intrasellar hypertension is the major mechanism for the causation of headache in these patients.¹¹

Radiologically EC present a diagnostic challenge and it is sometime impossible to make a diagnosis preoperatively. The main differentials are craniopharyngioma and Ratke’s cleft cyst. The hypodensity of epidermoid lesions is characteristic of these tumours, the lack of enhancement attributed to their low vascularity. Diffusion-weighted (DW) imaging can be helpful as ECs appear hyperintense in comparison to arachnoid cysts and other tumours commonly confused with these cysts.² We do not usually do DW imaging for the parasellar region as EC are very rare in this region.

Gross total resection is the mainstay of treatment of intracranial ECs.¹² This is mainly due to the risk of recurrence. However, this may not always be possible as the cyst wall can be adherent to the surrounding neurovascular structures.¹³

The most common complications noted after resection of ECs include chemical meningitis, hydrocephalus, infectious meningitis and cranial nerve palsies.¹³

In conclusion, we present a rare and unusual case of EC of the pituitary stalk. Only five other cases are reported which are mainly in the neurosurgical literature.

To our knowledge this is the first case description of IEC presenting with adrenal crisis as part of anterior hypopituitarism. Our patient had appropriate hormone replacements prior to surgery. Postoperatively there was marked improvement in his headache.

Learning points.

• Infundibular epidermoid cysts (IECs) are extremely rare but can present with disruption in the pituitary functions leading to life-threatening sequelae.

• Preoperative diagnosis can be very challenging as it mimics other cystic conditions such as papillary craniopharyngioma and Rathke’s cleft cysts.

• Although ECs are considered slow-growing tumours but can occasionally grow rapidly as in our case.

• Complete resection of IEC is the treatment of choice but this may not be achievable due to the surrounding neuroanatomy.

• Preoperative hypopituitarism is unlikely to be reversed following resection and these patients may require lifelong pituitary hormonal replacement.