Pituitary metastases of Hürthle cell carcinoma of the thyroid

Abstract

An 85-year-old man was referred to endocrinology following the discovery of an incidental pituitary mass on cranial imaging which was thought to be a non-functioning adenoma during an admission with headaches, lethargy, confusion and hyponatraemia. He had a history of Hürthle cell carcinoma of the thyroid treated with total thyroidectomy, ablative radioiodine therapy and thyroxine replacement. Subsequently, he developed metastatic spread to the neck, lungs and skeleton. About 9 months later, the patient had deterioration of vision. MRI showed a rapidly expanding pituitary mass with compression of the optic chiasm. Biochemical investigations confirmed hypocortisolism and hypogonadism. The patient underwent trans-sphenoidal resection of the pituitary mass followed by external beam radiotherapy to the pituitary bed. Histopathology confirmed a metastatic deposit of Hürthle cell carcinoma, which is a rare and aggressive variant of follicular thyroid carcinoma.

Background

Differentiated thyroid carcinoma (DTC) comprises follicular (FTC) and papillary thyroid carcinoma. Hürthle cell carcinoma (HCC) is an uncommon and aggressive variant of FTC. Metastases to the pituitary gland are uncommon and, when they do occur, are usually from either a lung or breast primary.¹ HCC has the highest rate of metastasis among all the DTCs, predominantly to lymph nodes and the lung.² Rarely does a DTC metastasise to the pituitary. There are fewer than 20 published cases of a pituitary metastasis arising from an FTC and only one report of a pituitary metastasis from HCC was found in our literature search.^{3 4} We describe another case of a pituitary metastasis from HCC.

Case presentation

An 85-year-old man was referred to the endocrine clinic with an incidental pituitary mass found during investigation for a 3-day history of headaches, lethargy and confusion. Investigations during the initial admission showed hyponatraemia (sodium 122 mmol/L) and hypocortisolism but no symptoms of an enlarging pituitary, including altered vision, polyuria and polydipsia. After discussion in the multidisciplinary team meeting, it was thought to be a probable non-functioning adenoma.

He had a history of HCC of the thyroid gland, initially diagnosed in 2010. Over time there had been metastatic spread locally in the neck and to lung and sternal bone. He had neck dissections with resection of the lymph nodes, an initial radioiodine ablative dose of 3.7 GBq and further therapeutic doses of 5.4 GBq and 5.3 GBq, respectively, over a 4-year period. In addition, he had external beam radiotherapy with 60 Gy in 30 fractions to the neck.

After a 6-month period of follow-up, imaging showed increasing pituitary mass deviating the chiasm to left. There were no visual symptoms at that point until about 2 months later when he developed narrowing of his peripheral vision. Ophthalmology review confirmed extensive visual field defects, predominantly in the left eye, including bitemporal hemianopsia, left nasal vertical hemianopsia, and superior and inferior defects in the right eye. In addition, there was impaired colour vision, which was worse in the left eye on Ishihara test. There was no relative afferent pupillary defect. He subsequently was referred to neurosurgery.

Investigations

Endocrine assessment confirmed hypocortisolism and hypogonadism (09:00 cortisol 53 nmol/L (50–2000 nmol/L); post-Synacthen stimulation cortisol 224 nmol/L (normal >420 nmol/L); testosterone <0.2 nmol/L (5.7–26.1 nmol/L) with low gonadotrophins. Thyroid function tests confirmed normal free thyroxine and triiodothyronine concentrations with suppression of the thyroid stimulating hormone to 0.02 mU/L (the patient was on a suppressive dose of thyroxine). The serum prolactin was modestly raised (501 mU/L; 45–375 mU/L) and the insulin-like growth factor was <15 µg/L (17–323 µg/L).

Serial contrast-enhanced MRI scans (see figure 1) showed a significant increase in the size of the intrasellar component of the pituitary tumour, which resulted in elevation of the chiasm. Over a 10-month period, the intrasellar component increased from 11×13 mm to 21×26 mm.

Figure 1.

These are coronal (top row) and sagittal (bottom row) slices of T1-weighted images taken from serial MRI scans of the pituitary with contrast and arrowheads showing the lesion. At diagnosis (A and D), the intrasellar component of the enhancing pituitary mass measured 13×11 mm and was causing deviation of the pituitary stalk and extension into the right cavernous sinus, but with no direct infiltration. Six months later (B and E), the intrasellar component had increased in size to 21×15 mm, with deviation of the pituitary stalk and optic chiasm. There is also further extension into the right cavernous sinus and early left cavernous sinus involvement with inferior extension into the sphenoid sinus and clivus. Four months later and preoperation (C and F), the intrasellar component was 26×21 mm and there is elevation of the chiasm.

Differential diagnosis

The differential diagnosis included a non-functioning pituitary macroadenoma or a pituitary metastasis.

Treatment

At the initial presentation, hydrocortisone was commenced with resolution of the hyponatraemia and the acute confusional state. Transphenoidal resection of the tumour was undertaken about 10 months after initial MRI finding of a pituitary tumour due to the progressive and rapid enlargement of the lesion with new visual disturbance. There were no postoperative complications. Subsequently, the patient received adjuvant radiotherapy with 45 Gy in 25 fractions to the pituitary bed about 3 months post-surgery. Follow-up images (figure 2) showed good debulking of the tumour with small foci of enhancement suggestive of either post-radiotherapy change or residual disease. The visual symptoms significantly improved.

Figure 2.

Coronal (top row) and sagittal (bottom row) slices of T1-weighted images taken from serial MRI pituitary with contrast and arrowheads showing the lesion. The immediate preoperative images (A and C) are shown on the left (as seen in figure 1) and these can be compared with the 5-month postoperative images (B and D) on the right, which show good debulking of the tumour with persistent small enhancing foci, which may represent post-radiotherapy effect; however, residual tumour cannot be entirely excluded.

Histopathology

The histopathology of the resected pituitary tissue showed fragments of tumour with hyalinised fibrous tissue and haemorrhage that contained nests of tumour cells forming acinic-like structures with irregular hyperchromatic nuclei and abundant eosinophilic to oncocytic cytoplasm (see figure 3). There were focal necrosis, and mitotic figures are conspicuous.

Figure 3.

Light microscopy: (A) H&E slide showing sheets of tumour cells forming occasional follicles. The tumour cells have irregular nuclei, occasional prominent nucleoli and abundant granular, eosinophilic cytoplasm; ×20; (B–D) immunohistochemistry shows that there is widespread tumorous expression of paired box gene 8 (B), thyroid transcription factor-1 (C) and thyroglobulin (D); ×20.

Immunohistochemistry showed that the tumour cells expressed paired box gene, thyroid transcription factor-1, thyroglobulin, CAM5.2 and CK7, widely. These tumour markers are highly indicative of a DTC (follicular/pappilary). There was a very focal expression of p53, and no expression of synaptophysin, chromogranin A or any of the pituitary hormones. The Ki67 proliferation index, which is a marker for cellsin mitosis, was about 10%, a level that is seen in malignant disease, rather than an adenoma. The morphology and immunophenotype were consistent with a metastatic deposit of Hürthle cell thyroid carcinoma.

Outcome and follow-up

A 5-month follow-up MRI scan of the pituitary with contrast showed good debulking of the pituitary tumour with small foci of enhancement suggestive of either post-radiotherapy change or residual tumour. He continued on hydrocortisone (10 mg morning, 5 mg mid-day and 5 mg evening) and levothyroxine (150 µg and 125 µg on alternate days) replacement. The visual acuity of the patient improved significantly, as well as his overall well-being.

Discussion

HCCs are a group of heterogeneous malignant tumours that exhibit diverse biological features and represent less than 5% of DTC.³ HCC is regarded as an oncocytic variant of FTC by the WHO.⁵ HCC is associated with a higher rate of metastatic disease, tumour recurrences and mortality.^{6 7} Hürthle cells, or oncocytes, are large cells characterised by the accumulation of altered mitochondria giving the cells abundant granular and eosinophilic cytoplasm along with distinct cell borders and large hyperchromatic nuclei containing prominent nucleoli.

Unusual metastatic sites described in the literature include the liver, breast, oesophagus, bronchus, retro-orbit, adrenal gland, abdomen, skull, skin and right atrium.

Metastases of HCC to the pituitary gland are extremely rare and the only report in the literature, from a PubMed search, is by Matyja et al.⁴ They described a middle-aged man who had a history of repeated thyroid surgeries for FTC and then presented with visual symptoms. MRI confirmed a homogeneous sella/parasella mass which was surgically excised. Histopathology of the tissue showed metastatic HCC. Incidentally, our patient was also a man, though HCC is said to be more common in women, with a female to male ratio of approximately 2:1–4:1.⁸

The clinical feature that suggests a pituitary metastasis rather than a primary pituitary adenoma is diabetes insipidus, but other features such as rapid enlargement leading to ophthalmoplegia and ptosis (due to mass effects) may also be relevant.⁹ It is important to note that our patient did not present with symptoms of diabetes insipidus. This is similar to the findings from other reports of pituitary metastases from thyroid carcinoma in the literature.¹⁰ It was postulated that this may be due to the fact that pituitary metastases from thyroid carcinomas tend to be parasellar lesions instead of intrasellar, which tend to affect pituitary tissue and interrupt the pituitary stalk.¹¹ As a result, metastases from thyroid carcinoma to the pituitary gland tend to present with features suggestive of mass effects rather than endocrine disruption of the pituitary stalk.

In summary, we described another case of HCC with metastasis to the pituitary gland. Doctors caring for patients with Hürthle cell variant of FTC should be aware of its potential to metastasise to the pituitary gland, especially in those patients who present with visual symptoms.

Patient’s perspective.

Next of kin perspective (wife)

I was initially very scared when he started feeling blurry and funny in his vision. I thought he was going to lose his sight. But after the treatments he got, he is very fine now without any problems with his vision. We are very pleased with the treatments he got.

Learning points.

• Metastatic Hürthle cell carcinoma to the pituitary, though extremely rare, can occur.

• A high index of suspicion of metastatic Hürthle cell carcinoma to the pituitary gland should be considered in patients with this oncocytic variant of follicular thyroid carcinoma presenting with visual deterioration.

• There is the need to consider early repeat MRI scans (3–6 months) in order to detect early enlargement of lesions, especially when metastasis is suspected.

• The absence of diabetes insipidus does not exclude metastatic deposit.