A very rare case of pituitary metastasis infiltrating a non-secretory gonadotroph adenoma

Background

Metastatic disease to the pituitary is reported to account for approximately 0.4% of all brain metastases and a carries a poor prognosis, with a median life span of 14 months (range 4 to 30 months) depending on the origin and stage of the primary cancer (1). Breast and lung cancers are the most common sites of origin (1, 2). Approximately 30% of pituitary metastases are silent, while the majority present with mass related symptoms such as retro orbital pain/headache, visual defects and ophthalmoplegia (3). The commonest endocrine manifestation is diabetes insipidus (70% of the symptomatic patients), followed by anterior hypopituitarism (15% of the symptomatic patients) (3).

Metastases to a pre-existing pituitary adenoma are extremely rare, with only 31 reported clinical cases in the world literature (4, 5). Endocrinological, visual and cranial nerve complications are found to be more frequent with a dual pituitary lesion. This is likely due to either hormonal hypersecretion from adenomas and/or hormonal deficiency caused by a greater mass effect (5).

In this paper we present a case of breast carcinoma metastasis to a pituitary adenoma and review the relevant literature.

Case presentation

An 83-year-old white man with a background history of metastatic breast carcinoma presented with a 2-week history of headache and bitemporal hemianopia. He was initially diagnosed with invasive ductal carcinoma of the right breast 5 years prior, which was treated with total mastectomy. His tumour was 4 cm in size, TNM stage PT2N0M0 and oestrogen receptor (ER) positive. Post-operatively, he was commenced on Tamoxifen. He later developed lymph node metastases and was switched to the Gonadotrophin releasing hormone (GnRH) analogue Goserelin 3.6 mg (GnRHA) monthly, in tandem with the aromatase inhibitor Letrozole 2.5 mg daily.

On presentation, brain and pituitary MRI revealed a 33 × 17 × 15 mm solid and cystic hyperintense lesion arising from the sellar and suprasellar regions with chiasmal compression (Fig. 1). His pituitary function tests revealed low random cortisol, morning testosterone (on GnRH analogue) and IGF-1 levels, with normal thyroid function and electrolytes (Table 1). He had no symptoms suggestive of diabetes insipidus (DI).

View Full Size

(A and B) Images are pre-operative, axial and sagittal T1 MRI showing 33 × 17 × 15 sold cystic hyperintense lesion arising from sellar and suprasellar regions (thin arrows) with left optic chiasm (thick arrow) compression.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2020, 1; 10.1530/EDM-20-0094

• Download Figure
• Download figure as PowerPoint slide

Differential diagnosis

Given his medical history of metastatic breast carcinoma, in addition to current use of GNRH analogue, our initial differentials included pituitary metastasis, pituitary adenoma or pituitary apoplexy.

Treatment

Initial treatment included IV followed by oral stress doses of hydrocortisone. Endoscopic transsphenoidal pituitary surgery was performed with an uneventful operative and post-operative course. Neuropathological examination of the resected tissue revealed a gonadotroph pituitary adenoma (demonstrating focal expression for follicular stimulating hormone (FSH) and luteinising hormone (LH), as well as widespread nuclear expression of gonadotroph transcription factor SF1), infiltrated by breast adenocarcinoma with positive oestrogen and progesterone receptors and HER2 (2+) similar to his primary breast carcinoma (Fig. 2).

View Full Size

Histopathology slides showing a pituitary adenoma composed of monomorphic cells with round to oval nuclei and abundant pale eosinophilic cytoplasm (A) with expression for follicular stimulating hormone (FSH) (B), luteinising hormone (LH) (C) and SF1 (D), infiltrated by metastatic adenocarcinoma (E), which was cytokeration 7 (F) and GATA3 (G) positive, consistent with origin from breast primary.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2020, 1; 10.1530/EDM-20-0094

• Download Figure
• Download figure as PowerPoint slide

Outcome and follow-up

He was discharged on hydrocortisone 10 mg in the morning and 5 mg afternoon. He was also educated about the glucocorticoid sick day rules and an educational leaflet was given. He underwent fractionated pituitary radiotherapy afterwards with a total dose of 25 Gy/5.

A post-operative (pre-radiotherapy) pituitary MRI in October 2019 showed a significant reduction in the tumour size of 13 × 14 × 9 mm without compression of the optic chiasm. There was a significant improvement in his visual symptoms and resolution of his headache. Repeat pituitary assessment 4 months post-radiation showed normal corticotropin and thyroid function tests (Table 1). His gonadotropins and testosterone remained suppressed (iatrogenic) and his IGF-1 stayed low. Interestingly, he had no evidence of DI.

Discussion

Metastatic disease to pituitary adenomas has been very rarely reported in the literature.Our case is the third description of a breast metastasis into a gonadotroph cell pituitary adenoma after that of Bret et al. and Mils et al. (5, 6). Differentiation between benign and metastatic pituitary gland lesions clinically can be difficult, but it is crucial for treatment options (1). Although diabetes insipidus (DI) occurs more frequently with metastatic disease, this is not always the case, as it did not occur with our patient. Ocular manifestations may not be helpful in differentiating between pituitary metastases and growing adenomas. However, the presence of rapidly progressive compressive symptoms on a background of malignancy, as in our patient, should always raise the suspicion of metastatic disease.

While imaging studies, including a dedicated pituitary scan, will show a sellar/stalk mass, it cannot confidently diagnose a metastasis or more rarely mixed tumours within the gland.The MRI in our case showed a large enhancing cystic solid lesion which was similar to earlier reported cases. Furthermore, intraoperatively, these pituitary lesions including our case have no characteristic features that may suggest the diagnosis of infiltrating neoplasm into an adenoma. Therefore, histopathology remains the definitive method to establish the diagnosis (1). Immunohistochemistry plays an essential role in the differentiation between the mixed components of a solitary lesion (1).

There are several theories that explain the occurrence of infiltrating metastases in pituitary adenomas. One attractive hypothesis relates to changes in the normal blood supply of the pituitary gland. It has been reported that pituitary adenomas can have additional arterial circulation, bypassing hypophyseal portal circulation, from carotid and meningeal arteries. This rich vascular supply of pituitary adenomas creates an extra access for metastases from the circulation. This has been observed specifically with metastases to non-functioning FSH/LH gonadotroph adenomas (7). Another proposed theory is the presence of certain growth factors produced by metastases which lead to direct binding and interaction with epithelial cell receptors of pituitary adenomas as was reported with metastatic renal cell carcinoma (8). Hormonal therapy, as in our patient, previous radiation and surgical intervention may also lead to significant changes in adenoma microstructures, resulting in the development of metastatic disease (9). Another interesting finding in our case, is the use of an GnRH analogue on a background of an undiagnosed pituitary lesion. GnRH analogues are currently used to treat prostate cancer and metastatic male breast cancer. There are several case reports of pituitary apoplexy with the use of GnRH. It was found that these agents may accelerate the growth of asymptomatic pituitary adenomas and cause haemorrhage/infarction (10). However, this was not a part of our patient’s presentation.

Conclusion

Metastases to a pituitary adenoma is an extremely rare condition with no specific clinical manifestations. However, it should always be considered in the differential diagnosis of rapid progression of pituitary disease, in particular when the patient has underlying malignancy. To our knowledge, this is the third case of breast adenocarcinoma metastasising to a gonadotroph pituitary adenoma.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Patient consent

Written informed consent has been obtained from the patient.

Author contribution statement

All authors included in this article made substantial contributions to the study, as well as assisted with critical revisions of the writing, and approved the final version for submission for publication.