Pituitary metastasis revisited: a retrospective single-center experience with diagnostic challenges and surgical nuances. Illustrative cases

Abstract

BACKGROUND

Pituitary metastases represent approximately 1% of all pituitary tumors and are associated with a poor prognosis. Although rare, early diagnosis and treatment are critical to limit rapid clinical decline. Because of their rarity, published data remain limited. The authors report their institutional experience at The Ottawa Hospital, focusing on clinical and radiological presentation, surgical management, adjuvant therapy, and outcomes.

OBSERVATIONS

The authors retrospectively reviewed the cases of adult patients undergoing endoscopic endonasal skull base surgery for pituitary metastases between 2016 and 2025. Inclusion criteria were histopathological confirmation and complete clinical data. Four patients (mean age 57 years) were identified; 3 had known primary malignancies. All of the patients had cranial nerve (CN) deficits. Headache was the most common symptom, followed by visual disturbance; diabetes insipidus occurred in 2 patients. Imaging showed bone erosion in all cases and cavernous sinus invasion in 1 patient. All patients underwent endoscopic resection. Tumors were adherent and highly vascular, requiring meticulous microsurgical dissection and hemostatic agents. Postoperative complications were minimal, with one CSF leak. All patients received adjuvant radiotherapy. CN improvement occurred in 3 patients. Three patients died, with a mean survival of 6.3 months postdiagnosis.

LESSONS

Pituitary metastases are associated with rapid clinical deterioration and poor survival. Multidisciplinary management and further research are needed to improve outcomes.

https://thejns.org/doi/10.3171/CASE26115

Pituitary metastases account for approximately 1% of all pituitary tumors and are typically associated with a poor cancer prognosis.^1–3 The most common primary sources are lung (39.7%) and breast (23.7%) cancers, followed by kidney, prostate, and thyroid malignancies, which together account for 3%–5% of cases.^1,4,5

Patients generally present in the 6th or 7th decade of life, with no significant sex predominance² and lesions most commonly involving the neurohypophysis, with only about 15% of cases affecting the anterior lobe.¹ Consequently, symptoms related to posterior pituitary dysfunction, such as diabetes insipidus (DI), are the most frequent clinical manifestations.^4,6 Additional presenting features may include symptoms resulting from compression of adjacent structures, such as headache, visual impairment, and cranial nerve (CN) palsies.

Although the incidence is uncommon, prompt diagnosis and treatment are critical to limit rapid clinical decline. Because of its rarity, there is limited literature addressing this type of tumor metastasis. We present our experience with patients harboring pituitary metastasis treated at The Ottawa Hospital, focusing on initial clinical and radiological presentation, surgical management, additional treatment, and outcomes.

Methods

A retrospective review of the skull base surgery database at The Ottawa Hospital, Civic Campus, was conducted to identify adult patients who underwent endoscopic endonasal skull base procedures between 2016 and 2025. Medical records were screened for inclusion based on a confirmed histopathological diagnosis of pituitary metastasis and the availability of comprehensive clinical data. Exclusion criteria included indeterminate pathology, incomplete clinical records, a history of prior CSF leaks, skull base trauma, or active infection at the time of surgery.

Relevant clinical, radiological, surgical, and follow-up data were extracted and analyzed. Variables included demographic information, preoperative assessment (symptoms, neurological deficits, and presence of active cancer at diagnosis), imaging characteristics of the tumor (including location and extent), endocrine abnormalities, surgical procedure performed, intraoperative complications, presence of metastatic disease outside the CNS, additional treatments received (e.g., radiation therapy), and overall survival. Tumor characteristics and extent were primarily evaluated using 3T MRI, except in 1 patient with a cardiac device, for whom CT imaging was used. All patients underwent full-body contrast-enhanced CT scanning in order to assess progression of their baseline disease status in the preoperative period. All patients also underwent baseline and dynamic preoperative endocrine evaluation. Hormonal deficiencies were diagnosed based on serum hormone levels falling below established reference thresholds for the corresponding endocrine axis. Partial hypopituitarism was defined as dysfunction of two hormonal axes, while panhypopituitarism was diagnosed when three or more axes were affected.

All procedures were performed using an endoscopic endonasal transsphenoidal approach. The surgical technique and instrumentation used for skull base access via this route have been previously described⁷ and were applied consistently in all cases.

Postoperative imaging with high-resolution 3T MRI was performed in all patients to assess the extent of resection and to monitor for residual or recurrent disease. Imaging follow-up was conducted at regular intervals in accordance with institutional protocols.

Illustrative Cases

Four patients underwent endoscopic endonasal surgery for pituitary metastasis. The mean age of diagnosis was 57 years, with an equal male-to-female ratio. Three of the 4 patients had a previous history of malignancy, including thyroid, breast, and renal cancer. However, the fourth patient had no known primary tumor at the time of diagnosis (Table 1).

TABLE 1.

Patient demographics, preoperative features, and tumor, surgical, and pathological characteristics

	Patient 1	Patient 2	Patient 3	Patient 4
Age (yrs)/sex	61/M	40/F	69/M	58/F
Clinical presentation	Headache, neck pain on rotation	Headache, burning facial pain, weight loss, leg pain	Headache, visual field changes	Diplopia
Primary cancer	Thyroid	Unknown	Renal	Breast
CN deficits	Rt CN XII	CNs II–VI	CN II	CN VI
Bony erosion	Yes	Yes	Yes	Yes
Surgery	Endonasal extended transclival	Endonasal extended transclival	Endonasal endoscopic conventional	Endonasal extended to petrous apex
Surgical complications	None	None	CSF leak	None
Additional metastatic sites	Cervical spine & pelvis	Thoracic spine, hip pathological fracture, breast mass in situ	Sternum (T3)	None reported

Patients had heterogeneous symptom manifestations and notable variations in presentation. Headache was the most common complaint, manifesting in 3 of the 4 patients; however, accompanying features varied. One patient presented with neck pain on rotation, whereas another experienced burning facial pain alongside systemic symptoms, including weight loss and discomfort in the lower extremities. Visual abnormalities were observed in 2 patients; one presented with visual field changes and headaches, and the other patient experienced isolated diplopia (Table 1).

Neurological examination revealed differing CN palsies among the patients. One patient presented with right hypoglossal nerve palsy (CN XII) (Fig. 1), while another patient experienced abnormalities in CNs II–VI. A third patient exhibited optic nerve (CN II) deficits, and the fourth had an isolated abducens nerve (CN VI) palsy (Table 1).

FIG. 1.

Case 1. A–C: T1-weighted post-contrast-enhanced MR images showing an enhancing mass located in the sellar and clival region extending to the right-sided occipital condyle, petrous bone, and anterior arch of C1 with intradural and extracranial parapharyngeal components causing extension into the carotid canal. D: Pathology specimen after resection confirming the presence of a follicular thyroid carcinoma. H&E stain, original magnification ×100.

Radiological examination revealed bony erosions in all 4 patients, and cavernous sinus involvement in a single case. Two patients presented with pituitary hormone abnormalities, which manifested as DI. Sella- or clivus-based lesions with heterogeneous contrast enhancement were commonly seen on MRI (Fig. 2). These lesions frequently extended into nearby structures like the clivus, petrous apex, Meckel’s cave, and jugular/hypoglossal foramina (Table 1). All patients were offered a surgical intervention due to the presence of mass effect of the lesions causing neurological decline.

FIG. 2.

Case 2. A and B: Sagittal CT images showing the presence of a hyperdense mass in the sellar/suprasellar region abutting the optic nerve and optic chiasm with associated erosion of the sellar floor and upper third of the clivus. C: This mass is of low signal intensity on a T2-weighted MR image and shows bilateral cavernous sinus extension. D–F:On T1-weighted post-contrast-enhanced MR images the sellar mass shows a suprasellar, cavernous sinus, and clival extension.

All patients underwent endoscopic endonasal resection, with the approach varying based on lesion location. Extension in the sagittal and coronal planes was decided according to the extension of the pathological disease. Of note, in every case there was evidence of important adhesion of the pathological tissue to the remaining pituitary gland as well as to the suprasellar arachnoid requiring meticulous microsurgical dissection. The tumors were consistently vascular, and hemostatic agents (thrombin and collagen matrix) were used to facilitate the course of the procedure. Intraoperative frozen-section analysis confirmed the presence of primary tumor metastasis in all cases. Pathological evaluation showed thyroid papillary carcinoma, triple-positive invasive ductal carcinoma of the breast (ER, PR, and HER), metastatic clear cell renal cell carcinoma (RCC) (Fig. 3), and metastatic non–small cell lung cancer originating from the breast (low ER positive, PR and HER negative). Further imaging revealed metastatic spread to the cervical and thoracic spine, as well as the pelvis (Table 1).

FIG. 3.

Case 3. A–C: CT images showing the presence of a hyperdense sellar and suprasellar mass that displaces the optic chiasm upward, causing erosion of the upper third of the clivus and sellar floor. D and E: Postoperative images confirming complete tumor resection. F: Pathology specimen after resection confirming the presence of clear cell tumor. Immunohistochemical analysis confirmed renal origin: RCC. H&E stain, original magnification ×100.

Adjuvant radiotherapy was provided to all patients; 1 patient received 20 Gy in 5 fractions, while another was treated with stereotactic CyberKnife intervention with 30 Gy in 5 fractions. Postoperative complications were minimal, with a CSF leak occurring in 1 patient. Endocrine hormonal profiles revealed progression to panhypopituitarism in patients with preoperative DI. Transient DI was also seen in 1 patient. The CN compromise documented preoperatively improved in 3 cases; it was persistent in the patient with a lower CN deficit (case 1). Three of the 4 patients died, with a mean survival rate of 6.3 months following diagnosis of pituitary metastasis (Table 2).

TABLE 2.

Postoperative features of the cases

Feature	Patient 1	Patient 2	Patient 3	Patient 4
Preop endocrine profile	Normal	DI	DI	Normal
Postop endocrine profile	Transient DI	Panhypopituitarism	Panhypopituitarism	Normal
Postop complementary treatment	CyberKnife 20 Gy/5 fractions	CyberKnife 25 Gy/5 fractions	CyberKnife 25 Gy/5 fractions	CyberKnife 30 Gy/5 fractions
Survival since diagnosis (mos)	6	4	9	Alive as of 2025; multiple organ tumor progression; currently in palliative care

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

Pituitary metastasis is believed to occur through the hematogenous route. In previous literature, it has been hypothesized that tumor cells travel systemically and may reach either the pituitary parenchyma or diaphragma sellae through portal vessels. Because of its direct blood supply from the hypophyseal arteries and close anatomical relation to the dura matter, the posterior pituitary gland has greater physical access to cancer cells—hence why it is the most commonly affected area.^5,8

This case series discusses 4 patients presenting with pituitary metastasis arising from breast, thyroid, and renal neoplasms. The variable clinical presentations across our patients are in line with the heterogeneity described in prior studies, with some patients showing classic symptoms such as headache and visual deficits, and others showing atypical features like burning facial pain or CN palsies. Radiological examination revealed that all lesions exhibited aggressive features including bony erosion and extension into surrounding structures, which is consistent with previously reported patterns. Comprehensive preoperative whole-body CT imaging was performed in all patients to definitively characterize the primary disease, differentiate recurrence from posttreatment changes (e.g., fibrosis or radiation necrosis), and accurately stage the malignancy to assess resectability. The choice of imaging modality was guided by the specific cancer type, with contrast-enhanced CT, MRI, and 18F-FDG PET/CT serving as the principal diagnostic tools. In our cohort, CT alone was sufficient given the primary tumor origin.

In our cohort, DI was observed in 2 patients with posterior pituitary involvement. This aligns with reports that metastasis most frequently appears in the neurohypophysis, with only 15% of cases involving the anterior lobe.^1,4,6 Additionally, the extent of morbidity of the disease and the presence of CN involvement in all patients also reflects the tumor’s tendency to invade adjacent structures, especially in advanced stages.

Each of our patients had a histologically confirmed diagnosis of metastasis to the pituitary gland from either breast, lung, thyroid, or renal cell carcinoma. The literature has shown that metastasis typically arises from the lung and breast, accounting for 39.7% and 23.7% of cases, respectively.^1,4,5 This form of malignancy was observed in 2 of our patients. Renal and thyroid primary malignancies were observed in the remaining 2 patients.

In regard to primary thyroid tumors, especially the papillary and follicular subtypes, cancers can spread to the pituitary gland, where they frequently manifest as hypopituitarism, DI, or visual symptoms. Despite surgical intervention, these cases show poor long-term outcomes and are usually linked to advanced, radioiodine-resistant disease.⁹ This is concurrent with the findings observed in our patient who had a papillary subtype of thyroid cancer and a survival rate of only 6 months after diagnosis of pituitary metastasis (case 1).

Likewise, similar to what was seen in our cohort, the literature has demonstrated that aggressive cases of RCC have the potential to spread to the pituitary gland. In a number of reported cases, large, hypervascular sellar masses that resemble primary pituitary tumors have been observed. Transsphenoidal resection for symptom relief is frequently necessary for these lesions, which often present with mass effect–related headaches, visual impairment, or panhypopituitarism.¹⁰ These symptoms were also seen in our patient with primary clear cell RCC, alongside initial DI, which progressed to panhypopituitarism after surgical intervention. Consistent with other malignant primary tumors with pituitary metastasis, prognosis for this form of metastasis is poor and palliative care is usually the first-line approach.¹⁰ Our RCC patient followed this pattern, requiring palliative surgery for symptom management, yet ultimately demonstrated disease progression and mortality.

Parallel with the existing literature, the majority of our patients had poor survival outcomes, with a mean postdiagnosis survival of 6.3 months. This parallels findings from Patel et al.,¹¹ who reported a median survival of 16.5 months in a larger series, and reinforces the aggressive course of pituitary metastasis, regardless of the primary site. It is also worth noting that despite the varying patient presentations and treatment modalities (including different modalities of radiation therapy) clinical deterioration was rapid.

Although surgery is not curative, it provided symptom relief in all patients and contributed to short-term clinical stabilization. The literature suggests that surgery may be associated with prolonged survival; for example, Patel et al.¹¹ reported a mean survival of 48.6 months in patients undergoing resection compared with 13.3 months in those treated with radiotherapy alone. However, this observation is likely influenced by selection and indication bias, and the extent of resection itself has not been established as an independent determinant of survival. Gross-total resection is often technically challenging due to invasion of adjacent structures and the vascular nature of these lesions. Similarly, Hong et al.¹² found that the absence of surgical treatment was associated with worse survival, and patients with solitary pituitary metastasis who received surgery and/or radiation therapy had improved 1-year overall survival compared with those receiving neither. Therefore, the extent of resection should be individualized and guided by the primary surgical objective: maximizing symptomatic improvement while minimizing morbidity.

Endoscopic endonasal procedures were effective and safe in alleviating mass effect, with no major associated complications. They should be considered a cornerstone in the treatment of metastases in this region. However, surgical planning must take into account factors such as adhesion of the lesion to surrounding sellar and suprasellar structures, which may require microsurgical maneuvers to ensure safe resection. Additionally, the use of hemostatic agents is often necessary, as these lesions tend to be highly vascular in nature.

Despite these observations, a major limitation in the field is the lack of standardized treatment protocols and prognostic models due to the rarity of pituitary metastases. There is a large gap in the literature that discusses optimal treatment methods, postsurgical outcomes, and favorable prognostic factors for longer life expectancy. As in our series, management often focuses on palliative approaches and treatment is tailored based on systemic disease burden and patient functionality.

Lessons

In summary, as seen in our cohort, patients with pituitary metastasis often have high-grade primary cancers, typically arising from the lung and breast. Because of the rapid clinical deterioration of the patients, survival outcomes are not typically favorable even with surgical and medical treatment. However, limited literature is available regarding this form of metastasis, which creates difficulty in establishing standardized treatment protocols or predicting outcomes reliably.

Acknowledgments

We thank The Ottawa Hospital, Ottawa, Ontario, Canada, for providing the necessary facilities during this research.

We used Grammarly to check sentence structure.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Alkherayf, Vargas-Moreno, Khairy, Yang. Acquisition of data: Alkherayf, Vargas-Moreno. Analysis and interpretation of data: Alkherayf, Dabbour, AlGhamdi, Vargas-Moreno, Lang, Yang. Drafting the article: Alkherayf, Dabbour, AlGhamdi, Vargas-Moreno, Khairy, Yang. Critically revising the article: Alkherayf, Dabbour, AlGhamdi, Khairy, Lang, Yang, Kilty. Reviewed submitted version of manuscript: Alkherayf, Dabbour, AlGhamdi, Khairy, Yang, Rabski, Kilty. Approved the final version of the manuscript on behalf of all authors: Alkherayf. Statistical analysis: Alkherayf, AlGhamdi, Vargas-Moreno, Lang. Administrative/technical/material support: Alkherayf, Lang, Kilty. Study supervision: Alkherayf, Yang, Rabski, Kilty.

Correspondence

Fahad Alkherayf: The Ottawa Hospital, Ottawa, ON, Canada. falkherayf@toh.ca.