Solitary pituitary metastasis from breast cancer masquerading as a pituitary macroadenoma: a report of 2 rare cases

Introduction

Breast cancer, occurring in the mammary glands (World Health Organization, 2021), is one of the most common malignant tumor worldwide and remains the leading cause of cancer-related deaths (1). It accounts for around 15% of all cancer-related deaths in women (2), with approximately 90% of these deaths attributed to metastasis. Unfortunately, 20–30% of patients diagnosed with breast cancer may eventually develop metastases (3). The bones, lungs, and liver are the most common sites for breast cancer metastasis (4-6).

Brain metastases are a devastating complication of malignant tumors, occurring for 8–10% of all patients with malignancies (7). Among intracranial metastases, pituitary metastasis (PM) is exceedingly rare; the pituitary gland is an infrequent site for metastatic neoplasms (8), with reports indicating that only 0.5% of sellar region neoplasms originate from malignant colonization (9). PM was first reported in 1857 (10). Although rare, the incidence of PM has increased in recent years due to advancements in systemic therapies and prolonged patient survival, with metastatic breast cancer being the most common source (11,12).

Accurate diagnosis of metastatic breast carcinoma is vital for effective treatment and can significantly improve patient outcomes. However, preoperative diagnosis and histological examination of PM are challenging due to its low incidence and atypical radiographic features (13). PM can mimic primary pituitary lesions. These lesions are difficult to distinguish from benign tumors based on symptoms and imaging features alone, leading to inaccurate diagnosis and a delay in diagnosis for several months (14). This poses a significant challenge for neurosurgeons, as a definitive diagnosis is often only confirmed after permanent pathology examination post-surgical resection, as seen in our two cases.

The purpose of this manuscript is to report two rare cases of breast cancer metastasis to the pituitary gland. We suggest that healthcare providers should be aware of the possibility of metastatic disease to the pituitary in patients with cancer history, particularly breast cancer. This awareness can lead to accurate diagnosis and timely treatment, thereby improving patient quality of life and survival. We present this article in accordance with the CARE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-24-284/rc).

Case presentation

Cases selection

We reviewed and documented the clinical characteristic, laboratory data, imaging abnormalities, pathological examinations (including immunohistochemistry studies), treatment methods, and follow-up information of two patients from the files of the Department of Pathology, Xiangya Hospital (Changsha, China).

Case 1

A 68-year-old Chinese woman was diagnosed with pituitary adenoma in another hospital in November 2020 and was managed conservatively with hydrocortisone (30 mg/day) and levothyroxine sodium (50 mg/day) without surgical intervention. Four months later, she presented to Xiangya Hospital for right-sided visual deficits and ptosis. The patient had no significant medical, family, or psycho-social history, but presented with a history of right breast cancer 5 years ago. The breast cancer was pathologically confirmed as invasive carcinoma of no special type, with estrogen receptor (ER)⁺, progesterone receptor (PR)⁺, and human epidermal growth factor receptor 2 (HER2)¹⁺ positivity. She underwent a right mastectomy and was in remission at the time of presentation. Magnetic resonance imaging (MRI) revealed a sellar region lesion with slightly longer T1 and T2 signals, measuring about 23 mm × 14 mm × 8 mm, compressing the right internal carotid artery and optic chiasm, with invasion into the cavernous sinus, initially diagnosed as benign pituitary macroadenoma (Figure 1). Laboratory investigations showed elevated carbohydrate antigen 19-9 (CA199) levels and hypothyroidism. Due to the progressive symptoms, the patient underwent resection of the pituitary mass 12 days after the MRI scan. Macroscopically, a grey-yellow hard mass of about 20 mm × 20 mm × 15 mm was completely resected. Intraoperative frozen biopsy samples suggested metastatic adenocarcinoma. Subsequent permanent pathology results combined with immunohistochemical stains confirmed metastatic breast cancer with GATA binding factor 3 (GATA3) (+), ER (3+, 90%), PR (1+, 10%), HER2 (1+) (Figure 2). Postoperatively, she received antibiotics (cefazolin, 2 g/day), hormonal therapy (hydrocortisone, 30 mg/day; levothyroxine sodium 50 mg/day), and electrolyte balance maintenance. She recovered well and was discharged after 1 week. Unfortunately, she returned 4 months later with left-sided visual deficits and ptosis, indicating disease recurrence. MRI revealed partial bone defects in the sphenoid sinus with mass invasion. Despite further intervention, she succumbed to systemic progression 5 months thereafter.

Figure 1 MRI with a slice thickness of 2 mm and a field strength of 3.0 T, demonstrating a sellar mass that is compressing the right internal carotid artery and optic chiasm, as well as invading the cavernous sinus. (A) Coronal T1-weighted gadolinium-enhanced scan, (B) sagittal T1-weighted gadolinium-enhanced scan, (C) axial T2-weighted scan (arrows: sellar lesion). L, left; R, right; A, anterior; P, posterior; MRI, magnetic resonance imaging.

Figure 2 Histopathological and immunohistochemical findings of the removed tumor. (A,B) HE staining shows glandular structures composed of enlarged, hyperchromatic cells with interstitial reaction. Immunohistochemical staining shows (C) HER2 (1+), (D) GATA3 (+), (E) ER (3+, 90%), and (F) PR (1+, 10%). HE, hematoxylin and eosin; HER2, human epidermal growth factor receptor 2; GATA3, GATA binding factor 3; ER, estrogen receptor; PR, progesterone receptor.

Case 2

A 41-year-old Chinese woman presented to a local hospital with a 3-month history of frailty, nausea, and vomiting, and was subsequently diagnosed with hyperthyroidism and treated with methimazole tablets. Two months later, she was referred to Xiangya Hospital for significant vision loss affecting her daily life. The patient had no significant medical, family, or psycho-social history, but presented with a history of right breast cancer treated with mastectomy and chemotherapy 1 year prior. The cancer was confirmed as invasive carcinoma of no special type with mucinous feathers. MRI demonstrated a sellar region lesion with isointense signals on both T1- and T2-weighted images, measuring approximately 23 mm × 20 mm × 16 mm, causing compression of the pituitary stalk and optic chiasm. The lesion was initially diagnosed as a benign pituitary macroadenoma (Figure 3). Laboratory findings showed elevated CA125 levels and hypothyroidism. Given the presumptive diagnosis, she underwent surgical resection of the pituitary mass. Macroscopically, a grey-white hard mass measuring about 10 mm × 5 mm × 5 mm was completely resected. Intraoperative frozen biopsy samples were initially interpreted as a benign pituitary macroadenoma. However, the resected mass was sent for further pathological examination, and, surprisingly, histological analysis combined with immunohistochemical staining revealed metastatic breast cancer with GATA3 (+), ER (2+, 75%), PR (1+, 5%), HER2 (0) (Figure 4). She recovered well postoperatively, receiving antibiotics, hormonal therapy, and electrolyte balance maintenance. She was discharged after 2 weeks and remained disease-free 11 months later.

Figure 3 MRI with a slice thickness of 2.5 mm and a field strength of 3.0 T, demonstrating a sellar mass causing compression of the pituitary stalk and optic chiasm. (A) Coronal T1-weighted gadolinium-enhanced scan, (B) sagittal T1-weighted non-enhanced scan, (C) coronal T2-weighted scan (arrows: sellar lesion). R, right; A, anterior; P, posterior; L, left; MRI, magnetic resonance imaging.

Figure 4 Histopathological and immunohistochemical findings of the removed tumor. (A,B) HE staining shows solid structure composed of enlarged, hyperchromatic cells. Immunohistochemical staining shows (C) HER2 (0), (D) GATA3 (+), (E) ER (2+, 75%), and (F) PR (1+, 5%). HE, hematoxylin and eosin; HER2, human epidermal growth factor receptor 2; GATA3, GATA binding factor 3; ER, estrogen receptor; PR, progesterone receptor.

In our two cases, all specimens were fixed in 10% neutral-buffered formalin, embedded in paraffin, and stained with hematoxylin and eosin for histological examination. During the initial case diagnosis, immunohistochemical staining was performed using formalin-fixed paraffin-embedded tissue sections and the Ventana Benchmark automated immunostainer (Ventana Medical System Inc., Roche, Tucson, AZ, USA). Appropriate positive and negative controls were evaluated for all the markers tested. Immunohistochemical results were evaluated by two qualified pathologists.

Ethical considerations

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent for publication of this case report and accompanying images was not obtained from the patients or the relatives after all possible attempts were made.

Discussion

Breast cancer ranks as the most prevalent malignant tumor in women (2), with 20–30% of patients developing metastases (3). Breast cancer has a high likelihood of metastasizing to distant organs, such as the bones, liver, and lungs, unfortunately, the 5-year overall survival rate of patients with metastasis is much lower than that in patients without metastasis (15). However, breast cancer metastasizing to the brain is rare, the pituitary gland is an infrequent site of metastatic neoplasms (8), it is reported that only 0.5% sellar region neoplasms originate from malignant colonization (9). There are researches suggested that the frequency of breast metastases to the pituitary can be increased by hormonal change (16). For example, anti-HER2 treatment may promote PM, but specific mechanism still needs further study.

We systematically searched two keywords: (I) “Pituitary metastases” and (II) “Breast cancer” in the PubMed database. We focused on publications within the last 20 years related to breast cancer metastasis to the pituitary gland, a condition that remains exceedingly rare. Less than 50 published papers have been identified in the English literature over the past two decades (excluding conference papers/abstracts, non-English studies, and studies without primary patient data) (Table 1). A total of 41 publications were retrieved, which included 45 patients with PMs from breast cancer. The age of these patients ranged from 39 to 83 years (mean age of 57.8 years), and all were female. The interval from breast cancer diagnosis to PM ranged from 1 to 21 years (mean of 6.65 years, with data from 7 patients missing). Prognosis for these patients is generally poor; 16 out of 43 patients died during follow-up (37.2%).

Additionally, various systematic reviews have reported on breast cancer metastasis to the pituitary gland, though their findings are not entirely consistent, they provide valuable insights (10,13,16,40,52). In 2022, a systematic review found that PM from breast cancer tends to occur at an average age of 59 years (range, 30–93 years). The median time from breast cancer diagnosis to PM was 60 months (mean 74 months, range, 0–228 months) (10). Another systematic review indicated that the mean survival post-PM diagnosis is approximately 13.6 months (16). Recently, Ng et al. reported on 169 cases of breast cancer metastasis to the pituitary, finding that the median survival for these patients was 22 months. They also noted that overall survival was significantly longer in patients receiving radiotherapy and chemotherapy, while the use of targeted drugs was not significantly associated with improved overall survival (52). Hematogenous spread, direct invasion through the skull base, extension from an adjacent bone metastasis, and meningeal spread through the supra-sellar cistern are the most potential routes of metastasis (28,53,54). The posterior lobe of the pituitary gland is the most common site of metastasis (69–79%) (55). When the posterior pituitary is affected, symptoms such as diabetes insipidus (DI), anterior pituitary dysfunction, cranial nerve dysfunction, headache, and hyperprolactinemia can occur (54,56). The presentation of PMs can vary and in fact most PMs may be clinically silent (31), only 7% were symptomatic. Apart from the common finding of DI, most symptoms are nonspecific (40). In 2018, Javanbakht et al. conducted a systematic review of 289 PM patients, including 71 cases of breast cancer metastasis to the pituitary. They found that symptoms were often absent or nonspecific, with 60% of cases presenting with pituitary dysfunction and clinical manifestations. The most common clinical presentations were DI and panhypopituitarism (each accounting for 27.7%) (40).

Although there is no consensus on the treatment of patients with PM at present, accurate diagnosis remains crucial. Chemotherapy may represent the first-line treatment, and studies suggest that targeted therapy and chemotherapy may be beneficial depending on the primary tumor type and extent of metastatic spread (57). Surgery is typically reserved for patients with neurological symptoms, as seen in our two cases. While surgical resection of PM can relieve neurological symptoms, it does not correlate with improved survival (58). Chandler et al. recommended that when PM is detected via frozen sections during surgery, the procedure should be halted, and the patient should be directed toward other treatment modalities (59). Additionally, Piedra et al. demonstrated that radiotherapy or γ-knife radiosurgery are effective options for symptom relief when metastases occur, with minimal impact on the adjacent visual structures and no resultant pituitary failure (17).

In our two cases, we observed that the PM from breast cancer can mimic the signs and symptoms of other benign pituitary conditions, such as pituitary macroadenoma and pituitary abscess. Their clinical presentations were nonspecific, including visual deficits, ptosis, frailty, nausea, and vomiting. Typically, when MRI results reveal aggressive features in a pituitary mass, malignancy should be considered over benign pituitary conditions. However, distinguishing between the two can be challenging in the early stages of PM. For example, in our cases, MRI findings alone were insufficient to differentiate PM from a primary pituitary adenoma, leading to an initial diagnosis of benign pituitary macroadenoma. Both patients underwent surgery due to worsening symptoms, and PM from breast cancer was only confirmed postoperatively through histological analysis and immunohistochemical staining. Due to the rarity and atypical radiographic appearance of PM, diagnosis and treatment in our cases were delayed. In 2023, Stringer et al. reported a case of pituitary abscess, where the initial MRI also suggested a pituitary macroadenoma. The patient ultimately underwent transsphenoidal drainage, revealing purulent material and confirming the diagnosis of a pituitary abscess (60), highlighting the importance of considering the utility of a lumbar puncture. Based on this, we further hypothesize that lumbar puncture with cytological analysis may play a significant role in differentiating between PM, pituitary macroadenoma, and pituitary abscess.

Our two cases highlight the importance of considering PM from breast cancer in patients with a history of breast cancer who present with symptoms suggestive of a benign pituitary macroadenoma, even though it is rare. Accurate diagnosis of metastatic breast carcinoma is vital for guiding appropriate treatment and potentially improving patient outcomes.

Conclusions

In conclusion, breast cancer metastasis to the pituitary gland is an exceedingly rare occurrence. The scarcity of PM from breast cancer, coupled with the lack of specific clinical and radiological features, complicates its differentiation from other sellar lesions, such as pituitary macroadenoma, making it difficult to choose an appropriate therapeutic approach, which in turn affects the patients’ quality of life and survival time. We report these two cases to emphasize the importance of considering PMs in pituitary lesions, particularly in patients with history of malignant cancer. Accurate differential diagnosis is essential for effective treatment.

Acknowledgments

We would like to thank Gaone Basetsana Kenosi for her help in polishing our paper.

Funding: This work was partially supported by Hunan Provincial Innovation Foundation for Postgraduate (No. CX20230328).

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-24-284/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-24-284/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-284/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent for publication of this case report and accompanying images was not obtained from the patients or the relatives after all possible attempts were made.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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