Pituitary Metastasis Associated With Colon Adenocarcinoma Mimicking Pituitary Macroadenoma: A Case Report and Review of the Literature

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Pituitary Metastasis Associated With Colon Adenocarcinoma Mimicking Pituitary Macroadenoma: A Case Report and Review of the Literature Jim S. Xie, BHSc, Laura Donaldson, MD, PhD, Sylvia Asa, MD, PhD, Edward Margolin, MD P ituitary metastasis (PM) is a rare manifestation of widespread malignancy, accounting for less than 1% of surgically treated pituitary tumors, less than 1% of all intracranial metastases, and less than 2% of all cancer autopsies (1–3). PM predominantly affects the elderly with no predilection for either sex (2,4). Only 2.5%–18.2% of PM cases exhibit symptoms attributable to mass effect on the pituitary gland or adjacent structures (5), which may include visual field defects, decreased visual acuity, ophthalmoplegia and diplopia secondary to cranial nerve palsies, anterior or posterior pituitary dysfunction, and headache (2,4). Ophthalmoplegia and diplopia are especially common manifestations of parasellar and suprasellar metastatic lesions because of propensity for this fast-growing lesion to expand laterally into cavernous sinuses (6). Based on systematic and literature reviews, the primary malignancies most frequently associated with PM are breast (24.6%– 37.2%) and lung cancers (23.5%–31.0%) (2,4,7). Colorectal cancer is a rare primary source of PM, comprising 2.8%– 4.0% of cases (2,4,7). In this report, we describe a patient with a known history of colon adenocarcinoma who presented with a pituitary mass resembling a macropituitary neuroendocrine tumor (PitNET). A 53-year-old man was diagnosed with colon cancer and treated with hemicolectomy and adjuvant chemotherapy and radiation. Approximately 1 year after his initial diagnosis, he was found to have a solitary pulmonary Michael G. DeGroote School of Medicine (JSX), McMaster University, Hamilton, Canada; Faculty of Medicine (LD, EM), Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada; Department of Pathology (SA), Faculty of Medicine, University of Toronto, Toronto, Canada; and Faculty of Medicine (EM), Department of Medicine (Div. Neurology), University of Toronto, Toronto, Canada. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). Address correspondence to Edward Margolin, MD, FRCSC, Dipl. ABO Associate Professor, Department of Ophthalmology and Visual Sciences, Department of Medicine, Division of Neurology, Director, Neuro-Ophthalmology and Strabismus Fellowship, University of Toronto, 801 Eglinton Avenue, West, Suite 301, Toronto ON M5N 1E3; E-mail: [e-mail] Xie et al: J Neuro-Ophthalmol 2023; 43: e211-e213 nodule and wedge resection was performed. A positron emission tomography scan at this time showed no evidence of other metastatic lesions. Four months later, he presented with new-onset diabetes insipidus (DI) and was started on desmopressin. No neuroimaging was performed until 2 months later, where head computed tomography (CT) in the community was initially interpreted as normal (Fig. 1A) but in later review showed pituitary enlargement. MRI of the brain 2 months later revealed heterogenous enhancement and marked enlargement of the pituitary gland and was reported as consistent with macro-PitNET (Fig. 1B, C). On ophthalmologic examination, vision was 20/25 and 20/ 30. There was no relative afferent pupillary defect. Optic nerves were normal on fundoscopy. 24-2 automated visual field testing, however, showed bitemporal field defects (Fig. 1D, E) consistent with optic chiasm compression. He was treated with trans-sphenoidal resection and surgical pathology revealed metastatic adenocarcinoma from colonic primary (Fig. 2). Unfortunately, his condition deteriorated and he passed away 5 weeks later. This case demonstrates that PM associated with colon adenocarcinoma may mimic macro-PitNET. Several mechanisms have been proposed for metastatic invasion of the pituitary gland. Hematogenous spread, either directly through systemic circulation to pituitary parenchyma or indirectly through portal vessels to the diaphragm sellae, may cause metastasis (2,8). Other hypotheses include meningeal dissemination through the suprasellar cistern and extension from metastatic lesions in the adjacent bone (9,10). Distinguishing PM from more common benign lesions such as PitNET is essential for effective treatment. However, diagnosis is challenging because of the rarity of PM and low specificity of clinical and radiologic findings for this condition (11,12). Features that have been suggested to be more characteristic of PM include the presence of cranial neuropathies, DI or adenohypophyseal dysfunction, rapid progression of symptoms, dumbbell-shaped lesions, bony erosion without sella enlargement, and lateral extension of the lesion on neuroimaging (2,4). Pituitary biopsy is ultimately needed to confirm the diagnosis of PM. A systematic search of PubMed and Embase yielded 9 English-language cases of PM associated with colon cancer e211 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Metastatic colon adenocarcinoma mimicking macro-PitNET. Sagittal contrast-enhanced CT head (A) showed an enlarged and enhancing pituitary gland. Coronal (B) and sagittal (C) T1 contrast-enhanced MRI images showed enlargement and heterogenous enhancement of the pituitary gland with a dumbbell shape. Hypointense areas within the mass (white arrow) indicate areas of necrosis. Optical coherence tomography of the peripapillary retinal nerve fiber layer (D) was normal, and 24-2 automated visual field testing (E) revealed bitemporal field defects. (see Supplemental Table 1, Supplemental Digital Content 1, http://links.lww.com/WNO/A527) (13–21). The median age was 56 (range 46–85), and 8/9 patients were male. Given that men only have a 1.5-fold increased risk of developing colorectal cancer compared with women, the disproportionate sex distribution may indicate male predominance in PM associated with colon carcinoma (22). PM was the first presentation of occult malignancy in 2 cases; the other patients had known histories of colon cancer. Visual disturbances (n = 8), especially temporal visual FIG. 2. Histology of the resected pituitary mass shows glands of metastatic colon carcinoma with focal necrosis and associated stromal fibrosis trapping residual adenohypophysial tissue. e212 field defects (n = 5) and headache (n = 4), were common presenting symptoms. Consistent with macro-PitNET, the size of the pituitary metastatic lesion was greater than 10 mm at presentation in all but one case that did not report MRI measurements. Serial MRI was performed in 6 cases and unanimously demonstrated lesion growth, even after radiotherapy and/or surgical intervention. Pituitary biopsy was performed in all but 2 cases; mediastinal lymph node and renal biopsy was chosen for one patient, and biopsy was not conducted in another patient because of high suspicion of PM. Notably, 5 of the 7 histopathologically confirmed PM cases involved composite tumors with regions of both colon carcinoma and PitNET, suggesting that these pathologies may frequently occur in tandem. This case, in combination with similar cases in the literature, highlights that PM may mimic macro-PitNET, emphasizing the importance of keeping PM in the differential diagnosis for pituitary masses. Our patient had a history of colon adenocarcinoma and presented with DI, one of the most common initial manifestations of PM (32.9%–42.3%) (2,4,7). By contrast, DI is an exceptionally rare (w1%) and typically late finding in PitNET (2,23). Thus, PM should be considered immediately in patients with known histories of malignancy who present with DI. This case also demonstrated that rapid lesion growth is a suspicious feature that warrants biopsy to decompress the optic chiasm and establish histological diagnosis. Monitoring lesion progression with serial neuroimaging may be Xie et al: J Neuro-Ophthalmol 2023; 43: e211-e213 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence helpful in distinguishing PM from the more common primary pituitary neoplasms. In summary, PM associated with colon adenocarcinoma presents a diagnostic challenge because clinical and radiologic features may resemble macro-PitNET. In any patient with a known history of malignancy who presents with a pituitary mass, metastatic disease should be kept in the differential diagnosis. Symptoms of DI and rapid lesion growth on neuroimaging raise suspicion of PM and warrant pituitary biopsy. STATEMENT OF AUTHORSHIP Conception and design: L. Donaldson, E. Margolin; Acquisition of data: J. S. Xie, L. Donaldson, E. Margolin; Analysis and interpretation of data: J. S. Xie, L. Donaldson, S. Asa, E. Margolin. Drafting the manuscript: J. S. Xie, L. Donaldson, E. Margolin; Revising it for intellectual content: J. S. Xie, L. Donaldson, S. Asa, E. Margolin. Final approval of the completed manuscript: J. S. Xie, L. Donaldson, S. Asa, E. Margolin. REFERENCES 1. Fassett DR, Couldwell WT. Metastases to the pituitary gland. Neurosurg Focus. 2004;16:E8. 2. He W, Chen F, Dalm B, Kirby PA, Greenlee JDW. Metastatic involvement of the pituitary gland: a systematic review with pooled individual patient data analysis. Pituitary. 2015;18:159–168. 3. Kovacs K. Metastatic cancer of the pituitary gland. Oncology. 1973;27:533–542. 4. Ng S, Fomekong F, Delabar V, Jacquesson T, Enachescu C, Raverot G, Manet R, Jouanneau E. Current status and treatment modalities in metastases to the pituitary: a systematic review. J Neurooncol. 2020;146:219–227. 5. Komninos J, Vlassopoulou V, Protopapa D, Korfias S, Kontogeorgos G, Sakas DE, Thalassinos NC. Tumors metastatic to the pituitary gland: case report and literature review. 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