Pituitary metastasis: From pathology to clinical and radiological considerations

  • M.M. Kameda-Smith
    Corresponding authors at: Department of Surgery, Division of Neurosurgery, Hamilton, General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada (M.M. Kameda-Smith). Pathology and Molecular Medicine, Department of Pathology and Molecular Medicine, Division of Anatomical Pathology, Neuropathology, Hamilton, General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada (J-Q. Lu).
    McMaster University, Canada

    Departments of Surgery, Canada
    Search for articles by this author
  • E. Zhang
    McMaster University, Canada

    Diagnostic Imaging, Canada
    Search for articles by this author
  • M. Lannon
    McMaster University, Canada

    Departments of Surgery, Canada
    Search for articles by this author
  • A. Algird
    McMaster University, Canada

    Departments of Surgery, Canada
    Search for articles by this author
  • K. Reddy
    McMaster University, Canada

    Departments of Surgery, Canada
    Search for articles by this author
  • J-Q. Lu
    Corresponding authors at: Department of Surgery, Division of Neurosurgery, Hamilton, General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada (M.M. Kameda-Smith). Pathology and Molecular Medicine, Department of Pathology and Molecular Medicine, Division of Anatomical Pathology, Neuropathology, Hamilton, General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada (J-Q. Lu).
    McMaster University, Canada

    Neuropathology, Canada
    Search for articles by this author


      • Comprehensive review of metastatic lesions to the pituitary.
      • Includes review of tumor-tumor metastasis and metastatic collision tumors.
      • Radiological insights to primary versus pituitary metastatic lesions.
      • Management of pituitary metastasis including surgical indications and adjuvant therapy.



      A review of the literature with respect to pituitary metastases (PM) with clinical and radiological considerations are summarized to facilitate clinical decision making in the management of PM


      A review of literature associated with PM and tumour to tumour metastases in the English literature was reviewed and summarized


      Pituitary metastases account for 1.0–3.6% of all surgically treated pituitary lesions. Often identified in parallel with extensive disseminated disease, once diagnosed, the prognosis is generally poor, although survival is highly heterogeneous and dependent on the primary tumor histology. Within this anatomical region is also the observation of tumor-to-tumor metastases and collision tumours. Both the tumor macro- and microenvironment play central roles to the progression of disease with distinctive radiological features that may suggest a metastatic sellar lesion as opposed to a primary pituitary lesion. Surgical resection is the first line of therapy followed by adjuvant chemoradiotherapy and endocrinological evaluation for hormonal supplementation


      PMs are relatively rare but important oncological entities representing disseminated disease in the majority of cases. Careful consideration of the relevant clinical history and radiological features can aid the clinician differentiate between a metastatic lesion to the pituitary region and a primary pituitary tumor. While surgical resection is first line therapy, stereotactic radiosurgery in carefully selected patients is emerging as a viable alternative.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Clinical Neuroscience
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Saeger W.
        • Lüdecke D.K.
        • Buchfelder M.
        • Fahlbusch R.
        • Quabbe H.-J.
        • Petersenn S.
        Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry.
        Eur J Endocrinol. 2007; 156: 203-216
        • Roessmann U.
        • Kaufman B.
        • Friede R.L.
        Metastatic lesions in the sella turcica and pituitary gland.
        Cancer. 1970; 25: 478-480<478::aid-cncr2820250227>;2-x
        • He W.
        • Chen F.
        • Dalm B.
        • Kirby P.A.
        • Greenlee J.D.W.
        Metastatic involvement of the pituitary gland: a systematic review with pooled individual patient data analysis.
        Pituitary. 2015; 18: 159-168
        • Komninos J.
        • Vlassopoulou V.
        • Protopapa D.
        • Korfias S.
        • Kontogeorgos G.
        • Sakas D.E.
        • et al.
        Tumors metastatic to the pituitary gland: case report and literature review.
        J Clin Endocrinol Metab. 2004; 89: 574-580
        • Morita A.
        • Meyer F.B.
        • Laws E.R.
        Symptomatic pituitary metastases.
        J Neurosurg. 1998; 89: 69-73
        • Cai H.
        • Liu W.
        • Feng T.
        • Li Z.
        • Liu Y.
        Clinical Presentation and Pathologic Characteristics of Pituitary Metastasis from Breast Carcinoma: Cases and a Systematic Review of the Literature.
        World Neurosurg. 2019; 124: 445-451.e2
        • Houck W.A.
        • Olson K.B.
        • Horton J.
        Clinical features of tumor metastasis to the pituitary.
        Cancer. 1970; 26: 656-659<656::aid-cncr2820260325>;2-m
        • Sioutos P.
        • Yen V.
        • Arbit E.
        Pituitary gland metastases.
        Ann Surg Oncol. 1996; 3: 94-99
        • Habu M.
        • Tokimura H.
        • Hirano H.
        • Yasuda S.
        • Nagatomo Y.
        • Iwai Y.
        • et al.
        Pituitary metastases: current practice in Japan.
        J Neurosurg. 2015; 123: 998-1007
        • Hägerstrand I.
        • Schönebeck J.
        Metastases to the pituitary gland.
        Acta Pathol Microbiol Scand. 1969; 75: 64-70
        • Barbaro D.
        • Desogus N.
        • Boni G.
        Pituitary metastasis of thyroid cancer.
        Endocrine. 2013; 43: 485-493
      1. F. Schill M. Nilsson D.S. Olsson O. Ragnarsson K. Berinder B. Edén Engström et al. Pituitary Metastases: A Nationwide Study on Current Characteristics With Special Reference to Breast Cancer 104 8 2019 2019 3379 3388 10.1210/jc.2019-00012

        • Zacharia B.E.
        • Romero F.R.
        • Rapoport S.K.
        • Raza S.M.
        • Anand V.K.
        • Schwartz T.H.
        Endoscopic Endonasal Management of Metastatic Lesions of the Anterior Skull Base: Case Series and Literature Review.
        World Neurosurg. 2015; 84: 1267-1277
        • Castle-Kirszbaum M.
        • Goldschlager T.
        • Ho B.
        • Wang Y.Y.
        • King J.
        Twelve cases of pituitary metastasis: a case series and review of the literature.
        Pituitary. 2018; 21: 463-473
        • Lithgow K.
        • Siqueira I.
        • Senthil L.
        • Chew H.S.
        • Chavda S.V.
        • Ayuk J.
        • et al.
        Pituitary metastases: presentation and outcomes from a pituitary center over the last decade.
        Pituitary. 2020; 23: 258-265
        • Duchen L.W.
        Metastatic carcinoma in the pituitary gland and hypothalamus.
        J Pathol Bacteriol. 1966; 91: 347-355
        • Yap H.Y.
        • Tashima C.K.
        • Blumenschein G.R.
        • Eckles N.
        Diabetes insipidus and breast cancer.
        Arch Intern Med. 1979; 139: 1009-1011
        • van Seters A.P.
        • Bots G.T.
        • van Dulken H.
        • Luyendijk W.
        • Vielvoye G.J.
        Metastasis of an occult gastric carcinoma suggesting growth of a prolactinoma during bromocriptine therapy: a case report with a review of the literature.
        Neurosurgery. 1985; 16: 813-817
        • Altay T.
        • Krisht K.M.
        • Couldwell W.T.
        Sellar and Parasellar Metastatic Tumors.
        Int J Surg Oncol. 2012; 2012: 1-9
      2. A. Popławska-Kita M. Wielogórska Ł. Poplawski K. Siewko A. Adamska P. Szumowski et al. Thyroid carcinoma with atypical metastasis to the pituitary gland and unexpected postmortal diagnosis 2020 2020 10.1530/EDM-19-0148

        • Ramsay J.A.
        • Kovacs K.
        • Scheithauer B.W.
        • Ezrin C.
        • Weiss M.H.
        Metastatic carcinoma to pituitary adenomas: a report of two cases.
        Exp Clin Endocrinol. 1988; 92: 69-76
        • Tally P.W.
        • Laws E.R.
        • Scheithauer B.W.
        Metastases of central nervous system neoplasms.
        Case report. J Neurosurg. 1988; 68: 811-816
        • Ruelle A.
        • Palladino M.
        • Andrioli G.C.
        Pituitary metastases as presenting lesions of malignancy.
        J Neurosurg Sci. 1992; 36: 51-54
        • Smedby K.E.
        • Brandt L.
        • Bäcklund M.L.
        • Blomqvist P.
        Brain metastases admissions in Sweden between 1987 and 2006.
        Br J Cancer. 2009; 101: 1919-1924
        • Lin X.
        • DeAngelis L.M.
        Treatment of Brain Metastases.
        J Clin Oncol. 2015; 33: 3475-3484
        • Freda P.U.
        • Post K.D.
        Differential diagnosis of sellar masses.
        Endocrinol Metab Clin North Am. 1999; 28: 81-117
        • Nelson P.B.
        • Robinson A.G.
        • Martinez A.J.
        Metastatic tumor of the pituitary gland.
        Neurosurgery. 1987; 21: 941-944
        • Joyce J.A.
        • Fearon D.T.
        T cell exclusion, immune privilege, and the tumor microenvironment.
        Science. 2015; 348: 74-80
        • Spill F.
        • Reynolds D.S.
        • Kamm R.D.
        • Zaman M.H.
        Impact of the physical microenvironment on tumor progression and metastasis.
        Curr Opin Biotechnol. 2016; 40: 41-48
        • Sato M.
        • Tamura R.
        • Tamura H.
        • Mase T.
        • Kosugi K.
        • Morimoto Y.
        • et al.
        Analysis of Tumor Angiogenesis and Immune Microenvironment in Non-Functional Pituitary Endocrine Tumors.
        J Clin Med. 2019; 8: 695
        • Cosío G.
        • Jeziorski M.C.
        • López-Barrera F.
        • de la Escalera G.M.
        • Clapp C.
        Hypoxia inhibits expression of prolactin and secretion of cathepsin-D by the GH4C1 pituitary adenoma cell line.
        Lab Investig J Tech Methods Pathol. 2003; 83: 1627-1636
        • Lu J.-Q.
        • Khalil M.
        • Hu W.
        • Sutherland G.R.
        • Clark A.W.
        Tumor-to-tumor metastasis: esophageal carcinoma metastatic to an intracranial paraganglioma.
        J Neurosurg. 2009; 110: 744-748
        • Barry S.
        • Carlsen E.
        • Marques P.
        • Stiles C.E.
        • Gadaleta E.
        • Berney D.M.
        • et al.
        Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors.
        Oncogene. 2019; 38: 5381-5395
      3. I. Lupi L. Manetti P. Caturegli M. Menicagli M. Cosottini A. Iannelli et al. Tumor infiltrating lymphocytes but not serum pituitary antibodies are associated with poor clinical outcome after surgery in patients with pituitary adenoma 95 1 2010 289 296 10.1210/jc.2009-1583

        • Heshmati H.M.
        • Kujas M.
        • Casanova S.
        • Wollan P.C.
        • Racadot J.
        • Effenterre Rémy.V.
        • et al.
        Prevalence of lymphocytic infiltrate in 1400 pituitary adenomas.
        Endocr J. 1998; 45: 357-361
        • Lafont C.
        • Desarmenien M.G.
        • Cassou M.
        • Molino F.
        • Lecoq J.
        • Hodson D.
        • et al.
        Cellular in vivo imaging reveals coordinated regulation of pituitary microcirculation and GH cell network function.
        Proc Natl Acad Sci U S A. 2010; 107: 4465-4470
        • Wang H.
        • Sun W.
        • Fu Z.
        • Si Z.
        • Zhu Y.
        • Zhai G.
        • et al.
        The Pattern of Visual Impairment in Patients with Pituitary Adenoma.
        J Int Med Res. 2008; 36: 1064-1069
        • Hinshaw D.C.
        • Shevde L.A.
        The Tumor Microenvironment Innately Modulates Cancer Progression.
        Cancer Res. 2019; 79: 4557-4566
        • Ilie M.D.
        • Vasiljevic A.
        • Raverot G.
        • Bertolino P.
        The Microenvironment of Pituitary Tumors-Biological and Therapeutic Implications.
        Cancers. 2019; 11: 1605
        • Marin F.
        • Kovacs K.T.
        • Scheithauer B.W.
        • Young W.F.
        The Pituitary Gland in Patients With Breast Carcinoma: A Histologic and Immunocytochemical Study of 125 Cases.
        Mayo Clin Proc. 1992; 67: 949-956
      4. Lu J-Q, Clark AW. Tumor-to-Tumor Metastasis: Extracranial Tumor Metastatic to Intracranial Tumors. In: Hayat MA, editor. Tumors Cent. Nerv. Syst. Vol. 3, Dordrecht: Springer Netherlands; 2011, p. 35–46.

        • Syed S.
        • Karambizi D.I.
        • Baker A.
        • Groh D.M.
        • Toms S.A.
        A Comparative Report on Intracranial Tumor-to-Tumor Metastasis and Collision Tumors.
        World Neurosurg. 2018; 116: 454-463.e2
        • Petraki C.
        • Vaslamatzis M.
        • Argyrakos T.
        • Petraki K.
        • Strataki M.
        • Alexopoulos C.
        • et al.
        Tumor to tumor metastasis: report of two cases and review of the literature.
        Int J Surg Pathol. 2003; 11: 127-135
        • Bret P.
        • Jouvet A.
        • Madarassy G.
        • Guyotat J.
        • Trouillas J.
        Visceral cancer metastasis to pituitary adenoma: report of two cases.
        Surg Neurol. 2001; 55: 284-290
        • Campbell B.C.V.
        • Mitchell P.J.
        • Churilov L.
        • Keshtkaran M.
        • Hong K.-S.
        • Kleinig T.J.
        • et al.
        Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost.
        Front Neurol. 2017; 8
        • Fraggetta F.
        • Galia A.
        • Grasso G.
        • D’Arrigo C.
        • Cristaudo C.
        • Giangaspero F.
        Pulmonary adenocarcinoma metastatic to pituitary craniopharyngioma.
        J Clin Pathol. 2000; 53: 946-947
        • Lu J.-Q.
        • Algird A.R.
        Intratumoral cavernous-like malformation in subependymomas.
        Br J Neurosurg. 2020; 34: 96-97
        • Koutourousiou M.
        • Kontogeorgos G.
        • Wesseling P.
        • Grotenhuis A.J.
        • Seretis A.
        Collision sellar lesions: experience with eight cases and review of the literature.
        Pituitary. 2010; 13: 8-17
        • Lim A.
        • Cerra C.
        • Pal P.
        • Kearney T.
        • Gnanalingham K.
        Visual loss from a pituitary mass: collision tumors of prostatic metastasis and suprasellar meningioma.
        J Neurol Surg Part Cent Eur Neurosurg. 2013; 74: e81-e84
        • Sogani J.
        • Yang W.
        • Lavi E.
        • Zimmerman R.D.
        • Gupta A.
        Sellar collision tumor involving metastatic lung cancer and pituitary adenoma: radiologic-pathologic correlation and review of the literature.
        Clin Imaging. 2014; 38: 318-321
        • Chiang M.-F.
        • Brock M.
        • Patt S.
        Pituitary metastases.
        Neurochirurgia (Stuttg). 1990; 33: 127-131
        • Scatliff J.H.
        • Bull J.W.D.
        The radiological manifestations of suprasellar metastatic tissue.
        Clin Radiol. 1965; 16: 66-70
        • Koshimoto Y.
        • Maeda M.
        • Naiki H.
        • Nakakuki K.
        • Ishii Y.
        MR of pituitary metastasis in a patient with diabetes insipidus.
        AJNR Am J Neuroradiol. 1995; 16: 971-974
        • Schubiger O.
        • Haller D.
        Metastases to the pituitary–hypothalamic axis. An MR study of 7 symptomatic patients.
        Neuroradiology. 1992; 34: 131-134
        • Moses A.M.
        • Clayton B.
        • Hochhauser L.
        Use of T1-weighted MR imaging to differentiate between primary polydipsia and central diabetes insipidus.
        AJNR Am J Neuroradiol. 1992; 13: 1273-1277
        • Côté M.
        • Salzman K.L.
        • Sorour M.
        • Couldwell W.T.
        Normal dimensions of the posterior pituitary bright spot on magnetic resonance imaging.
        J Neurosurg. 2014; 120: 357-362
        • Kim Y.H.
        • Lee B.J.
        • Lee K.J.
        • Cho J.H.
        A case of pituitary metastasis from breast cancer that presented as left visual disturbance.
        J Korean Neurosurg Soc. 2012; 51: 94-97
        • Mayr N.A.
        • Yuh W.T.C.
        • Muhonen M.G.
        • Koci T.M.
        • Tali E.T.
        • Nguyen H.D.
        • et al.
        Pituitary metastases: MR findings.
        J Comput Assist Tomogr. 1993; 17: 432-437
        • Eichler A.F.
        • Loeffler J.S.
        Multidisciplinary Management of Brain Metastases.
        Oncologist. 2007; 12: 884-898
        • Hwang J.M.
        • Kim Y.H.
        • Kim T.M.
        • Park S.H.
        Differential Diagnosis and Management of a Pituitary Mass with Renal Cell Carcinoma.
        J Korean Neurosurg Soc. 2013; 54: 132
        • McCormick P.c.
        • Post K.d.
        • Kandji A.d.
        • Hays A.P.
        Metastatic Carcinoma to the Pituitary Gland.
        Br J Neurosurg. 1989; 3: 71-79
        • Patchell R.A.
        The management of brain metastases.
        Cancer Treat Rev. 2003; 29: 533-540
        • Moon R.D.C.
        • Singleton W.G.B.
        • Smith P.
        • Urankar K.
        • Evans A.
        • Williams A.P.
        Slow-growing pituitary metastasis from renal cell carcinoma: literature review.
        World Neurosurg. 2021; 145: 416-425
        • Ho R.-W.
        • Huang H.-M.
        • Ho J.-T.
        The Influence of Pituitary Adenoma Size on Vision and Visual Outcomes after Trans-Sphenoidal Adenectomy: A Report of 78 Cases.
        J Korean Neurosurg Soc. 2015; 57: 23
        • Piedra M.P.
        • Brown P.D.
        • Carpenter P.C.
        • Link M.J.
        Resolution of diabetes insipidus following gamma knife surgery for a solitary metastasis to the pituitary stalk.
        Case report. J Neurosurg. 2004; 101: 1053-1056
        • Mormando M.
        • Puliani G.
        • Barnabei A.
        • Lauretta R.
        • Bianchini M.
        • Chiefari A.
        • et al.
        A Rare Case of Pituitary Melanoma Metastasis: A Dramatic and Prolonged Response to Dabrafenib-Trametinib Therapy.
        Front Endocrinol. 2020; 11
        • Sturgeon C.T.
        • Davis F.E.
        • Catz B.
        • Petit D.
        • Starr P.
        Treatment of thyroid cancer metastases with TSH and I131 during thyroid hormone medication.
        J Clin Endocrinol Metab. 1953; 13: 1391-1407