Abstract
Non-functioning pituitary carcinomas (NFPC) are defined as tumours of adenophyseal origin with craniospinal or systemic dissemination, with the absence of a hormonal hypersecretion syndrome. These are a histologically heterogenous group of tumours, comprising gonadotroph, null cell, “silent” tumours of corticotroph, somatotroph or lactotroph cell lineages as well as plurihormonal Pit-1 tumours. NFPC are exceedingly rare, and hence few cases have been described. This review has identified 38 patients with NFPC reported in the literature. Recurrent invasive non-functioning pituitary adenomas (NFPA) were observed in a majority of patients. Various factors have been identified as markers of the potential for aggressive behaviour, including rapid tumour growth, growth after radiotherapy, gain or shift of hormone secretion and raised proliferative markers. Typically, there is a latency of several years from the original presentation with an NFPA to identification of metastases and only 5 cases reported with rapidly progressive malignant disease within 1 month of presentation. Therapeutic options include debulking surgery, radiation therapy and chemotherapy with temozolomide recommended as first line systemic treatment. Although long-term survivors are described, prognosis remains generally very poor (median survival 8 months). Improvements in molecular tumour profiling may assist in predicting tumour behaviour, guide therapeutic choices and identify novel therapies.
Similar content being viewed by others
References
Lloyd RV, Osamura R, Kloppel G, Rosai J (2017) WHO classification of tumours of endocrine organs, vol 10, 4 edn. IARC, Lyon
Kaltsas GA, Grossman AB (1998) Malignant pituitary tumours. Pituitary 1(1):69–81
Pernicone PJ, Scheithauer BW, Sebo TJ, Kovacs KT, Horvath E, Young WF Jr, Lloyd RV, Davis DH, Guthrie BL, Schoene WC (1997) Pituitary carcinoma: a clinicopathologic study of 15 cases. Cancer 79(4):804–812
Imboden PN, Borruat FX, De Tribolet N, Meagher-Villemure K, Pica A, Gomez F (2004) Non-functioning pituitary carcinoma. Pituitary 7(3):149–156. https://doi.org/10.1007/s11102-005-3411-3
Doniach I (1992) Pituitary carcinoma. Clin Endocrinol 37(2):194–195
Hansen TM, Batra S, Lim M, Gallia GL, Burger PC, Salvatori R, Wand G, Quinones-Hinojosa A, Kleinberg L, Redmond KJ (2014) Invasive adenoma and pituitary carcinoma: a SEER database analysis. Neurosurg Rev 37(2):279–285. https://doi.org/10.1007/s10143-014-0525-y (discussion 285–276)
van der Zwan JM, Mallone S, van Dijk B, Bielska-Lasota M, Otter R, Foschi R, Baudin E, Links TP, Rarecare WG (2012) Carcinoma of endocrine organs: results of the RARECARE project. Eur J Cancer 48(13):1923–1931. https://doi.org/10.1016/j.ejca.2012.01.029
Dudziak K, Honegger J, Bornemann A, Horger M, Mussig K (2011) Pituitary carcinoma with malignant growth from first presentation and fulminant clinical course–case report and review of the literature. J Clin Endocrinol Metab 96(9):2665–2669. https://doi.org/10.1210/jc.2011-1166
Negishi K, Suzuki T, Masuda Y, Masugi Y, Teramoto A, Ohama E (1988) Two autopsy cases of primary pituitary carcinoma. No To Shinkei 40(5):491–496
Mountcastle RB, Roof BS, Mayfield RK, Mordes DB, Sagel J, Biggs PJ, Rawe SE (1989) Pituitary adenocarcinoma in an acromegalic patient: response to bromocriptine and pituitary testing: a review of the literature on 36 cases of pituitary carcinoma. Am J Med Sci 298(2):109–118
Mete O, Lopes MB (2017) Overview of the 2017 WHO classification of pituitary tumors. Endocr Pathol. https://doi.org/10.1007/s12022-017-9498-z
Lopes MBS (2017) The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. Acta Neuropathol. https://doi.org/10.1007/s00401-017-1769-8
Molitch ME, Russell EJ (1990) The pituitary “incidentaloma”. Ann Intern Med 112(12):925–931
Nishioka H, Inoshita N, Mete O, Asa SL, Hayashi K, Takeshita A, Fukuhara N, Yamaguchi-Okada M, Takeuchi Y, Yamada S (2015) The complementary role of transcription factors in the accurate diagnosis of clinically nonfunctioning pituitary adenomas. Endocr Pathol 26(4):349–355. https://doi.org/10.1007/s12022-015-9398-z
Fernandez A, Karavitaki N, Wass JA (2010) Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol 72(3):377–382. https://doi.org/10.1111/j.1365-2265.2009.03667.x
Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A (2006) High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 91(12):4769–4775. https://doi.org/10.1210/jc.2006-1668
Kaltsas GA, Nomikos P, Kontogeorgos G, Buchfelder M, Grossman AB (2005) Clinical review: diagnosis and management of pituitary carcinomas. J Clin Endocrinol Metab 90(5):3089–3099. https://doi.org/10.1210/jc.2004-2231
Amar AP, Hinton DR, Krieger MD, Weiss MH (1999) Invasive pituitary adenomas: significance of proliferation parameters. Pituitary 2(2):117–122
Raverot G, Burman P, McCormack AI, Heaney AP, Petersenn S, Popovic V, Trouillas J, Dekkers O (2017) European Society of Endocrinology clinical practice guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol. https://doi.org/10.1530/EJE-17-0796
McCormack AI, Dekkers OM, Petersenn S, Popovic V, Trouillas J, Raverot G, Burman P (2017) Use of temozolomide in a large cohort of patients with aggressive pituitary tumours and pituitary carcinomas: results from a European Society of Endocrinology (ESE) survey. Endocr Abstracts. https://doi.org/10.1530/endoabs.49.OC12.2
Lee JC, Pekmezci M, Lavezo JL, Vogel H, Katznelson L, Fraenkel M, Harsh G, Dulai M, Perry A, Tihan T (2017) Utility of Pit-1 immunostaining in distinguishing pituitary adenomas of primitive differentiation from null cell adenomas. Endocr Pathol. https://doi.org/10.1007/s12022-017-9503-6
Cooper O (2015) Silent corticotroph adenomas. Pituitary 18(2):225–231. https://doi.org/10.1007/s11102-014-0624-3
Wade AN, Baccon J, Grady MS, Judy KD, O’Rourke DM, Snyder PJ (2011) Clinically silent somatotroph adenomas are common. Eur J Endocrinol 165(1):39–44. https://doi.org/10.1530/EJE-11-0216
Saeger W, Ludecke DK, Buchfelder M, Fahlbusch R, Quabbe HJ, Petersenn S (2007) Pathohistological classification of pituitary tumors: 10 years of experience with the German pituitary tumor registry. Eur J Endocrinol 156(2):203–216. https://doi.org/10.1530/eje.1.02326
Horvath E, Kovacs K, Smyth HS, Cusimano M, Singer W (2005) Silent adenoma subtype 3 of the pituitary–immunohistochemical and ultrastructural classification: a review of 29 cases. Ultrastruct Pathol 29(6):511–524. https://doi.org/10.1080/01913120500323514
Mete O, Gomez-Hernandez K, Kucharczyk W, Ridout R, Zadeh G, Gentili F, Ezzat S, Asa SL (2016) Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. Mod Pathol 29(2):131–142. https://doi.org/10.1038/modpathol.2015.151
Erickson D, Scheithauer B, Atkinson J, Horvath E, Kovacs K, Lloyd RV, Young WF Jr (2009) Silent subtype 3 pituitary adenoma: a clinicopathologic analysis of the Mayo Clinic experience. Clin Endocrinol 71(1):92–99. https://doi.org/10.1111/j.1365-2265.2008.03514.x
Roncaroli F, Scheithauer BW, Horvath E, Erickson D, Tam CK, Lloyd RV, Kovacs K (2010) Silent subtype 3 carcinoma of the pituitary: a case report. Neuropathol Appl Neurobiol 36(1):90–94. https://doi.org/10.1111/j.1365-2990.2009.01043.x
Roncaroli F, Scheithauer BW, Young WF, Horvath E, Kovacs K, Kros JM, Al-Sarraj S, Lloyd RV, Faustini-Fustini M (2003) Silent corticotroph carcinoma of the adenohypophysis: a report of five cases. Am J Surg Pathol 27(4):477–486
Lee M, Lupp A, Mendoza N, Martin N, Beschorner R, Honegger J, Schlegel J, Shively T, Pulz E, Schulz S, Roncaroli F, Pellegata NS (2015) SSTR3 is a putative target for the medical treatment of gonadotroph adenomas of the pituitary. Endocr Relat Cancer 22(1):111–119. https://doi.org/10.1530/ERC-14-0472
Dai C, Sun B, Liu X, Bao X, Feng M, Yao Y, Wei J, Deng K, Yang C, Li X, Ma W, Wang R (2017) O-6-Methylguanine-DNA methyltransferase expression is associated with pituitary adenoma tumor recurrence: a systematic meta-analysis. Oncotarget 8(12):19674–19683. https://doi.org/10.18632/oncotarget.14936
Kovacs K, Rotondo F, Horvath E, Syro LV, Di Ieva A, Cusimano MD, Munoz DG (2015) Letter to the editor. Endocr Pathol 26(1):93–94. https://doi.org/10.1007/s12022-014-9342-7
Kovacs K (2006) The 2004 WHO classification of pituitary tumors: comments. Acta Neuropathol 111(1):62–63. https://doi.org/10.1007/s00401-005-1095-4
Chiloiro S, Doglietto F, Trapasso B, Iacovazzo D, Giampietro A, Di Nardo F, de Waure C, Lauriola L, Mangiola A, Anile C, Maira G, De Marinis L, Bianchi A (2015) Typical and atypical pituitary adenomas: a single-center analysis of outcome and prognosis. Neuroendocrinology 101(2):143–150. https://doi.org/10.1159/000375448
De Caro DB, Solari M, Pagliuca D, Villa F, Guadagno A, Cavallo E, Colao LM, Pettinato A, Cappabianca G (2017) P.: Atypical pituitary adenomas: clinical characteristics and role of ki-67 and p53 in prognostic and therapeutic evaluation: a series of 50 patients. Neurosurg Rev 40(1):105–114. https://doi.org/10.1007/s10143-016-0740-9
DeLellis RA, Lloyd RV, Heitz PU, Eng C (2004) World health organization classification of tumours: pathology and genetics of tumours of endocrine organs, 3rd edn. IARC Press, Lyon
Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horvath E, Pernicone PJ, Murray D, Laws ER Jr (1996) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38(1):99–106 (discussion 106–107)
Mete O, Ezzat S, Asa SL (2012) Biomarkers of aggressive pituitary adenomas. J Mol Endocrinol 49(2):R69–R78. https://doi.org/10.1530/JME-12-0113
Heaney AP (2011) Clinical review: pituitary carcinoma: difficult diagnosis and treatment. J Clin Endocrinol Metab 96(12):3649–3660. https://doi.org/10.1210/jc.2011-2031
Trouillas J, Roy P, Sturm N, Dantony E, Cortet-Rudelli C, Viennet G, Bonneville JF, Assaker R, Auger C, Brue T, Cornelius A, Dufour H, Jouanneau E, Francois P, Galland F, Mougel F, Chapuis F, Villeneuve L, Maurage CA, Figarella-Branger D, Raverot G, members of HYPOPRONOS, Barlier A, Bernier M, Bonnet F, Borson-Chazot F, Brassier G, Caulet-Maugendre S, Chabre O, Chanson P, Cottier JF, Delemer B, Delgrange E, Di Tommaso L, Eimer S, Gaillard S, Jan M, Girard JJ, Lapras V, Loiseau H, Passagia JG, Patey M, Penfornis A, Poirier JY, Perrin G, Tabarin A (2013) A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol 126(1):123–135. https://doi.org/10.1007/s00401-013-1084-y
Miermeister CP, Petersenn S, Buchfelder M, Fahlbusch R, Ludecke DK, Holsken A, Bergmann M, Knappe HU, Hans VH, Flitsch J, Saeger W, Buslei R (2015) Histological criteria for atypical pituitary adenomas: data from the German pituitary adenoma registry suggests modifications. Acta Neuropathol Commun 3:50. https://doi.org/10.1186/s40478-015-0229-8
Thapar K, Scheithauer BW, Kovacs K, Pernicone PJ, Laws ER Jr (1996) p53 expression in pituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions. Neurosurgery 38(4), 765–770 (discussion 770–761)
Gejman R, Swearingen B, Hedley-Whyte ET (2008) Role of Ki-67 proliferation index and p53 expression in predicting progression of pituitary adenomas. Hum Pathol 39(5):758–766. https://doi.org/10.1016/j.humpath.2007.10.004
Nudleman KL, Choi B, Kusske JA (1985) Primary pituitary carcinoma: a clinical pathological study. Neurosurgery 16(1):90–95
Sakamoto T, Itoh Y, Fushimi S, Kowada M, Saito M (1990) Primary pituitary carcinoma with spinal cord metastasis–case report. Neurol Med Chir 30(10):763–767
Marques P, Mafra M, Calado C, Martins A, Monteiro J, Leite V (2014) Aggressive pituitary lesion with a remarkably high Ki-67. Arq Bras Endocrinol Metabol 58(6):656–660
Pasquel FJ, Vincentelli C, Brat DJ, Oyesiku NM, Ioachimescu AG (2013) Pituitary carcinoma in situ. Endocr Pract 19(3):e69–e73. https://doi.org/10.4158/EP12351.CR
Luzi P, Miracco C, Lio R, Malandrini A, Piovani S, Venezia SG, Tosi P (1987) Endocrine inactive pituitary carcinoma metastasizing to cervical lymph nodes: a case report. Hum Pathol 18(1):90–92
Holthouse DJ, Robbins PD, Kahler R, Knuckey N, Pullan P (2001) Corticotroph pituitary carcinoma: case report and literature review. Endocr Pathol 12(3):329–341
Melcescu E, Gannon AW, Parent AD, Fratkin JF, Nicholas WC, Koch CA, Galhom A (2013) Silent or subclinical corticotroph pituitary macroadenoma transforming into cushing disease: 11-year follow-up. Neurosurgery 72(1):E144–E146. https://doi.org/10.1227/NEU.0b013e3182750850
Karavitaki N, Ansorge O, Wass JA (2007) Silent corticotroph adenomas. Arq Bras Endocrinol Metabol 51(8):1314–1318
Daems T, Verhelst J, Michotte A, Abrams P, De Ridder D, Abs R (2009) Modification of hormonal secretion in clinically silent pituitary adenomas. Pituitary 12(1):80–86. https://doi.org/10.1007/s11102-008-0085-7
Annamalai AK, Dean AF, Kandasamy N, Kovacs K, Burton H, Halsall DJ, Shaw AS, Antoun NM, Cheow HK, Kirollos RW, Pickard JD, Simpson HL, Jefferies SJ, Burnet NG, Gurnell M (2012) Temozolomide responsiveness in aggressive corticotroph tumours: a case report and review of the literature. Pituitary 15(3):276–287. https://doi.org/10.1007/s11102-011-0363-7
Brown RL, Muzzafar T, Wollman R, Weiss RE (2006) A pituitary carcinoma secreting TSH and prolactin: a non-secreting adenoma gone awry. Eur J Endocrinol 154(5):639–643. https://doi.org/10.1530/eje.1.02141
Pichard C, Gerber S, Laloi M, Kujas M, Clemenceau S, Ponvert D, Bruckert E, Turpin G (2002) Pituitary carcinoma: report of an exceptional case and review of the literature. J Endocrinol Invest 25(1):65–72. https://doi.org/10.1007/BF03343963
Lopes MB, Scheithauer BW, Schiff D (2005) Pituitary carcinoma: diagnosis and treatment. Endocrine 28(1):115–121. https://doi.org/10.1385/ENDO:28:1:115
Ragel BT, Couldwell WT (2004) Pituitary carcinoma: a review of the literature. Neurosurg Focus 16(4):E7
Daly AF, Tichomirowa MA, Beckers A (2009) The epidemiology and genetics of pituitary adenomas. Best Pract Res Clin Endocrinol Metab 23(5):543–554. https://doi.org/10.1016/j.beem.2009.05.008
McCutcheon IE, Pieper DR, Fuller GN, Benjamin RS, Friend KE, Gagel RF (2000) Pituitary carcinoma containing gonadotropins: treatment by radical excision and cytotoxic chemotherapy: case report. Neurosurgery 46(5):1233–1239 (discussion 1239–1240)
Koyama J, Ikeda K, Shose Y, Kimura M, Obora Y, Kohmura E (2007) Long-term survival with non-functioning pituitary carcinoma: case report. Neurol Med Chir 47(10):475–478
Xiao J, Zhu Z, Zhong D, Ma W, Wang R (2015) Improvement in diagnosis of metastatic pituitary carcinoma by 68 Ga DOTATATE PET/CT. Clin Nucl Med 40(2):e129–e131. https://doi.org/10.1097/RLU.0000000000000462
Garmes HM, Carvalheira JBC, Reis F, Queiroz LS, Fabbro MD, Souza VFP, Santos AO (2017) Pituitary carcinoma: A case report and discussion of potential value of combined use of Ga-68 DOTATATE and F-18 FDG PET/CT scan to better choose therapy. Surg Neurol Int 8:162. https://doi.org/10.4103/sni.sni_498_16
Heaney AP, Melmed S (2004) Molecular targets in pituitary tumours. Nat Rev Cancer 4(4):285–295. https://doi.org/10.1038/nrc1320
Sav A, Rotondo F, Syro LV, Di Ieva A, Cusimano MD, Kovacs K (2015) Invasive, atypical and aggressive pituitary adenomas and carcinomas. Endocrinol Metab Clin North Am 44(1):99–104. https://doi.org/10.1016/j.ecl.2014.10.008
Pei L, Melmed S, Scheithauer B, Kovacs K, Prager D (1994) H-ras mutations in human pituitary carcinoma metastases. J Clin Endocrinol Metab 78(4):842–846. https://doi.org/10.1210/jcem.78.4.8157709
Arzt E, Chesnokova V, Stalla GK, Melmed S (2009) Pituitary adenoma growth: a model for cellular senescence and cytokine action. Cell Cycle 8(5):677–678. https://doi.org/10.4161/cc.8.5.8083
Alexandraki KI, Munayem Khan M, Chahal HS, Dalantaeva NS, Trivellin G, Berney DM, Caron P, Popovic V, Pfeifer M, Jordan S, Korbonits M, Grossman AB (2012) Oncogene-induced senescence in pituitary adenomas and carcinomas. Hormones 11(3):297–307
Rickert CH, Scheithauer BW, Paulus W (2001) Chromosomal aberrations in pituitary carcinoma metastases. Acta Neuropathol 102(2):117–120
Vandeva S, Tichomirowa MA, Zacharieva S, Daly AF, Beckers A (2010) Genetic factors in the development of pituitary adenomas. Endocr Dev 17:121–133. https://doi.org/10.1159/000262534
Yang Z, Zhang T, Gao H (2016) Genetic aspects of pituitary carcinoma: a systematic review. Medicine 95(47):e5268. https://doi.org/10.1097/MD.0000000000005268
Saeger W (2005) Pituitary tumors: prognostic indicators. Endocrine 28(1):57–66
Scheithauer BW, Gaffey TA, Lloyd RV, Sebo TJ, Kovacs KT, Horvath E, Yapicier O, Young WF Jr, Meyer FB, Kuroki T, Riehle DL, Laws ER Jr (2006) Pathobiology of pituitary adenomas and carcinomas. Neurosurgery 59(2):341–353. https://doi.org/10.1227/01.NEU.0000223437.51435.6E (discussion 341–353)
Jia W, Zhu J, Martin TA, Sanders AJ, Yang X, Cheng S, Yu H, Jia G, Liu X, Lu R, Jiang WG (2015) Expression of metastasis-associated gene-1 is associated with bone invasion and tumor stage in human pituitary adenomas. Cancer Genom Proteom 12(3):113–118
Oystese KA, Casar-Borota O, Normann KR, Zucknick M, Berg JP, Bollerslev J (2017) Estrogen receptor alpha, a sex-dependent predictor of aggressiveness in nonfunctioning pituitary adenomas: sstr and sex hormone receptor distribution in NFPA. J Clin Endocrinol Metab 102(9):3581–3590. https://doi.org/10.1210/jc.2017-00792
Wei Z, Zhou C, Liu M, Yao Y, Sun J, Xiao J, Ma W, Zhu H, Wang R (2015) MicroRNA involvement in a metastatic non-functioning pituitary carcinoma. Pituitary 18(5):710–721. https://doi.org/10.1007/s11102-015-0648-3
Frost AR, Tenner S, Tenner M, Rollhauser C, Tabbara SO (1995) ACTH-producing pituitary carcinoma presenting as the cauda equina syndrome. Arch Pathol Lab Med 119(1):93–96
Waltz TA, Brownell B (1966) Sarcoma: a possible late result of effective radiation therapy for pituitary adenoma: report of two cases. J Neurosurg 24(5):901–907. https://doi.org/10.3171/jns.1966.24.5.0901
Scheithauer BW, Randall RV, Laws ER Jr, Kovacs KT, Horvath E, Whitaker MD (1985) Prolactin cell carcinoma of the pituitary: clinicopathologic, immunohistochemical, and ultrastructural study of a case with cranial and extracranial metastases. Cancer 55(3):598–604
Krueger EM, Seibly J (2017) Seeding of a pituitary adenoma or atypical: pituitary carcinoma? Cureus 9(5):e1211. https://doi.org/10.7759/cureus.1211
Landman RE, Horwith M, Peterson RE, Khandji AG, Wardlaw SL (2002) Long-term survival with ACTH-secreting carcinoma of the pituitary: a case report and review of the literature. J Clin Endocrinol Metab 87(7):3084–3089. https://doi.org/10.1210/jcem.87.7.8667
Ciric I, Ragin A, Baumgartner C, Pierce D (1997) Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience. Neurosurgery 40(2):225–236 (discussion 236–227)
Ding D, Starke RM, Sheehan JP (2014) Treatment paradigms for pituitary adenomas: defining the roles of radiosurgery and radiation therapy. J Neurooncol 117(3):445–457. https://doi.org/10.1007/s11060-013-1262-8
Losa M, Bogazzi F, Cannavo S, Ceccato F, Curto L, De Marinis L, Iacovazzo D, Lombardi G, Mantovani G, Mazza E, Minniti G, Nizzoli M, Reni M, Scaroni C (2016) Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas. J Neurooncol 126(3):519–525. https://doi.org/10.1007/s11060-015-1991-y
Greenman Y, Stern N (2016) Paradoxical and atypical responses to pasireotide in aggressive ACTH-secreting pituitary tumors. Pituitary 19(6):605–611. https://doi.org/10.1007/s11102-016-0755-9
Lasolle H, Cortet C, Castinetti F, Cloix L, Caron P, Delemer B, Desailloud R, Jublanc C, Lebrun-Frenay C, Sadoul JL, Taillandier L, Batisse-Lignier M, Bonnet F, Bourcigaux N, Bresson D, Chabre O, Chanson P, Garcia C, Haissaguerre M, Reznik Y, Borot S, Villa C, Vasiljevic A, Gaillard S, Jouanneau E, Assie G, Raverot G (2017) Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas. Eur J Endocrinol 176(6):769–777. https://doi.org/10.1530/EJE-16-0979
Bengtsson D, Schroder HD, Andersen M, Maiter D, Berinder K, Feldt Rasmussen U, Rasmussen AK, Johannsson G, Hoybye C, van der Lely AJ, Petersson M, Ragnarsson O, Burman P (2015) Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide. J Clin Endocrinol Metab 100(4):1689–1698. https://doi.org/10.1210/jc.2014-4350
Zacharia BE, Gulati AP, Bruce JN, Carminucci AS, Wardlaw SL, Siegelin M, Remotti H, Lignelli A, Fine RL (2014) High response rates and prolonged survival in patients with corticotroph pituitary tumors and refractory cushing disease from capecitabine and temozolomide (CAPTEM): a case series. Neurosurgery 74(4):E447–E455. https://doi.org/10.1227/NEU.0000000000000251 (discussion E455)
Kil WJ, Cerna D, Burgan WE, Beam K, Carter D, Steeg PS, Tofilon PJ, Camphausen K (2008) In vitro and in vivo radiosensitization induced by the DNA methylating agent temozolomide. Clin Cancer Res 14(3):931–938. https://doi.org/10.1158/1078-0432.CCR-07-1856
Raverot G, Sturm N, de Fraipont F, Muller M, Salenave S, Caron P, Chabre O, Chanson P, Cortet-Rudelli C, Assaker R, Dufour H, Gaillard S, Francois P, Jouanneau E, Passagia JG, Bernier M, Cornelius A, Figarella-Branger D, Trouillas J, Borson-Chazot F, Brue T (2010) Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience. J Clin Endocrinol Metab 95(10):4592–4599. https://doi.org/10.1210/jc.2010-0644
Marchesi F, Turriziani M, Tortorelli G, Avvisati G, Torino F, De Vecchis L (2007) Triazene compounds: mechanism of action and related DNA repair systems. Pharmacol Res 56(4):275–287. https://doi.org/10.1016/j.phrs.2007.08.003
Murakami M, Mizutani A, Asano S, Katakami H, Ozawa Y, Yamazaki K, Ishida Y, Takano K, Okinaga H, Matsuno A (2011) A mechanism of acquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma: case report. Neurosurgery 68(6):E1761–E1767. https://doi.org/10.1227/NEU.0b013e318217161a (discussion E1767)
Hirohata T, Asano K, Ogawa Y, Takano S, Amano K, Isozaki O, Iwai Y, Sakata K, Fukuhara N, Nishioka H, Yamada S, Fujio S, Arita K, Takano K, Tominaga A, Hizuka N, Ikeda H, Osamura RY, Tahara S, Ishii Y, Kawamata T, Shimatsu A, Teramoto A, Matsuno A (2013) DNA mismatch repair protein (MSH6) correlated with the responses of atypical pituitary adenomas and pituitary carcinomas to temozolomide: the national cooperative study by the Japan Society for Hypothalamic and Pituitary Tumors. J Clin Endocrinol Metab 98(3):1130–1136. https://doi.org/10.1210/jc.2012-2924
Dworakowska D, Grossman AB (2009) The pathophysiology of pituitary adenomas. Best Pract Res Clin Endocrinol Metab 23(5):525–541. https://doi.org/10.1016/j.beem.2009.05.004
Cerovac V, Monteserin-Garcia J, Rubinfeld H, Buchfelder M, Losa M, Florio T, Paez-Pereda M, Stalla GK, Theodoropoulou M (2010) The somatostatin analogue octreotide confers sensitivity to rapamycin treatment on pituitary tumor cells. Cancer Res 70(2):666–674. https://doi.org/10.1158/0008-5472.CAN-09-2951
Gorshtein A, Rubinfeld H, Kendler E, Theodoropoulou M, Cerovac V, Stalla GK, Cohen ZR, Hadani M, Shimon I (2009) Mammalian target of rapamycin inhibitors rapamycin and RAD001 (everolimus) induce anti-proliferative effects in GH-secreting pituitary tumor cells in vitro. Endocr Relat Cancer 16(3):1017–1027. https://doi.org/10.1677/ERC-08-0269
Zatelli MC, Minoia M, Filieri C, Tagliati F, Buratto M, Ambrosio MR, Lapparelli M, Scanarini M, Uberti EC (2010) Effect of everolimus on cell viability in nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 95(2):968–976. https://doi.org/10.1210/jc.2009-1641
Lee M, Wiedemann T, Gross C, Leinhauser I, Roncaroli F, Braren R, Pellegata NS (2015) Targeting PI3K/mTOR signaling displays potent antitumor efficacy against nonfunctioning pituitary adenomas. Clin Cancer Res 21(14):3204–3215. https://doi.org/10.1158/1078-0432.CCR-15-0288
Ben-Shlomo A, Cooper O (2017) Role of tyrosine kinase inhibitors in the treatment of pituitary tumours: from bench to bedside. Curr Opin Endocrinol Diabetes Obes 24(4):301–305. https://doi.org/10.1097/MED.0000000000000344
Eigler T, Ben-Shlomo A (2014) Somatostatin system: molecular mechanisms regulating anterior pituitary hormones. J Mol Endocrinol 53(1):R1–R19. https://doi.org/10.1530/JME-14-0034
Ortiz LD, Syro LV, Scheithauer BW, Ersen A, Uribe H, Fadul CE, Rotondo F, Horvath E, Kovacs K (2012) Anti-VEGF therapy in pituitary carcinoma. Pituitary 15(3):445–449. https://doi.org/10.1007/s11102-011-0346-8
Richardson TE, Shen ZJ, Kanchwala M, Xing C, Filatenkov A, Shang P, Barnett S, Abedin Z, Malter JS, Raisanen JM, Burns DK, White CL, Hatanpaa KJ (2017) Aggressive behavior in silent subtype III pituitary adenomas may depend on suppression of local immune response: a whole transcriptome analysis. J Neuropathol Exp Neurol 76(10):874–882. https://doi.org/10.1093/jnen/nlx072
Mei Y, Bi WL, Greenwald NF, Du Z, Agar NY, Kaiser UB, Woodmansee WW, Reardon DA, Freeman GJ, Fecci PE, Laws ER Jr, Santagata S, Dunn GP, Dunn IF (2016) Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors. Oncotarget 7(47):76565–76576. https://doi.org/10.18632/oncotarget.12088
Baldari S, Ferrau F, Alafaci C, Herberg A, Granata F, Militano V, Salpietro FM, Trimarchi F, Cannavo S (2012) First demonstration of the effectiveness of peptide receptor radionuclide therapy (PRRT) with 111In-DTPA-octreotide in a giant PRL-secreting pituitary adenoma resistant to conventional treatment. Pituitary 15(Suppl 1):S57–S60. https://doi.org/10.1007/s11102-011-0373-5
Priola SM, Esposito F, Cannavo S, Conti A, Abbritti RV, Barresi V, Baldari S, Ferrau F, Germano A, Tomasello F, Angileri FF (2017) Aggressive pituitary adenomas: the dark side of the moon. World Neurosurg 97:140–155. https://doi.org/10.1016/j.wneu.2016.09.092
Komor J, Reubi JC, Christ ER (2014) Peptide receptor radionuclide therapy in a patient with disabling non-functioning pituitary adenoma. Pituitary 17(3):227–231. https://doi.org/10.1007/s11102-013-0494-0
Maclean J, Aldridge M, Bomanji J, Short S, Fersht N (2014) Peptide receptor radionuclide therapy for aggressive atypical pituitary adenoma/carcinoma: variable clinical response in preliminary evaluation. Pituitary 17(6):530–538. https://doi.org/10.1007/s11102-013-0540-y
Kovacs GL, Goth M, Rotondo F, Scheithauer BW, Carlsen E, Saadia A, Hubina E, Kovacs L, Szabolcs I, Nagy P, Czirjak S, Hanzely Z, Kovacs K, Horvath E, Korbonits M (2013) ACTH-secreting crooke cell carcinoma of the pituitary. Eur J Clin Invest 43(1):20–26. https://doi.org/10.1111/eci.12010
Waligorska-Stachura J, Gut P, Sawicka-Gutaj N, Liebert W, Gryczynska M, Baszko-Blaszyk D, Blanco-Gangoo AR, Ruchala M (2016) Growth hormone-secreting macroadenoma of the pituitary gland successfully treated with the radiolabeled somatostatin analog (90)Y-DOTATATE: case report. J Neurosurg 125(2):346–349. https://doi.org/10.3171/2015.6.JNS15363
Beauchesne P, Trouillas J, Barral F, Brunon J (1995) Gonadotropic pituitary carcinoma: case report. Neurosurgery 37(4):810–815 (discussion 815–816)
Bush ZM, Longtine JA, Cunningham T, Schiff D, Jane JA Jr, Vance ML, Thorner MO, Laws ER Jr, Lopes MB (2010) Temozolomide treatment for aggressive pituitary tumors: correlation of clinical outcome with O(6)-methylguanine methyltransferase (MGMT) promoter methylation and expression. J Clin Endocrinol Metab 95(11):E280–E290. https://doi.org/10.1210/jc.2010-0441
Cartwright DM, Miller TR, Nasr AJ (1994) Fine-needle aspiration biopsy of pituitary carcinoma with cervical lymph node metastases: a report of two cases and review of the literature. Diagn Cytopathol 11(1):68–73
Fadul CE, Kominsky AL, Meyer LP, Kingman LS, Kinlaw WB, Rhodes CH, Eskey CJ, Simmons NE (2006) Long-term response of pituitary carcinoma to temozolomide: report of two cases. J Neurosurg 105(4):621–626. https://doi.org/10.3171/jns.2006.105.4.621
He L, Forbes JA, Carr K, Nickols NH, Utz A, Moots P, Weaver K (2016) Response of silent corticotroph pituitary carcinoma to chemotherapy: case report. J Neurosurg Sci 60(2):272–280
Kamiya-Matsuoka C, Cachia D, Waguespack SG, Crane CH, Mahajan A, Brown PD, Nam JY, McCutcheon IE, Penas-Prado M (2016) Radiotherapy with concurrent temozolomide for the management of extraneural metastases in pituitary carcinoma. Pituitary 19(4):415–421. https://doi.org/10.1007/s11102-016-0721-6
Kumar K, Macaulay RJ, Kelly M, Pirlot T (2001) Absent p53 immunohistochemical staining in a pituitary carcinoma. Can J Neurol Sci 28(2):174–178
Morokuma H, Ando T, Hayashida T, Horie I, Inoshita N, Murata F, Ueki I, Nakamura K, Imaizumi M, Usa T, Kawakami A (2012) A case of nonfunctioning pituitary carcinoma that responded to temozolomide treatment. Case Rep Endocrinol 2012:645914. https://doi.org/10.1155/2012/645914
Moshkin O, Syro LV, Scheithauer BW, Ortiz LD, Fadul CE, Uribe H, Gonzalez R, Cusimano M, Horvath E, Rotondo F, Kovacs K (2011) Aggressive silent corticotroph adenoma progressing to pituitary carcinoma: the role of temozolomide therapy. Hormones 10(2):162–167
Vieira Neto L, Chimelli L, Pereira PJ, Gasparetto EL, Bines J, Wildemberg LE, Gadelha MR (2013) The role of temozolomide in the treatment of a patient with a pure silent pituitary somatotroph carcinoma. Endocr Pract 19(6):e145–e149. https://doi.org/10.4158/EP12400.CR
Roncaroli F, Nose V, Scheithauer BW, Kovacs K, Horvath E, Young WF Jr, Lloyd RV, Bishop MC, Hsi B, Fletcher JA (2003) Gonadotropic pituitary carcinoma: HER-2/neu expression and gene amplification: report of two cases. J Neurosurg 99(2):402–408. https://doi.org/10.3171/jns.2003.99.2.0402
Tufton N, Roncaroli F, Hadjidemetriou I, Dang MN, Denes J, Guasti L, Thom M, Powell M, Baldeweg SE, Fersht N, Korbonits M (2017) Pituitary carcinoma in a patient with an SDHB mutation. Endocr Pathol. https://doi.org/10.1007/s12022-017-9474-7
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Lenders, N., McCormack, A. Malignant transformation in non-functioning pituitary adenomas (pituitary carcinoma). Pituitary 21, 217–229 (2018). https://doi.org/10.1007/s11102-017-0857-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11102-017-0857-z