[en] BACKGROUND: The term double pituitary adenomas (DPA) is usually referred to those rare lesions showing two distinct cellular components. Genetic background may sustain the proliferation of more than one cell at the same time but no information is available on the presence of aip mutations in these patients. AIM: We report the prevalence and the endocrinological, neuroradiological, histopathological and genetic features of DPA detected in a large surgical series. The contribution of pituitary transcription factor immunostains in DPA was also evaluated. SUBJECTS AND METHODS: One-hundred-forty-four patients undergoing surgery for tumors of the sellar region were evaluated. Histopathology, immunohistochemistry and the mutational analysis for the entire coding region of the AIP and MEN1 genes were performed. RESULTS: One-hundred-seventeen patients out of 144 had a pituitary adenoma. DPA was found in 3 (2.6%) out of 117 patients with pituitary adenoma. Immunohistochemistry and transcription factors analysis demonstrated two not yet described histotype associations in DPA. The coexistence of somatotroph-lactotroph and silent mammosomatotroph histotype in 1 case and the coexistence of sparsely granulated lactotroph and null cell adenomas in the remaining two cases were first identified. Sequencing data for the coding region of the aip and the menin gene resulted in wild type sequences in all patients with DPA. CONCLUSIONS: The prevalence of DPA observed in our unselected surgical series is not negligible (2.6%). Furthermore, the evaluation of the treatment outcome would suggest that the clinical management of DPAs requires a careful diagnostic approach and follow- up.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Magri, F.
Villa, C.
Locatelli, D.
Scagnelli, P.
Lagonigro, M. S.
Morbini, P.
Castellano, M.
Gabellieri, E.
Rotondi, M.
Solcia, E.
Daly, Adrian ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Chiovato, L.
Language :
English
Title :
Prevalence of double pituitary adenomas in a surgical series: Clinical, histological and genetic features.
Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 2006, 91: 4769-75.
Asa S. Pratical Pituitary Pathology. What does the pathologist need to know? Arch Pathol Lab Med 2008, 132: 1231-40.
Kontogeorgos G, Kovacs K, Horvath E, Scheithauer BW. Multiple adenomas of the human pituitary. A retrospective autopsy study with clinical implications. J Neurosurg 1991, 74: 243-7.
Asa SL, Ezzat S. The cytogenesis and pathogenesis of pituitary adenomas. Endocr Rev 1988, 19: 798-827.
Osamura RY, Kajiya H, Takei M, et al. Pathology of the human pituitary adenomas. Histochem Cell Biol 2008, 130: 495-507.
Kim K, Yamada S, Usui M, Sano T. Preoperative identification of clearly separated double pituitary adenomas. Clin Endocrinol 2004, 61: 26-30. (Pubitemid 38951642)
Syro LV, Horvath E, Kovacs K. Double adenoma of the pituitary: a somatotroph adenoma colliding with a gonadotroph adenoma. J Endocrinol Invest 2000, 23: 37-41. (Pubitemid 30105318)
Sano T, Horiguchi H, Xu B, et al. Double pituitary adenomas: six surgical cases. Pituitary 1999, 1: 243-50.
Kannuki S, Matsumoto K, Sano T, Shintanl Y, Bando H, Saito S. Double pituitary adenoma-two case reports. Neurol Med Chir (Tokyo) 1996, 36: 818-21.
Kontogeorgos G, Scheithauer BW, Horvath E, et al. Double adenomas of the pituitary: a clinicopathological study of 11 tumors. Neurosurgery 1992, 31: 840-9.
Meij BP, Lopes MB, Vance ML, Thomer MO, Laws ER Jr. Double pituitary lesions in three patients with Cushing's disease. Pituitary 2000, 3: 159-68.
Tomita T, Gates E. Pituitary adenomas and granular cell tumors. Incidence, cell type, and location of tumor in 100 pituitary glands at autopsy. Am J Clin Pathol 1999, 111: 817-25.
Tomita T, Kuziez M, Watanabe I. Double tumors of anterior and posterior pituitary gland. Acta Neuropathol 1981, 54: 161-4.
Tolis G, Bertrand G, Carpenter S, McKenzie JM. Acromegaly and galactorrhea-amenorrhea with two pituitary adenomas secreting growth hormone or prolactin. A case report Ann Intern Med 1978, 89: 345-58.
McKelvie PA, McNeill P. Double pituitary adenomas: a series of three patients. Pathology 2002, 34: 57-60. (Pubitemid 34155230)
Shimizu C, Koike T, Sawamura Y. Double pituitary adenomas with distinct histological features and immunophenotypes. J Neurol Neurosurg Psychiatry 2004, 75: 140.
Jastania RA, Alsaad KO, Al-Shraim M, Kovacs K, Asa SL. Double adenomas of the pituitary: transcription factors Pit-1, T-pit, and SF-1 identify cytogenesis and differentiation. Endocr Pathol 2005, 16: 187-94.
Daly AF, Jaffrain-Rea ML, Beckers A. Clinical and genetic features of familial pituitary adenomas. Horm Metab Res 2005, 37: 347-54. (Pubitemid 41008768)
Daly AF, Jaffrain-Rea ML, Ciccarelli A, et al. Clinical characterization of familial isolated pituitary adenomas. J Clin Endocrinol Metab 2006, 91: 3316-23.
Al Brahim NY, Rambaldini G, Ezzat S, Asa SL. Complex endocrinopathies in MEN-diagnostic dilemmas in endocrine oncology. Endocrine Pathol 2007, 18: 37-41.
Trouillas J, Labat-Moleur F, Sturm N, et al. A case-control study in a series of 77 patients versus 2509 non-MEN1 patients. Am J Surg Pathol 2008, 32: 534-43.
Vierimaa O, Georgitsi M, Lehtonen R, et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science 2006, 312: 1228-30.
Gadelha MR, Prezant TR, Une KN, et al. Loss of heterozygosity on chromosome 11q13 in two families with acromegaly/gigantism is independent of mutations of the multiple endocrine neoplasia type I gene. J Clin Endocrinol Metab 1999, 84: 249-56.
Cazabat L, Libè R, Perlemoine K, et al. Germline inactivating mutations of the aryl hydrocarbon receptor-interacting protein gene in a large cohort of sporadic acromegaly: mutations are found in a subset of young patients with macroadenomas. Eur J Endocrinol 2007, 157: 1-8.
Georgitsi M, Raitila A, Karhu A, et al. Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations. Proc Natl Acad Sci USA 2007, 104: 4101-5.
Toledo RA, Lourenco DM Jr, Liberman B, et al. Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma. J Clin Endocrinol Metab 2007, 92: 1934-7. (Pubitemid 46997212)
Barlier A, Vanbellinghen JF, Daly AF, et al. Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas. J Clin Endocrinol Metab 2007, 92: 1952-5.
Daly AF, Vanbellinghen JF, Khoo SK, et al. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab 2007, 92: 1891-6.
Villa C, Magri F, Morbini P, et al. Silent familial isolated pituitary adenomas: histopathological and clinical case report Endocr Pathol 2008, 19: 40-6.
DeLellis R, Lloyd RV, Heitz PU, Eng C. WHO Classification of tumours. Pathology & genetics. Tumours of Endocrine Organs. 2004.
Al-Brahim NY, Asa SL My approach to pathology of the pituitary gland. J Clin Pathol 2006, 59: 1245-53.
Johnsen DE, Woodruff WW, Allen IS, Cera PJ, Funkhouser GR, Coleman LL. MR imaging of the sellar and juxtasellar regions. Radiographics 1991, 11: 727-58.
Asa SL, Kovacs K, Singer W. Human fetal adenohypophysis: morphologic and functional analysis in vitro. Neuroendocrinology 1991, 53: 562-72.
Gadelha MR, Une KN, Rohde K, Vaisman M, Kineman RD, Frohman LA. Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12. J Clin Endocrinol Metab 2000, 85: 707-14. (Pubitemid 32273658)
Leontiou CA, Gueorguiev M, van der Spuy J, et al. The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas. J Clin Endocrinol Metab 2008, 93: 2390-401.
Arafat AM, Mohlig M, Weickert MO, et al. Growth hormone response during oral glucose tolerance test: the impact of assay method on the estimation of reference values in patients with acromegaly and in healthy controls, and the role of gender, age, and body mass index. J Clin Endocrinol Metab 2008, 93: 1254-62.
Alexopoulou O, Bex M, Abs R, T'sjoen G, Velkeniers B, Maiter D. Divergence between growth hormone and insulin-like growth factor-1 concentrations in the follow up of acromegaly. J Clin Endocrinol Metab 2008, 93: 1324-30.
