, Volume 16, Issue 4, pp 515–522 | Cite as

Aggressive and malignant prolactin pituitary tumors: pathological diagnosis and patient management

  • Ilyess Zemmoura
  • Anne Wierinckx
  • Alexandre Vasiljevic
  • Michel Jan
  • Jacqueline Trouillas
  • Patrick François


According to the World Health Organization classification of pituitary tumors, only tumors with systemic metastasis must be considered as carcinomas. Invasive tumors with multiple recurrences are only classified as aggressive tumors or “atypical adenomas”. To illustrate the problems encountered in the pathological diagnosis of pituitary carcinoma and in patient management, we present two male patients operated on for an aggressive prolactin pituitary adenoma with and without metastasis. In case 1, 5 surgeries, 3 irradiations, increased doses of dopamine agonists, and trials of temozolomide and carboplatine-VP16 failed to control tumor progression and the appearance of metastases which lead to death 16 years after onset. In case 2, based on the initial diagnosis of an aggressive-invasive adenoma that was resistant to dopamine agonists, gamma-Knife irradiation was initially performed on the intra-cavernous remnant. Eight years after onset, the remnant remained stabilized and the plasma PRL normalized under dopamine agonist. From these 2 cases alongside other cases found in the literature, we propose that the association of certain clinical signs (male sex, dopamine-resistant hyperprolactinemia), radiological signs (invasive macro or giant tumor on MRI) and histological signs (angiogenesis, Ki-67 > 3 %, p53 positive, mitoses >2 per high power field, vascular invasion, up-regulation of genes related to invasion and proliferation, and allelic loss of chromosome 11) might suggest aggressiveness and be suspicious of malignancy before the appearance of metastasis. The early detection of an aggressive phenotype of a prolactin pituitary tumor should permit the earlier establishment of the optimum therapeutic strategy associating surgery and radiotherapy to delay or inhibit metastasis.


Aggressive pituitary tumor Pituitary carcinoma Prolactinoma Hyperprolactinemia Classification 


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Ilyess Zemmoura
    • 1
    • 2
    • 6
  • Anne Wierinckx
    • 3
    • 4
  • Alexandre Vasiljevic
    • 3
    • 4
    • 5
  • Michel Jan
    • 1
    • 2
  • Jacqueline Trouillas
    • 3
    • 4
    • 5
  • Patrick François
    • 1
    • 2
  1. 1.Service de NeurochirurgieCHU de ToursToursFrance
  2. 2.Université François Rabelais de ToursToursFrance
  3. 3.Neuro-Oncology and Neuro-Inflammation Team, INSERM, U1028, CNRS, UMR5292Lyon Neuroscience Research CenterLyonFrance
  4. 4.Faculté de Médecine Lyon-EstUniversité de Lyon, Lyon 1LyonFrance
  5. 5.Centre de Pathologie Est, Groupement Hospitalier EstHospices Civils de LyonLyonFrance
  6. 6.Service de NeurochirurgieCHRU BretonneauToursFrance

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