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A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case–control study of 410 patients with 8 years post-operative follow-up

Abstract

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case–control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.

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Acknowledgments

We thank Emily Witty from Angloscribe for help with the translation into English, A. Reynaud for her excellent technical assistance, P. Gérardi for typing the manuscript, Dr David Forman and Dr Alexandre Vasiljevic for helpful criticisms. Co-authors of HYPOPRONOS are 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. This work was supported by grants from the Ministère de la Santé (Programme Hospitalier de Recherche Clinique National no 27-43, HYPOPRONOS) and research contracts with the Institut National de la Santé et de la Recherche Médicale and the Ligue Contre le Cancer Rhône-Alpes.

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Trouillas, J., Roy, P., Sturm, N. et al. 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, 123–135 (2013). https://doi.org/10.1007/s00401-013-1084-y

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Keywords

  • Classification
  • Pituitary tumour
  • Pituitary adenoma