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.

SSTR3 is a putative target for the medical treatment of gonadotroph adenomas of the pituitary

“…Six (5.6%) were atypical adenomas defined according to the current WHO classification (Lloyd et al 2004). When classified following the grading criteria proposed by Trouillas et al (2013), 63 GPAs were grade 1a, nine were 1b, 39 were 2a, and 7 (6.5%) were 2b. Pathological features of an example of grade 2b adenoma are shown in Supplementary Figure 1, see section on supplementary data given at the end of this article.…”

“…Lloyd et al 2004) 5.6% (6/108) Grade 2b (ref. Trouillas et al 2013) 6.5% (7/108) HPF, high-power field. a Seven patients recurred within the study period; the other 11 patients presented with recurrent lesions whose primary tumors were removed before 2005.…”

Clinical and Neurological Manifestations of Non-Functioning Pituitary Adenomas (NFPA). Is it ok to Suspect an Early Invasiveness?

“…Trouillas J et al [19] carried out a multicenter study with 410 patients of which 19 of them (4.63%) were described to have a pituitary corticotropinoma. Five of these were considered to be invasive with a high proliferation index.…”

Topoisomerase 2 alpha as a prognostic factor in pituitary tumors

“…The new prognostic clinico-pathological classification of pituitary adenomas proposed by Trouillas et al [5] also uses these markers of cell cycle for tumor grading.…”