Initial pathology in aggressive pituitary tumours and carcinomas: 2b or not 2b?—that is the question

From a cohort of 171 patients comprising 121 aggressive pituitary tumours (APT) and 50 pituitary carcinomas (PC), the clinicopathological or five-tiered classification based on tumour invasion and proliferation evaluated by at least 2 proliferative markers over the cut-offs (Ki-67 ≥3% or ≥10%, p53 positive or expressed in %, mitotic count >2%), could be applied on 43 tumours: 20 PC and 23 APT. At the initial surgery, 29/ 43 tumours (67.4%) were grade 2b (invasive and proliferative) of which 44.8% developed metastases during follow-up (PC, grade 3). Out of these 29 tumours, 55.1% had a Ki-67 ≥10%, and were classified grade 2b* (invasive and highly proliferative). There was one tumour grade 1b* (non-invasive and highly proliferative) which metastazed. Out of the 43 tumours, 30.2 % were grade 2a (invasive and non-proliferative). The sensitivity and the specificity of grade 2b for the diagnosis of APT at the initial surgery, were 68% and 90% respectively. The comparison of the high percentage (67.4%) of grade 2b tumours in this selected cohort of APT/PC with the low percentage (8.8%) in a surgical cohort of unselected tumours shows that the initial pathological diagnosis of grade 2b tumour may be considered, in the clinic, as representing a diagnosis of APT. In addition, a significant subgroup of tumours, which will develop metastases supports the proposal that an aggressive grade 2b tumour is “a tumour with malignant potential” or “a malignant tumour without metastases”. So, the clinician may take into account the pathological diagnosis, at the initial surgery, to propose a strict follow-up and to consider earlier use of radiotherapy and/or of temozolomide in the presence of tumours with aggressive behaviour.