Clinicopathological characteristics, clinical outcome, and prognostic factors for pituitary carcinomas: lessons from a systematic review of 207 cases

P. Raymond*^a (Dr), G. Raverot^b (Prof), M. Diana Ilie^c (Mrs)

^a Endocrinology Department, CHRU de Brabois, Vandoeuvre Les Nancy, FRANCE ; ^b Endocrinology Department, “Groupement Hospitalier Est” Hospices Civils de Lyon, Lyon, FRANCE ; ^c Cancer Research Center of Lyon, Inserm U1052, CNRS UMR5286, Claude Bernard Lyon 1 University, Bron, FRANCE

* perrine.raymond@hotmail.fr

Introduction: The evolution of a PitNET into a pituitary carcinoma (PC), defined by the appearance of metastases, remains difficult to predict. In addition, PCs are difficult to manage and have poor survival rates. Our aim was to investigate the clinicopathological characteristics at the initial diagnosis and at PC diagnosis, alongside with the management and outcome of PCs, and to identify potential prognostic factors associated with the clinical outcome.
Material and Methods: Systematic review of all published PC cases since 1936.
Results: 207 cases were included, of which 42% were corticotroph and 32% were lactotroph carcinomas. Lactotroph carcinomas were overrepresented in male patients (62%), while a 1:1 sex ratio was observed for corticotroph carcinomas. At the initial diagnosis, the vast majority of tumors (97%) were ≥10 mm; nevertheless, microadenomas were encountered in four cases. 91 PitNETs (47%) were nonfunctioning at the initial diagnosis; of these, 32 (35%) became functioning during follow-up. The highest percentage of non-functioning tumors becoming functioning was noted for the corticotroph subtype, with 31 cases (65%). Interestingly, only 39% of the corticotroph cases underwent bilateral adrenalectomy before PC diagnosis. Median time between initial and PC diagnosis was 7 years (0-43), with a median survival rate of 186 months since initial diagnosis (0-396), and 36 months since PC diagnosis (0-192). Neither the histological subtype, nor the metastases localization affected the survival rate. An initial Ki67 index ≥10% was associated with a lower survival rate (p=0.01). Early metastases (diagnosed ≤60 months after initial diagnosis) were also associated with a lower survival rate compared to late metastases, p=0.001. Interestingly, the cases with early metastases had higher initial Ki67 index, higher Ki67 index for the recurrent tumor and higher Ki67 index for the metastasis than the ones with late metastases (p=0.01, p=0.007, and p=0.01, respectively). Regarding treatment, temozolomide use was associated with a better survival rate (p=0.01).
Discussion: A Ki67 index ≥10% is associated with a poor prognosis, i.e., with early metastasis and a shorter survival. Its presence should lead to an intensified surveillance and to a more timely management, which will hopefully result in better outcomes for these patients.

The author has declared no conflict of interest.