Highlights d Molecular classes of PitNETs are identified by integrated pangenomic analyses d PitNETs molecular classification mainly reflects pituitary lineage, driven by PIT1 d Gonadotroph signatures are found in some corticotroph and somatotroph PitNETs d USP8-mutated corticotroph PitNETs correspond to a group with limited aggressiveness

X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in 2 families was dominant with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight SDS score of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF-1 and prolactin, usually due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high somatostatin receptor subtype-2 expression in tumor tissue. Postoperative adjuvant pegvisomant achieved control of IGF-1 all 5 cases in which it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management.

Temozolomide treatment may be an effective option for some aggressive pituitary tumors or carcinomas. Response to a trial of three cycles of treatment seems sufficient to identify responders and more reliable than patient MGMT status.

This large prospective cohort study confirms the very low prevalence of germline AIP mutations in patients with apparently sporadic pituitary adenomas. We propose to limit AIP testing to patients diagnosed before age 40 yr with apparently sporadic large pituitary adenomas, especially GH- or PRL-secreting adenomas.

Context: Adequate postoperative management of nonfunctioning pituitary macroadenomas (NFMAs) remains a challenge for the clinician. Objective: To identify predictive factors of NFMA relapse after initial surgery. Patients and methods: This retrospective study included 142 patients operated for an NFMA in two academic centers (CHU Bicêtre in France and UCL St Luc in Belgium). The rate of tumor relapse, defined as recurrence after total surgical resection or regrowth of a surgical remnant, as well as predictive factors was analyzed. Results: During a mean follow-up of 6.9 years, 10 out of 42 patients (24%) who had complete macroscopic resection of their tumor had recurrence, and 47 out of 100 patients (47%) with a surgical remnant experienced regrowth. The overall relapse rates were 25, 43, and 61% at 5, 10, and 15 years respectively. Invasion of the cavernous sinus, absence of immediate radiotherapy after the first neurosurgery, and immunohistochemical features of the tumor (mainly positive immunostaining for several hormones or for hormones other than gonadotropins) were independent risk factors for tumor relapse. Incomplete excision was only associated with relapse when invasion was withdrawn from the analysis, suggesting that these two factors are closely linked. Conclusion: NFMAs frequently recur/regrow after initial surgery, particularly when tumor is invasive, precluding complete removal. Immunohistochemical features such as positive immunostaining for several hormones or for hormones other than gonadotropins could help to predict undesirable outcomes.