Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.

Endoscopic transsphenoidal resection of skull base lesions has been introduced widely as an alternative to microscopic transmucosal approaches. We report the introduction of this technique to our unit, including the learning curve recognized for this procedure, comparing techniques in a concurrent case-control fashion. All patients operated on for sellar, suprasellar, or clival lesions were considered for endoscopic surgery, with 51 patients undergoing endoscopic surgery and 46 having microscopic surgery with the operating method determined by the availability of the ear, nose, and throat surgeon involved with the procedures. Endoscopic surgery compared favorably with microscopic surgery with respect to endocrine control, length of stay, diabetes insipidus, and cerebrospinal fluid leakage. A learning curve was found with a significant fall in complication rates between the first third and most recent third of the cohort. Endoscopic skull base surgery has superior results to microscopic approaches once the initial learning curve is overcome, but this can be done quickly and safely.

Purpose:To compare in a group of patients with cerebral gliomas the estimates of K trans between a conventionally established pharmacokinetic model and a recently developed first pass method. Materials and Methods:Glioma patients (23) were studied using T 1 -weighted dynamic contrast-enhanced magnetic resonance imaging (MRI), and two alternative pharmacokinetic models were used for analysis to derive the volume transfer constant K trans . These were a modified version of the established model (yielding K TK ) and a recently published method based on first pass leakage profile (FP) of contrast bolus (yielding K fp ). Results:We found a strong correlation between intra-tumoral median K TK and K fp (rho ϭ 0.650, P Ͻ 0.01), but the values from the conventional model were consistently and significantly higher (mean of inter-tumoral K fp and K TK medians were 0.018 minute -1 and 0.284 minute -1 , respectively, P Ͻ 0.001). The spatial distribution of K TK and K fp showed poor correlation in the presence of large vascular structures and good correlation elsewhere.Conclusion: K TK and K fp produce similar biologic information within voxels not dominated by vascular tissue. The FP method avoids erroneous overestimation of K trans in areas of significant intravascular contrast. Findings are in keeping with the predictions of previous mathematical simulations.

Object. The authors conducted a study to examine the incidence, classification, and progression of spinal tumors in patients with neurofibromatosis Type 2 (NF2) treated at a single center, and to examine relationships with the known mutational subtypes of NF2. Methods. They performed a retrospective review of clinical records, neuroimaging studies, and genetic data obtained in 61 patients with NF2. Forty-one (67%) of 61 patients harbored one or more spinal tumors. Thirty-four patients had undergone serial spinal magnetic resonance imaging during a mean follow-up period of 52 months (range 10–103 months; median 53 months). In 16 patients there were multiple extramedullary tumors smaller than 5 mm, which did not progress. Fourteen patients harbored at least one extramedullary tumor that was greater than 5 mm; of these, radiological progression was demonstrated or spinal tumor excision was performed during the follow-up period in eight cases (57%). Eleven patients harbored intramedullary cord tumors in addition to small and large extramedullary tumors, three (27%) of which exhibited radiological progression. In cases in which genotypes were known, protein-truncating mutations were significantly more likely to be associated with the presence of spinal tumors than in other types (p = 0.03, Fisher exact test). No associations between clinical behavior of spinal tumors and genotype, however, could be demonstrated. Conclusions. Spinal tumors in cases involving NF2 are heterogeneous in type, distribution, and behavior but larger-size tumors are more likely to progress significantly. Intramedullary tumors usually accompany multiple extramedullary tumors. In the authors' experience subtyping of the NF2 mutation has not yet influenced management. Protein-truncating mutations are associated with an increased prevalence of spinal tumors.