Transcriptome Analysis Reveals Distinct Patterns Between the Invasive and Noninvasive Pituitary Neuroendocrine Tumors.

Although most pituitary neuroendocrine tumors (PitNETs)/pituitary adenomas remain intrasellar, a significant proportion of tumors show parasellar invasive growth and 6% to 8% infiltrate the bone structures, thus affecting the prognosis. There is an unmet need to identify novel markers that can predict the parasellar growth of PitNETs. Furthermore, mechanisms that regulate bone invasiveness of PitNETs and factors related to tumor vascularization are largely unknown. We used genome-wide mRNA analysis in a cohort of 77 patients with PitNETs of different types to explore the differences in gene expression patterns between invasive and noninvasive tumors with respect to the parasellar growth and regarding the rare phenomenon of bone invasiveness. Additionally, we studied the genes correlated to the contrast enhancement quotient, a novel radiological parameter of tumor vascularization. Most of the genes differentially expressed related to the parasellar growth were genes involved in tumor invasiveness. Differentially expressed genes associated with bone invasiveness are involved in NF-κB pathway and antitumoral immune response. Lack of clear clustering regarding the parasellar and bone invasiveness may be explained by the influence of the cell lineage-related genes in this heterogeneous cohort of PitNETs. Our transcriptomics analysis revealed differences in the molecular fingerprints between invasive, including bone invasive, and noninvasive PitNETs, although without clear clustering. The contrast enhancement quotient emerged as a radiological parameter of tumor vascularization, correlating with several angiogenesis-related genes. Several of the top genes related to the PitNET invasiveness and vascularization have potential prognostic and therapeutic application requiring further research.

Natural history and surgical outcome of Rathke's cleft cysts-A study from the Swedish Pituitary Registry.

OBJECTIVE: Rathke's cleft cysts are benign, embryological remnants in the pituitary gland. The majority of them are small and asymptomatic but a few may become large, and cause mass effects, pituitary hormone deficiencies and visual impairment. Recommendations for the follow-up of Rathke's cleft cysts vary since data on the natural history are sparse. PATIENTS AND DESIGN: Data at diagnosis and at 1, 5 and 10 years for patients with a Rathke's cleft cyst (434 at diagnosis, 317 females) were retrieved from the Swedish Pituitary Registry. Cysts ≤3 mm in diameter were excluded from the study. MEASUREMENTS: Data included demographics, cyst size, pituitary function, visual defects and surgery. RESULTS: The mean age at diagnosis was 45 years. In patients with cysts <10 mm in diameter (n = 204) 2.9% had pituitary hormone deficiencies and 2% had visual field impairments. Cyst size did not progress during the 5 years. Cysts with a diameter of ≥10 mm that were not operated (n = 174) decreased in size over the years (p < .01). Pituitary hormone deficiencies and visual impairments were more frequent (18% and 5.7%, respectively) but were stable over time. Transphenoidal surgery was performed in 56 patients of whom 51 underwent surgery before the 1-year follow-up. The mean cyst diameter at diagnosis was 18 mm (range: 9─30 mm), 36% had pituitary hormone deficiency, 45% had visual field defects and 20% had impaired visual acuity. One year after surgery 60% had no cyst remnants, 50% had a pituitary deficiency, 26% had visual field defects and 12% had impaired visual acuity. No major changes were observed after 5 years. Twelve of the operated patients had a follow-up at 10 years, in eight the cyst remnants or recurrences increased in size over time (p < .05). CONCLUSIONS: Rathke's cleft cysts with a size less than 10 mm rarely grow and our results indicate that radiological follow-up can be restricted to 5 years. In contrast, progression of postoperative remnants or recurrent cysts is more likely and require long-term follow-up.