Impact of histopathological classification of non-functioning adenomas on long term outcomes: comparison of the 2004 and 2017 WHO classifications.

PURPOSE: Outcomes of patients with non-functioning pituitary adenomas categorized using the 2004 and 2017 WHO classification systems are understudied. We report outcomes from the University of Virginia of patients with non-functioning pituitary adenomas categorized using both systems. METHODS: We constructed a database from all 239 patients who underwent resection of a non-functioning pituitary adenoma between 2003 and 2015 and had at least 5 years of follow-up. Pathologic diagnosis was determined under both the 2004 and 2017 WHO classification systems. We compared the rates of recurrence and progression between subtypes using univariate and multivariate Cox regression analyses. RESULTS: Nearly 30% of the tumors in our database were classified as null cell adenomas under the 2004 classification system, whereas only 10% of the tumors were classified as null cell adenomas using the 2017 classification system. Most of these tumors were reclassified as either corticotroph or gonadotroph adenomas. Despite our relatively large cohort and average follow-up of nearly 9 years, we did not detect a significant difference in recurrence and progression between subtypes. CONCLUSIONS: The majority of null cell adenomas diagnosed under the 2004 WHO classification system are reclassified as gonadotroph or corticotroph adenomas under the 2017 WHO classification system. Rates of progression and recurrence between subtypes are not as different as previously believed at our institution and require a larger cohort to further investigate.

Microhemorrhage is an early event in the pulmonary fibrotic disease of PECAM-1 deficient FVB/n mice.

Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1) deficient mice in the FVB/n strain exhibit fatal chronic pulmonary fibrotic disease. The illness occurs in the absence of a detectable pro-inflammatory event. PECAM-1 is vital to the stability of vascular permeability, leukocyte extravasation, clotting of platelets, and clearance of apoptotic cells. We show here that the spontaneous development of fibrotic disease in PECAM-1 deficient FVB/n mice is characterized by early loss of vascular integrity in pulmonary capillaries, resulting in spontaneous microbleeds. Hemosiderin-positive macrophages were found in interstitial spaces and bronchoalveolar lavage (BAL) fluid in relatively healthy animals. We also observed a gradually increasing presence of hemosiderin-positive macrophages and fibrin deposition in the advanced stages of disease, corresponding to the accumulation of collagen, IL-10 expression, and myofibroblasts expressing alpha smooth muscle actin (SMA). Together with the growing evidence that pulmonary microbleeds and coagulation play an active part in human pulmonary fibrosis, this data further supports our hypothesis that PECAM-1 expression is necessary for vascular barrier function control and regulation of homeostasis specifically, in the pulmonary environment.