Purpose Growth hormone (GH) pituitary tumors are associated with significant morbidity and mortality. Current treatments, including surgery and medical therapy with somatostatin analogues (SSA), dopamine agonists and/or a GH receptor antagonist, result in disease remission in approximately half of patients. Predictors of GH tumor response to different therapies have been incompletely defined based on histologic subtype, particularly densely (DG) versus sparsely (SG) granulated adenomas. The aim of this study was to examine our own institutional experience with GH adenomas and correlate how subtype related to clinical parameters as well as response to surgery and medical therapies. Methods A retrospective chart review of 101 acromegalic patients operated by a single neurosurgeon was performed. Clinical data were correlated with histologic subtype and disease control, as defined by IGF-1 levels, and random growth hormone levels in response to surgery and/or medical therapies. Results SG tumors, compared to DG, occurred in younger patients (p=0.0010), were 3-fold larger (p=0.0030), but showed no differences in tumor-invasion characteristics (p=0.12). DG tumors had a higher rate of remission in response to surgery compared to SG, 65.7% vs. 14.3% (p<0.0001), as well as to medical therapy with SSAs (68.8% for DG vs. 28.6% for SG tumors; p=0.028). SG tumors not controlled with SSAs consistently responded to a switch to, or addition of, a GH receptor antagonist. Conclusions Histological GH tumor subtyping implicates a different clinical phenotype and biologic behavior, and provides prognostic significance for surgical success and response to medical therapies.

Introduction Inflammatory markers have long been observed in the brain, cerebrospinal fluid (CSF), and plasma of Alzheimer's disease (AD) patients, suggesting that inflammation contributes to AD and might be a therapeutic target. However, non‐steroidal anti‐inflammatory drug trials in AD and mild cognitive impairment (MCI) failed to show benefit. Our previous work seeking to understand why people with the inflammatory disease rheumatoid arthritis are protected from AD found that short‐term treatment of transgenic AD mice with the pro‐inflammatory cytokine granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) led to an increase in activated microglia, a 50% reduction in amyloid load, an increase in synaptic area, and improvement in spatial memory to normal. These results called into question the consensus view that inflammation is solely detrimental in AD. Here, we tested our hypothesis that modulation of the innate immune system might similarly be used to treat AD in humans by investigating the ability of GM‐CSF/sargramostim to safely ameliorate AD symptoms/pathology. Methods A randomized, double‐blind, placebo‐controlled trial was conducted in mild‐to‐moderate AD participants (NCT01409915). Treatments (20 participants/group) occurred 5 days/week for 3 weeks plus two follow‐up (FU) visits (FU1 at 45 days and FU2 at 90 days) with neurological, neuropsychological, blood biomarker, and imaging assessments. Results Sargramostim treatment expectedly changed innate immune system markers, with no drug‐related serious adverse events or amyloid‐related imaging abnormalities. At end of treatment (EOT), the Mini‐Mental State Examination score of the sargramostim group increased compared to baseline ( P = .0074) and compared to placebo ( P = .0370); the treatment effect persisted at FU1 ( P = .0272). Plasma markers of amyloid beta (Aβ40 [decreased in AD]) increased 10% ( P = .0105); plasma markers of neurodegeneration (total tau and UCH‐L1) decreased 24% ( P = .0174) and 42% ( P = .0019), respectively, after sargramostim treatment compared to placebo. Discussion The innate immune system is a viable target for therapeutic intervention in AD. An extended treatment trial testing the long‐term safety and efficacy of GM‐CSF/sargramostim in AD is warranted.

Spindle cell oncocytoma (SCO) is a rare sellar-region tumor recently codified in the World Health Organization (WHO) 2007 Classification as a grade I neoplasm. Despite this grading, recurrences have been demonstrated but, to date, extensive recurrent bleeding into these tumors has not been documented. A 70-year-old woman first presented in 1996 with visual difficulties and was found to have a sellar-region mass with heterogeneous neuroimaging features, leading to preoperative diagnosis of craniopharyngioma. Transsphenoidal, gross total resection was achieved despite extensive intraoperative bleeding; pathology showed an unusual spindle cell neoplasm which could not be further classified. She received no further treatment and was lost to our follow-up until 2009, when she again presented with visual deterioration. Neuroimaging demonstrated recurrence of a large sellar-region tumor with heterogeneous signal characteristics, prompting re-resection. Review of her original and recurrent tumor allowed diagnosis of SCO; extensive intratumoral hemorrhage of varying ages and widespread hemosiderin accounted for her complex neuroimaging features. Vimentin, S100, and galectin-3 immunoreactivity was consistent with SCO. EM demonstrated abundant mitochondria, short intercellular junctions, and absence of neurosecretory granules. Thyroid disease was documented clinically. SCOs are sufficiently rare that documentation of unusual features is important. Recurrent bleeding with resultant complex neuroimaging is unique to this case, but appears to overlap with a related sellar-region tumor, pituicytoma. The presence of thyroid disease also links SCO with pituicytoma. The 13-year interval to recurrence is the longest reported to date in SCO; WHO grade I designation may be premature for this neoplasm.

Computed tomography (CT) plays a pivotal role in the diagnosis of acute stroke and in treatment decision making. CT perfusion imaging performed with intravenous iodinated contrast material allows calculation of the time to peak enhancement, mean transit time, and cerebral blood volume, important parameters for differentiating between an ischemic penumbra, which might benefit from intravascular therapy with thrombolytic agents, and infarcted tissue, which would not benefit from such therapy. Differentiation between the two entities is important because thrombolytic therapy is associated with an increased risk for intracranial hemorrhage. A finding of delay in peak enhancement or increased mean transit time in a region with normal or only slightly abnormal cerebral blood volume is suggestive of an ischemic penumbra; however, accurate interpretation of the CT perfusion parameters may be difficult in the presence of a cerebrovascular anatomic variant or physiologic condition that produces benign oligemia leading to a false appearance of penumbra. For this reason, CT perfusion parameters must be correlated with the clinical history and findings at unenhanced head CT, angiography or CT angiography, and diffusion-weighted magnetic resonance imaging. The authors identify five possible causes of false penumbras, each of which produces a different pattern at imaging: upstream flow restriction, evolution of ischemic change, vascular dysregulation, positioning of the patient's head at an angle during image acquisition, and variant anatomy in the circle of Willis. Familiarity with the imaging patterns and causes of false penumbras may increase the radiologist's confidence in diagnosis and help avoid costly errors in treatment.