Noonan syndrome, PTPN11 mutations, and brain tumors. A clinical report and review of the literature.

Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus. He developed epilepsy 2 years later. The temporal tumor was surgically resected because of increasing crises and worsening radiological signs. Microscopy showed nodules with specific glioneuronal elements or glial nodules, leading to the diagnosis of dysembryoplastic neuroepithelial tumor (DNT). Immunohistochemistry revealed positive nuclear staining with Olig2 and pERK in small cells. SHP2 plays a key role in RAS/MAPK pathway signaling which controls several developmental cell processes and oncogenesis. An amino-acid substitution in the N-terminal SHP2 domain disrupts the self-locking conformation and leads to ERK activation. Glioneuronal tumors including DNTs and pilocytic astrocytomas have been described in NS. This report provides further support for the relation of DNTs with RASopathies and for the implication of RAS/MAPK pathways in sporadic low-grade glial tumors including DNTs. © 2017 Wiley Periodicals, Inc.

Epilepsy surgery of "low grade epilepsy associated neuroepithelial tumors": A retrospective nationwide Italian study.

OBJECTIVE: To analyze the attitude and results of Italian epilepsy surgery centers in the surgical management of "low grade epilepsy associated neuroepithelial tumors" (LEATs). METHODS: We conducted a retrospective study enrolling 339 consecutive patients with LEATs who underwent surgery between January 2009 and June 2015 at eight Italian epilepsy surgery centers. We compared demographic, clinical, pathologic, and surgical features of patients with favorable (Engel class I) and unfavorable (Engel class II, III, and IV) seizure outcome. In addition, we compared patients with tumor-associated focal cortical dysplasia (FCD) and patients with solitary tumors to identify factors correlated with FCD diagnosis. RESULTS: Fifty-five (98.2%) of 56 patients with medically controlled epilepsy were seizure-free after surgery, compared to 249 (88.0%) of 283 patients with refractory epilepsy. At multivariate analysis, three variables independently predict unfavorable seizure outcome in the drug-resistant group. Age at surgery is largely the most significant (p = 0.001), with an odds ratio (OR) of 1.04. This means that the probability of seizure recurrence grows by 4% for every waited year. The resection site is also significant (p = 0.039), with a relative risk (RR) of 1.99 for extratemporal tumors. Finally, the completeness of tumor resection has a trend toward significance (p = 0.092), with an RR of 1.82 for incomplete resection. Among pediatric patients, a longer duration of epilepsy was significantly associated with preoperative neuropsychological deficits (p < 0.001). A statistically significant association was observed between FCD diagnosis and the following variables: tailored surgery (p < 0.001), temporal resection (p = 0.001), and surgical center (p = 0.012). SIGNIFICANCE: Our nationwide LEATs study gives important insights on factors predicting seizure outcome in refractory epilepsy and determining variability in FCD detection. Timely surgery, regardless of pharmacoresistance and oriented to optimize epileptologic, neuropsychological, and oncologic outcomes should be warranted.

A rare case of pituicytoma-related hyperprolactinemia due to mass effect on infundibular stalk-Case report.

INTRODUCTION AND IMPORTANCE: Pituicytomas are extremely rare cancers of the sellar and suprasellar region that appear from the infundibulum or posterior pituitary. World Health Organization in 2007, described pituicytoma as a low-grade tumour (Grade I) in the taxonomy of CNS cancers. The tumour can frequently simulate a pituitary adenoma and is also linked with hormonal disorders. Distinguishing a pituitary adenoma from a pituicytoma can be challenging. We present a rare case report where an elderly female showed high levels of prolactin mainly due to mass effects along with diagnostic, imaging, and immunohistochemical characteristics of pituicytoma. CASE PRESENTATION: A 50-year-old female known case of hypothyroidism, complained of headache associated with dizziness and blurry vision. Her prolactin levels were high which led to the suspicion of pituitary involvement and underwent MRI. The imaging study revealed a well-defined, completely suprasellar, homogenously enhancing mass lesion arising from the left lateral aspect of the pituitary infundibulum. The initial differential diagnosis from the imaging included an ectopic pituitary gland, adenoma, pituicytoma, or hypothalamic glioma. She underwent a right supra-orbital craniotomy for debulking of the pituitary stalk lesion. The histopathological diagnosis was pituicytoma, WHO grade I. CLINICAL DISCUSSION: The clinical manifestations are mostly depended upon the tumour mass and position. They typically present due to mass effects leading to hormonal disorders. The imaging studies are the backbone of the clinical diagnosis along with the histopathological findings. Surgical resection is the preferred treatment for pituicytoma, with an exceptionally low recurrence rate (4.3 %) following complete removal. CONCLUSION: Pituicytomas are slow-growing, benign glial growths. It is challenging to diagnose before surgery as its clinical manifestations and imaging findings look like those of non-functional pituitary adenomas. The effective treatment for pituicytoma is gross total resection by the endoscopic method or transcranial technique.