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Distant spread of pituitary adenoma outside the sellar/suprasellar region is classified as pituitary carcinoma. Cerebrospinal fluid (CSF)-born spread of pituitary adenoma can occur after tumor cell spillage into the CSF space after surgery, irradiation, or apoplexy and is not necessarily related to intrinsic tumor biology.To systematically review the literature and describe the clinical characteristics and treatment strategies of patients with pituitary carcinomas. We further present 2 cases from our institution.A single-center retrospective review of patients with pituitary adenoma spread to distant intracranial locations between 2000 and 2020 was performed. Electronic databases were searched from their inception to May 25, 2021, and studies describing patients with pituitary spread to distant locations were included.Of 1210 pituitary adenoma cases reviewed, 2 (0.16%) showed tumor spread to distant locations. We found 134 additional cases (from 108 published articles) resulting in a total of 136 cases (61.9% were male). The time to tumor spread ranged between 0 and 516 months (median: 96 months). The follow-up duration ranged between 0 and 240 months (median: 11.5 months). All but 2 patients (98.5%) underwent surgical resection before adenoma spread. The 2 exceptions included a patient with evidence of an apoplectic event on autopsy and another patient with leptomeningeal pituitary spread but an unclear history of apoplexy. Elevated tumor markers were not linked to poor outcomes.Distant spread of pituitary adenoma may occur after surgery, irradiation, or apoplexy. It is not necessarily associated with a malignant clinical course.

BackgroundHigh-grade gliomas likely remodel the metabolic machinery to meet the increased demands for amino acids and nucleotides during rapid cell proliferation. Glycine, a non-essential amino acid and intermediate of nucleotide biosynthesis, may increase with proliferation. Non-invasive measurement of glycine by magnetic resonance spectroscopy (MRS) was evaluated as an imaging biomarker for assessment of tumor aggressiveness.MethodsWe measured glycine, 2-hydroxyglutarate (2HG), and other tumor-related metabolites in 35 glioma patients using an MRS sequence tailored for co-detection of glycine and 2HG in gadolinium-enhancing and non-enhancing tumor regions on 3T MRI. Glycine and 2HG concentrations as measured by MRS were correlated with tumor cell proliferation (MIB-1 labeling index), expression of mitochondrial serine hydroxymethyltransferase (SHMT2), and glycine decarboxylase (GLDC) enzymes, and patient overall survival.ResultsElevated glycine was strongly associated with presence of gadolinium enhancement, indicating more rapidly proliferative disease. Glycine concentration was positively correlated with MIB-1, and levels higher than 2.5 mM showed significant association with shorter patient survival, irrespective of isocitrate dehydrogenase status. Concentration of 2HG did not correlate with MIB-1 index. A high glycine/2HG concentration ratio, >2.5, was strongly associated with shorter survival (P ConclusionsThe data suggest that aggressive gliomas reprogram glycine-mediated one-carbon metabolism to meet the biosynthetic demands for rapid cell proliferation. MRS evaluation of glycine provides a non-invasive metabolic imaging biomarker that is predictive of tumor progression and clinical outcome.Key Points1. Glycine and 2-hydroxyglutarate in glioma patients are precisely co-detected using MRS at 3T.2. Tumors with elevated glycine proliferate and progress rapidly.3. A high glycine/2HG ratio is predictive of shortened patient survival.

Mucoepidermoid carcinoma (MEC) is the most common primary salivary gland malignancy. While salivary gland neoplasia is rare in children, MEC is much more likely to occur in the pediatric population than Warthin tumor, a common benign salivary gland neoplasm associated with smoking and older age. The recently-reported Warthin-like variant of MEC bears a striking histologic resemblance to Warthin tumor, representing a potential diagnostic pitfall. Therefore, low-power observation of Warthin-like features in pediatric salivary gland tumors should prompt careful diagnostic consideration of Warthin-like MEC. Two cases of Warthin-like MEC in the parotid glands of teenaged patients were identified in the archives of the Department of Pathology at Children’s Medical Center in Dallas, Texas. Surgical material for each case was reviewed and both diagnoses were verified. Fluorescence in situ hybridization (FISH) for CRTC1–MAML2 fusion was performed in both cases. Histologically, neither tumor exhibited the classic bilayer of oncocytic epithelial cells characteristic of Warthin tumor. Instead, the neoplastic epithelial cells exhibited architectural and cytologic atypia, with mucous cells interspersed. CRTC1–MAML2 gene fusions were identified via FISH and confirmed the diagnosis of MEC in both cases. Of note is that the second patient’s tumor recurred with features of conventional MEC, indicating the potential for Warthin-like MEC to undergo this morphologic change. The present cases illustrate that Warthin-like MEC, like conventional MEC, may occur in the pediatric population. Pediatric and head and neck pathologists must be aware of this variant’s existence and diagnostic criteria to avoid misdiagnosis as benign Warthin tumor.

Noonan syndrome is a genetic condition with a heterogeneous phenotype and multisystem involvement. The pathogenesis of this disorder has been attributed to the mutations in the RAS/MAPK signaling pathway involved in cell proliferation and differentiation. The most common clinical presentations are related to cardiovascular abnormalities with congestive heart failure as the most common mechanism of death. We present the autopsy findings from a Noonan syndrome patient who died as a result of an unusual form of right ventricular obstruction associated with a rare PTPN11 variant previously reported without details of the cardiac findings. Discussion follows that includes overview of the incidence, genetic causes, types of right-sided obstructive lesions, PTPN11 genotype—cardiac phenotype correlations, and other potential mechanisms that may contribute to disease heterogeneity.

Pleomorphic xanthoastrocytoma (PXA) is a slow-growing neoplasm that predominantly affects the pediatric and young adult population. This neoplasm has a good prognosis, with a median 10-year survival rate of 70%. The majority of tumors are supratentorial and arise in the temporal lobe, while spinal tumors are extremely rare, with only 8 reported cases. Molecular perturbations involving the MAPK/ERK signaling pathway have been described in PXAs. The most common mutation is BRAF V600E in 60%-80% of cases. Other mechanisms activating this pathway in the absence of this mutation are rare and include CRAF (RAF1) fusion genes. We report a PXA case in the cervical spinal cord of a 49-year-old man with slowly progressive coordination difficulties and extremity numbness. The tumor was negative for the V600E mutation, but 2 RNA sequencing platforms detected a QKI-RAF1 fusion (t(6; 3)(q26; p25)), which has not been previously reported in PXAs. This fusion is known to activate MAPK/ERK and PI3K/mTOR signaling. Although first- and second-generation RAF inhibitors are predicted to be ineffective, this fusion may be targetable by the novel RAF inhibitor LY3009120 and to some extent by the MEK inhibitor trametinib. Genetic analysis to screen for MAPK/ERK pathway mutations is warranted on PXAs negative for the V600E mutation.

Adult brainstem gliomas are difficult to classify based on radiologic and histologic features. A K27M mutation in histone 3 has been described to identify high-grade midline gliomas associated with a particularly unfavorable prognosis. While initially considered a pediatric entity, it is now known that H3K27M-mutant brainstem gliomas occur in all age groups, but they are less well understood in adults. We studied clinical, radiologic, and pathologic features of 25 brainstem gliomas diagnosed at our institution between 1994 and 2017 in subjects at least 18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their median overall survival was significantly shorter than in the H3-wildtype group (p = 0.004). Although the mutation was invariably associated with a poor prognosis, our study also illustrates the radiologic and pathologic heterogeneity in this molecular tumor subtype. The results showed that H3K27M-mutant status and clinically aggressive course cannot be ruled out based on low-grade histology on the initial biopsy, exophytic growth, only focal or minimal enhancement or an extrapontine location, such as midbrain or medulla. These results favor an integrated approach employing a combination of clinical, radiologic, histologic features as well as H3K27M immunohistochemistry for the diagnostic subclassification of adult brainstem gliomas.