Posttraumatic extraskeletal chondroma of the posterior neck: A systematic literature review on a rare finding and report of a case.

Extraskeletal chondromas (EC) are uncommon, benign cartilaginous tumours. Most common locations are upper and lower extremities. Location in the neck is extremely rare and reported only within the anterior compartment. Data are limited to just four case reports in the paediatric population. The first case of EC in neck's posterior compartment is described herein. EC present peculiar features on imaging. Aetiology is unclear; however, trauma has been suggested as possible causative mechanism. Treatment of choice is surgical excision; recurrence is not uncommon, but additional removal seems to be resolutive. All cases in literature were asymptomatic, except for one presenting respiratory stridor. The present patient suffered from neck functional limitation and upper limb hypoesthesia. Symptoms improved after surgery in both cases. Imaging follow-up at 6 months in the present case showed no sign of recurrence. ECs are rare, benign lesions. However, they may be preoperatively misinterpreted as more malignant counterparts (both radiologically or histologically), so accurate diagnostic work-up and planning of the surgical procedure are essential.

Hemorrhagic Suprasellar Central Nervous System Embryonal Tumor in an Adult: Uncommon Features of an Extremely Rare Neoplasm.

BACKGROUND: Occurrences of suprasellar central nervous system (CNS) embryonal tumors in adults are extremely rare. Hemorrhagic onset is further uncommon, with only anecdotic cases reported in the literature. The authors describe the case of a 57-year-old man affected by a suprasellar CNS embryonal tumor, with hemorrhagic onset and a unique diffusion pattern along the optic pathways. MATERIAL AND METHODS: A 57-year-old man presenting with acute visual acuity worsening and left homonymous hemianopia was referred to our hospital. Neuroradiologic studies demonstrated an infiltrating, high-grade lesion involving the optic chiasm and right retrochiasmatic pathways with a hemorrhagic area in the ipsilateral pulvinar. RESULTS: The patient underwent microsurgical biopsy. Pathologic assessment confirmed the diagnosis of CNS embryonal tumor, not otherwise specified (NOS) according to the 2016 World Health Organization (WHO) classification of CNS tumors. The patient was referred to a multimodal adjuvant treatment; he eventually died 4 months after surgery. Competent literature has been systematically reviewed in the light of the relevant changes made in the last version of the WHO classification. CONCLUSION: Embryonal tumors should be considered in the differential diagnosis for sellar and suprasellar space-occupying lesions, despite the rarity of the disease and the uncommon features at time of presentation. As per our knowledge, this is the first case ever described of hemorrhagic suprasellar embryonal tumor with a diffusion pattern along white matter fibers. Histogenesis, biomolecular and neuroradiologic features, and classification of embryonal tumors are an open field of research, with considerable implications for the definition of better diagnostic pitfalls and therapeutic regimens.

18F-FAZA PET/CT in pretreatment assessment of hypoxic status in high-grade glioma: correlation with hypoxia immunohistochemical biomarkers.

BACKGROUND: To investigate the correlation between 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET data and hypoxia immunohistochemical markers in patients with high-grade glioma (HGG). PATIENTS AND METHODS: Prospective study including 20 patients with brain MRI suggestive for HGG and undergoing 18F-FAZA PET/CT before treatment for hypoxia assessment. For each 18F-FAZA PET scan SUVmax, SUVmean and 18F-FAZA tumour volume (FTV) at 40, 50 and 60% threshold of SUVmax were calculated; hypoxic volume was estimated by applying different thresholds (1.2, 1.3 and 1.4) to tumour/blood ratio. Seventeen patients were analysed. The immunohistochemical analysis assessed the following parameters: hypoxia-inducible factor 1α, carbonic anhydrase IX (CA-IX), glucose transporter-1, tumour vascularity and Ki-67. RESULTS: 18F-FAZA PET showed a single lesion in 15/17 patients and multiple lesions in 2/17 patients. Twelve/17 patients had grade IV glioma and 5/17 with grade III glioma. Bioptic and surgical samples have been analysed separately. In the surgical subgroup (n = 7) a positive correlation was observed between CA-IX and SUVmax (P = 0.0002), SUVmean40 (P = 0.0058), SUVmean50 (P = 0.009), SUVmean60 (P = 0.0153), FTV-40-50-60 (P = 0.0424) and hypoxic volume1.2-1.3-1.4 (P = 0.0058). In the bioptic group (n = 10) tumour vascularisation was inversely correlated with SUVmax (P = 0.0094), SUVmean40 (P = 0.0107), SUVmean50 (P = 0.0094) and SUVmean60 (P = 0.0154). CONCLUSIONS: The correlation of 18F-FAZA PET parameters with CD31 and CA-IX represents a reliable method for assessing tumour hypoxia in HGG. The inverse correlation between tumour vascularisation, SUVmax and SUVmean suggest that highly vascularized tumours might present more oxygen supply than hypoxia.

Sexual Dimorphism in Cellular and Molecular Features in Human ACTH-Secreting Pituitary Adenomas.

(1) Background. Cushing's disease presents gender disparities in prevalence and clinical course. Little is known, however, about sexual dimorphism at the level of the corticotrope adenoma itself. The aim of the present study was to evaluate molecular features of ACTH-secreting pituitary adenomas collected from female and male patients with Cushing's disease. (2) Methods. We analyzed 153 ACTH-secreting adenomas collected from 31 men and 122 women. Adenomas were established in culture and ACTH synthesis and secretion assessed in basal conditions as well as during incubation with CRH or dexamethasone. Concurrently, microarray analysis was performed on formalin-fixed specimens and differences in the expression profiles between specimens from male and female patients identified. (3) Results. ACTH medium concentrations in adenomas obtained from male patients were significantly lower than those observed in adenomas from female patients. This could be observed for baseline as well as modulated secretion. Analysis of corticotrope transcriptomes revealed considerable similarities with few, selected differences in functional annotations. Differentially expressed genes comprised genes with known sexual dimorphism, genes involved in tumour development and genes relevant to pituitary pathophysiology. (4) Conclusions. Our study shows for the first time that human corticotrope adenomas present sexual dimorphism and underlines the need for a gender-dependent analysis of these tumours. Differentially expressed genes may represent the basis for gender-tailored target therapy.

Ubiquitin-Specific Protease 8 Mutant Corticotrope Adenomas Present Unique Secretory and Molecular Features and Shed Light on the Role of Ubiquitylation on ACTH Processing.

BACKGROUND: Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been shown to occur in ACTH-secreting pituitary adenomas, thus calling attention to the ubiquitin system in corticotrope adenomas. OBJECTIVES: Assess the consequences of USP8 mutations and establish the role of ubiquitin on ACTH turnover in human ACTH-secreting pituitary adenomas. METHODS: USP8 mutation status was established in 126 ACTH-secreting adenomas. Differences in ACTH secretion and POMC expression from adenoma primary cultures and in microarray gene expression profiles from archival specimens were sought according to USP8 sequence. Ubiquitin/ACTH coimmunoprecipitation and incubation with MG132, a proteasome inhibitor, were performed in order to establish whether ubiquitin plays a role in POMC/ACTH degradation in corticotrope adenomas. RESULTS: USP8 mutations were identified in 29 adenomas (23%). Adenomas presenting USP8 mutations secreted greater amounts of ACTH and expressed POMC at higher levels compared to USP wild-type specimens. USP8 mutant adenomas were also more sensitive to modulation by CRH and dexamethasone in vitro. At microarray analysis, genes associated with endosomal protein degradation and membrane components were downregulated in USP8 mutant adenomas as were AVPR1B, IL11RA, and PITX2. Inhibition of the ubiquitin-proteasome pathway increased ACTH secretion and POMC itself proved a target of ubiquitylation, independently of USP8 sequence status. CONCLUSIONS: Our study has shown that USP8 mutant ACTH-secreting adenomas present a more "typical" corticotrope phenotype and reduced expression of several genes associated with protein degradation. Further, ubiquitylation is directly involved in intracellular ACTH turnover, suggesting that the ubiquitin-proteasome system may represent a target for treatment of human ACTH-secreting adenomas.

Cushing's disease due to double pituitary ACTH-secreting adenomas: the first case report.

Double pituitary adenomas are rare occurrences in autoptical, surgical and neuroradiological series and are mostly due to non-functioning pituitary adenomas, GH-secreting and prolactin-secreting adenomas. ACTH secreting tumours are more rare and, to our knowledge, two distinct ACTH-producing adenomas within the same pituitary have never been reported. We herewith describe a 56 year old woman with Cushing' s disease due to two clearly distinct ACTH-secreting pituitary adenomas. She presented with signs and symptoms of hypercortisolism and hormonal testing was indicative for pituitary-dependent Cushing' s syndrome. Sellar MRI visualized an asymmetric pituitary gland with suspect lesions in both the right and the left pituitary lobes. Both lesions were removed during transsphenoidal surgery and remission of hypercortisolism ensued. Pathology confirmed the existence of two distinct adenomas located in different sites in the gland. Both presented ACTH immunoreactivity but displayed distinct morphological features. Our case indicates that double ACTH-secreting pituitary adenomas may occur in patients with Cushing' s disease. Careful radiological, surgical and pathological examination is necessary to recognize this condition and avoid surgical failure.

C-11 choline versus F-18 fluorodeoxyglucose for imaging meningiomas: an initial experience.

PURPOSE: Positron emission tomography/computed tomography (PET/CT) with C-11 choline has been used for staging, restaging, and follow-up of various tumors, whereas its role for imaging meningiomas has only been preliminarily explored. The aim of this study was to compare C-11 choline and F-18 fluorodeoxyglucose (F-18 FDG) uptake in meningiomas and relate these findings to the histopathological analysis. METHODS: Two sequential three-dimensional PET/CT scans with 370 MBq (10 mCi) of C-11 choline and 370 MBq (10 mCi) of F-18 FDG were performed 2 hours apart in 7 patients with histologically confirmed meningiomas. Five patients had WHO grade I and 2 had WHO grade II meningioma. For each scan, two-dimensional regions of interest were drawn on tumor boundaries and on the contralateral side on CT images and copied to the corresponding PET images. SUVmax and tumor-to-background ratio were calculated. RESULTS: Relative to the contralateral side, C-11 choline uptake was increased in all meningiomas, whereas F-18 FDG uptake was decreased in 6 patients and increased in 1 of the 2 patients with grade II meningiomas. In the whole group, SUVmax of C-11 choline and F-18 FDG were 3.6 +/- 1.3 and 5.7 +/- 1.3, respectively. The tumor-to-background ratio for C-11 choline was much higher than that for F-18 FDG (5.3 +/- 0.8 vs. 0.9 +/- 0.2, respectively) (P < 0.001). The uptake of C-11 choline was higher in patients with grade II than in grade I meningiomas. CONCLUSIONS: These preliminary results suggest that C-11 choline may better image meningiomas in comparison with F-18 FDG. Clinical applications of C-11 choline PET/CT for grading and follow-up of meningiomas need to be assessed in further studies.