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Neurofibromatosis type 2 [NF2; MIM # 101000] is an autosomal dominant disorder characterised by the occurrence of vestibular schwannomas (VSs), schwannomas of other cranial, spinal and cutaneous nerves, cranial and spinal meningiomas and/or other central nervous system (CNS) tumours (e.g., ependymomas, astrocytomas). Additional features include early onset cataracts, optic nerve sheath meningiomas, retinal hamartomas, dermal schwannomas (i.e., NF2-plaques), and (few) café-au-lait spots. Clinically, NF2 children fall into two main groups: (1) congenital NF2 - with bilateral VSs detected as early as the first days to months of life, which can be stable/asymptomatic for one-two decades and suddenly progress; and (2) severe pre-pubertal (Wishart type) NF2- with multiple (and rapidly progressive) CNS tumours other-than-VS, which usually present first, years before VSs [vs. the classical adult (Gardner type) NF2, with bilateral VSs presenting in young adulthood, sometimes as the only disease feature]. Some individuals can develop unilateral VS associated with ipsilateral meningiomas or multiple schwannomas localised to one part of the peripheral nervous system [i.e., mosaic NF2] or multiple non-VS, non-intradermal cranial, spinal and peripheral schwannomas (histologically proven) [schwannomatosis]. NF2 is caused by mutations in the NF2 gene at chromosome 22q12.1, which encodes for a protein called merlin or schwannomin, most similar to the exrin-readixin-moesin (ERM) proteins; mosaicNF2 is due to mosaic phenomena for the NF2 gene, whilst schwannomatosis is caused by coupled germ-line and mosaic mutations either in the SMARCB1 gene [SWNTS1; MIM # 162091] or the LZTR1 gene [SWNTS2; MIM # 615670] both falling within the 22q region and the NF2 gene. Data driven from in vitro and animal studies on the merlin pathway [e.g., post-translational and upstream/downstream regulation] allowed biologically targeted treatment strategies [e.g., Lapatinib, Erlotinib, Bevacizumab] aimed to multiple tumour shrinkage and/or regression and tumour arrest of progression with functional improvement.La neurofibromatosi tipo 2 [NF2] è una malattia genetica a trasmissione autosomica dominante [MIM # 101000]. Clinicamente è caratterizzata da: (1) schwannomi bilaterali del (VIII) nervo acustico/vestibolare; (2) cataratta giovanile o amartomi retinici; (3) schwannomi a carico dei nervi periferici e dei nervi cranici; (4) tumori multipli del sistema nervoso centrale (es., meningiomi, astrocitomi, ependimomi); (5) lesioni cutanee: (a) placche NF2 (schwannomi cutanei); (b) (poche) macchie caffellatte; (6) “malformazioni dello sviluppo corticale cerebrale”. La prevalenza della (forma sintomatica di) NF2 nella popolazione generale è di 1 su 100.000-200.000 individui con un’incidenza di 1 su 33.000 nati. La forma classica a esordio nel giovane adulto è conosciuta come forma di Gardner, (esordio intorno ai 20-30 anni d’età) con manifestazioni legate agli schwannomi bilaterali del nervo acustico/vestibolare (diminuzione/perdita progressiva dell’udito, tinnito, vertigini) e/o più raramente con manifestazioni da (altri) tumori del sistema nervoso centrale e/o periferico. In età pediatrica il fenotipo è diverso (forma di Wishart): per primi compaiono abitualmente i tumori del sistema nervoso centrale in assenza di schwannomi vestibolari; si possono avere macchie caffellatte e placche NF2 e solo dopo anni i tumori del nervo cranico VIII e di altri nervi cranici. Il quadro è più grave. Esiste anche una forma “congenita” ad esordio nei primi giorni/mesi di vita, con schwannomi vestibolari di piccole dimensioni (stabili nel tempo: anche per anni/decenni ma con improvvisa e rapida progressione) e numerose placche NF2; in questa forma le altre manifestazioni (es. meningiomi, altri tumori, altri schwannomi) sono spesso più gravi e progressive delle altre forme. Il gene responsabile della NF2 è localizzato sul cromosoma 22q12.1. Il prodotto genico della NF2 è conosciuto con il nome di schwannomina o merlina [dalla famiglia di proteine 4.1 del tipo moesina-ezrina-radixina/ERM alla quale appartiene il gene della NF2) e ha funzioni di regolazione della crescita e del rimodellamento cellulare (soppressione della crescita cellulare e della tumorigenesi)]. Alcune persone possono presentare tutte le (o parte delle) manifestazioni della NF2 in un emilato o in segmenti corporei circoscritti [NF2 a mosaico]. Altre persone presentano schwannomi (confermati istologicamente) dei nervi periferici (non intradermici) e/o delle radici gangliari in assenza di tumori del nervo vestibolare (o di altri nervi cranici: anche se in alcuni casi vi possono essere anche tumori unilaterali o bilaterali del nervo acustico/vestibolare e/o dei nervi cranici misti) o di altri segni diagnostici per la NF2 [Schwannomatosi, SWNTS]. L’esordio in questa forma è intorno ai 30 anni d’età (sono conosciuti casi in età pediatrica) con tumori in svariate sedi (abitualmente tronco e arti). Si conoscono due forme principali: (1) SWNTS1 [MIM # 162091] causata da alterazioni del gene SMARCB1 [regolatore della cromatina actina-dipendente associato alla matrice e correlato alle proteina SWI/SBF, sub-famiglia B, membro di tipo 1; MIM # 601607], sul cromosoma 22q11.23 (posizione centromerica rispetto al gene della NF2); (2) SWNTS2 [MIM # 615670] causata da alterazioni del gene LZTR1 [regolatore della trascrizione di tipo 1 legato alla Leucina; MIM # 600574], cromosoma 22q11.21 (posizione centromerica rispetto al gene SMARCB1) che codifica per una proteina, membro della super-famiglia BTB-kelch. Il meccanismo molecolare della Schwannomatosi comprende: (1) mutazione germinale del gene SMARCB1 o del gene LZTR1; (2) ampia delezione all’interno del cromosoma 22 (con perdita del gene NF2 e dell’allele intatto SMARCB1 o LZTR1); e (3) mutazione somatica dell’allele intatto del gene NF2 [meccanismo conosciuto come “four hits”: “Quadrupla alterazione” (su entrambi gli alleli dei due geni SWNTS/NF2), con tre passaggi consecutivi]. Negli ultimi anni, accanto alle tradizionali terapie chirurgiche e/o radioterapiche sono stati anche impiegati diversi farmaci “biologici” (es., Lapatinib e Bevacizumab) con effetti di riduzione/arresto della crescita dei tipici tumori NF2.

A 13 year-old boy, previously diagnosed as having Neurofibromatosis Type 1 (NF1) but otherwise healthy, was referred to our Department for headache, vomiting, ataxia and VI-VII left cranial nerve palsy. Emergency head CT scan was performed, immediately followed by contrast-enhanced MR scan with Echo-Planar (EPI) water diffusibility study. A large ovalar mass lesion was evident in the left cerebellar hemisphere, hyperdense on CT, hypointense in T2-weighted images, isointense to grey matter in FLAIR and T1-weighted images, with clear mass effect on the surrounding structures, but only mild peripheral contrast-enhancement in the anterior part of the mass, these features resembling those of a desmoplastic medulloblastoma. However, the EPI Diffusion-weighted images (DWI) and corresponding Apparent Diffusion Coefficient (ADC) maps consistently showed increased water diffusivity, a pattern not compatible with the dense cell-packing typical of medulloblastomas. The pathological analysis of the surgical specimen indeed showed focal neoplastic cell clusters interspersed in a diffusely altered cerebellar cortex. Neoplastic cells exhibited large eosinophilic cytoplasma, hyperchromatic and multinucleolated nuclei, and frequent mitoses, a pattern indicative of anaplastic astrocytoma. The case presented supports the evidence that NF1 is associated with increased risk of developing several different neoplasms, beside the well-known pilocytic astrocytomas of the optic pathway. As these neoplasms may exhibit misleading imaging features at CT or " conventional" MRI study, the assessment of water diffusivity may provide useful data for reaching a correct pre-operative diagnosis, since it reflects the histological architecture of the neoplastic tissue

A 58-year-old-man with unstable angina developed a violent retrosternal and interscapular pain during coronary angiography with no associated ECG abnormalities. The patient was immediately submitted to transesophageal echocardiography, which revealed an echo-free space behind the ascending aorta thought to be consistent with an aortic dissection. To confirm this finding the patient underwent contrast-enhanced helical CT, which ruled out a dissection but revealed a small hypoattenuating, ill-defined area within the lateral wall of the left ventricle, consistent with an acute myocardial infarction. The finding was first confirmed by bedside echocardiography and later validated by laboratory tests. Review of the left coronary angiogram showed the culprit lesion at the origin of a major acute marginal branch of the circumflex artery.

Learning objectives Background Imaging findings OR Procedure details Conclusion Personal Information References, Learning objectives: The aim of this exhibit is to describe clinical features and imaging findings of mucopolysaccharidoses (MPS). We discuss briefly several clinical properties of these metabolic disorders, reporting many epidemiological and pathophysiological data...

The introduction of new oral contrast agents that enhance image quality has increased the importance of magnetic resonance imaging (MRI) in the management of ulcerative colitis. The aim of our study was to investigate the usefulness of a new negative superparamagnetic oral contrast (ferumoxil) alone or in association with gadolinium i.v. in the assessment of the disease. Twenty-eight patients with clinically active ulcerative colitis and 10 control subjects entered the study. In each patient a clinical,endoscopic,histological,and MRI evaluation was performed. In particular,in 14 patients affected by ulcerative colitis (group A) and in five controls,magnetic resonance images were acquired 1 h after the oral administration of 900 ml of ferumoxil,while the remaining 14 patients (group B) and five controls were submitted to double-contrast MRI (ferumoxil and gadolinium). In both groups,wall thickness,length of affected bowel segments,and,in group B,also percent contrast enhancement were calculated.

A series of meta-analyses of randomised controlled trials raised the question of whether the three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) was more or less effective than optimal-dose single-agent carboplatin for women with advanced ovarian cancer.

A new version of the Lagrangian particle model MicroSpray is proposed. It simulates the dense gas dispersion in situations characterized by the presence of buildings, other obstacles, complex terrain, and possible occurrence of low wind speed conditions. Its performances are compared to an atmospheric CFD model output and to a field experiment (Thorney Island).

We investigated the role of CT in guiding fine-needle biopsy (FNB) in small (< 2 cm phi) lung lesions, reviewing 2109 CT-guided biopsies of peripheral lung nodules performed 1983 to 1993. "Peripheral" refers to non intrabronchial lesions, independent of the nodule position in the chest. Two hundred lesions < 2 cm phi were selected, 52 of them with complete clinical and surgical follow-up. This group was compared with 195 lung lesions > 2 cm phi for CT-guided FNB sensitivity, specificity and diagnostic accuracy. Cytologic specimens were positive for malignancy in 40/52 cases (76.9%) and negative in 12 (23.1%). Clinical-surgical follow-up confirmed all the positive cytologic findings (40 cases), while 2 of the extant 12 cases were false negatives (95.20% sensitivity, 100% specificity and 96.15% diagnostic accuracy). 158 of 195 nodules > 2 cm phi and with clinical-surgical follow-up (81.3%) were positive for malignancy and 34 were negative (17.43%) (98.75% sensitivity, 97.14% specificity and 98.46% diagnostic accuracy). Pneumothorax occurred in 33 patients (16.5%) with nodules < 2 cm phi as a complication of biopsy. Hemoptysis occurred in 15 patients (7.5%). In the whole group of lung lesions, the complications were pneumothorax in 80 patients (4.1%), hemoptysis in 199 (10.4%) and hypotensive vagal crises in 92 patients (4.8%). We conclude that CT is the best guidance for FNB also in small lung nodules, providing high sensitivity and specificity and low complication rates. Finally, the result of this procedure depends on the operator's skills.

Background. High Resolution Computed Tomography (HRCT) play the major role in the assessment of Interstitial Lung Disease (ILD). Aim and methods. The aim of this study is to demonstrate that estimation of disease extent given by HRCT is much better than with standard chest X-ray in different forms of interstitial disorders. Results. The study has been carried out on sixty patients with ILD. HRCT proved to allow a better assessment of type, distribution and severity of parenchymal abnormalities, even in the absence of clinical and/or functional impairment. Conclusions. However, HRCT findings cannot be assumed as characteristic of definite forms of ILD.

The authors analyze the advantages of MR imaging in the detection, staging and follow-up of malignant soft-tissue sarcomas. The role of MR imaging is retrospectively evaluated in 34 patients (16 men and 18 women) ranging in age from 3 to 82 years (mean: 38); 19 of them had a primary neoplasm, while the extant 15 patients were examined after surgery, and residual or recurrent tumors were present. Ten examinations were performed on an 0.5 T imager (CGR Magniscan 5000), and 27 were obtained with a 1.5 T system (Magnetom 42 SP Siemens). In all cases T1 and T2 sequences were acquired; in 3 patients T1-weighted sequences were performed after Gd-DTPA administration. In the 19 patients with primary tumors pathologic specimens were obtained. The value of MR imaging in the evaluation and characterization of soft-tissue sarcomas and its capabilities in detecting neurovascular encasement and bone involvement are discussed. Post-Gd-DTPA scans may help in the differentiation of necrotic areas from active tumors. MR diagnostic criteria of malignancy, including tissue heterogeneity and irregular margins, were not fulfilled in 3 of the studied cases.

A 58-year-old-man with unstable angina developed a violent retrosternal and interscapular pain during coronary angiography with no associated ECG abnormalities. The patient was immediately submitted to transesophageal echocardiography, which revealed an echo-free space behind the ascending aorta thought to be consistent with an aortic dissection. To confirm this finding the patient underwent contrast-enhanced helical CT, which ruled out a dissection but revealed a small hypoattenuating, ill-defined area within the lateral wall of the left ventricle, consistent with an acute myocardial infarction. The finding was first confirmed by bedside echocardiography and later validated by laboratory tests. Review of the left coronary angiogram showed the culprit lesion at the origin of a major acute marginal branch of the circumflex artery.