Prognostic value of EGFR expression in de novo and progressed atypical and anaplastic meningiomas: an immunohistochemical and fluorescence in situ hybridization pilot study.

AIM: The aim of this study was to assess both the epidermal growth factor receptor (EGFR) protein expression by immunohistochemistry and the EGFR gene amplification by fluorescence in situ hybridization in meningiomas of different grade, in order to evaluate their possible role in the development of the disease. EGFR protein belongs to the family of tyrosine kinase growth factor receptors, which also includes HER2, HER3 and HER4. Elevated expression or activity of EGFR has been reported in several cancers, including brain tumours. EGFR activation can enhance the malignant potential of epithelial tissues. METHODS: We investigated whether there was a difference in the EGFR protein expression and the EGFR gene amplification between the so called de novo malignant meningiomas and recurrent meningiomas with or without malignant progression from a previously lower grade tumor. Our goal was to evaluate if EGFR expression was a useful marker to select patients affected by meningioma with a major risk of recurrences. We also assessed the prognostic value of the EGFR expression on overall survival. RESULTS: Progression from benign meningiomas to atypical or anaplastic meningiomas correlated with an increase in the expression of EGFR protein. Our study shows that EGFR immunostaining in meningiomas directly correlates to the tumor's grade. The EGFR expression did not correlate with the overall survival and the recurrence-free survival of the patients affected by meningioma (de novo, recurrent and progressed). CONCLUSION: We submit that the EGFR expression is not a useful prognostic element to identify patients with a major risk of meningioma recurrence.

Endometrial carcinoma: MR staging and causes of error.

PURPOSE: This study was undertaken to prospectively determine the diagnostic capabilities of magnetic resonance (MR) imaging in detecting myometrial and cervical invasion and lymph node involvement in endometrial carcinoma and to identify the causes of errors in staging endometrial carcinoma. MATERIALS AND METHODS: Twenty consecutive patients with a histological diagnosis of endometrial carcinoma underwent preoperative MR imaging. MR findings were compared with surgical staging, considered as the standard of reference. RESULTS: In assessing myometrial invasion, MR imaging showed 70% accuracy, 80% sensitivity, 40% specificity, 80% positive predictive value (PPV), and 40% negative predictive value (NPV). In detecting cervical invasion, MR imaging had 95% accuracy, 100% sensitivity, 94.4% specificity, 66.7% PPV, and 100% NPV. In evaluating lymph node involvement, MR imaging showed 100% accuracy, sensitivity, specificity, PPV and NPV. Errors in evaluating myometrial invasion were caused by polypoid tumour, adenomyosis and leiomyomas, whereas those in evaluating cervical invasion were caused by dilatation and curettage. CONCLUSIONS: MR imaging is a reliable technique for preoperative evaluation of endometrial carcinoma. Its main limitation is differentiating between stage IA and IB carcinomas, which is not highly important for surgical planning. Cooperation between the gynaecologist and radiologist is mandatory to avoid staging errors.

[(123) I]FP-CIT-SPECT asymmetry index to differentiate Parkinson's disease from vascular parkinsonism.

OBJECTIVES: Differential diagnosis between vascular parkinsonism (VP) and Parkinson's Disease (PD) is often difficult, due to the overlap in clinical presentation and the lack of specificity at neuroimaging. Aim of the study was to identify a possible reliable marker at SPECT imaging useful to distinguish the two conditions. MATERIAL AND METHODS: We studied 20 PD, 20 VP and 20 essential tremor (ET) patients as control group, who had undergone a cerebral [(123) I] FP-CIT SPECT. A semiquantitative analysis was performed on DaTSCAN SPECT imaging and to establish the degree of asymmetry of the ligand uptake the Striatal Asymmetry Index (SAI) was used. RESULTS: The binding of the ligand in the most affected side resulted significantly lower in VP than in ET patients but higher compared to PD patients. SAI was significantly higher in PD compared to VP (P < 0.001) and ET (P < 0.001) groups. We found that a cut-off of SAI greater than 14.08 could differentiate PD from VP with a 100% specificity and a 50% sensitivity. CONCLUSIONS: SAI detected using [(123) I]FP-CIT SPECT can be used to differentiate VP and PD with a good degree of certainty.

A rare location of benign osteoblastoma: case study and a review of the literature.

Osteoblastoma is a solitary, benign bone tumor that is rarely localized in the frontal sinus. It consists of hypocellular mineralized tissue that may form large masses or irregular trabeculae. A 31 year old man came to our attention with a 7 month history of diplopia, photophobia, frontal headhaches and progressive exophthalmos with proptosis of the left eye. The patient was submitted to computed tomography (CT) which allowed to appraise the extension of the lesion. The mass expanded inside the left frontal sinus and the upper ethmoidal cells invading the left orbital roof. Considering the extension of the tumor, the site and the connections with contiguous structures, a combination of endoscopic endonasal technique with intraorbital approach was performed. At histological examination typical features of benign osteoblastoma were observed. The sites of predilection for the tumor are the long bones, vertebral column, and small bones of hands and feet. Its occurrence in the skull and jaw bones is relatively rare and represents only 15% of all osteoblastomas. To our knowledge, only 5 cases of osteoblastoma of the frontal sinus have been previously reported in the English-language literature. This report describes a case of benign osteoblastoma in a rare site, namely, the frontal sinus with particular attention about the differential diagnosis and the treatment.    

Attention modulation regulates both motor and non-motor performance: a high-density EEG study in Parkinson's disease.

We have previously shown that, in early stages of Parkinson's disease (PD), patients with higher reaction times are also more impaired in visual sequence learning, suggesting that movement preparation shares resources with the learning of visuospatial sequences. Here, we ascertained whether, in patients with PD, the pattern of the neural correlates of attentional processes of movement planning predict sequence learning and working memory abilities. High density Electroencephalography (EEG, 256 electrodes) was recorded in 19 patients with PD performing reaching movements in a choice reaction time paradigm. Patients were also tested with Digit Span and performed a visuomotor sequence learning task that has an important declarative learning component. We found that attenuation of alpha/beta oscillatory activity before the stimulus presentation in frontoparietal regions significantly correlated with reaction time in the choice reaction time task, similarly to what we had previously found in normal subjects. In addition, such activity significantly predicted the declarative indices of sequence learning and the scores in the Digit Span task. These findings suggest that some motor and non motor PD signs might have common neural bases, and thus, might have a similar response to the same behavioral therapy. In addition, these results might help in designing and testing the efficacy of novel rehabilitative approaches to improve specific aspects of motor performance in PD and other neurological disorders.

Disruption of structural brain networks in Primary Open Angle Glaucoma.

Primary open angle glaucoma (POAG) is one of the most common causes of permanent blindness in the world. Recent studies have originated the hypothesis that POAG could be considered as a central nervous system pathology which results in secondary visual involvement. The aim of this study is to assess possible structural whole brain connectivity alterations in POAG by combining multi-shell diffusion weighted imaging, multi-shell multi-tissue probabilistic tractography, graph theoretical measures and a newly designed disruption index, which evaluates the global reorganization of brain networks in group-wise comparisons. We found global differences in structural connectivity between Glaucoma patients and controls, as well as in local graph theoretical measures. These changes extended well beyond the primary visual pathway. Furthermore, group-wise and subject-wise disruption indices were found to be statistically different between glaucoma patients and controls, with a positive slope. Overall, our results support the hypothesis of a whole-brain structural reorganization in glaucoma which is specific to structural connectivity, possibly placing this disease within the recently defined groups of brain disconnection syndrome.

Prevalence of Parkinson's disease and other types of parkinsonism in the Aeolian Archipelago, Sicily.

OBJECTIVE: To estimate prevalence of Parkinson's disease (PD) and other types of parkinsonism in the Aeolian Archipelago, Sicily. METHODS: We studied the frequency of PD and other types of parkinsonism in the Aeolian Archipelago (population 13,431). All potential cases were identified from available medical information sources. To ensure the completeness of the case-findings, a screening questionnaire was also mailed to residents aged 40 years and over. Subjects were considered prevalent if they fulfilled the SNES diagnostic criteria for PD, on prevalence day (January 1, 2001). RESULTS: We identified 17 patients with parkinsonism from medical sources, and 4 from mail-survey. Prevalence for all types of parkinsonism was 156.3/100,000 (95% CI 99.4-234.8). Fourteen subjects fulfilled diagnostic criteria for PD giving a crude prevalence of 104.2/100,000 (95% CI 59.4-170.7) and 422.5/100,000 in the population aged 60 years and over. CONCLUSIONS: Prevalence of all types of parkinsonism and PD found in the Aeolian Archipelago is lower than that previously reported in Sicily.

Parotid gland involvement in Heerfordt syndrome: a case report.

Sarcoidosis is a multisystemic granulomatous disease characterized by the presence of noncaseating granulomas, the exact etiology of which is yet to be determined. Most of patients show granulomas located in the lungs or in the related lymph nodes. However, lesions can affect any organ. Noncaseating granulomas are not a pathognomonic sign of sarcoidosis, being observed also in other diseases, therefore the diagnosis is often of exclusion. We report a case of sarcoidosis with parotid gland involvement in the context of a Heerfordt syndrome, discussing about its clinical presentation, pathogenesis, pathology and differential diagnosis with other granulomatous diseases.

Thyroid transcription factor 1 (TTF-1) and p63 expression in two primary thyroid papillary carcinomas of branchial cleft cysts.

Malignant lateral cervical cysts can be related to metastatic tumors or rarely to primary thyroid carcinoma arising in branchial cleft cysts. This study evaluates the expression of thyroid-associated transcription factor-1 (TTF-1) and p63 in three branchial cleft cysts and in two primary thyroid papillary carcinoma of branchial cleft cysts. TTF-1 was negative in the nuclei of the lining epithelia of branchial cleft cysts, but positive in the adjacent normal thyroid tissue, while TTF-1 was positive in the nuclei of the lining epithelia and in the nuclei of the papillae and follicles in branchial cleft cysts with ectopic thyroid carcinoma. P63 was positive in the nuclei of the lining epithelia of branchial cleft cysts, but negative in the adjacent normal thyroid tissue. Papillary thyroid carcinoma of branchial cleft cysts displayed p63-positive foci. In conclusion, our results demonstrate that TTF-1 cannot distinguish between primary and metastatic tumors of branchial cleft cysts. The detection of p63 in papillary thyroid carcinomas of branchial cleft cysts could suggest that p63 contributes to the onset of this tumor. It is really important to evaluate if the case has a metastatic derivation or represents papillary thyroid carcinoma arising in ectopic thyroid tissue in a branchial cleft cyst.

About a case of GIST occurring during pregnancy with immunohistochemical expression of epidermal growth factor receptor and progesterone receptor.

The coexistence of gastrointestinal stromal tumors (GISTs) and pregnancy is very rare. We are the first to add to the literature a case report of GIST occurring during pregnancy with immunohistochemical staining for epidermal growth factor receptor (EGFR) and progesterone receptor (PgR). A role of PgR and EGFR in tumor growth should not be excluded, and these findings indicate that the expression of these receptors could provide pertinent biological information required to determine adequate therapeutic regimens. In conclusion, considering that GIST occurring during pregnancy is a rare event, with frequent delay in diagnosis, it is important to consider this diagnosis for early recognition, correct diagnosis, and a better outcome.

Differences in Gaussian diffusion tensor imaging and non-Gaussian diffusion kurtosis imaging model-based estimates of diffusion tensor invariants in the human brain.

PURPOSE: An increasing number of studies have aimed to compare diffusion tensor imaging (DTI)-related parameters [e.g., mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD)] to complementary new indexes [e.g., mean kurtosis (MK)/radial kurtosis (RK)/axial kurtosis (AK)] derived through diffusion kurtosis imaging (DKI) in terms of their discriminative potential about tissue disease-related microstructural alterations. Given that the DTI and DKI models provide conceptually and quantitatively different estimates of the diffusion tensor, which can also depend on fitting routine, the aim of this study was to investigate model- and algorithm-dependent differences in MD/FA/RD/AD and anisotropy mode (MO) estimates in diffusion-weighted imaging of human brain white matter. METHODS: The authors employed (a) data collected from 33 healthy subjects (20-59 yr, F: 15, M: 18) within the Human Connectome Project (HCP) on a customized 3 T scanner, and (b) data from 34 healthy subjects (26-61 yr, F: 5, M: 29) acquired on a clinical 3 T scanner. The DTI model was fitted to b-value =0 and b-value =1000 s/mm(2) data while the DKI model was fitted to data comprising b-value =0, 1000 and 3000/2500 s/mm(2) [for dataset (a)/(b), respectively] through nonlinear and weighted linear least squares algorithms. In addition to MK/RK/AK maps, MD/FA/MO/RD/AD maps were estimated from both models and both algorithms. Using tract-based spatial statistics, the authors tested the null hypothesis of zero difference between the two MD/FA/MO/RD/AD estimates in brain white matter for both datasets and both algorithms. RESULTS: DKI-derived MD/FA/RD/AD and MO estimates were significantly higher and lower, respectively, than corresponding DTI-derived estimates. All voxelwise differences extended over most of the white matter skeleton. Fractional differences between the two estimates [(DKI - DTI)/DTI] of most invariants were seen to vary with the invariant value itself as well as with MK/RK/AK values, indicating substantial anatomical variability of these discrepancies. In the HCP dataset, the median voxelwise percentage differences across the whole white matter skeleton were (nonlinear least squares algorithm) 14.5% (8.2%-23.1%) for MD, 4.3% (1.4%-17.3%) for FA, -5.2% (-48.7% to -0.8%) for MO, 12.5% (6.4%-21.2%) for RD, and 16.1% (9.9%-25.6%) for AD (all ranges computed as 0.01 and 0.99 quantiles). All differences/trends were consistent between the discovery (HCP) and replication (local) datasets and between estimation algorithms. However, the relationships between such trends, estimated diffusion tensor invariants, and kurtosis estimates were impacted by the choice of fitting routine. CONCLUSIONS: Model-dependent differences in the estimation of conventional indexes of MD/FA/MO/RD/AD can be well beyond commonly seen disease-related alterations. While estimating diffusion tensor-derived indexes using the DKI model may be advantageous in terms of mitigating b-value dependence of diffusivity estimates, such estimates should not be referred to as conventional DTI-derived indexes in order to avoid confusion in interpretation as well as multicenter comparisons. In order to assess the potential and advantages of DKI with respect to DTI as well as to standardize diffusion-weighted imaging methods between centers, both conventional DTI-derived indexes and diffusion tensor invariants derived by fitting the non-Gaussian DKI model should be separately estimated and analyzed using the same combination of fitting routines.

p63 expression in odontogenic cysts.

A total of 123 cases of odontogenic cysts, distributed as follows: 30 follicular (FC), 35 radicular (RC), 53 keratocysts, 1 glandular odontogenic and 4 calcifying odontogenic cysts, were analysed by immunohistochemistry for expression of p63, a component of p53 protein family. In RCs p63 positivity was not only in basal and parabasal layers but also in the intermediate layer and about 1/3 of cases displayed a percentage of stained cells comprised between 0 and <5%, and about 2/3 between >5% and <50%. In FCs positivity was confined to basal and parabasal layers of the epithelium and in the majority of FCs the stained cells were comprised between 0 and <5%. OKCs displayed the most intense and diffuse p63 labeling. In conclusion, these data suggest that p63 expression may be useful to identify cysts type with more aggressive and invasive phenotype supporting the hypothesis of a suprabasal proliferative compartment in OKCs.

Correlation of alpha 2 beta 1 integrin expression with histological type and hormonal receptor status in breast carcinomas.

Interactions between cells and extracellular matrix are mediated in part by a family of alpha beta heterodimeric molecules known as integrins. Immunohistochemical studies have shown that benign hyperplastic/neoplastic mammary epithelium expressed high levels of alpha 2 beta 1 collagen/laminin receptor. In contrast, malignant cells of breast carcinoma exhibited marked diminuition or loss of the alpha 2 beta 1 integrin. A correlation has been suggested between the loss of the alpha 2 beta 1 expression and the increased invasiveness of neoplastic cells. This study investigated the expression of alpha 2 beta 1 integrin and its extracellular ligand collagen TV by using monoclonal antibodies on the cryostat section of 124 invasive mammary carcinomas. Two patterns of alpha 2 beta 1 immunoreactivity, i.e. pericellular and basolateral, were identified in breast carcinomas and correlated with their histological type. In most invasive ductal carcinomas of no special type (NOS), integrin staining tended to decrease in both pericellular and basolateral aspects. Loss of basolateral staining for alpha 2 beta 1 integrin corresponded closely to the loss of immunoreactivity for collagen IV. Mucinous and medullary carcinomas showed strongly alpha 2 beta 1 pericellular staining, but no basolateral reactivity or collagen IV expression. Only two of the infiltrating lobular carcinomas expressed strong pericellular reactivity. In 82 ductal carcinomas NOS, the abnormally low expression/absence of alpha 2 beta 1 integrin correlated with estrogen and progesterone receptor negativity (p < 0.04 and p < 0.002, respectively). No correlation between integrin expression, histological grade, nodal involvement and proliferative activity was found. The results of the present study suggest that changes in alpha 2 beta 1 expression correlate with the histological type and hormonal receptor status in breast carcinomas. The clinical implications of these findings remain to be elucidated.

Immunohistochemical expression of type VI collagen in superficial fibromatoses.

The expression of type VI collagen was studied immunohistochemically in 26 cases of superficial fibromatoses (palmar, plantar and penile) using an immunoperoxidase method for light microscopic visualization. The polyclonal antibody against type VI collagen used in this study was isolated from human placenta and its specifity was tested by immunoblotting assay. All cases consisted of multiple nodules showing a variable degree of cellularity and fibrosis. Depending on the predominant histological appearance of these nodules, each case was assigned to the three following phases: proliferative, involutional and residual. Morphologically normal palmar and plantar aponeuroses were included as controls. Immunohistochemical findings showed that type VI collagen was present as longitudinal thin fibers in normal palmar and plantar aponeuroses. A differential expression of this collagen was found in the different stages of superficial fibromatoses. Type VI collagen was markedly expressed as a distinct fibrillar network in the extracellular matrix (ECM) surrounding proliferating stromal cells in proliferative and involutional phases. Its expression completely disappeared from the connective tissue undergoing fibrotic transformation during involutional and residual phases. The results of the present study suggest that type VI collagen is an extracellular marker of stromal tissue proliferation and is involved in the early phases of tissue remodelling occurring in the superficial fibromatoses.

Correlated expression of BCL-2 protein, estrogen receptor, cathepsin D and low growth fraction (PCNA) in intracystic papillary breast carcinoma.

The expression of BCL-2 protein was evaluated immunohistochemically in 23 intracystic papillary carcinomas (IPCs) of the breast. Twenty-two patients were female and one male, aged 49-90 years (median 72). Twenty-one cases had a benign behaviour, while two cases developed local recurrence. Of the 23 tumours, 19 (82%) were immunoreactive for BCL-2, the majority of positive carcinomas showing intense cytoplasmic staining of more than 50% neoplastic cells. The intensity of BCL-2 expression was significantly correlated with prognostic markers such as estrogen receptor (ER) positivity (p = 0.001), cathepsin D (CD) reactivity in the neoplastic cells (p = 0.001) and low growth fraction, evaluated by proliferating cell nuclear antigen (PCNA) immunostaining (p = 0.008). An inverse relationship was also found between BCL-2 and p53 protein (p = 0.001). Three cases of high grade (G3) IPC expressed p53, high PCNA index, and CD (the latter only in the stromal cells), but no immunostaining for BCL-2 and ER. Thus, absence of BCL-2 expression in high grade IPC was associated with ER-negative, rapidly proliferating and p53-positive immunophenotype. All high grade tumours showed invasion of the cystic wall. Local recurrence developed in one of these. The authors conclude that BCL-2 immunoreactivity in IPC is related with tumour grade and with a range of molecular markers of favourable prognosis such as ER positive status, CD expression in the neoplastic cells, and low PCNA index. These findings are consistent with the indolent clinical course and the very favourable prognosis of IPC of the breast.

Myofibroblastoma of the breast with hemangiopericytoma-like pattern and pleomorphic lipoma-like areas. Report of a case with diagnostic and histogenetic considerations.

Myofibroblastoma (MFB) of the breast is an uncommon benign spindle cell tumor which may exhibit a wide spectrum of histological features. We report an unusual case of MFB of the male breast, showing cellular areas with a hemangiopericytoma-like pattern similar to that observed in solitary fibrous tumor (SFT) and extensive fibromyxoid areas containing numerous atypical stromal cells. The association of these atypical cells with mature adipocytes and microcystic and/or myxoid degenerative changes resembled pleomorphic lipoma-like and myxoid liposarcoma-like features, respectively. To our knowledge, these peculiar morphological findings have not been previously reported in MFB of the breast. They should be recognized to avoid confusion with other mesenchymal tumors, especially with hemangiopericytoma, pleomorphic lipoma (PL), spindle-cell lipoma (SCL) and myxoid liposarcoma. A case of MFB of the breast showing morphological features also commonly seen in SFT and PL/SCL is further morphological evidence in support of the speculation that the mesenchymal tumors of the breast, also known under the terms benign spindle cell tumors, fibromas, SFTs, SCLs and MFBs, are histogenetically related lesions.

Correlation between histological grade, MIB-1, p53, and recurrence in 69 completely resected primary intracranial meningiomas with a 6 year mean follow-up.

Sixty-nine intracranial, totally excised meningiomas were immunostained for MIB-1 and p53 protein expression. According to the 1993 WHO criteria, revised by Perry et al., the 69 meningiomas were classified into: grade I = 54 benign meningiomas, grade II = 10 atypical meningiomas, grade III = 5 malignant meningiomas. The patients were followed until death or for an average of 6.7 years. The 69 meningiomas were divided into two groups, according to the absence (n = 42) or presence (n = 27) of recurrences. In the last group we included 3 patients who died of meningioma recurrence. According to the percentage of MIB-1 positively stained cells, meningiomas were divided into three groups: <1% (n = 36), 1-10% (n = 28), >10% (n = 5). We found the MIB-1 labeling index (LI) <1% in 33 grade I (61%) and in 3 grade II (30%) meningiomas. On the other hand, 7 grade II (70%) and all grade III (100%) meningiomas presented a MIB-1 LI >1%. Correlation between histological grade and MIB-1 LI was statistically significant (p = 0.0006). The correlation between MIB-1 LI and follow-up was also highly significant (p < 0.001): the majority of meningiomas which did not recur (32/42 equal to 76%) were characterized by a low (<1%) MIB-1 LI. In the recurrence group MIB-1 LI was significantly higher than in the disease-free patients' group. Moreover, MIB-1 appeared to be a prognostic parameter not strongly related to the histological grade. In fact, it was significantly higher in recurrent histologically benign meningiomas, as compared with benign meningiomas without recurrence (p = 0.0006). Positive p53 protein expression (>1%) was shown in 26/45 meningiomas (57%), with an LI of 1-10% in 18 (40%) and an LI of >10% in 8 (17%) meningiomas. Although the p53 LI tended to be higher in atypical and malignant meningiomas, no significant correlation was found between the p53 expression and the recurrence (p = 0.05). The authors conclude that quantitative MIB-1 labeling is a useful technique in the routine diagnostic assessment of meningiomas, and helpful in obtaining more information about prognosis and thereby in planning the most suitable treatment.

Spinal meningeal mesenchymal chondrosarcoma. Report of a new case and review of the literature.

A case of T12-L2 intraspinal extradural meningeal mesenchymal chondrosarcoma is described in a patient presenting with a clinical history of low-back pain and weakness of the lower limbs. Magnetic resonance T1-weighted Gadolinium enhanced imaging, showed an intraspinal extradural mass, extending from T12 to L2, located anterolaterally into the spinal canal and pushing posteriorly the conus medullaris. The mass was completely removed and postoperative histological diagnosis was of mesenchymal chondrosarcoma. The patient was completely symptoms-free after surgery. Intraspinal meningeal mesenchymal chondrosarcoma and treatment options are reviewed.

Lhermitte duclos disease and Cowden disease: clinical, pathological and neuroimaging study of a case.

The authors report the case of a 26-year-old female patient affected by Lhermitte Duclos disease and Cowden disease. Preoperative MRI allowed a correct diagnosis which was confirmed by pathological examination. The authors stress the possibility that Lhermitte Duclos and Cowden disease be a single phakomatosis; for this reason all the patients affected by Lhermitte-Duclos should be screened for the presence of multiple hamartomas or malignant neoplastic lesions typical of Cowden disease.