Acute revascularization treatments for ischemic stroke in the Stroke Units of Triveneto, northeast Italy: time to treatment and functional outcomes.

It is not known whether the current territorial organization for acute revascularization treatments in ischemic stroke patients guarantees similar time to treatment and functional outcomes among different levels of institutional stroke care. We aimed to assess the impact of time to treatment on functional outcomes in ischemic stroke patients who received intravenous thrombolysis (IVT) alone, bridging (IVT plus thrombectomy), or primary thrombectomy in level 1 and level 2 Stroke Units (SUs) in Triveneto, a geographical macroarea in Northeast of Italy. We conducted an analysis of data prospectively collected from 512 consecutive ischemic stroke patients who received IVT and/or mechanical thrombectomy in 25 SUs from September 17th to December 9th 2018. The favorable outcome measures were mRS score 0-1 and 0-2 at 3 months. The unfavorable outcome measures were mRS score 3-5 and death at 3 months. We estimated separately the possible association of each variable for time to treatment (onset-to-door, door-to-needle, onset-to-needle, door-to-groin puncture, needle-to-groin puncture, and onset-to-groin puncture) with 3-month outcome measures by calculating the odds ratios (ORs) with two-sided 95% confidence intervals (CI) after adjustment for pre-defined variables and variables with a probability value ≤ 0.10 in the univariate analysis for each outcome measure. Distribution of acute revascularization treatments was different between level 1 and level 2 SUs (p < 0.001). Among 182 patients admitted to level 1 SUs (n = 16), treatments were IVT alone in 164 (90.1%), bridging in 12 (6.6%), and primary thrombectomy in 6 (3.3%) patients. Among 330 patients admitted to level 2 SUs (n = 9), treatments were IVT alone in 219 (66.4%), bridging in 74 (22.4%), and primary thrombectomy in 37 (11.2%) patients. Rates of excellent outcome (51.4% vs 45.9%), favorable outcome (60.1% vs 58.7%), unfavorable outcome (33.3% vs 33.8%), and death (9.8% vs 11.3%) at 3 months were similar between level 1 and 2 SUs. No significant association was found between time to IVT alone (onset-to-door, door-to-needle, and onset-to-needle) and functional outcomes. After adjustment, door-to-needle time ≤ 60 min (OR 4.005, 95% CI 1.232-13.016), shorter door-to-groin time (OR 0.991, 95% CI 0.983-0.999), shorter needle-to-groin time (OR 0.986, 95% CI 0.975-0.997), and shorter onset-to-groin time (OR 0.994, 95% CI 0.988-1.000) were associated with mRS 0-1. Shorter door-to-groin time (OR 0.991, 95% CI 0.984-0.998), door-to-groin time ≤ 90 min (OR 12.146, 95% CI 2.193-67.280), shorter needle-to-groin time (OR 0.983, 95% CI 0.972-0.995), and shorter onset-to-groin time (OR 0.993, 95% CI 0.987-0.999) were associated with mRS 0-2. Longer door-to-groin time (OR 1.007, 95% CI 1.001-1.014) and longer needle-to-groin time (OR 1.019, 95% CI 1.005-1.034) were associated with mRS 3-5, while door-to-groin time ≤ 90 min (OR 0.229, 95% CI 0.065-0.808) was inversely associated with mRS 3-5. Longer onset-to-needle time (OR 1.025, 95% CI 1.002-1.048) was associated with death. Times to treatment influenced the 3-month outcomes in patients treated with thrombectomy (bridging or primary). A revision of the current territorial organization for acute stroke treatments in Triveneto is needed to reduce transfer time and to increase the proportion of patients transferred from a level 1 SU to a level 2 SU to perform thrombectomy.

A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas.

BACKGROUND: The INI1/SMARCB1 gene protein product has been implicated in the direct pathogenesis of schwannomas from patients with one form of schwannomatosis [SWNTS1; MIM # 162091] showing a mosaic pattern of loss of protein expression by immunohistochemistry [93% in familial vs. 55% in sporadic cases]. AIM OF STUDY: To verify whether such INI1/SMARCB1 mosaic pattern could be extended to all schwannomas arising in the sporadic and familial schwannomatoses [i.e. to SMARCB1-related (SWNTS1) or LZTR1-related (SWNTS2) schwannomatosis or to SMARCB1/LZTR1-negative schwannomatosis] and whether it could be involved in classical NF2 or solitary peripheral schwannomas METHODS: We blindly analysed schwannoma samples obtained from a total of 22 patients including (a) 2 patients (2 males; aged 38 and 55 years) affected by non-familial SMARCB1-associated schwannomatosis (SWTNS1); (b) 1 patient (1 female; aged 33 years) affected by familial schwannomatosis (SWTNS1/ SMARCB1 germ line mutations); (c) 5 patients (3 males, 2 females; aged 33 to 35 years) affected by non-familial (sporadic) LZTR1-associated schwannomatosis (SWNTS2); (d) 3 patients (3 males; aged 35 to 47 years) affected by familial schwannomatosis (SWTNS2/ LZTR1 germ line mutations); (e) 2 patients (1 male, 1 female; aged 63 and 49 years, respectively) affected by non-familial schwannomatosis (SWTNS, negative for SMARCB1, LZTR1 and NF2 gene mutations); (f) 4 patients (3 males, 1 females; aged 15 to 24 years) affected by classical NF2 (NF2: harbouring NF2 germ line mutations; and (g) 5 patients (3 males, 2 females; aged 33 to 68 years) who had solitary schwannomas. [follow-up = 15-30 years; negative for constitutional/somatic mutation analysis for the SMARCB1, LZTR1 and NF2 genes] were (blindly) analyzed. The INI1/SMARCB1 immunostaining pattern was regarded as (1) diffuse positive nuclear staining [= retained expression] or (2) mosaic pattern [mixed positive/negative nuclei = loss of expression in a subset of tumour cells]. RESULTS: All solitary peripheral schwannomas and NF2-associated vestibular schwannomas showed diffuse nuclear INI1/SMARCB1 staining in 97-100% of neoplastic cells; schwannomas obtained from all cases of non-familial and familial schwannomatosis and NF2-associated non-vestibular schwannomas showed a mosaic pattern ranging from 10 to 70% of INI1/SMARCB1-positive expression. We did not record a complete lack of nuclear staining. CONCLUSIONS: The present data suggests that (a) mosaic loss of immunohistochemical INI1/SMARCB1 expression, despite the interlesional variability, is a reliable marker of schwannomatosis regardless of the involved gene and it might help in the differential diagnosis of schwannomatosis vs. solitary schwannomas and (b) INI1/SMARCB1 expression is not useful in the differential with mosaic NF2, since NF2-associated peripheral schwannomas show the same immunohistochemical pattern.

Vulvar Melanoma Associated with Lichen Sclerosus in a Child: Case Report and Literature Review.

The authors describe the sixth pediatric case to date of primary vulvar melanoma associated with lichen sclerosus and propose a practical management for such a rare cancer.

Long-term therapy with temozolomide is a feasible option for newly diagnosed glioblastoma: a single-institution experience with as many as 101 temozolomide cycles.

OBJECT: The objective of this study was to report the authors' experience with the long-term administration of temozolomide (TMZ; > 6 cycles, up to 101) in patients with newly diagnosed glioblastoma and to analyze its feasibility and safety as well as its impact on survival. The authors also compared data obtained from the group of patients undergoing long-term TMZ treatment with data from patients treated with a standard TMZ protocol. METHODS: A retrospective analysis was conducted of 37 patients who underwent operations for glioblastoma between 2004 and 2012. Volumetric analysis of postoperative Gd-enhanced MR images, obtained within 48 hours, confirmed tumor gross-total resection (GTR) in all but 2 patients. All patients received the first cycle of TMZ at a dosage of 150 mg/m(2) starting on the second or third postsurgical day. Afterward, patients received concomitant radiochemotherapy according to the Stupp protocol. With regard to adjuvant TMZ therapy, the 19 patients in Group A, aged 30-72 years (mean 56.1 years), received 150 mg/m(2) for 5 days every 28 days for more than 6 cycles (range 7-101 cycles). The 18 patients in Group B, aged 46-82 years (mean 64.8 years), received the same dose, but for no more than 6 cycles. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was analyzed for both groups and correlated with overall survival (OS) and progression-free survival (PFS). The impact of age, sex, Karnofsky Performance Scale score, and Ki 67 staining were also considered. RESULTS: All patients but 1 in Group A survived at least 18 months (range 18-101 months), and patients in Group B survived no more than 17 months (range 2-17 months). The long-term survivors (Group A), defined as patients who survived at least 12 months after diagnosis, were 51.3% of the total (19/37). Kaplan-Meier curve analysis showed that patients treated with more than 6 TMZ cycles had OS and PFS that was significantly longer than patients receiving standard treatment (median OS 28 months vs 8 months, respectively; p = 0.0001; median PFS 20 months vs 4 months, respectively; p = 0.0002). By univariate and multivariate Cox proportional hazard regression analysis, MGMT methylation status and number of TMZ cycles appeared to be survival prognostic factors in patients with glioblastoma. After controlling for MGMT status, highly significant differences related to OS and PFS between patients with standard and long-term TMZ treatment were still detected. Furthermore, in Group A and B, the statistical correlation of MGMT status to the number of TMZ cycles showed a significant difference only in Group A patients, suggesting that MGMT promoter methylation was predictive of response for long-term TMZ treatment. Prolonged therapy did not confer hematological toxicity or opportunistic infections in either patient group. CONCLUSIONS: This study describes the longest experience so far reported with TMZ in patients with newly diagnosed glioblastomas, with as many as 101 cycles, who were treated using GTR. Statistically significant data confirm that median survival correlates with MGMT promoter methylation status as well as with the number of TMZ cycles administered. Long-term TMZ therapy appears feasible and safe.

Immuno-expression of endoglin and smooth muscle actin in the vessels of brain metastases. Is there a rational for anti-angiogenic therapy?

Despite ongoing clinical trials, the efficacy of anti-angiogenic drugs for the treatment of brain metastases (BM) is still questionable. The lower response rate to anti-angiogenic therapy in the presence of BM than in metastatic disease involving other sites suggests that BM may be insensitive to these drugs, although the biological reasons underlining this phenomenon are still to be clarified. With the aim of assessing whether the targets of anti-angiogenic therapies are actually present in BM, in the present study, we analyzed the microvessel density (MVD), a measure of neo-angiogenesis, and the vascular phenotype (mature vs. immature) in the tumor tissue of a series of BM derived from different primary tumors. By using immunohistochemistry against endoglin, a specific marker for newly formed vessels, we found that neo-angiogenesis widely varies in BM depending on the site of the primary tumor, as well as on its histotype. According to our results, BM from lung cancer displayed the highest MVD counts, while those from renal carcinoma had the lowest. Then, among BM from lung cancer, those from large cell and adenocarcinoma histotypes had significantly higher MVD counts than those originating from squamous cell carcinoma (p=0.0043; p=0.0063). Of note, MVD counts were inversely correlated with the maturation index of the endoglin-stained vessels, reflected by the coverage of smooth muscle actin (SMA) positive pericytes (r=-0.693; p<0.0001). Accordingly, all the endoglin-positive vessels in BM from pulmonary squamous cell carcinoma and renal carcinoma, displayed a mature phenotype, while vessels with an immature phenotype were found in highly vascularized BM from pulmonary large cell and adenocarcinoma. The low MVD and mature phenotype observed in BM from some primary tumors may account for their low sensitivity to anti-angiogenic therapies. Although our findings need to be validated in correlative studies with a clinical response, this should be taken into account in therapeutic protocols in order to avoid the adverse effects of useless therapies.

Discordance rate of HER2 status in primary gastric carcinomas and synchronous lymph node metastases: a multicenter retrospective analysis.

BACKGROUND: The assessment of human epidermal growth factor receptor 2 (HER2) gene amplification is essential in order to identify those patients affected by advanced gastric cancer who may benefit from Trastuzumab targeted therapy. MATERIALS AND METHODS: With the aim to investigate the concordance rate in HER2 status between primary gastric carcinoma (GC) and synchronous lymphnode metastases, we investigated HER2 status in a cohort of 108 surgical formalin-fixed paraffin-embedded specimens of GC and matched synchronous metastatic lymph nodes collected from three different units of Anatomic Pathology in southern of Italy. Fleiss-Cohen weighted k statistics were used to assess the concordance rate of HER2 status. RESULTS: HER2 amplification was observed in 17% of primary GCs and the overall concordance rate with corresponding nodal metastases was 90.74%. Changes in HER2 status between primary GC and matched synchronous metastases were evidenced in 10 (9.26%) cases. Of these, 6 cases were HER2 amplified in the primary GC and not amplified in the metastases, while 4 were HER2 not amplified in the primary tumour and amplified in the lymph node metastases. CONCLUSIONS: Although at present the simultaneous determination of HER2 in advanced gastric cancer and corresponding metastatic lymph nodes is not mandatory, the possibility that the synchronous metastases of GC have a different HER2 status from that of the primary tumour is of remarkable significance; Indeed this may have influence on the therapeutic management and prognosis of the patients.

Spinal neurofibromatosis with central nervous system involvement in a set of twin girls and a boy: further expansion of the phenotype.

BACKGROUND: Familial spinal neurofibromatosis is a form of neurofibromatosis 1 (NF1), consisting of extensive, symmetrical, histologically proven, multiple neurofibromas of the spinal roots at every level and of all major peripheral nerves sometimes associated with typical NF1 stigmata; most cases underlie NF1 gene mutations. OBJECTIVES: The objectives of this study are (1) to report the findings in a set of 16-year-old monozygotic twin girls and a 14-year-old boy and (2) to review the existing literature. METHODS AND RESULTS: In this article, we report the cases of three children who (1) had manifested mildly different symptomatic neuropathy (twins, aged 4 years; and a boy, aged 9 years) associated with massive, symmetrical neurofibromas; (2) had few café-au-lait spots with irregular margins and pale brown pigmentation; (3) were presented with, at brain magnetic resonance imaging (MRI), bilateral, NF1-like high-signal abnormalities in the basal ganglia; (4) yielded missense NF1 gene mutations in exon 39; and (5) had unaffected parents with negative NF1 genetic testing as well as discuss 12 families and 20 sporadic and 5 additional cases that presented spinal neurofibromatosis within classical NF1 families (53 cases) that were reported in the literature. CONCLUSIONS: This article presents the first report on (1) spinal neurofibromatosis in a set of affected monozygotic twins; (2) the earliest onset of the disease; and (3) the occurrence of high signal lesions in the brain at MRI.

Primary peripheral PNET/Ewing's sarcoma arising in the meninges, confirmed by the presence of the rare translocation t(21;22) (q22;q12).

Peripheral primitive neuroectodermal tumor/Ewing's sarcoma (ES) (pPNET/ES) of intracranial origin are very rare. These tumors are characterized by specific translocations involving a gene on chromosome 22q12, the most common being t(11;22) (q24;q12). We report a case of 37-year-old man with pPNET/ES arising in the meninges and bearing the rare translocation t(21;22) (q22;q12). The tumor was composed of sheets and nests of monotonous small cells with round to oval nuclei, finely dispersed chromatin, small nucleolus and scant cytoplasm. We discuss the importance of the differential diagnosis with central primitive neuroectodermal tumors (cPNET).

Muscular metastasis from mesocolic and duodenal leiomyosarcoma. A case report and a review of the literature.

BACKGROUND: Mesenteric and duodenal leiomyosarcomas are very rare malignancies. Muscular metastases from leiomyosarcoma are even more rare. Surgery is the only chance of cure and should be attempted whenever possible. The relief of symptoms and the prevention of recurrences are ultimately the aims of surgery. We present a unique case of mesocolic and duodenal leiomyosarcoma with muscular metastases. CASE REPORT: A 61 year old woman was treated by radical resection including left neftectomy and left hemicolectomy for a leiomyosarcoma of the left mesocolon. Three years after the first surgery a leiomyosarcoma of the duodenal wall was diagnosed. Following a careful evaluation that ruled out the presence of other secondary locations, she underwent pancreatoduodenectomy. Three months later she observed a small, mildly painful swelling in the left thigh, rapidly growing to a diameter of 4 cm over a month period. The MRI showed a low-signal intensity malignancy in T2-weighted images whereas the lesion was homogeneously enhanced by Gadolinium on T1-weighted imaging. The histological examination after excision confirmed the clinical suspicion of a metastasis from high grade leiomyosarcoma. Successively the patient underwent a palliative chemotherapy treatment with epirubicin and ifosfamide for three cycles. The patient experienced a progression of disease with multiple pulmonary and encephalic metastases five months later. CONCLUSION: Muscular metastases from leiomyosarcoma are occasionally described in the literature. The apparition of muscular metastases is considered a negative prognostic factor and shortly precedes massive distant diffusion of the malignancy. Denervation syndrome can be a risk factor for muscular metastases. To our knowledge, this is the first report of a skeletal-muscle metastasis following mesenteric and duodenal leiomyosarcoma.

Solitary cutaneous histiocytosis with granular cell changes: a morphological variant of reticulohistiocytoma?

We first report a case of granular cell histiocytosis occurring as a solitary polypoid lesion of the nipple in a 15-year-old girl. Histologically, the lesion was composed of a dermal population of medium- to large-sized, short spindle- to round- to epithelioid-shaped cells with eosinophilic cytoplasm containing numerous and small diastase-resistant periodic acid-Schiff (PAS) positive granules. No associated inflammatory cells were observed. Immunohistochemical studies, revealing immunoreactivity exclusively to vimentin and CD68, were consistent with their histiocytic profile. Based on clinical, morphological and immunohistochemical features, the diagnosis of 'solitary cutaneous histiocytosis with granular cell changes' was proposed. The absence of an inflammatory cell component, such as lymphocytes and leucocytes, along with no history of a previous trauma or medical treatment, suggest that the present lesion could fit into the morphological spectrum of the so-called solitary epithelioid histiocytoma, also known as reticulohistiocytoma. Alternatively, the possibility of a histiocytic reaction to unknown stimuli cannot be completely ruled out. Nevertheless, awareness of solitary cutaneous histiocytosis with granular cell changes is useful to avoid confusion with other dermal tumors, especially 'granular cell tumor' and 'dermal non-neural granular cell tumor'.

Histological evaluation of prostatic tissue following transurethral laser resection (TULaR) using the 980 nm diode laser.

OBJECTIVES: In the present study, we performed for the first time an histological evaluation after 980 nm diode laser treatment of bladder outlet obstruction secondary to benign prostatic hypertrophy (BPH). The aim was to demonstrate the possibility of obtaining sufficient tissue for histological examination and the possibility of obtaining an histological diagnosis on the specimen obtained by laser resection. MATERIALS AND METHODS: 86 patients with BPH were selected for laser surgery and 10 patients for transurethral prostate resection. The prostate tissue samples collected from laser surgery and transurethral resection of the prostate (TURP) were fixed in 10% formalin and serial sections with a slice thickness of 5-7 micron embedded in paraffin and stained with haematoxylin and eosin. RESULTS: Samples obtained using the 980 nm diode laser ranged in size from 4 mm to 30 mm and showed brownish, smooth margins. Lasered tissue showed a coagulation rim of 0.5 mm (range: 0.2-1 mm) and adjacent to the vaporized tissue, coagulated connective tissue and glandular epithelia were seen. Beyond this zone a complete detachment of glandular epithelia from the connective tissue was observed. Stromal oedema associated with ectasic vessels but without extravasation of red blood cells, haemosiderin deposition and haemorrhagic areas were also retrieved. All cases showed occlusion of small vessels beyond the zone of coagulated tissue. Unlike laser treatment, samples obtained from TURP showed extravasation of red blood cells, haemosiderin deposition and haemorrhagic areas. CONCLUSIONS: The 980 nm diode laser provides high rates of tissue ablation, associated with excellent haemostasis. It has been shown that tissue samples can be obtained with this technique, which allow a histological diagnosis of BPH to be made. The current method involving the 980 nm diode laser induces a vaporesection of prostate tissue and the acronym of TULaR (transurethral laser resection) has therefore been created to describe this technique.

Giant cell ependymoma of the cervical spinal cord: case report and review of the literature.

Ependymomas account for 2-6% of all central nervous system neoplasms. They develop from the ependymal cells that line the ventricular cavities of the brain and the central canal of the spinal cord, as well as from ependymal clusters in the filum terminale. Giant cell ependymoma (GCE) is a rare subtype, with few cases reported, mostly in the brain. We describe the case of a cervical spinal cord ependymoma with pleomorphic giant cells and focal calcifications occurring in a 25-year-old woman. Magnetic resonance imaging revealed a large multicystic and partially enhancing intramedullary tumour extending from C2 to C5. Intraoperative analysis of frozen section tissue fragments suggested a malignant tumour; however, an obvious cleavage plane was present around most of the mass, and a macroscopically complete tumour removal could be achieved. Subsequently, paraffin sections and immunohistochemical investigations revealed unequivocal evidence of a GCE with focal calcifications. This case, the second giant-cell ependymoma to be described in the spinal cord and the first with focal calcifications, highlights the features of GCE and the discrepancy between the worrisome histological appearance, the surgical findings and the clinical relatively good prognosis.

Spindle cell/pleomorphic lipoma of the oral cavity.

We herein report a rare case of a lipomatous tumor of the buccal mucosa, showing intermediate morphological features between spindle cell and pleomorphic lipomas, for which the term spindle cell/pleomorphic lipoma is proposed. The presence of multinucleated floretlike cells may pose differential diagnostic problems, especially with spindle cell variant of well-differentiated liposarcoma. Morphological features helpful in the distinction between these tumors are emphasized. Although androgen receptors have been documented in most spindle cell lipomas, suggesting a potential pathogenetic role of sex steroid hormones, no immunoreactivity for androgen, estrogen, and progesterone receptors was obtained in our case. These findings would suggest a different pathogenetic pathway in spindle cell/pleomorphic lipoma of the oral cavity.

The unique simultaneous occurrence of a squamous cell carcinoma and a granular cell tumor of the tongue at the same site: a histological and immunohistochemical study.

We report a case of a 47-year-old man with a granular cell tumor (GCT) of the tongue colocalized with a squamous cell carcinoma. To our knowledge, this is the first case to be reported in the literature with such an association. Furthermore, we performed an immunohistochemical analysis with p63 to distinguish pseudoepitheliomatous hyperplasia from invasive squamous cell carcinoma. Clinicians and pathologists must be made aware of this potential diagnostic pitfall so that the workup of a tongue lesion does not end prematurely with a benign diagnosis of granular cell tumor with overlying pseudoepitheliomatous hyperplasia.

Expression pattern of estroprogestinic receptors in sinonasal inverted papilloma.

Inverted papilloma (IP) is a locally destructive, benign neoplasm of the nose and paranasal sinuses with a high tendency for recurrence, a significant potential for malignancy, and an etiology that today is still uncertain. The expression of hormonal receptors in neoplastic tissues has been the focus of intensive research for its potential diagnostic, prognostic, and therapeutic significance. The aim of this study was to assess the potential estroprogestinic receptor expression in patients undergoing sinus surgery for IP. A retrospective study was carried out, on surgical specimens of 73 patients who underwent endoscopic sinus surgery for first manifestation of sinonasal IP (primitive IP group) and in 21 subjects who had developed a recurrence (relapsed IP group). The results of the immunohistochemical analysis of the first group showed the absence of receptor expression for PGR in all cases analyzed and the presence of a low positivity for ER in 11 cases (P > 0.082). Similarly, in the second group the results showed a low presence of ER receptors in 3 of the 21 cases (P > 0.068), while there was no evidence of PGR receptors in the examined samples. In addition, in 11 of the cases only 3 were considered positive (27.2%) showing a recurrence during follow-up (P > 0.068).Our results suggest that the sinonasal IP is a benign tumor independent of estrogen and progesterone, and the receptors for these hormones are therefore unsuitable as predictors of relapse or possible prognostic indicators and therapeutic targets.

A rare cystic non-functioning neuroendocrine pancreatic tumor with an unusual presentation.

This report describes a patient with a cystic non-functioning neuroendocrine glucagon cell pancreatic tumor presenting with demyelination of the optical nerve that had initially provoked marked monolateral reduced vision and had led to a suspected diagnosis of multiple sclerosis. Cystic degeneration is uncommon in endocrine pancreatic tumors due to their abundant vascular supply. Very few cases of cystic neuroendocrine non-functioning pancreatic tumors have been reported in the international literature. The presence of atypical neurological symptoms, such as sudden visual impairment, should be taken into account in the differential diagnosis for such tumors. The prognosis is poor, because most of these tumors are malignant and diagnosed at an advanced stage. The three-year disease-free survival of our patient, however, encourages the use of aggressive surgical treatment.

Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme.

MiR-671-5p is encoded by a gene localized at 7q36.1, a region amplified in human glioblastoma multiforme (GBM), the most malignant brain cancer. To investigate whether expression of miR-671-5p were altered in GBM, we analyzed biopsies from a cohort of forty-five GBM patients and from five GBM cell lines. Our data show significant overexpression of miR-671-5p in both biopsies and cell lines. By exploiting specific miRNA mimics and inhibitors, we demonstrated that miR-671-5p overexpression significantly increases migration and to a less extent proliferation rates of GBM cells. Through a combined in silico and in vitro approach, we identified CDR1-AS, CDR1, VSNL1 as downstream miR-671-5p targets in GBM. Expression of these genes significantly decreased both in GBM biopsies and cell lines and negatively correlated with that of miR-671-5p. Based on our data, we propose that the axis miR-671-5p / CDR1-AS / CDR1 / VSNL1 is functionally altered in GBM cells and is involved in the modification of their biopathological profile.

p63 overexpression associates with poor prognosis in head and neck squamous cell carcinoma.

p63 belongs to a protein family that includes 2 structurally related proteins, p53 and p73. The aim of this study was to investigate the biologic role of p63 in oral tumorigenesis and its possible role as prognostic marker in oral cancer. Ninety-four cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analyzed for p63 expression by immunohistochemistry. Normal oral mucosa showed a basal and parabasal expression of p63. Five (5.3%) cases of oral cancer showed less than 10% of positive tumor cells; in 33 (35.1%) cases the positive tumor cells comprised between 10% and less than 30%, in 36 (38.3%) cases the positive tumor cells comprised between 30% and less than 50%, and in 20 (21.3%) cases the positive tumor cells were more than 50%. There was also a statistically significant correlation between p63 expression and tumor differentiation: p63 expression was amplified in poorly differentiated tumors (P < .05). When analyzed for prognostic significance, patients with perineural infiltration had poorer survival rates than the group with no perineural infiltration (P < .05) and patients with increased p63 expression had poorer survival rates than the group with reduced p63 expression (P < .05). The statistical analysis showed no significant correlation between p63 expression, sex, age, tumor size, staging, recurrence, and metastasis. Cases with diffuse p63 expression were more aggressive and poorly differentiated and related to a poorer prognosis. These data suggest that p63 expression may be useful to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers.

Primary C1-2, intradural, extramedullary meningeal sarcoma with glial fibrillary acidic protein-immunoreactive components: a spinal gliosarcoma? Case report and review of the literature.

The authors report an exceedingly rare case of a patient harboring a primary, spinal, C1-2, intradural, extramedullary meningeal sarcoma in which there were glial fibrillary acidic protein-immunoreactive components, but, importantly, no physical connection with neural tissue. On initial diagnostic imaging, neuroradiological features suggestive of a spinal meningioma were demonstrated in this 73-year-old man. He underwent a C1-2 laminectomy and removal of the posterior ring of the foramen magnum, and the lesion was excised. Histological and immunohistochemical testing showed a gliosarcoma. The clinical, radiological, and operative data are reviewed, as are the histopathological findings. To the authors' knowledge, this is the first case of a primary spinal intradural extramedullary gliosarcoma reported in the literature.