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Data on somatic heterogeneity and germline–somatic interaction in multiple primary melanoma (MPM) patients are limited. We investigated the mutational status of BRAF, NRAS, and TERT promoter genes in 97 melanomas of 44 MPM patients and compared molecular and immunohistochemical findings. We further evaluated the association of somatic alterations with the germline MC1R genotype. Mutations in BRAF gene were identified in 41.2% (40/97) of melanomas, in NRAS in 2.1% (2/97), and in TERT promoter in 19.6% (19/97). Distribution of BRAF mutations did not differ across multiple melanomas (P = 0.85), whereas TERT promoter changes decreased from first to subsequent melanomas (P = 0.04). Intrapatient discrepancy of BRAF mutations among multiple tumors was detected in 14 of 44 MPM patients (32%) and of BRAF/NRAS/TERT promoter genes in 20 of 44 (45%). We observed a high rate of agreement between allele-specific TaqMan assay and immunohistochemistry in BRAFV600E detection (κ = 0.83, P

Background Cyclooxygenase-2 (COX-2), an inflammation-associated enzyme, has been implicated in tumorigenesis and progression of glioblastoma (GBM). The poor survival of GBM was mainly associated with the presence of glioma stem cells (GSC) and the markedly inflammatory microenvironment. To further explore the involvement of COX-2 in glioma biology, the effects of NS398, a selective COX-2 inhibitor, were evaluated on GSC derived from COX-2 expressing GBM cell lines, i.e., U87MG and T98G, in terms of neurospheres’ growth, autophagy, and extracellular vesicle (EV) release. Methods Neurospheres’ growth and morphology were evaluated by optical and scanning electron microscopy. Autophagy was measured by staining acidic vesicular organelles. Extracellular vesicles (EV), released from neurospheres, were analyzed by transmission electron microscopy. The autophagic proteins Beclin-1 and LC3B, as well as the EV markers CD63 and CD81, were analyzed by western blotting. The scratch assay test was used to evaluate the NS398 influence on GBM cell migration. Results Both cell lines were strongly influenced by NS398 exposure, as showed by morphological changes, reduced growth rate, and appearance of autophagy. Furthermore, the inhibitor led to a functional change of EV released by neurospheres. Indeed, EV secreted by NS398-treated GSC, but not those from control cells, were able to significantly inhibit adherent U87MG and T98G cell migration and induced autophagy in recipient cells, thus leading to effects quite similar to those directly caused by NS398 in the same cells. Conclusion Despite the intrinsic diversity and individual genetic features of U87MG and T98G, comparable effects were exerted by the COX-2 inhibitor NS398 on both GBM cell lines. Overall, our findings support the crucial role of the inflammatory-associated COX-2/PGE2 system in glioma and glioma stem cell biology.

Mutations in MAPK signalling genes are driver events in melanoma, and have therapeutic relevance in the metastatic and adjuvant setting. This study evaluated the intra-patient heterogeneity of BRAF, NRAS and c-KIT mutational status between 30 primary melanomas and 39 related metastases, using molecular analysis and immunohistochemistry. BRAF mutations were identified in 46.7% of primary melanomas and 48.7% of metastases and NRAS mutations in 20% and 25.6%, respectively. Intra-patient heterogeneity was detected in 13.3% of patients for both BRAF and NRAS genes and was not associated with clinico-pathological characteristics of melanomas or metastases. High consistency was observed between immunostaining and molecular methods for BRAFV600E (k = 0.90; p

The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is being increasingly investigated. HtrA1 overexpression inhibits cell growth and proliferation by influencing apoptosis, invasiveness and migration of tumour cells. In the present study, HtrA1 expression was analysed in 228 colon tissue samples from patients with CRC, adenoma with high-grade dysplasia (AHD), adenoma with low-grade dysplasia (ALD), ulcerative colitis of >10 year duration (UCL), ulcerative colitis of

Oral squamous cell carcinoma (OSCC) is often associated with a poor prognosis. The purpose of the present study was to investigate survival and the risk of mortality in OSCC with regard to stage, tumor site and p53 expression. A retrospective study was performed on 150 non-consecutive cases of OSCC that were observed between January 1992 and January 2012, and were selected from a total of 580 patients according to the criteria of the homogeneity of histopathological grading (G2). The medical records were reviewed for 48 cases with disease at stage I [37 males, age 64.7±5.7 years (mean age±standard deviation); 11 females, age 70.0±3.37 years]; 27 cases with stage II (15 males, age 64.5±5.6 years; 12 females, age 69.2±3.9 years); 58 cases with stage IVa (42 males, age 66.9±5.3 years; 16 females, age 64.2±6.5 years); and 17 cases with stage IVb (16 males, age 65.7±5.4 years; 1 female, age 69 years). Monoclonal p53 antibody (clone DO-7) was used to perform the p53 immunohistochemical study. A significant association was found between the site of the tumor and p53 overexpression (P50% showed a poor survival rate (P50% in association with a higher risk of mortality compared with when p53 overexpression is

Our previous study on 75 cases of advanced oral squamous cell carcinomas (SCC) treated by neoadjuvant chemotherapy, radical surgery, and radiotherapy showed that overexpression of p53 of more than 50% indicated a strong probability of genetic mutation, and tumours that are characterised by this p53 pattern respond poorly to treatment and have a poor prognosis (p= 0.0001). We have studied the same cohort of patients retrospectively to investigate the incidence of human papillomavirus-16 (HPV16) infection, the relation to the overexpression or mutation of the p53 gene, and the association with overall survival. There were 57 men and 18 women, mean age 67 (range 57-72) years. HPV16 infectivity was found in 66 patients (88%) - 49/57 men (86%) and 17/18 women (94%). There was no significant difference between the sexes (p=0.32). The cumulative survival of the entire group after a follow-up of 38 months was 26% (SE 6.4). The log rank test indicated that the combination of HPV-16 infectivity and p53mutation was significantly related to prognosis (p=0.000). On the other hand HPV16 infectivity alone was not significantly related to prognosis (p=0.78) The incidence of HPV-16 infection decreased with increasing immune p53 expression (p=0.005), whereas that of the HPV16+p53mutation combination increased with increasing immune p53 expression (p=0.000). The results show the importance of the investigation of HPV and p53 expression to define prognosis in oral SCC.

Gemas den neuesten Richtlinien der Weltgesundheitsorganisation (WHO) sollte die Diagnose eines malignen fibrosen Histiozytoms (MFH) nur fur Lasionen mit Tumorzellen ohne Nachweis einer bestimmten Ausdifferenzierung gestellt werden. Somit handelt sich es sich um eine Ausschlussdiagnose, weshalb die Bezeichnung hochgradig undifferenziertes pleomorphes Sarkom (UPS) vorzuziehen ist. Weichteilsarkome konnen mit einer Inzidenz von ca. 20 Fallen/1 Mio. Einwohner/Jahr in allen Korperteilen auftreten. Weichteiltumoren des Penis machen etwa 5 % samtlicher Tumoren des Penis aus, die Inzidenz der Penissarkome wird auf ca. 0,6–1 Falle/100.000 Patienten geschatzt. In der Literatur wurden bisher nur 7 Falle beschrieben. Diese Kasuistik beschreibt den Fall eines 61-jahrigen kaukasischen Mannes mit einer schmerzlosen Masse im oberen Schwellkorperbereich. Eine Inzisionsbiopsie mit nachfolgender breiter immunohistochemischer Untersuchung ergab ein hochgradig undifferenziertes pleomorphes Sarkom oder pleomorphes storiformes MFH. Neben dem Fallbericht stellen die Autoren einen Literaturreview zur Vertiefung der Diskussion uber die schwierige Diagnosestellung vor.

Data on somatic heterogeneity and germline-somatic interaction in multiple primary melanoma (MPM) patients are limited. We investigated the mutational status of BRAF, NRAS, and TERT promoter genes in 97 melanomas of 44 MPM patients and compared molecular and immunohistochemical findings. We further evaluated the association of somatic alterations with the germline MC1R genotype. Mutations in BRAF gene were identified in 41.2% (40/97) of melanomas, in NRAS in 2.1% (2/97), and in TERT promoter in 19.6% (19/97). Distribution of BRAF mutations did not differ across multiple melanomas (P = 0.85), whereas TERT promoter changes decreased from first to subsequent melanomas (P = 0.04). Intrapatient discrepancy of BRAF mutations among multiple tumors was detected in 14 of 44 MPM patients (32%) and of BRAF/NRAS/TERT promoter genes in 20 of 44 (45%). We observed a high rate of agreement between allele-specific TaqMan assay and immunohistochemistry in BRAF

In literature there are few reports about multiple CGCG. But this is the first report of bilateral CGCG of the mandibular angles in three females from the same family. This report describes three cases of females from the same family - a mother and two young daughters - with bilateral CGCG in their jaw angles. All the lesions were surgically removed and the histopathologic diagnosis was always identical: giant cell central granulomas, with patterns that were absolutely superimposable between them and with that of the mother. The hypothesis is that this presentation of CGCG may be defined as hereditary bilateral CGCG of the mandibular angles (or also, cherubism-like lesions).

Background: The aim of the study was to compare the prognostic value of histological and endoscopic activity in patients with ulcerative colitis (UC). Methods: Patients in clinical remission for 1 year under treatment with mesalazine underwent a planned colonoscopy with biopsies. Histological activity was scored using the histological activity index (HAI). Endoscopic activity was scored using the Mayo endoscopic subscore (MES). The clinical course was evaluated measuring relapses needing steroids during a follow up of 3 years. Results: A total of 52 patients were enrolled into the study and followed up for 3 years. At baseline 29 patients (55.77%) had no endoscopic lesions, and 17 patients (32.69%) showed no histological alteration. At 3 years of follow up, overall, 26 patients (50%) were still in steroid-free remission. Using univariate logistic regression analysis, both histological (HAI ⩾ 1) and endoscopic activity (MES ⩾ 1) were significantly associated with outcome, showing, respectively, a relapse risk (odds ratio [OR]) 16.4 times higher than histological remission (HAI 0) (96% confidence interval [CI]: 3.2–84.3) and 6.3 times higher with respect to endoscopic remission (MES 0) (96% CI: 1.9–21.3). After multivariate logistic regression analysis, histological activity was the only factor significantly associated with outcome (OR 10.2; 95% CI: 1.7–59.4). Conclusions: Histological activity has the most powerful prognostic value in predicting the need for steroids in patients with UC in stable clinical remission on mesalazine. It could be considered as a target of therapy in UC.

J Oral Pathol Med (2012) 41: 16–20 Background: Oral cancer is the sixth most common malignancy in developed countries, representing almost 3% of malignant tumors. Tobacco use and alcohol consumption are well-established risk factors. However, the observation that most patients with oral cancer have not been exposed to these risk factors suggests that additional causes may promote oral carcinogenesis. A link has been suggested between human papillomavirus (HPV) and oral cavity cancer but the significance of HPV contribution to oral carcinogenesis as well as the prevalence of HPV infection in normal oral cavity mucosa remains debated. Methods: In this study, the prevalence of oral HPV infection was evaluated in 81 randomly selected Northern Italian subjects with clinically normal oral mucosa using a nested PCR on DNA extracted by oral smears. Results and conclusions: No HPV-related lesions were detectable in any of the smears analyzed by cytological approach. nPCR identified HPV DNA in only one (1.2%) of the specimens obtained from clinically healthy oral mucosa and subsequent characterization assigned the positive case to HPV type 90. These data suggest that the incidence of HPV infection in the healthy population might be very low and that other risk factors are likely responsible to promote oral carcinogenesis.

Dystroglycan (DG) is a non-integrin adhesion molecule connecting the extracellular matrix to the actin cytoskeleton. Decreased expression of DG has been reported in several human cancers and related to tumour aggressiveness.Expression of the alpha-DG subunit was evaluated by immunostaining in a series of oral squamous cell carcinoma (OSCC) and its relation with traditional prognostic indicators and with the clinical outcome of the patients was evaluated.Alpha-DG expression was easily detected in normal epithelium with a mean percentage of positive cells80% but was undetectable in a significant fraction (59%) of OSCC. Loss of alpha-DG staining correlated with higher tumour grade (p = 0.04) and stage (p = 0.01), with nodal involvement (p = 0.001) and with an increased risk of recurrence (p = 0.002) and death (p = 0.004) in a univariate analysis, but it was not confirmed as an independent predictor of clinical outcome in a multivariate analysis.Loss of alpha-DG expression, which corresponds to loss of a functional DG complex, is a frequent event in human OSCC. Further studies are warranted on the role of this molecule in the entire multistep process of oral squamous tumorigenesis.

Background: Aberrant Wingless type 1 glycoprotein (Wnt) pathway in ameloblastomas and a role of syndecan-1 (SDC1) in activating Wnt signalling were perspected. SDC1 shifting from epithelium to stroma was reported in invasive non-odontogenic neoplasms. The aim of this study was to reveal the role of SDC1 and Wnt1 in intraosseous ameloblastomas (IAs). Methods: SDC1 and Wnt1 expressions were investigated in 29 ameloblastoma subtypes and seven tooth buds. Results: SDC1 immunostaining strongly depicted stromal cells, extracellular matrix (ECM) and basement membranes of ameloblastomas. It also showed epithelial tumour cells in the acanthomatous and plexiform subtypes, and it often occurred in stellate reticulum cells and basal ameloblasts of tooth buds. Parallel Wnt1 expression occurred in ameloblastomatous epithelial cells, but it was common in basal cells of tooth buds too. Statistically, a significant correlation was found between the percentage of IAs-bearing SDC1-positive stromal cells and ECM and the percentage of IAs-bearing Wnt1-positive epithelial cells. Conclusions: A role of SDC1 in stromal cells and ECM can be hypothesized as a critical factor for carcinogenesis and local invasiveness of IAs.

Ameloblastomas are epithelial tumors of odontogenic origin, biologically characterized by local recurrence. Among different etiologic factors, HPV infection has been recently postulated to be somehow involved in ameloblastoma etiopathogenesis. To address this issue, we studied 18 ameloblastomas by means of immunohistochemistry, in situ hybridization (conventional and amplified), polymerase chain reaction and nested-polymerase chain reaction analyses using laser capture microdissection in order to detect the occurrence of HPV in this setting. No evidence of HPV infection was detected by morphological examination, immunohistochemistry, in situ hybridization and conventional polymerase chain reaction, while nested-polymerase chain reaction showed a weak positive band in two cases. However, the subsequent restriction enzyme analysis carried out from the nested-polymerase chain reaction amplification products of these two samples excluded the presence of HPV subtypes 16, 18, 31, 33, 35, 52, and 58. The search for HPV 6 and 11 in the same specimens was also negative. In conclusion, our data do not support an etiopathogenetic evidence for HPV in ameloblastoma.

An abnormal expression of cyclin D3, a key regulator of the cell cycle, has been documented in a variety of human malignancies, and the cyclin D3 gene, mapping to 6p21, may be deregulated in plasma cell myeloma and non-Hodgkin's lymphoma as a result of the t(6;14)(p21.1;q32.3) translocation and/or gene amplification. In the current study, we for the first time investigated by immunohistochemistry and fluorescence in situ hybridization (FISH) the prevalence of cyclin D3 abnormalities in follicular lymphomas (FLs), comparing the results with traditional clinicopathologic characteristics, p27 and skp2 immunoreactivity (IR) and Ki-67 labeling index (LI). Cyclin D3, skp2 and Ki-67 IR significantly increased from grade I to grade III FL (p = 0.0003, p = 0.0001 and p < 0.0001, respectively), while p27 IR was significantly (p < 0.0001) more prevalent in low-grade tumors. Cyclin D3 IR was directly correlated with the Ki-67 LI (p < 0.0001) and inversely correlated with p27 IR (p = 0.050). None of the 13 cases analyzed by FISH showed the t(6;14) translocation, but in 2 (15.3%) grade I FLs 3 cyclin D3 signals were detected. Cohybridization with probes specific for the centromeric region and the long arm of the chromosome 6 indicated trisomy in one case and a pattern highly suggestive for the presence of an isochromosome 6p in the other case. Our data suggest that the t(6;14) translocation may be extremely uncommon in FL and that a deregulated expression of cyclin D3, possibly due to epigenetic mechanisms, may be involved in the pathogenesis of high-grade tumors.

Much of the morbidity of intracranial meningiomas is related to the degree of tumour vascularity and the extent of peritumoural vasogenic oedema. Several studies have shown that vascular endothelial growth factor (VEGF) is up-regulated in meningiomas, although its relationship with tumour vasculature is still unclear. In order to better understand the angiogenic assessment of intracranial meningiomas, we analysed its vascular pattern, both as number and as morphologic configuration of microvessels. Moreover, we investigated the mRNA-VEGF expression, relating this expression to vascular pattern. A total of 40 intracranial meningiomas, classified as benign (31 cases), atypical (7 cases), and anaplastic (2 cases) were analysed. RT-PCR analyses of mRNA-VEGF and competitive-PCR were performed. VEGF expression and microvessel density (MVD) were also immunohistochemically investigated. Grade II-III meningiomas showed numerous small microvessels (mean: 34), while the majority of Grade I showed few larger vessels (mean: 13.09) (P = 0.000003). A microvessel pattern overlapping into atypical subtype was found in eignt of the 31 (25.8%) Grade I meningiomas. A significant association was found between grading and vascular pattern (P = 0.0002), as well as between the MVD and the immunohistochemical expression of VEGF (P = 0.0005). The expression of mRNA agreed with the immunohistochemical expression of the protein (P < 0.0001). A total of 39 cases expressed the 121 VEGF isoform and, among these, 28 cases also expressed the 165 isoform. Only 9 cases expressed both isoforms 165 and 189. Grade II and III meningiomas showed a preponderant expression of soluble isoforms (121 and 165). These results prompt us to speculate that the microvessel pattern could underlie a higher metabolic demand, probably due to a rapid growth with a consequent worse clinical behaviour of the tumour. In this sense, the vascular pattern may be used as a prognostic factor, in order to mostly focus attention on those Grade I meningiomas which have a higher likelihood of either recurrence or development of perilesional oedema. The pattern of vasculature itself seems to be dependent on the types of VEGF isoforms: the Grade II-III meningiomas (that presented numerous microvessels) expressed the soluble isoforms 121 and 165, while the isoform 189 was more frequently detected in Grade I meningiomas.

The authors describe the preliminary investigation of the natural mummies found in the church of the Holy Trinity in Popoli (inner Abruzzo region, Central Italy) and dating back from 1734 to 1845. The project was featuredas an episode in the National Geographic Channel series "The Mummy Road Show". The mummy of a male individual, 35-40 years old, underwent non-destructive examination with radiological, endoscopical, histological and X-ray diffraction analysis. The individual, belonging to high social class, was found affected by caries, paradontal disease, rib fractures, calcification of the diaphragm and renal urolythiasis. The recovery and complete investigation of the whole series of human remains will offer the opportunity to trace an anthropologic and paleopathologic profile of this interesting community.

Many evidence support the view that endometriotic cyst may exert detrimental effect on the surrounding ovarian microenvironment so representing a risk to functionality of adjacent follicles. Patients with benign ovarian cyst (endometriotic, follicular and dermoid cysts) subjected to laparoscopic cystectomy were enrolled in the present retrospective study in order to analyze whether endometriotic tissue could negatively affect the surrounding normal ovarian cortex more severely than other ovarian cysts. To this end we carried out immunohistochemistry analysis and comparative determination of the transcription factor FOXO3A, oxidized DNA adduct 8-OHdG (8-hydroxy-2 0 -deoxyguanosine) and damaged proteins known as AGEs (Advanced Glycation End products) as markers of ovarian stress response and molecular damage. Our results show that all the markers analyzed were present in normal ovarian tissue surrounding benign cysts. We observed higher levels of FOXO3A (15.90 ± 0.28), 8-OHdG (13.33 ± 2.07) and AGEs (12.58 ± 4.34) staining in normal ovarian cortex surrounding endometriotic cysts in comparison with follicular cysts (9.04 ± 0.29, 2.67 ± 2.67, 11.31 ± 2.95, respectively) and dermoid cysts (2.02 ± 0.18, 4.33 ± 2.58 and 10.56 ± 4.03, respectively). These results provide evidence that ovarian endometrioma is responsible for more severe alterations to cellular biomolecules than follicular and dermoid cysts.

To understand if repeated cycles (2-4 rounds) of gonadotropin stimulation could affect intracellular localization/content of proteins controlling cell cycle progression in mouse fallopian tubes (FT) and ovaries.FT and ovaries of estrous mice (control) and of stimulated mice were analyzed to detect Oct-3/4, Sox-2, p53, β-catenin, pAKT and cyclin D1 localization/content. Spindles and chromosome alignment were analyzed in ovulated oocytes.After round 4, FT and ovaries of control and stimulated groups showed no differences in Oct-3/4, Sox-2 and β-catenin localization nor in Oct-3/4, Sox-2, p53, β-catenin and pAKT contents. Cyclin D1 level increased significantly in FT of treated mice. Oocytes number decreased meanwhile frequency of abnormal meiotic spindles increased with treatments.Repetitive stimulations affected oocyte spindle morphology but did not induce changes in a set of proteins involved in cell cycle progression, usually altered in ovarian cancer. The significant increase of cyclin D1 in the FT requires further investigation.

The forkhead transcription factor FoxP3 plays an important role in regulatory T cell (Treg) functions. Tregs are critical in maintaining immunologic tolerance. It has been shown that vaccination against FoxP3-expressing cells is associated with enhancement of tumor immunity. Tregs appear to be increased in blood and in the tumor microenvironment of patients with different cancer types. Tumor cells themselves can express FoxP3. The present study investigates the possible role of FoxP3 expression in a series of human papillary thyroid cancers with a mean follow-up time of 15 years.One hundred five cases of papillary thyroid carcinoma (PTC) were investigated, and FoxP3 expression was evaluated in both tumor cells and tumor-associated infiltrates. For all patients, clinical/pathologic features were considered and the results analyzed by statistical tests.Of the 105 PTC cases, 45 (43%) scored FoxP3-positive and 60 (57%) were negative. FoxP3 staining was localized predominantly in the cytoplasm of tumor cells. In some cases, both nuclear and cytoplasmic staining was seen in infiltrating cells. FoxP3 expression in tumor cells was correlated with the presence of extrathyroid invasion (p=0.04) and distant metastasis (p=0.04), but not with overall survival. Interestingly, FoxP3 expression in neoplastic cells was significantly associated with a resistance phenotype to radioiodine treatment (p=0.041).The data show an association of FoxP3 expression with features of PTC that seem to have a specific impact on radioiodine sensitivity.

Objective: CD133 is a pentaspan membrane protein expressed by the so-called cancer stem cells (CSC) in the majority of human cancers. The aim of this study was to analyze CD133 expression levels in specimens of oral cancer and to evaluate its relation with disease evolution. Methods: Expression of the CD133 protein was evaluated by immunostaining in a series of oral squamous cell carcinoma (OSCC) and its relation with traditional prognostic indicators and the clinical outcome of patients was analyzed. Results: CD133 expression was highly variable amongst different samples with a median percentage of positive cells of 5 (range 0 - 80; mean = 11) and CD133 staining was not detectable in tumor cells in 29 (43%) cases. No correlation was observed with age at diagnosis, gender and grading while a significant correlation was observed with tumor stage. Kaplan-Meier curves of disease-free survival displayed a significant separation between the negative and positive groups of patients (p = 0.001 by log-rank test) but CD133 staining did not confirm to be an independent predictor of clinical outcome in a multivariate analyses. Conclusion: Expression of CD133 was detectable in the majority of OSCC samples and correlated significantly with tumor stage and the clinical outcome of patients in terms of disease-free survival. Further studies are warranted on a larger series of cases to elucidate the role of CD133 in the development and progression of OSCC and its suitability as a prognostic biomarker.

Objective The majority of patients with lung cancer are treated on the basis of a diagnosis made from the analysis of a small tumour biopsy or a cytological sample and histotype is becoming a critical variable in clinical workup as it has led to the introduction of newer biologically targeted therapies. Consequently, simply classifying cancers as small cell lung cancers or non-small cell lung cancers is no longer sufficient. Methods From 2009 to 2011, a review of the histo-cytological database was conducted to identify all small biopsy and cytology specimens collected for diagnostic purposes in patients with a thoracic lesion. In total, 941 patients were studied by examining exfoliative and/or aspirative cytological samples. To establish the accuracy of these methods, cytological and biopsy diagnoses were compared with each other and with subsequent resection specimens when available. Moreover, during the diagnostic workup, we examined a validated panel of immunohistochemical markers. Results The diagnostic concordance of pre-operative diagnoses with surgical samples was high in both cytology and biopsy samples [κ = 0.71, confidence interval (CI) = 0.6–0.81; P

Ce document passe en revue les possibilites de diagnostic du cancer gastrique au debut au moyen de la videoendoscopie assistee d’un systeme informatique pour le traitement et l’analyse de l’image. Les principales fonctions du traitement de l’image du systeme sont le grossissement, l’etirement des contrastes et l’amelioration des contours. Les fonctions analytiques incluent la mesure des dimensions reelles (longueurs, perimetres et surfaces). L’utilisation de videendoscopes electroniques couples a ce systeme digital de traitement d’image et d’analyse se sont averes cliniquement tres utiles dans notre service d’endoscopie, ameliorant la precision du diagnostic pre-operatoire du cancer gastrique de 30 % durant la periode comprise entre 1987 et 1989 et de 70,60 % de 1990 a 1993. Nous avons en particulier note un taux plus eleve de diagnostics preoperatoires precis pour les cancers gastriques precoces de petite taille. Les fonctions d’analyse ont ete utilisees pour mesurer les dimensions du cancer gastrique au debut. On a pu enregistrer un taux de precision tres important des mesures prises sous endoscopie assistee par ordinateur. En fait, aucune difference significative n’a ete demontree entre les valeurs mesurees en preoperatoire et celles relevees en post-operatoire sur les biopsies.

We have analysed concentrations of the p53 protein in advanced oral carcinomas immunohistochemically and genetically to detect the percentage of overexpression of this antioncogene that indicates a high probability of mutation. This would point to it being a useful prognostic factor, if we consider the importance of the relation between genetic alterations of p53 and poor overall survival. Seventy-five non-consecutive patients with oral squamous cell carcinoma and metastatic nodes were enrolled if there was homogeneity in histopathological grading (G2) of their tumours, and they were treated according to a multidisciplinary treatment plan. Monoclonal antibodies, extraction of DNA, and amplification of the polymerase chain reaction (PCR) were used for the immunohistochemical and genetic analyses. There was a significant inverse correlation between p53 overexpression and response to chemotherapy and a stronger association between high P53 overexpression (%) and a genetic mutation of p53 (p = 0.0001). More than 50% overexpression indicated a strong probability of genetic mutation. There was no association between response to chemotherapy and age-groups or TNM classification (p = 0.2), but there was a significant one between sex and site of tumour (p < 0.001). Three prognostic factors were significantly related to prognosis: site of tumour (p = 0.01), response to chemotherapy (p = 0.002), and immuno p53 (p = 0.0001). A tumour that is characterised by p53 overexpression of more than 50% indicates a poor prognosis. © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Emerging evidence indicates that interactions between chemokine receptors and their ligands may have a critical role in several steps of tumor development, including tumor growth, progression, and metastasis. In this report, we retrospectively evaluated CXCR4 expression in a consecutive series of 200 papillary thyroid carcinomas. We investigated the relationship between the clinicopathological features of the tumors and mutations in the BRAF gene to verify whether overexpression of CXCR4 is linked to more aggressive behavior in thyroid tumors. CXCR4 protein expression was evaluated by immunohistochemical staining. A final staining score was calculated by adding the score representing the percentage of positive cells to the intensity score. The CXCR4 expression of each papillary thyroid carcinoma sample was normalized by calculating the z score for each final staining score. Univariate analysis was used to correlate CXCR4 expression with the papillary thyroid carcinoma variant, the degree of neoplastic infiltration, the American Joint Commission on Cancer stage, the presence of lymphocytic thyroiditis and the mutation status of the BRAF gene. Multiple regression analysis confirmed a strong association between CXCR4, BRAF mutation and the degree of neoplastic infiltration. These data clearly indicate that the chemokine receptor expression induced by oncogenic activation could be the major determinant of the local aggressiveness of neoplastic cells. In conclusion, our data indicate that CXCR4 expression and BRAF mutation status could cooperatively induce and promote a more aggressive phenotype in papillary thyroid carcinoma through several pathways and specifically increase the tumors' spread outside of the thyroid gland.

The agar technique represents an important method to obtain optimal orientation of small specimens during paraffin embedding and to avoid tissue loss during processing. This method is advisable for ocular, temporal artery, gastrointestinal, cervical, and skin biopsies and may be applied with formalin-fixed specimens as well as with fresh tissue. Microwave oven can be successfully used to make the small specimen orientation technique with agar quicker and easier. Ann Diagn Pathol 5:107-109, 2001.

The diagnosis of solitary fibrous tumor (SFT) is usually straightforward if the typical morphologic features, including a wide variety of growth patterns, are identified. We report the clinical, radiologic, and pathologic findings of a rare case of intraoral SFT which exhibited a predominant leiomyomatous-like appearance, closely reminiscent of a leiomyoma, at both incisional and excisional biopsy. Histologically, the tumor was composed predominantly of intersecting fascicles of eosinophilic spindle-shaped cells, variably set in a fibrous stroma. A focal hemangiopericytoma-like growth pattern with alternating hypercellular and hypocellular areas, as well as the deposition of dense keloid-type collagen, raising the suspicion of SFT, could be identified only after a careful examination of the whole tumor. Immunohistochemistry was helpful in confirming the diagnosis of SFT, revealing a diffuse staining of neoplastic cells for vimentin, CD34, bcl-2 protein, and, focally, CD99. Myogenic markers (α-smooth muscle actin, desmin, h-caldesmon) were not expressed. The pathologist should be aware of this variant of intraoral leiomyomatous-like SFT to avoid a misdiagnosis of leiomyoma. The distinction of SFT from leiomyoma in the oral cavity is important to assure both correct treatment and prognostic information.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a recently identified death factor that acts as a potent apoptosis inducer in ameloblastomas.The expression of TRAIL and its receptors (TRAIL-R), and the location of apoptotic cells were evaluated in 15 cases of ameloblastoma using immunohistochemistry and an in situ DNA nick-end labeling method. The proliferative activity of ameloblastomas was analyzed by determining the Ki-67 labeling index.TRAIL and TRAIL-R were diffusely expressed in ameloblastomas, without clear correlation with the location of apoptotic cells. Apoptosis and proliferation were opposite in the peripheral and central components of the ameloblastomas. In some ameloblastoma variants, apoptosis and proliferation seemed to modify in the same direction.TRAIL and its receptors might be involved in neoplastic transformation of odontogenic epithelium and might suggest some intrinsic regulation of neoplastic cell proliferation and death in ameloblastomas, thus explaining their slow growth and inability to metastasize.

Parotid gland metastatic tumours are rare, usually arising from a primary mucosal or cutaneous cancer located in the ipsilateral head and neck region, although metastases from a primary cancer outside the head and neck region are possible. Hepatocellular carcinoma (HCC) rarely metastasizes to the head and neck region and the parotid glands are an even more unusual site. The authors describe the case of an 82-year-old male who presented with a right parotid mass. Percutaneous incisional biopsy with histological and immunohistochemical studies suggested metastatic HCC. Radiological investigations excluded other metastatic lesions. This case illustrates the difficulties that may be encountered when seeking a definitive diagnosis of parotid gland masses and underlines the need for collaboration between clinicians and pathologists when diagnosing a parotid enlargement.

Platelet gel is used to facilitate wound healing in virtue of the growth factors released from activated platelets at the site of lesion, but little is known about the specific mechanisms underlying cellular repair.To evaluate, in vitro, cellular effects of different concentrations of platelet gel -released supernatant on endothelial cells.Platelet concentrate was produced at the Service of Immunohaematology and Transfusion of San Salvatore Hospital of L'Aquila, using multiple bags. Platelet gel was obtained by adding thrombin and calcium gluconate to the concentrates and then centrifuging to recover the supernatant. Human umbilical vein endothelial cells were isolated from umbilical cord veins and grown in appropriate conditions. To study their viability, cells were treated with different concentrations of supernatant and XTT assays were performed on the 3 days following treatment. Endothelial cell motility and invasiveness were assayed using modified Boyden chambers with filters coated with 0.1% gelatin (for the motility test) or with a thick layer of the reconstituted basement membrane Matrigel (for the invasion test). The supernatant, added at various concentrations to the lower compartment of the chamber, was used as an attractant. Umbilical cells were added to the upper compartment of the chamber. After 4 hours (for the motility test) or 6 hours (for the invasion test), filters were stained and the migrated cells in five high-power fields were counted.When used at specific concentrations, platelet gel-released supernatant is able to induce proliferation and to stimulate motility and invasiveness of endothelial human cells. Higher concentrations induce a reversion of the stimulatory processes.There is a large body of evidence indicating that platelets and their derivatives have the potential for a substantial therapeutic role in tissue regeneration. The results of this in vitro study highlight the need for an in-depth analysis of technical protocols for the most appropriate and effective use of platelet gel for in vivo applications.

Summary Angiogenesis is a central process in the growth of solid tumors. The purpose of our study was to analyze the angiogenic pattern in squamous and basal cell carcinomas and to point out differences in microvessel density that could explain their different biological behaviour. Thirty-nine skin tumors (26 basal and 13 squamous cell carcinomas) were analyzed. In all samples, the microvessels density (MVD) and the levels of vascular endothelial growth factor mRNA (VEGFmRNA) were analyzed, together with the inter-relationship between these two variables. Using the median value of the entire series (33 vessels per 2.22 mm2), tumors with low and high MVD were identified. The majority of cancers with high vascularization belonged to the squamous histotype (12 of 39), while 19 of the 26 basal cell carcinomas showed a lower number of microvessels than the median value (p = 0.0001). The median value of VEGFcDNA quantitation allowed us to distinguish tumors with high VEGF expression (>470 molecules cDNA) from those with low (≦470 molecules) VEGF expression: 20 of the 26 basal cell carcinomas showed low VEGF expression, while 11 of the 13 squamous cell carcinomas showed high VEGFcDNA levels (p = 0.0003). Moreover, a significant association between a high microvessel density and high VEGFmRNA levels (p = 0.006) was found. Furthermore, when studying VEGF expression by immunohistochemistry, we obtained similar results and noted a correlation with VEGFmRNA expression (p The association between high vascularization, high VEGF levels, and squamous cell histotype suggests the possible role of neoangiogenesis in determining the more aggressive biological behaviour of this type ofcancer.

The Goseki grading system, based on intracellular mucin content and tubular differentiation, was originally created to study the influence of histologic type on the mode of extension of gastric carcinoma. The prognostic value of this grading system was subsequently proposed and even recently supported, but controversies still remain about this topic. We applied the Goseki system on 114 cases of node-negative primary gastric cancer and compared Goseki groups with the other clinicopathologic features of the patients. Statistical analysis showed a significant correlation between Goseki grading and Laurèn classification, but failed to reveal any prognostic significance for this grading system. We believe that Goseki classification should not be routinely used for prognostic purposes.

Res_por:Nos ultimos anos efetuamos um estudo sistematico dos restos humanos da regiao de Abruzzo (Italia) de modo a criar um mapa do material paleopatologico. Esta e uma regiao de montanhas e terras altas com condicoes climaticas e ambientais favoraveis a mumificacao natural. Investigamos os vestigios mumificados e esqueleticos de oito series, algumas das quais apresentadas pela primeira vez na literatura paleopatologica, compreendendo um periodo que vai desde o primeiro milenio a.C. ate ao seculo XIX. Estas series, em conjunto com outras que planeamos estudar futuramente, confirmam o grande interesse paleopatologico da nossa regiao.

The recent introduction of digital film scanners in the medical-scientific field provided everyone dealing with light-microscopy an easy method to obtain low-power photomicrographs from entire histological sections. Direct scanning of the common microscope slide allows the easy creation of high quality images. The digital images obtained may be improved or retouched using dedicated software and then printed on paper or film. The required instrumentation is relatively unexpensive and neither skilled staff nor expertise of photographic techniques is required. This reduces costs and saves time. The obtained images may be employed in histopathology, embryology, histochemistry, image analysis and telepathology, and are suitable for scientific papers, educational purposes and lecturing, as well as for daily reporting. The authors bring their personal experience in this field, making also a complete literature review on the topic.

Granular cell tumor (GCT) is a relatively rare neoplasm, and almost always benign in its prognostic behavior. Location of this tumor in the breast presents serious problems for differential diagnosis, both from a clinical point of view and at gross pathological examination, because of its resemblance to carcinoma. Fine needle aspiration biopsy and intraoperative frozen section examination may not be of any further help. The histogenesis of these lesions has been widely debated in the past, but no universally accepted conclusion has been reached. Most GCTs appear to be derived from Schwann cells, but many different neoplastic and non-neoplastic lesions show granular cell changes. Therefore, GCT should not be considered as a single entity but as the result of a cytoplasmic change due to still unknown metabolic alterations that may occur in various cell types. No firm conclusions can be drawn regarding the suspected hormonal influence on the development of breast GCT. The authors describe three typical cases of breast GCT that occurred in patients of different ages, and discuss the most important questions concerning this lesion.

We examined 705 surgical specimens of total and subtotal gastrectomy for gastric cancer, from the Surgical Pathology Department of L'Aquila, Atri and Avezzano, during the period from January 1972 to December 1991. For each case at least 15 samplings were taken, from the tumor itself and from the mucosa which appeared macroscopically normal. The cases were then classified according to the criteria proposed by Lauren and by Ming and the staging of the disease using the UICC's pTNM. Applying Ming's classification, it was evident a clear prevalence of the infiltrative (78.6%), rather than the expansive type (21.4%). Lauren's classification showed a slight prevalence of the diffuse type (56.5%), compared with the intestinal type. Intestinal metaplasia, chronic atrophic gastritis and dysplasia were found more frequently in the intestinal and expansive histotypes. These are the forms having a better prognosis and which in our results represent a minority of cases, therefore identifying the geographic area as a low risk area. With regards to the pTNM staging, T3's resulted the most numerous; T1's, or early gastric cancers (EGC), represented instead 15.7% of the total. Such a percentage is rather high in comparison with the mean percentage in western countries with low risk of disease. In reference to the macroscopic variants, a clear prevalence of the ulcerated forms (66.5%) was noted, in contrast with Ming and other Authors, that declare a slight prevalence of the fungating type. Also considering the histotypes there is a certain discrepancy between the data of Ming and ours; in fact, in our study the infiltrative type prevails, representing 78.6% against 33.6% found by Ming. Such a result can be usefully correlated to the high percentage of the ulcerated forms observed in our study and to the relative scarcity of fungating forms; these variants themselves, according to Ming, are usually related to the expansive type of gastric carcinoma. We also noted, in EGC, a remarkable age difference in regards to the diffuse type; the mean age of the 57 patients with this type classified as T1 was 52.2 years against the 63.0 years of the 341 patients with T1. The patients with T1 diffuse type carcinoma were not only 10.8 years younger than the patients with advanced gastric cancer of corresponding histotype, but were also 10 years younger than patients with EGC of intestinal type. Such data could support the hypothesis that EGC, diffuse type, has a peculiar biologic behavior.

The authors carried out a p53 genetic research on native DNA in 15 oral-maxillofacial squamous cell carcinomas, lymph nodes metastasis, treated with neoadjuvant chemotherapy, checking the p53 "status" and the clinical response to the chemotherapeutic treatment (three 5-FU/CDDP cycles).The authors found p53 mutations in 3/15 cases. In these cases, at post-chemo restaging, it resulted 2 progressions and 1 stability of disease. In the 12 cases with wildtype p53: 4 objective improvements and partial responses (PR), respectively, of 55% (1), 60% (1), 65% (1), 70% (1), 75% (2) and 90% (2). The 15 patients were treated then by surgery and adjuvant chemotherapy (three C-F cycles). These results seem to confirm the outcome of the researches "in vitro" and they provide first correlations between p53 mutations and chemoresistance in oral squamous cell carcinomas. The survival evaluation also, in the examined cases, shows, but with medium-term follow-up, the tendency to a poor prognosis when p53 is altered.This research outlines the possibility, also for oral and maxillofacial tumors, to utilize, p53 as a prognostic and chemoresponse marker, useful, with the otherwise well-known prognostic factors, for the evaluation of advanced cancers, in the interests of a more suitable therapeutic protocol.

Analyses of biochemical and microbiological parameters such as pH, N-nitroso compound (NOC) concentration, carcinoembryonic antigen (CEA) level, and total viable counts (TVCs), and identification of microorganisms were carried out on 65 fasting gastric juice samples obtained at endoscopy from 45 patients previously submitted to partial gastrectomy for benign peptic ulcer disease (23 Billroth I, 22 Billroth II/Reichel-Polya) and 20 normal controls. Biopsy specimens were taken to determine histology, the Helicobacter pylori status, and both tissue CEA immunoreactivity and level. Significantly higher mean pH values, NOC and CEA concentrations, and TVCs were found in partial gastrectomies compared with normal controls. In relation to surgical methods, higher mean pH values, NOC concentrations, TVCs, and anaerobic bacterial counts were observed in the juice of patients with Billroth II compared with Billroth I gastrectomies. Mild CEA immunoreactivity and apical CEA localization were found significantly more often in Billroth II than in Billroth I stumps. Intensive CEA immunoreactivity and cytoplasmatic localization were found significantly more often in Billroth I than in Billroth II stumps. Independent of the type of surgical reconstruction, higher mean NOC levels were recorded in patients with more severe histological changes and H. pylori infection. Higher mean CEA levels in gastric juice and tissue were detected in the gastric stumps with more severe histological changes. All these data suggest that high levels of NOCs in the gastric juice could be a cofactor in gastric stump carcinogenesis and determination of CEA level in gastric juice and tissue could be included as a very useful marker in quantifying this process.

Ectopic adrenal tissue is a not uncommon clinical finding, especially in children. These aberrant rests have been reported in various locations, such as kidney, testis and related structures, female genital tract and supradiaphragmatic region. The most common site in the male genital district is the spermatic cord. We report a case of ectopic adrenal in the spermatic cord, occasionally found in an asymptomatic 42-years-old man. No other pathologic condition of urogenital tract was present. The nodule measured 0.5 cm in diameter and was histologically arranged in three well defined layers, with predominance of the zona fasciculata. No adrenal medullary tissue was observed. The pathogenesis of this ectopic tissue near the testis can be explained by the embryologic relationship between adrenal cortex and the gonad. Finally, we reviewed the relevant literature and the main clinical implications of this condition.

A case of adenosarcoma of the uterus in a 59-year-old woman is here reported. Adenosarcoma is a low malignant potential tumor with a benign glandular and a malignant stromal component. The treatment is usually hysterectomy with bilateral salpingo-oophorectomy. Debated is the usefulness of adjuvant chemotherapy, while radiation treatment is not beneficial. Long term follow-up is necessary for these patients because of high recurrence risk, mostly in cases with myometrial invasion.