Assessment of apoptotic index in various grades of oral epithelial dysplasia: A cross-sectional study.

CONTEXT: : Oral cancer is a major health problem worldwide. In cancer, the equilibrium between cell proliferation and apoptosis is disturbed. The defect in the apoptotic pathway allows cells to proliferate with genetic abnormalities. Thus, the apoptotic index (AI) can be used to assess the significance of apoptosis as a proliferative marker in oral epithelial dysplasia. AIMS: To assess the apoptotic index in various grades of epithelial dysplasia. OBJECTIVES: 1) To calculate the apoptotic index in various grades of oral epithelial dysplasia, 2) To compare the apoptotic index between various grades of oral epithelial dysplasia, 3) To predict the biologic behavior of oral epithelial dysplasia based on an apoptotic index. SETTINGS AND DESIGN: Cross-sectional tissue analyzing study. METHODS AND MATERIALS: This study constituted 30 cases, previously diagnosed with various grades of oral epithelial dysplasia (OED). AI was calculated as the number of apoptotic bodies/cells expressed as a percentage of the total number of cells counted in each case. STATISTICAL ANALYSIS USED: Statistical analysis was carried out using ANOVA test. RESULTS: A statistically significant difference was observed between mild dysplasia and severe dysplasia where P = 0.002. The mean AI was increased progressively with increasing grades of OED. CONCLUSIONS: This study demonstrated the clinical significance of apoptosis in assessing disease progression in Oral Potentially Malignant Disorder (OPMD) which may be used as a prognostic indicator in OED. This would, in turn, help in knowing the prognosis of the disease and to develop targeted drug therapy.

Successful management of diffuse bilateral pseudoangiomatous stromal hyperplasia of the mammary glands by reductive mammoplasty.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast condition commonly presented as an incidental microscopic finding. However, it can also manifest as a mass-forming lesion (tumorous PASH) or as gigantomastia (diffuse PASH). Most of the previously reported cases are unilateral tumorous PASH treated by mastectomy. In this article, we reported a rare case of diffuse bilateral PASH. A 21-year-old woman presented with a two-year history of bilateral breast enlargement and neck pain. Physical examination revealed asymmetrical bilateral macromastia with profound ptosis. Breast ultrasound demonstrated no cysts or masses in both breasts. The decision was made to perform an inverted T bilateral reductive mammoplasty which was performed successfully through a superior-central pedicle approach. Microscopic examination of the specimens confirmed the diagnosis of PASH without any evidence for malignancy. Nine months postoperatively, the size for both breasts was optimal the patient was satisfied. Recognition and reporting of this rare form of PASH is essential for proper investigation, pathology understanding, risk factors recognition, prognosis assessment and treatment methods selection.

Congruence Between 1994 WHO Classification of Endometrial Hyperplasia and Endometrial Intraepithelial Neoplasia System.

OBJECTIVES: To assess congruence between World Health Organization (WHO) 1994 and endometrial intraepithelial neoplasia (EIN) classification systems of endometrial hyperplasia. METHODS: Systematic review and meta-analysis were performed by searching electronic databases for studies that classified endometrial hyperplasia according to both WHO 1994 and EIN systems. Congruence was based on the rate of specimens classified as EIN in WHO categories, which should be virtually 0.000 in nonatypical hyperplasia (NAH) and 1.000 in atypical hyperplasia (AH). Subgroup analyses were performed based on architecture complexity. RESULTS: Eight studies with 1,352 hyperplasias were included. Congruence with EIN criteria was fair in NAH (0.241) and moderate in AH (0.815). Subgroup analyses of NAH showed high congruence in simple NAH (0.065), null in complex NAH (0.517), null in simple AH (0.148), and high in complex AH (0.901). CONCLUSIONS: WHO 1994 system is not congruent with the EIN system and cannot be directly translated into a dual classification.

Clinicopathologic study of 60 cases of urothelial neoplasms with inverted growth patterns: Reclassification by international consultation on urologic disease (ICUD) recommendations.

BACKGROUND: Most urothelial neoplasms of the bladder show an exophytic papillary pattern, but some show an inverted growth pattern. In 2004, the World Health Organization (WHO) released a detailed histologic classification system for papillary urothelial neoplasms, but not for inverted forms. The International Consultation on Urologic Disease (ICUD) recommendations of 2012 are applicable to inverted/endophytic papillary lesions as follows: 1) inverted papilloma (IP), 2) inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP), 3) inverted papillary urothelial carcinoma, low grade, non-invasive (IPUCLG-NI), 4) inverted papillary urothelial carcinoma, high grade, non-invasive (IPUCHG-NI), 5) inverted papillary urothelial carcinoma, high grade, invasive (IPUCHG-I). However, only atypical cellular morphology was considered for classification in the 2012 ICUD recommendations, and data to support to validate this new grading system are lacking. METHODS: Sixty cases of inverted urothelial papillary tumors were classified into 5 categories according to 2012 ICUD and 2016 WHO/ISUP recommendations to evaluate their clinical, pathological, and immunohistochemical characteristics. Two subgroups were defined as subgroup 1, IP and IPUNLMP, and subgroup 2, IPUCLG-NI, IPUCHG-NI, and IPUCHG-I. Clinical features (age, sex, history of urothelial carcinoma, smoking history, size, and multifocality) and histologic features (nuclear pleomorphism, mitotic count, mitosis level, apoptosis, luminal necrosis, trabecular thickening, anastomosing trabeculae, hypercellularity, loss of polarity, peripheral palisading, palisading with central streaming, and discohesiveness) were evaluated. Immunohistochemical stains for CK20, CD44, P53, p16, Ki-67, cyclin D1 and c-erbB2 were performed. RESULTS: A total of 60 cases were classified as 10 cases of IP, 29 cases of IPUNLMPs, 15 cases of IPUCLG-NI, 4 cases of IPUCHG-NI, and 2 cases of IPUCHG-I. Compared to subgroup 1, subgroup 2 showed larger tumor size, more nuclear irregularity, higher mitotic count (hot spot and per 10 high power fields), more upper level mitosis (>1/2), and more frequent apoptosis, luminal necrosis, surface papillary component, trabecular thickening, anastomosing irregular trabeculae, hypercellularity, loss of polarity, peripheral palisading with central streaming, and discohesiveness, and absence of umbrella cells and urothelial eddies. CK20, Ki67, and c-erbB2 were the only markers that were differently expressed in the two subgroups, with more expression in subgroup 2. CONCLUSIONS: The 2012 ICUD recommendations are valid to classify inverted papillary urothelial tumors. However, other histologic features besides atypical cellular morphology should also be considered to distinguish subgroup 1 and subgroup 2 inverted papillary urothelial tumors.

Incidence of reactive hyperplastic lesions in the oral cavity: a 10 year retrospective study in Santa Catarina, Brazil / Incidência de lesões hiperplásicas reativas na cavidade bucal: estudo retrospectivo de 10 anos em Santa Catarina, Brasil

Abstract Introduction Reactive hyperplastic lesions develop in response to a chronic injury simulating an exuberant tissue repair response. They represent some of the most common oral lesions including inflammatory fibrous hyperplasia, oral pyogenic granuloma, giant cell fibroma, peripheral ossifying fibroma, and peripheral giant cell lesions. Objective The incidence of those lesions was investigated in an oral pathology service, and the clinical characteristics, associated etiological factors, concordance between the clinical and histopathological diagnostic was determined. Methods A total of 2400 patient records were screened from 2006 to 2016. Clinical features were recorded from biopsy reports and patients' files. Results A total of 534 cases of reactive hyperplastic lesions were retrieved and retrospectively studied, representing 22.25% of all diagnoses. The most frequent lesion was inflammatory fibrous hyperplasia (72.09%), followed by oral pyogenic granuloma (11.79%), giant cell fibroma (7.30%), peripheral ossifying fibroma (5.24%), and peripheral giant cell lesions (3.55%). Females were predominantly affected (74.19%), the gingiva and alveolar ridge were the predominant anatomical site (32.89%), and chronic traumatism was presented as the main etiological factor. The age widely ranges from the 1st decade of life to the 7th. Clinically, the reactive hyperplastic lesions consisted of small lesions (0.5-2 cm) and shared a strong likeness in color to the oral mucosa. The concordance between the clinical and histopathological diagnostic was high (82.5%). Conclusion Reactive hyperplastic lesions had a high incidence among oral pathologies. The understanding of their clinical features helps to achieve a clearer clinical and etiological diagnosis, and the knowledge of factors related to their development. This may contribute to adequate treatment and positive prognosis.

Resumo Introdução As lesões hiperplásicas reativas se desenvolvem em resposta a uma lesão crônica que estimula uma resposta acentuada de reparo tecidual. Elas representam uma das lesões orais mais comuns, inclusive hiperplasia fibrosa inflamatória, granuloma piogênico oral, fibroma de células gigantes, fibroma periférico ossificante e lesão periférica de células gigantes. Objetivo A incidência dessas lesões foi investigada em um serviço de patologia bucal e as características clínicas, os fatores etiológicos associados e a concordância entre os diagnósticos clínico e histopatológico foram determinados. Método Foram selecionados 2.400 registros de pacientes entre 2006 e 2016. As características clínicas foram registradas a partir de laudos de biópsia e dos prontuários dos pacientes. Resultados Um total de 534 casos de lesões hiperplásicas reativas foram recuperados e retrospectivamente estudados, representando 22,25% de todos os diagnósticos. A lesão mais frequente foi hiperplasia fibrosa inflamatória (72,09%), seguida por granuloma piogênico oral (11,79%), fibroma de células gigantes, (7,30%), fibroma periférico ossificante (5,24%) e lesão periférica de células gigantes (3,55%). O sexo feminino foi predominante (74,19%), a gengiva e a crista alveolar foram o local anatômico predominante (32,89%) e o traumatismo crônico foi demonstrado como o principal fator etiológico. A idade variou desde a 1ª década de vida até a 7ª. Clinicamente, as LHR consistiram em pequenas lesões (0,5 a 2 cm) que apresentaram uma forte semelhança de cor com a mucosa oral. A concordância entre o diagnóstico clínico e histopatológico foi alta (82,5%). Conclusão As lesões hiperplásicas reativas apresentaram alta incidência entre as patologias bucais. A compreensão das características clínicas ajuda na realização de um diagnóstico clínico e etiológico mais claro, bem como determinar os fatores relacionados ao seu desenvolvimento. Dessa forma contribui para um tratamento adequado e um prognóstico positivo.

Weak Cytotoxic T Cells Activation Predicts Low-Grade Dysplasia Persistence in Ulcerative Colitis.

INTRODUCTION: In patients with ulcerative colitis (UC), dysplasia develops in 10%-20% of cases. The persistence of low-grade dysplasia (LGD) in UC in 2 consecutive observations is still an indication for restorative proctocolectomy. Our hypothesis is that in the case of weak cytotoxic activation, dysplasia persists. We aimed to identify possible immunological markers of LGD presence and persistence. METHODS: We prospectively enrolled 112 UC patients who underwent screening colonoscopy (T0) who had biopsies taken from their sigmoid colon. Ninety of them had at least a second colonoscopy (T1) with biopsies taken in the sigmoid colon and 8 patients had dysplasia in both examinations suggesting a persistence of LGD in their colon. Immunohistochemistry and real time polymerase chain reaction for CD4, CD69, CD107, and CD8ß messenger RNA (mRNA) expression and flow cytometry for epithelial cells expressing CD80 or HLA avidin-biotin complex were performed. Non-parametric statistics, receiver operating characteristic curves analysis, and logistic multiple regression analysis were used. RESULTS: Thirteen patients had LGD diagnosed at T0. The mucosal mRNA expression of CD4, CD69, and CD8ß was significantly lower than in patients without dysplasia (P = 0.033, P = 0.046 and P = 0.007, respectively). A second colonoscopy was performed in 90 patients after a median follow-up of 17 (12-25) months and 14 of the patients were diagnosed with LGD. In these patients, CD8ß mRNA expression at T0 was significantly lower in patients without dysplasia (P = 0.004). A multivariate survival analysis in a model including CD8ß mRNA levels and age >50 demonstrated that both items were independent predictors of dysplasia at follow-up (hazard ratio [HR] = 0.47 [95% confidence interval [CI]: 0.26-0.86], P = 0.014, and HR = 13.32 [95% CI: 1.72-102.92], P = 0.013). DISCUSSION: These data suggest a low cytotoxic T cell activation in the colonic mucosa of UC patients who do not manage to clear dysplasia. Thus, low level of CD8ß mRNA expression in non-dysplastic colonic mucosa might be considered in future studies about the decision making of management of LGD in UC.

Pattern of distribution of reactive localised hyperplasia of the oral cavity in patients at a tertiary health institution in Nigeria.

BACKGROUND: Reactive localized hyperplastic lesions of the oral cavity (RHLs) are relatively common peripheral lesions which present as a range of clinically similar lesions at dental centers. Diagnosis can be challenging if dentists are unfamiliar with their clinicopathological across various populations. OBJECTIVE: This study reviews the pattern of distribution of RHLs of the oral mucosa in a hospital- the Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Ile-Ife. MATERIALS AND METHODS: We reviewed 10 years data from the archives of the Department of Oral Maxillofacial Surgery and Oral Pathology, Obafemi Awolowo University, Nigeria. Information on RHLs were extracted and recorded on standardized data forms and analyzed using STATA. RESULTS: The most common lesions were pyogenic granuloma (43.7%) and focal fibrous hyperplasia (39.7%), respectively. RHLs were found to be more frequent in women (66.7%) than men (33.3%). The most common locations of involvement was the gingivae (84.6%), and lesions were more common in the 9-29 year age group and the mean age was 37.7 (±21.1) years. The relationship between age group and reactive lesions was however not statistically significant. CONCLUSION: The major benefit of this study is an improved knowledge of the frequency and distribution of oral reactive lesions in sub-Saharan Africa which may be highly beneficial when establishing a diagnosis and treatment plan in clinical practice.

Evaluation of lymph node ratio and morphologic patterns of nodal reactive hyperplasia in primary organ malignancy.

BACKGROUND: Lymph node ratio (LNR) in cancer staging is the ratio of nodal metastases (LNM) to total nodes harvested (LNH). Reactive nodal hyperplasia can exhibit morphological patterns I to VI. AIMS: To measure LNR and evaluate it with tumor stage, tumor grade, LN reactive patterns, and LN size. SETTING AND DESIGN: Retrospective, observational study of 100 cancer resections including breast, gastrointestinal (GIT), genitourinary (GUT), and head, face, neck, and thyroid (HFNT). MATERIALS AND METHODS: Total 1463 LNs were reviewed for metastases and reactivity patterns I-VI as per the World Health Organization (WHO) protocol. LNR was calculated from LNM and LNH. STATISTICAL ANALYSIS USED: Association between qualitative variables was assessed by the Chi-square test and Fisher's exact test, those between quantitative variables using the unpaired t-test and Mann-Whitney U test. RESULTS: Mean LNH (23.7) was highest in HFNT and lowest (6.6) in GIT (P = 0.008). Mean LNR was highest (0.29) in breast and least (0.06) in HFNT (P = 0.861). Commonest LN reactive patterns were sinus histiocytosis (60), mixed (48), and follicular hyperplasia (46) (P = 0.000). Maximum cases of breast (59.6%), GUT (53.8%), and HFNT (45%) belonged to stage T2, while GIT (60.0%) to stage T3 (P = 0.000). Maximum well-differentiated cases belonged to HFNT (13, 59.0%), while moderately poorly differentiated cases of breast (38, 55.8% and 7, 70.0%) (P = 0.000). The largest and smallest metastatic LN was 2.4 cm and 0.4 cm (P = 0.009). LNs with thickened capsule showed nodal metastases in 75.7% (P = 0.003871). CONCLUSIONS: LNH and LNR cut-off values show organ-wise variation and need standardization. LNR shows stronger relation with tumor grade than tumor stage. Commonest LN reactive patterns include sinus histiocytosis and follicular hyperplasia. Thickened LN capsule strongly suggests nodal metastases. A longitudinal follow-up is warranted to study prognostic association between LNR and LN reactive pattern.

Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination: Diagnostic efficacy, prevalence, and factors predicting for Bethesda category I results. / Punción-aspiración con aguja fina ecoguiada de nódulos tiroideos con valoración citológica in situ: eficacia diagnóstica, prevalencia y factores predictores de los resultados de categoría Bethesda I.

BACKGROUND AND OBJECTIVE: Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination may decrease the number of Bethesda categoryI cytologies. The study objective was to evaluate our second-year experience with this procedure to analyze diagnostic efficacy, prevalence, and factors predicting for Bethesda categoryI results. PATIENTS AND METHOD: A retrospective study was conducted of 279 nodules from 233 patients. Ultrasound -guided fine needle aspiration was performed according to the 2015 criteria of the American Thyroid Association. A specimen of each aspiration was air-fixed on site before Diff-Quik staining and microscopic examination to assess its suitability; otherwise, nodule aspiration was repeated up to 5times. Diagnostic efficacy was assessed based on sensitivity and specificity on the cytological categories BethesdaII and BethesdaVI. RESULTS: Diagnostic sensitivity and specificity were both 100%, 5.4% Bethesda categoryI results were obtained, and variables independently associated were age (4.7% increase per year of life) and nodule volume (2.3% increase per each 1mL of volume). CONCLUSIONS: Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination allows for a high diagnostic efficacy and has been shown to be a highly relevant procedure because it has a very low rate of cytological results of Bethesda categoryI, whose risk has been higher in older subjects and with larger nodules.

Incidence of reactive hyperplastic lesions in the oral cavity: a 10 year retrospective study in Santa Catarina, Brazil.

INTRODUCTION: Reactive hyperplastic lesions develop in response to a chronic injury simulating an exuberant tissue repair response. They represent some of the most common oral lesions including inflammatory fibrous hyperplasia, oral pyogenic granuloma, giant cell fibroma, peripheral ossifying fibroma, and peripheral giant cell lesions. OBJECTIVE: The incidence of those lesions was investigated in an oral pathology service, and the clinical characteristics, associated etiological factors, concordance between the clinical and histopathological diagnostic was determined. METHODS: A total of 2400 patient records were screened from 2006 to 2016. Clinical features were recorded from biopsy reports and patients' files. RESULTS: A total of 534 cases of reactive hyperplastic lesions were retrieved and retrospectively studied, representing 22.25% of all diagnoses. The most frequent lesion was inflammatory fibrous hyperplasia (72.09%), followed by oral pyogenic granuloma (11.79%), giant cell fibroma (7.30%), peripheral ossifying fibroma (5.24%), and peripheral giant cell lesions (3.55%). Females were predominantly affected (74.19%), the gingiva and alveolar ridge were the predominant anatomical site (32.89%), and chronic traumatism was presented as the main etiological factor. The age widely ranges from the 1st decade of life to the 7th. Clinically, the reactive hyperplastic lesions consisted of small lesions (0.5-2cm) and shared a strong likeness in color to the oral mucosa. The concordance between the clinical and histopathological diagnostic was high (82.5%). CONCLUSION: Reactive hyperplastic lesions had a high incidence among oral pathologies. The understanding of their clinical features helps to achieve a clearer clinical and etiological diagnosis, and the knowledge of factors related to their development. This may contribute to adequate treatment and positive prognosis.

Platform-independent gene expression signature differentiates sessile serrated adenomas/polyps and hyperplastic polyps of the colon.

BACKGROUND: Sessile serrated adenomas/polyps are distinguished from hyperplastic colonic polyps subjectively by their endoscopic appearance and histological morphology. However, hyperplastic and sessile serrated polyps can have overlapping morphological features resulting in sessile serrated polyps diagnosed as hyperplastic. While sessile serrated polyps can progress into colon cancer, hyperplastic polyps have virtually no risk for colon cancer. Objective measures, differentiating these types of polyps would improve cancer prevention and treatment outcome. METHODS: RNA-seq training data set and Affimetrix, Illumina testing data sets were obtained from Gene Expression Omnibus (GEO). RNA-seq single-end reads were filtered with FastX toolkit. Read mapping to the human genome, gene abundance estimation, and differential expression analysis were performed with Tophat-Cufflinks pipeline. Background correction, normalization, and probe summarization steps for Affimetrix arrays were performed using the robust multi-array method (RMA). For Illumina arrays, log2-scale expression data was obtained from GEO. Pathway analysis was implemented using Bioconductor package GSAR. To build a platform-independent molecular classifier that accurately differentiates sessile serrated and hyperplastic polyps we developed a new feature selection step. We also developed a simple procedure to classify new samples as either sessile serrated or hyperplastic with a class probability assigned to the decision, estimated using Cantelli's inequality. RESULTS: The classifier trained on RNA-seq data and tested on two independent microarray data sets resulted in zero and three errors. The classifier was further tested using quantitative real-time PCR expression levels of 45 blinded independent formalin-fixed paraffin-embedded specimens and was highly accurate. Pathway analyses have shown that sessile serrated polyps are distinguished from hyperplastic polyps and normal controls by: up-regulation of pathways implicated in proliferation, inflammation, cell-cell adhesion and down-regulation of serine threonine kinase signaling pathway; differential co-expression of pathways regulating cell division, protein trafficking and kinase activities. CONCLUSIONS: Most of the differentially expressed pathways are known as hallmarks of cancer and likely to explain why sessile serrated polyps are more prone to neoplastic transformation than hyperplastic. The new molecular classifier includes 13 genes and may facilitate objective differentiation between two polyps.

Adrenal cortical hyperplasia: diagnostic workup, subtypes, imaging features and mimics.

Adrenal cortical hyperplasia manifests radiologically as a non-malignant growth, or enlargement, of the adrenal glands, specifically the cortex, although the cortex cannot be definitively identified by conventional imaging. Controlled by the pituitary gland, the adrenal cortex drives critical processes, such as the production of cortisol, mineralocorticoid and sex hormones. Any disruption in the multiple enzymes and hormones involved in these pathways may cause serious or life-threatening symptoms, often associated with anatomical changes in the adrenal glands. Diagnosis and treatment of adrenal cortical hyperplasia requires a thorough clinical evaluation. As imaging has become more robust so has its role in the diagnosis and treatment of adrenal conditions. CT has been the primary modality for adrenal imaging owing to reproducibility, temporal and spatial resolution and broad access. MRI serves a complimentary role in adrenal imaging and can be used to further evaluate indeterminate CT findings or serve as an adjunct tool without the use of ionizing radiation. Ultrasound and fluoroscopy (genitography) are most commonly used in children and foetuses to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation, laboratory workup and imaging features of adrenal cortical hyperplasia, both congenital and acquired.

A novel and robust method for testing bimodality and characterizing porcine adipocytes of adipose tissue of 5 purebred lines of pig.

Adipocyte sizes from adipose tissue of mature animals form a bimodal distribution, thus reporting mean cell size is misleading. The objectives of this study were to develop a robust method for testing bimodality of porcine adipocytes, describe the size distribution with an informative metric, and statistically test hypertrophy and appearance of new small adipocytes, possibly resulting from hyperplasia or lipid filling of previously divided fibroblastic cells. Ninety-three percent of adipose samples measured were bimodal (P < 0.0001); therefore, we describe and propose a method of testing hyperplasia or lipid filling of previously divided fibroblastic cells based upon the probability of an adipocyte falling into 2 chosen competing "bins" as adiposity increases. We also conclude that increased adiposity is correlated positively with an adipocyte being found in the minor mode (r = 0.46) and correlated negatively with an adipocyte being found in the major mode (r = -0.22), providing evidence of either hyperplasia or lipid filling of previously divided fibroblastic cells. We additionally conclude that as adiposity increases, the mode of the major distribution of cells occurs at a larger diameter of adipocyte, indicating hypertrophy.

Lingual tonsil: clinically applicable macroscopic anatomical classification system.

OBJECTIVE: To classify the adult lingual tonsil according to the macroscopic appearance. STUDY DESIGN: Prospective study. LEVEL OF EVIDENCE: Four. METHODS: Lingual tonsils were classified according to their appearance and relationship to surrounding structures. This was possible following serial views of lingual tonsils. The classification was named 'Swansea classification for lingual tonsil', representing the place of origin. The classification was then discussed with fellow clinicians. Independent professional observers graded lingual tonsil pictures. Intra-observer agreements were measured to validate the classification. RESULTS: A total of 22 professional observers went through a set of six pictures of three different grades of lingual tonsil. The pictures were then graded for validation. The intra-observer agreement was 0.81, confirming good agreement. CONCLUSION: Swansea classification for lingual tonsil is reliable and reproducible. This classification should be routinely used during ENT examination, enabling accurate documentation and providing opportunities for future research and audit of practice.

Effect of Vandetanib on Lung Tumorigenesis in Transgenic Mice Carrying an Activating Egfr Gene Mutation.

Vandetanib (ZactimaTM) is a novel, orally available inhibitor of both vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinase. In the present study, a line of transgenic mice with a mouse Egfr gene mutation (delE748-A752) corresponding to a human EGFR mutation (delE746-A750) was established. The transgenic mice developed atypical adenomatous hyperplasia to adenocarcinoma of the lung at around 5 weeks of age and died of lung tumors at approximately 17 weeks of age. In the mice treated with vandetanib (6mg/kg/day), these lung tumors disappeared and the phosphorylations of EGFR and VEGFR-2 were reduced in lung tissues to levels comparable to those of non-transgenic control mice. The median overall survival time of the transgenic mice was 28 weeks in the vandetanib-treated group and 17 weeks in the vehicle-treated group. Vandetanib significantly prolonged the survival of the transgenic mice (log-rank test, p＜ 0.01); resistance to vandetanib occurred at 20 weeks of age and the animals died from their lung tumors at about 28 weeks of age. These data suggest that vandetanib could suppress the progression of tumors harboring an activating EGFR mutation.

[Preneoplastic lesions and precursors of urothelial cancer]. / Präneoplastische Läsionen und Vorstufen des Urothelkarzinoms.

As even a mere thickening of the urothelium can harbor genetic changes identical to that of low grade papillary urothelial tumors, it is not always possible to clearly recognize a precursor lesion of urothelial carcinoma by routine histological diagnostics. Complementary immunohistochemical and molecular diagnostic methods assist the recognition of these entities. These methods especially help to identify clinically important genetically unstable cells as the hallmark of carcinoma in situ (CIS). Little is known about the clinical significance of the morphological subtypes of CIS, which range from large cell to micropapillary variants. For a better understanding of special types of bladder cancer (e.g. adenocarcinoma and squamous cell carcinoma), it seems to be important to define the phenotype and the molecular pattern of non-urothelial lesions, such as intestinal metaplasia and squamous metaplasia, better and more precisely.

Interlaboratory variability in the grading of dysplasia in a nationwide cohort of colorectal adenomas.

AIMS: Although high-grade dysplasia (HGD) is a risk factor for malignant transformation and the future development of adenomas/carcinomas, grade is not incorporated in the Dutch guidelines for colonoscopy surveillance, partly because of presumed interobserver variability. The aim of this study was to analyse, in a nationwide cohort of colorectal adenomas, the interlaboratory variability in the grading of dysplasia in daily practice. METHODS AND RESULTS: From the Dutch Pathology Registry, all synoptically reported classic adenomas in The Netherlands in 2013 were identified. The proportion of adenomas with HGD was determined for biopsies and polypectomies, and compared between 37 laboratories by the use of multivariable logistic regression analyses. In total, 21 030 colonoscopies of 20 270 patients were included. HGD was reported in 530 (3.6%) of 14 866 adenomas diagnosed on biopsies (range between laboratories: 0-13.6%) and in 983 (11.8%) of 8346 adenomas diagnosed on polypectomies (range: 3.1-42.9%). After adjustment for case mix, 13 (35%) laboratories reported a significantly lower or higher frequency of HGD than average. CONCLUSIONS: We observed considerable interlaboratory variation in the grading of dysplasia in colorectal adenomas, which could be only partly explained by differences in case mix. Therefore, better standardization of grading criteria is needed before grade of dysplasia can usefully be incorporated in colonoscopy surveillance guidelines.

[Terminology and classification of condylar hyperplasia: Two case reports and review]. / Kondiler hiperplazinin terminolojisi ve siniflandirilmasi: Iki olgu sunumu ve derleme.

Condylar hyperplasia is characterized by the growth of mandibular condyle. Its etiology and pathogenesis remain controversial. It often occurs unilaterally and leads to facial asymmetry and malocclusion. In the literature, it was also classified according to anomalies accompanied by the growth of other components of the mandible. Differential diagnosis of condylar hyperplasia usually includes tumors of temporomandibular joint. In this article, we discuss the term "condylar hyperplasia" and its classification considering two patients with condylar growth.

Comparative study of Western and Japanese criteria for biopsy-based diagnosis of gastric epithelial neoplasia.

BACKGROUND: In Western countries, gastric cancer (GC) is diagnosed when there is histological evidence of invasion into the lamina propria or beyond the submucosa. In Japan and some other countries, however, diagnosis of GC is based on the degree of structural and cytological abnormality of tumor glands. The aim of the present study was to compare the accuracy of the Western and Japanese criteria for diagnosis of GC. METHODS: The study included 233 consecutive patients with a postoperative diagnosis of submucosal invasive GC who underwent gastrectomy or endoscopic submucosal dissection. All pretreatment biopsy specimens were independently reviewed by two experts in gastrointestinal pathology employing both the Western and Japanese diagnostic criteria. Diagnostic agreement between pretreatment biopsy specimens and the corresponding resected specimens was evaluated, together with the interobserver agreement for each of the criteria. RESULTS: On the basis of the Western and Japanese criteria, the pretreatment biopsy diagnosis was noncancerous (including dysplasia) in 44 lesions and 1 lesion, respectively. Diagnostic accuracy based on biopsy was 81.1% for the Western criteria and 99.5% for the Japanese criteria (P < 0.001). Interobserver agreement based on the Western and Japanese criteria was 73.8% and 96.5%, respectively (P < 0.001). Invasion into the submucosa was detected by biopsy in only 25 cases. CONCLUSIONS: The Japanese criteria are significantly more accurate for pretreatment biopsy diagnosis of GC. The Western criteria could lead to underdiagnosis of a lesion as high-grade dysplasia, even if submucosal invasive cancer is present.

[Differential diagnostics of sebaceous tumors]. / Differenzialdiagnostik der Talgdrüsentumoren.

Sebaceous tumors are epithelial tumors with a differentiation towards sebaceous adnexal structures of the skin. They imitate the epithelial cells of mature sebaceous glands, sebaceous ducts, immature (embryonic) sebaceous structures or sebaceous glands that are not stimulated by hormones (mantle structures). This article explains the classification of sebaceous tumors on the basis of the normal histology of sebaceous glands. Clinical and histopathological criteria are given for the most important sebaceous tumors. The differential diagnosis of sebaceoma, sebaceous adenoma and various types of sebaceous carcinoma is emphasized. The importance of a specific diagnosis of adnexal tumors is demonstrated by tumor-associated syndromes with involvement of other organs (e.g., Muir-Torre syndrome and Birt-Hogg-Dubé syndrome). Furthermore, conceptional controversies, problems in differential diagnosis and the impact of immunohistochemical staining in the assessment of sebaceous tumors are considered.