Glandular Atypia Research Articles

False-Positive Atypical Endocervical Cells in Conventional Pap Smears: Cyto-Histological Correlation and Analysis

Introduction: Endocervical glandular atypia is relatively rarely diagnosed by Pap smears. A significant proportion of follow-up histological samples show no premalignant or malignant lesions. The observed cytomorphological findings in premalignant glandular lesions overlap with histologically proven reactive lesions. Methods: A total of 45 conventional Pap smears diagnosed as atypical endocervical cells, not otherwise specified (AEC, NOS) with human papillomavirus (HPV) status available were blindly evaluated in a search for 38 cytomorphological features representing background, architectural, cellular, and nuclear features. Of the cases, 30 represented histologically proven benign changes, and 15 represented histologically proven adenocarcinoma in situ (AIS) or endocervical adenocarcinoma (EAC) cases. The benign biopsies were re-evaluated, and the associations of the cytomorphological features or combinations of them with specific histological features and entities were statistically examined. Results: The most frequent histological findings in the benign group were squamous metaplasia, inflammation, tubal metaplasia, and microglandular hyperplasia. The statistical analysis revealed cytological features associated with squamous metaplastic changes, inflammation, and microglandular hyperplasia. Unfortunately, no cytomorphological feature was sufficiently specific to confidently leave the lesion without follow-up and histological correlation. Degeneration and nuclear crowding were the most salient features that distinguished the instances of glandular atypia with benign follow-up histology from those with histologically proven AIS or EAC (26.7 vs. 60.0%, p = 0.030, and 50.0 vs. 86.7%, p = 0.017). Conclusion: Additional methods besides cytomorphology are required to reliably distinguish smears with AEC, NOS harbouring only benign histological changes from those exhibiting endocervical glandular malignancy.

Diagnostic value of occult haemolacria

To study tears for occult (latent) haemolacria in women and compare the representativeness of the main methods of tear examination. Tear samples from 72 women aged between 18 and 46 years were evaluated using two methods: microscopic and chemical with reagent test strips. In the follicular phase of the menstrual cycle, erythrocytes in tears were detected in 59.1% (13) subjects, which was significantly higher (χ2=4.2, p=0.041) compared to the luteal phase - erythrocytes were detected in 40.9% (9) women. The proportion of women in the luteal phase of the cycle who had single epithelial cells in the tear (76.9%) was significantly lower (χ2=5.2, p=0.022) than in women in the follicular phase (83.9%). The predictive value of the chemical method was 0.53 of that of the microscopic one. Microscopically, blood was detected in 30.6% of tear samples, while chemically - in 16.7%. An associative relationship was found between occult haemolacria in women and a diagnosis of endometriosis (K=0.75, p≤0.05). The proportion of women with erythrocytes in tears determined with the chemical method was 41.7% in patients with endometriosis, which was significantly higher (χ2=6.5, p=0.011) than 11.7% in women without endometriosis. Fluctuations of hormones during the menstrual cycle are reflected in tear composition, manifested as an increase in the number of epithelial cells in the luteal phase, and erythrocytes in the follicular phase. Erythrocytes found in a tear amid accumulations of epithelial cells, their glandular atypia and neutrophilic infiltration in patients with endometriosis may indicate the manifestation of extragenital endometriosis. The microscopic method turned out to be more sensitive in detecting occult haemolacria, and additionally it provided information about other cells. At the same time, the chemical method, which was relatively diagnostically informative, faster and technically simpler, can be used for screening.

Detection and Outcome of Endocervical Atypia in Cytology in Primary HPV Screening Programme

Most endocervical adenocarcinomas (EAC) are associated with high-risk HPV (hrHPV) infection, with HPV genotypes 16, 18 and 45 accounting for >90% of the cases. Among endocervical glandular lesions, screening with hrHPV test has previously shown to predict the outcome better than cytology, although around one-fifth of the EAC remain negative both in hrHPV testing and cytology. The study consists of two consecutive HPV-primary screening rounds, conducted in 2012–2015 and 2017–2020. Of the 87 women aged 35 to 60 years of age diagnosed with Atypical endocervical cells, NOS or Atypical endocervical cells, favor neoplastic cytology during the first screening round, 63 (72.4%) were hrHPV positive and 24 (27.6%) were hrHPV negative. Among hrHPV positive patients, three EAC, two adenocarcinomas in situ (AIS), one AIS + high-grade intraepithelial lesion (HSIL) and 13 HSIL were found. Of the histologically verified lesions, 68.4% (13/19) were purely of squamous origin. All the EAC and AIS were HPV16 or HPV 18 positive. No high-grade histological lesions were found among the hrHPV negative patients with cytological glandular atypia. A later database search revealed one HPV-negative, gastric-type mucinous EAC that was missed by the HPV primary screening.

Sensitivity of cervical cytology in endometrial cancer detection in a tertiary hospital in Spain.

IntroductionCervical cytology is a well‐stablished cervical cancer screening method. However, due to the anatomical continuity of the genital tract, it can also detect signs of endometrial disease. Our aim was to estimate the sensitivity of cervical cytology in endometrial cancer detection and prognosis in a large population over a 30‐year period in a large academic tertiary hospital in Spain.MethodologyWe performed a search for women diagnosed with endometrial cancer from 1990 to 2020, who were surgically treated and had a previous cervical cytology result. Information Technologies Department databases from Bellvitge University Hospital and the Screenwide case–control study's database were used. Cervical cytology results were classified as abnormal when squamous lesions, glandular atypia or malignant cells were identified.ResultsOverall, we evaluated 371 women with endometrial cancer and a documented cervical cytology performed within 3 years previous to surgical treatment. Overall, the sensitivity of cervical cytology for endometrial cancer detection was 25.6%. Several clinico‐pathological characteristics, such as non‐endometrioid histology and a higher stage, were correlated with higher sensitivity.DiscussionWe observed a low sensitivity of cervical cytology to effectively diagnose endometrial cancer. However, recent technological advances using genomics and epigenomics may offer a promising perspective to detect endometrial cancer with high sensitivity in these cervical specimens.

The role of Pap smear in the diagnostics of endocervical adenocarcinoma.

In the high-income countries, the amount of cervical adenocarcinomas is on the rise. The pap smear sampling has a low sensitivity and a low specificity for endocervical malignancies, and there are only a few cytomorphological features, that are specifically associated with glandular atypia. In this study, 298 pap smears of 60 patients with endocervical adenocarcinoma or adenocarcinoma in situ (AIS) and 30 patients with high-grade intraepithelial lesion (HSIL) in histology were reviewed. The pap smear type (screening/clinical), the HPV status and the time from sampling to the histological confirmation of diagnosis were recorded for each case. Despite that no cytomorphological features could be associated with adenocarcinoma statistically, 70% of the pap smears were initially correctly diagnosed as an endocervical glandular lesion. Palisading cell borders, nuclear pleomorphism and the lack of single atypical cells present simultaneously were found to be associated with adenocarcinoma and AIS with the corresponding ORs of 5.89 (95% CI 1.96-17.70), 3.71 (95% CI 1.14-12.02) and 10.76 (95% CI 1.20-59.50). This combination of features was seen in smears taken up to 5years before the histological diagnosis. Of all our screening samples, 10.9% were HPV-positive. There were no HPV-negative samples among patients with adenocarcinoma.

Cellular changes diagnosed by cérvico-vaginal cytology in a public health laboratory of Teresina-PI

<p>Cervical cancer is one of the most common malignant diseases of women, which begins with precursor lesions that can progress to become invasive cancers. However, its development can be prevented by cytology screening and appropriate treatment. This study aimed to verify the frequency of the cellular alterations of the female genital tract in women assisted by a clinical laboratory of Teresina – Piaui, Brazil, in 2016. The data were collected from the cervical cytology reports of 2016. 9040 reports were analyzed, among which 8,095 (89.55%) had negative oncology and 945 (10.45%) were positive. It was identified 1.97% of squamous cells of indeterminate significance, with 5.84%, low-grade intraepithelial lesions (LSIL), 1.33% of high-grade intraepithelial lesions, 1.25% of glandular cell atypia (ACG) and 0.06% of invasive squamous cell carcinoma. Regarding the level of schooling, women who did not complete elementary school corresponded to the higher percentage to attend to cytopathological exams. It is concluded that the incidence of atypia was considerably higher than described in the literature. Thus, it is recommended the adoption of strategies of health promotion designed to improve the cytopathological care.</p>

SUN-475 Thyroid Extranodal Diffuse Large B-Cell Lymphoma in Setting of Gastric Large B-Cell Lymphoma

Background: We report a case of concomitant thyroid and gastric diffuse large B-cell lymphoma (DLBCL). Clinical Case: A 73 year-old man presented with melena of 2 days duration. EGD revealed a 1.5 x 0.7 cm gastric ulcer. Biopsy revealed marked chronic active gastritis with glandular atypia, positive for H. pylori. Repeat biopsy of the same ulcer post H. pylori treatment demonstrated high-grade B-cell lymphoma. Immunostains were positive for CD20, CD10, BCL6, cyclin D and negative for CD 23 and CD 30. More than 95% of tumor cells expressed Ki-67, while 10% expressed MUM-1 and BCL2. Benign T cells stained positive for CD3 and CD5. FISH was negative for gene rearrangement involving BCL-6/BCL-2 and C-MYC. Staging PET/CT showed hypermetabolic regions involving the stomach wall, large left neck mass and right lung focus. The neck focus had a max SUV 48.5 (8 fold greater than the other sites), that localized to a soft tissue mass measuring 4.9 x 2.7 cm. FNA of the left-sided thyroid mass showed diffuse large B-cell lymphoma with immunostain positive for CD20 and negative for cytokeratin AE1-3, PAX8, and CD 10. The morphology was similar to that of abnormal lymphoid cells in the gastric biopsy. Patient had normal thyroid function tests but positive autoimmune thyroid disease markers (TPO and anti-TG antibody). Treatment with R-CHOP resulted in shrinkage of neck mass. Conclusion: Hypermetabolic regions revealed by PET/CT at distant sites from primary tumor require further evaluation including biopsy as indicated. Clinical correlation and response to chemotherapy can provide supplemental information in the overall assessment of the disease process.

Profile of women with cervical changes from a city in the Northeast Brazil

ABSTRACT Introduction: In Brazil, cervical cancer is the fourth leading cause of cancer death. It reached 5,430 deaths in the year 2013, with estimated 16,370 new cases by 2018. Its occurrence has been associated with previous human papillomavirus (HPV) infection for the development of intraepithelial lesions; however, several factors can influence this appearance, including number of sexual partners and infections by other microorganisms. Objective: The profile of women from the city of Caruaru, Pernambuco, Brazil, with atypia, cervical intraepithelial lesions and cancer, was verified. Material and method: Documentary, analytical, retrospective study, carried out through the collection of information in the database of the State Department of Health of Pernambuco, by TabNet, referring to the tests in the laboratory of the municipality of Caruaru, Pernambuco, Brazil. Results: During the study period, 18,466 tests were evaluated. From the samples evaluated, 735 (4.31%) were squamous and glandular atypia, 167 (0.98%) intraepithelial lesions, and one (0.005%) cancer. Coccus, Gardnerella vaginalis and Lactobacilli were the most evident agents in cervical alterations. Discussion: Studies demonstrate the intimate relationship between infectious agents and the development of cervical lesions and cancers. Gardnerella vaginalis was the most frequent agent in the presence of abnormalities was identified as a facilitator of HPV penetration. Conclusion: Women infected by Gardnerella vaginalis and older than 30 years of age are more exposed to the development of alterations. Guidelines on prevention and screening should be continuous strategies in public services. Understanding these risk factors is a paramount concern because they are involved in the prevention and etiology process of cervical lesions and cancer.

Endoscopic and clinicopathological features of intramucosal, histologically mixed-type, low-grade, well-differentiated gastric tubular adenocarcinoma with the potential for late-onset lymph node metastasis

BackgroundIntramucosal, histologically mixed-type, low-grade (LG), well-differentiated gastric tubular adenocarcinomas (tub1s; LG-tub1s) have larger mean diameters and exhibit a higher frequency of the gastric mucin phenotype (G-phenotype) than pure LG-tub1s. In proportion to their increases in diameter, G-phenotype differentiated-type early gastric cancer (EGC) tumours reportedly grow to eventually contain (an) undifferentiated-type component(s) and LG-tub1s, which are included in differentiated-type EGCs, reportedly exhibit changes in their glandular architectural and cytological atypia grades from LG to high-grade (HG) and can grow to contain a moderately differentiated tubular adenocarcinoma (tub2) component and undifferentiated components. Because they generally show a higher frequency of malignancy relative to tumours with a higher atypia grade and lower differentiation degree, it is suggested that, among mixed-type LG-tub1s, G-phenotype LG-tub1s containing an HG-tub2 component (LG-tub1s > HG-tub2) with undifferentiated components might lead to late-onset metastasis to lymph nodes even after a successful endoscopic submucosal dissection (ESD). We aimed to clarify the endoscopic and clinicopathological features of these G-phenotype LG-tub1s > HG-tub2.MethodsOf the 13,217 oesophagogastroduodenoscopies performed at our institutions between September 2008 and March 2016, 185 EGC lesions were evaluated in this retrospective observational study. Among these EGC lesions, 60 intramucosal LG-tub1s were divided into 53 tub1 (44 pure LG-tub1s and nine LG-tub1s containing HG-tub1) lesions and seven LG-tub1 > tub2 (LG-tub1 containing LG- and HG-tub2) lesions.ResultsThe frequencies of the superficial depressed type (P = 0.026), reddish colour (P = 0.006), HG of contained tub2s (P = 0.006), and G-phenotype (P = 0.028) were significantly higher in the LG-tub1 > tub2 group than those in the tub1 group. However, the largest lesion of the LG-tub1 > tub2 group had a superficial flat appearance, an isochromatic colour, an HG-tub2 and an undifferentiated component, and a large diameter greater than 30 mm, and it exhibited a G-phenotype.ConclusionsIntramucosal G-phenotype LG-tub1s > HG-tub2 are potential premalignant stomach neoplasms that may have specific endoscopic and clinicopathological features. However, G-phenotype LG-tub1s > HG-tub2 with undifferentiated component, which potentially show higher malignancy than those without undifferentiated components might change from a reddish to isochromatic colour. Accurately diagnosing, treating, and following-up G-phenotype LG-tub1s > HG-tub2 might decrease the number of patients who experience late-onset metastasis after ESD.

Barrettʼs Esophagus Lesion Identification With Volumetric Laser Endomicroscopy: Interobserver Agreement Between Expert and Novice Users

Introduction: Volumetric Laser Endomicroscopy (VLE) is used to detect Barrett's esophagus (BE) dysplasia. VLE features of glandular atypia, increased surface signal intensity, and lack of layering are associated with BE dysplasia. Experienced VLE users show high interobserver agreement in identifying a region of interest (ROI) containing these features. The accuracy of novice users in dysplastic ROI identification is unknown. The study aim was to determine the interobserver agreement between novice and experienced VLE users for dysplastic ROI identification. Methods: 18 VLE scans (12 high-grade dysplasia; 6 intramucosal adenocarcinoma) from a US based multicenter registry were selected. To optimize interpretation, scans were divided into videos corresponding to 1 cm of circumferential BE, representing ˜200 cross-sectional images. Each video was divided into four quadrants. For each quadrant, reviewers were asked to select the timeframe with the most representative features of dysplasia. If a quadrant contained no features of dysplasia, reviewers were asked to rate it as non-dysplastic BE. Expert VLE raters had experience reviewing >50 VLE scans. Novice VLE raters were endoscopists with no VLE experience who were presented a 20 minute tutorial of images/videos on VLE features of BE dysplasia. High agreement among VLE reviewers in each group (experts vs. novice) was defined by ≥75% agreement on the quadrant diagnosis (dysplastic vs. non-dysplastic) and ≥50% agreement on timeframe (±5 sec). Results: A total of 31 videos (124 quadrants) were reviewed by 4 expert and 4 novice VLE users. There was high agreement among expert users in 95 (77%) quadrants of which 61 (64%) quadrants were rated as dysplastic. There was high agreement among novice users in 88 (71%) quadrants of which 60 (68%) quadrants were rated as dysplastic. Expert and novice users agreed on the diagnosis of dysplasia in 44 (56%) of 78 quadrants. 17 (22%) quadrants were rated by experts as dysplastic and by novice users as non-dysplastic. 17 (22%) quadrants were rated by novice users as dysplastic and experts as non-dysplastic. There was no interobserver agreement between novice and expert groups in identifying a ROI concerning for dysplasia (kappa -0.27). Conclusion: There was no agreement in identification of dysplastic ROIs with VLE between novice and expert users, highlighting the importance of additional training of novice users in the use of this technology.

Dietary Phenethyl Isothiocyanate Protects Mice from Colitis Associated Colon Cancer.

We have previously reported alleviation of dextran sodium sulfate (DSS)-induced ulcerative colitis signs in phenethyl isothiocyanate (PEITC)-treated mice. Here we investigated chemoprotective activities of PEITC in mice with Azoxymethane-DSS induced colitis associated colon carcinogenesis. We also examined the molecular mediators associated with the PEITC effects using relevant cell lines. A 0.12% PEITC-enriched mouse-diet reduced mucosal and submucosal inflammation as well as glandular atypia by 12% and the frequency of adenocarcinoma by 17% with a concomitant improvement in overall disease activity indices compared to the diseased control group. Lipopolysaccharide-induced in vitro up-regulation of key mediators of inflammation, immune response, apoptosis, and cell proliferation were attenuated by 10 μM PEITC. Three of these mediators showed concentration-dependent reduction in respective mRNAs. Furthermore, PEITC inhibited Nuclear factor kappa B1 (NFκB1) proteins in a concentration-dependent manner. The NFκB1 mRNA expression inversely correlated (r = −0.940, p = 0.013) with tri-methylation of lysine 27 on histone 3 near its promoter region in a time-dependent manner. These results indicate that PEITC may slow down the development of colon carcinogenesis in an inflammatory intestinal setting which is potentially associated with epigenetic modulation of NFκB1 signaling.

Accuracy of computer-aided diagnosis based on narrow-band imaging endocytoscopy for diagnosing colorectal lesions: comparison with experts

Real-time characterization of colorectal lesions during colonoscopy is important for reducing medical costs, given that the need for a pathological diagnosis can be omitted if the accuracy of the diagnostic modality is sufficiently high. However, it is sometimes difficult for community-based gastroenterologists to achieve the required level of diagnostic accuracy. In this regard, we developed a computer-aided diagnosis (CAD) system based on endocytoscopy (EC) to evaluate cellular, glandular, and vessel structure atypia in vivo. The purpose of this study was to compare the diagnostic ability and efficacy of this CAD system with the performances of human expert and trainee endoscopists. We developed a CAD system based on EC with narrow-band imaging that allowed microvascular evaluation without dye (ECV-CAD). The CAD algorithm was programmed based on texture analysis and provided a two-class diagnosis of neoplastic or non-neoplastic, with probabilities. We validated the diagnostic ability of the ECV-CAD system using 173 randomly selected EC images (49 non-neoplasms, 124 neoplasms). The images were evaluated by the CAD and by four expert endoscopists and three trainees. The diagnostic accuracies for distinguishing between neoplasms and non-neoplasms were calculated. ECV-CAD had higher overall diagnostic accuracy than trainees (87.8 vs 63.4%; [Formula: see text]), but similar to experts (87.8 vs 84.2%; [Formula: see text]). With regard to high-confidence cases, the overall accuracy of ECV-CAD was also higher than trainees (93.5 vs 71.7%; [Formula: see text]) and comparable to experts (93.5 vs 90.8%; [Formula: see text]). ECV-CAD showed better diagnostic accuracy than trainee endoscopists and was comparable to that of experts. ECV-CAD could thus be a powerful decision-making tool for less-experienced endoscopists.

Risk stratification of Barrett's oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study

Barrett's oesophagus predisposes to adenocarcinoma. However, most patients with Barrett's oesophagus will not progress and endoscopic surveillance is invasive, expensive, and fraught by issues of sampling bias and the subjective assessment of dysplasia. We investigated whether a non-endoscopic device, the Cytosponge, could be coupled with clinical and molecular biomarkers to identify a group of patients with low risk of progression suitable for non-endoscopic follow-up. In this multicentre cohort study (BEST2), patients with Barrett's oesophagus underwent the Cytosponge test before their surveillance endoscopy. We collected clinical and demographic data and tested Cytosponge samples for a molecular biomarker panel including three protein biomarkers (P53, c-Myc, and Aurora kinase A), two methylation markers (MYOD1 and RUNX3), glandular atypia, and TP53 mutation status. We used a multivariable logistic regression model to compute the conditional probability of dysplasia status. We selected a simple model with high classification accuracy and applied it to an independent validation cohort. The BEST2 study is registered with ISRCTN, number 12730505. The discovery cohort consisted of 468 patients with Barrett's oesophagus and intestinal metaplasia. Of these, 376 had no dysplasia and 22 had high-grade dysplasia or intramucosal adenocarcinoma. In the discovery cohort, a model with high classification accuracy consisted of glandular atypia, P53 abnormality, and Aurora kinase A positivity, and the interaction of age, waist-to-hip ratio, and length of the Barrett's oesophagus segment. 162 (35%) of 468 of patients fell into the low-risk category and the probability of being a true non-dysplastic patient was 100% (99% CI 96-100) and the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 0% (0-4). 238 (51%) of participants were classified as of moderate risk; the probability of having high-grade dysplasia was 14% (9-21). 58 (12%) of participants were classified as high-risk; the probability of having non-dysplastic endoscopic biopsies was 13% (5-27), whereas the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 87% (73-95). In the validation cohort (65 patients), 51 were non-dysplastic and 14 had high-grade dysplasia. In this cohort, 25 (38%) of 65 patients were classified as being low-risk, and the probability of being non-dysplastic was 96·0% (99% CI 73·80-99·99). The moderate-risk group comprised 27 non-dysplastic and eight high-grade dysplasia cases, whereas the high-risk group (8% of the cohort) had no non-dysplastic cases and five patients with high-grade dysplasia. A combination of biomarker assays from a single Cytosponge sample can be used to determine a group of patients at low risk of progression, for whom endoscopy could be avoided. This strategy could help to avoid overdiagnosis and overtreatment in patients with Barrett's oesophagus. Cancer Research UK.

Volumetric laser endomicroscopy in the detection of neoplastic lesions of the esophagus

Volumetric laser endomicroscopy (VLE) in a 64-year-old man ith Barrett’s esophagus revealed two regions with intramuosal adenocarcinoma missed by high magnification narrow-band maging. On VLE, these regions where characterized by lack of egular striations in the architecture, jagged shaped ducts sugestive of glandular atypia, and heterogenous signal intensity onsistent with irregular nuclei (Arrows, Fig. 1; Normal, Fig. 2). istopathology on targeted endoscopic mucosal resection showed igh-grade dysplasia with focal intramucosal adenocarcinoma, and igh-grade dysplasia with papillary intramucosal adenocarcinoma, espectively. Because dysplasia cannot be visualized with standard

Reproducibility of cervical cytopathology following an intervention by an external quality control laboratory.

This study assessed the effects of a continued education program on the agreement between cervical cytopathology exams interpreted by local laboratories and interpretation made by an external quality control laboratory (LabMEQ). Overall, 9,798 exams were analyzed between 2007 and 2008, prior to implementation of a continued education program, and 10,028 between 2010 and 2011, following implementation. Continued education consisted of theoretical and practical classes held every two months. The chi-square test and the kappa coefficient were used in the statistical analysis. Following implementation of continued education, the rate of false-negative results, and those leading to delays in clinical management fell in eight laboratories and the rate of false-positive results in five. Agreement between the results reported by the laboratories and the findings of LabMEQ, evaluated according to clinical management, remained excellent in three laboratories (kappa >0.80 and <1.0), went from good (kappa >0.60 and <0.80) to excellent in seven and from excellent to good in two. Agreement regarding the identification of metaplastic epithelium was poor (kappa = 0.25) but progressed to excellent following the implementation of continued education (kappa = 0.950). Agreement between cytopathology results improved significantly following implementation of continued education in cases reported as unsatisfactory (P < 0.001), atypical squamous cells of undetermined significance, cannot exclude high-grade squamous intraepithelial lesion (P < 0.001), low-grade squamous intraepithelial lesion (P < 0.001), and glandular atypia (P < 0.001). Continued education contributed towards improving the reproducibility of cervical cytopathology, decreased the rates of false-negative and false-positive results, and reduced delays in clinical management.

Molecular Characterization of an Endometrial Endometrioid Adenocarcinoma Metastatic to a Thyroid Hürthle Cell Adenoma Showing Cancerization of Follicles

Tumor-to-tumor metastasis is rare. Herein, we present a unique case of endometrial endometrioid adenocarcinoma metastatic to a thyroid Hürthle cell adenoma 9years after initial diagnosis. On histologic examination of the thyroid, the malignant endometrioid glands and single cells (donor tumor) were dispersed within the Hürthle cell adenoma (recipient tumor). In several sections of the adenoma with still preserved microfollicular architecture, malignant endometrial adenocarcinoma cells were admixed within oncocytic adenomatous epithelium (so-called "cancerization of the follicles"). This unusual phenomenon, to our knowledge, is a novel finding in the thyroid gland. Immunohistochemistry, subsequently elicited clinical history, and morphologic comparison of the tumor in the thyroid to the primary endometrial tumor confirmed the origin of the donor tumor cells. Molecular analysis of both the metastatic and primary endometrial tumors demonstrated PIK3CA and PTEN mutations in both tumors, as is characteristic of well-differentiated endometrioid tumors of the endometrium. Amplification of chromosome 1q was detected in both sites; however, only the metastatic tumor showed loss of chromosomes 2, 9, and 22. The morphologic differential diagnosis of metastatic endometrioid adenocarcinoma in the thyroid includes columnar cell variant of papillary thyroid carcinoma (CCVPTC) arising in a preexisting adenoma, endocrine glandular atypia within an adenoma, and metastasis from other anatomic sites. Histomorphologic differences among these entities may be subtle; therefore, knowledge of and morphologic comparison with prior malignancies and immunohistochemistry can be helpful in rendering the correct diagnosis.

Prevalence of Pap smear abnormalities among women who attend Sexually Transmitted Diseases (STD) clinic, Colombo

Introduction: Cervical cancer ranks as the second most frequent cancer among women in Sri Lanka. It has been now well established that oncogenic subtypes of human papillomavirus (HPV) is a necessary cause of cervical cancer. An abnormal Pap smear may indicate an infection, inflammation or cervical cytological abnormality. Objectives: The objective of this study was to ascertain the prevalence of Pap smear abnormalities among women who attend Sexually Transmitted Disease (STD) clinic, Colombo Method: A total of 1300 females who underwent routine Pap smear screening at STD clinic, Colombo in the year 2010 and 2011 were analysed for the prevalence of all forms of Pap smear abnormalities including cervical cytological abnormalities. Cytology was interpreted according to the national guideline which is based on Bethesda system 2001. Results: Prevalence of all forms of abnormal Pap smears was 24.2% while the prevalence of cervical cytological abnormalities was only 2.2% in the sample, out of which 1 .4% were low grade squamous intraepithelial lesions (LGSIL), 0.5% were high grade squamous intraepithelial lesions (HGSIL) and 0.3% were glandular cell atypia. The cervical cancer prevalence in the sample was 0.077%. Conclusions: All forms of Pap smear abnormalities among STD clinic attendees were relatively high (24.2%) due to concurrent infections and inflammation. The rate of cervical cytological abnormalities was 2.2% while the cervical cancer rate was 0.077% in the sample. There was no significant difference between groups with and without cervical cytological changes. Sri Lanka Journal of Venereology Vol.5(1) 2014: 20-30

Valor de la biopsia endometrial en el diagnóstico de embarazo ectópico

Se encuentra la alteración atípica endometrial asociada a la presencia de tejido coriónico en el 50% de 44 casos de Embarazo Ectópico. En 36.36 (16 casos) se encuentra reacción decidual. Basado en el concepto clásico de que el embarazo ectópico, puede diagnosticarse sólo por la presencia de reacción decidual y el nuevo concepto de atipia relacionada con la presencia de tejido coriónico, esta sugerencia se hubiera hecho en 63.63 %. La atipla glandular, es pues, un nuevo aporte para el diagnóstico de Embarazo Ectópico, acrecentándose el valor de la biopsia como medio auxiliar ginecológico. Se llama la atención sobre la importancia y significación de las alteraciones en grado menor o atipias mínimas y sobre la ocurrencia en el epitelio de revestimiento (40.9 %). Se describe por primera vez la ocurrencia de atipia glandular en un caso de endometriosis interna asociada a embarazo ectópico. Proponemos la denominación de Lesión Arias-Stella a las alteraciones atípicas glandulares endometriales, por haber sido este estudioso peruano, el primero que las señaló en el endometrio en relación de tejido coriónico. Se describe la ocurrencia de necrosis hialina de aspecto fibrinoide en el estroma de dos casos. No hay relación entre la atipia glandular y procesos inflamatorios locales. No hay alteraciones atípicas en el epitelio tubario a las similares del endometrio. Se demuestra una correlación entre la presencia de atipias en el endometrio y el estado de vitalidad de las vellosidades coriales.

Coordinate loss of MAP3K7 and CHD1 promotes aggressive prostate cancer.

Prostate cancer subtypes are poorly defined and functional validation of drivers of ETS rearrangement-negative prostate cancer has not been conducted. Here, we identified an ETS(-) subtype of aggressive prostate cancer (ERG(-)MAP3K7(del)CHD1(del)) and used a novel developmental model and a cell line xenograft model to show that cosuppression of MAP3K7 and CHD1 expression promotes aggressive disease. Analyses of publicly available prostate cancer datasets revealed that MAP3K7 and CHD1 were significantly codeleted in 10% to 20% of localized tumors and combined loss correlated with poor disease-free survival. To evaluate the functional impact of dual MAP3K7-CHD1 loss, we suppressed Map3k7 and/or Chd1 expression in mouse prostate epithelial progenitor/stem cells (PrP/SC) and performed tissue recombination experiments in vivo. Dual shMap3k7-shChd1 PrP/SC recombinants displayed massive glandular atypia with regions of prostatic intraepithelial neoplasia and carcinoma apparent. Combined Map3k7-Chd1 suppression greatly disrupted normal prostatic lineage differentiation; dual recombinants displayed significant androgen receptor loss, increased neuroendocrine differentiation, and increased neural differentiation. Clinical samples with dual MAP3K7-CHD1 loss also displayed neuroendocrine and neural characteristics. In addition, dual Map3k7-Chd1 suppression promoted E-cadherin loss and mucin production in recombinants. MAP3K7 and CHD1 protein loss also correlated with Gleason grade and E-cadherin loss in clinical samples. To further validate the phenotype observed in the PrP/SC model, we suppressed MAP3K7 and/or CHD1 expression in LNCaP prostate cancer cells. Dual shMAP3K7-shCHD1 LNCaP xenografts displayed increased tumor growth and decreased survival compared with shControl, shMAP3K7, and shCHD1 xenografts. Collectively, these data identify coordinate loss of MAP3K7 and CHD1 as a unique driver of aggressive prostate cancer development.

Double Channel Pylorus as a Complication of Peptic Ulcer Disease

Introduction: Double channel pylorus is a rare condition consisting of a gastro duodenal fistula extending from the gastric antrum to the duodenal bulb through an accessory canal. The double pylorus is a destructive but relatively benign complication of peptic ulcer disease. It could be congenital or acquired. Case Report: A 73-year-old female with history of cirrhosis secondary to non-alcoholic steatohepatitis with splenomegaly, thrombocytopenia, and peptic ulcer disease was admitted to the hospital for progressive shortness of breath and noted to have iron deficiency anemia. The patient underwent screening upper endoscopy as a part of screening for esophageal varices. She was noted to have some antral thickening extending to pylorus. Biopsies showed that the thickening was only focal fibrosis and reactive glandular atypia, but no tumor. Six months later, the patient was readmitted with worsening shortness of breath, and was found to have anemia and positive occult blood. Colonoscopy was done as a part of work-up, which was completely normal. Later, the patient underwent esophagogastroduodenoscopy (EGD). On EGD, the changes were consistent with mild gastritis and a duplicate opening lying adjacent to pyloric channel. The scope was passed through both the openings. First was the native pyloric channel. The duplicated pyloric channel seemed to open into the second part of the duodenum, and there was a large, clean bases ulcer, but no fistulas. There was shelve of normal tissue diving the 2 openings. Upper GI series was also done to confirm the diagnosis. Discussion: The prevalence of double pylorus varies from 0.06 to 0.4%; however, its real incidence remains unknown. It occurs more often in men (2:1), as well as with other peptic diseases. Malignant tumors resulting in formation of double pylorus is extremely rare. Clinical symptoms are similar to those of peptic ulcer disease. They are identified on upper endoscopy and can also be seen on barium meal study. Convergence of double pyloric canals resulting into 1 large gastrointestinal passage can predispose to bile reflux. Other complications, like hemorrhage or intractable pain, may require surgical intervention. Double channel pylorus is a rare but important complication of peptic ulcer disease, and should be identified early to prevent complications.