Neoplastic Epithelium Research Articles

1-L-MT, an IDO inhibitor, prevented colitis-associated cancer by inducing CDC20 inhibition-mediated mitotic death of colon cancer cells.

Indoleamine 2,3-dioxygenase 1 (IDO1), known as IDO, catabolizes tryptophan through kynurenine pathway, whose activity is correlated with impaired clinical outcome of colorectal cancer. Here we showed that 1-L-MT, a canonical IDO inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. Our results showed that inhibition of IDO decreased the transcription of CDC20, which resulted in G2/M cycle arrest of HCT-116 and HT-29. Furthermore, 1-L-MT induced mitochondria injuries and caused apoptotic cancer cells. Importantly, 1-L-MT protected mice from azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon carcinogenesis, with reduced mortality, tumor number and size. What is more, IDO1-/- mice exhibited fewer tumor burdens and reduced proliferation in the neoplastic epithelium, while, 1-L-MT did not exhibit any further protective effects on IDO-/- mice, confirming the critical role of IDO and the protective effect of 1-L-MT-mediated IDO inhibition in CRC. Furthermore, 1-L-MT also alleviated CRC in Rag1-/- mice, demonstrating the modulatory effects of IDO independent of its role in modulating adaptive immunity. Taken together, our findings validated that the anti-proliferation effect of 1-L-MT in vitro and the prevention of CRC in vivo were through IDO-induced cell cycle disaster of colon cancer cells. Our results identified 1-L-MT as a promising candidate for the chemoprevention of CRC.

Evaluation of the extent of interstitial fibrosis in oral squamous cell carcinoma compared with normal oral mucosa and oral epithelial dysplasia.

Objective: To evaluate the extent of interstitial fibrosis in samples of normal oral mucosa (NOM), oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Materials and method: Descriptive study. Eighteen samples of NOM, 15 samples of OED, and 13 samples of OSCC were analyzed; all stained with Masson’s trichrome stain. The areas of greatest fibrosis underlying the normal, dysplastic, and malignant neoplastic oral epithelium were identified in order to determine the extent of interstitial fibrosis. Interstitial fibrosis was classified according to its proportion in the total image, being 0 (without fibrosis), +1 (1-25%), 2+ (26-50%), 3+ (51-75%) and +4 (76-100%). Variables were analyzed using the Kruskal-Wallis test and Dunn’s Pairwise post-hoc test. Results: The samples of NOM and OED did not present interstitial fibrosis (type 0) in the majority of the cases respectively. OSCC samples were characterized by an extension of type 2+ interstitial fibrosis in 45% of all cases of OSCC. The extent of interstitial fibrosis was different between NOM and OSCC (p<0.001), and between OED and OSCC (p<0.001). Conclusion: The extent of interstitial fibrosis is directly proportional to the malignization of the analyzed samples, being an adequate marker for OSCC.

Rare variant of metaplastic carcinoma of the breast: a case report and review of the\xa0literature

BackgroundMetaplastic carcinoma encompasses a group of neoplasms characterized by differentiation of the neoplastic epithelium into squamous cells and/or mesenchymal-looking elements. Spindle cell carcinoma is a rare variant of this special histological type. Its prognosis remains poor, with a high rate of local recurrence and distant metastasis. To date, only a small number of cases have been described. There is no clear agreement on this histological subtype.Case presentationWe report a case of a 53-year-old Moroccan woman who consulted our institution following palpation of a nodule of the left breast. Mammography in combination with breast ultrasonography revealed a lesion classified as Breast Imaging Reporting and Data System 4 with microcalcification. The patient was diagnosed with spindle cell carcinoma of the breast. The diagnosis was based primarily on histological and immunohistochemical studies of the breast biopsy and secondarily on the surgical specimen. No local or distant metastasis was found. The treatment used was total surgical excision followed by radiotherapy.ConclusionsWe describe the features (epidemiological, clinical, histological, immunohistochemical, and therapeutic outcomes) of our patient’s case and compare them with literature data.

Glomeruloid Microvascular Proliferation, Desmoplasia, and High Proliferative Index as Potential Indicators of High Grade Canine Choroid Plexus Tumors.

Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRβ, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT.

Changes in in vivo confocal microscopic findings of ocular surface squamous neoplasia during treatment with topical interferon alfa-2b

PurposeTo evaluate in vivo confocal microscopy (IVCM) findings of ocular surface squamous neoplasia (OSSN) during treatment with topical interferon alfa-2b (IFN alfa-2b). MethodsIn this prospective interventional case series, 20 eyes from 20 patients with OSSN were treated with topical IFN alfa-2b 3 million IU/mL four times a day. Treatment was continued for 2 or 3 months after clinical resolution. IVCM was done at baseline, on a monthly basis, and at the end of treatment. Confocal images were evaluated in conjunction with clinical findings during treatment. Limbal dendritic cell (DC) density within the involved areas was calculated manually in confocal images. ResultsTopical therapy resulted in clinical resolution of neoplasia in 80% of eyes. Main features of OSSN on IVCM were hyper-reflectivity of epithelium, demarcation line between neoplastic and normal epithelium, and pleomorphic cells. These findings became less prominent in response to IFN alfa-2b therapy. However, some degree of residual epithelial hyper-reflectivity could be detected in 9 (56.2%) subjects who responded to therapy at time of treatment cessation. Limbal DCs density within involved areas was significantly increased at month 1 follow-up compared to baseline only in responders (P < .0001). There was a trend toward higher limbal DCs density in responders to topical IFN alfa-2b than non-responders (208.6 ± 53.5 vs. 153.1 ± 48.2 cell/mm2, respectively; P = .08) at month 1 follow-up. ConclusionsIVCM is proposed as an adjunctive tool for monitoring OSSN during topical treatment. IVCM documents epithelial cell response as well as limbal DC density increase during topical IFN therapy.

Low frequency of BRAF V600E immunoexpression in mandibular ameloblastomas: An institutional study.

Background:Ameloblastoma is an uncommon, benign neoplasm of odontogenic epithelium commonly affecting the posterior mandible (almost 80%) particularly in the molar/ramus region, with occasional tumors involving the maxilla. Recently, there has been much interest generated after the reports of BRAF V600E mutations in ameloblastomas with a frequency of 46%–80% using both molecular as well as immunohistochemical (IHC) techniques. We sought to assess the presence of BRAF V600E expression in ameloblastomas in Indian patients and correlate the same with clinical behavior and histological variants by performing IHC analysis with anti-BRAF V600E antibody.Materials and Methods:Thirty formalin-fixed paraffin-embedded tissues of mandibular ameloblastomas were examined by anti-BRAF V600E antibody and correlated with clinicopathologic and histological parameters. Cytoplasmic staining of neoplastic epithelium was considered positive for BRAF V600E expression.Statistical Analysis:Data analysis was performed using Chi-square test and Student's t-test with statistical software IBM SPSS statistics 20.0.Results:BRAF V600E antibody showed positive expression only in 33.3% (10/30) cases. About 66.7% (4/6) recurrent cases and 63.6% (7/11) plexiform cases showed statistically significant association of P = 0.05 and P = 0.021, respectively, among cases with positive BRAF V600E immunoexpression.Conclusion:We report the lowest frequency (33.3%) of BRAF V600E immunoexpression in mandibular ameloblastomas in Indian population. However, a significant association of BRAF V600E-positive immunoexpression with recurrence and plexiform pattern could underline its role as a therapeutic marker for ameloblastoma.

Dysplasia can be a pain in the gut

In the gastrointestinal tract, the term 'dysplasia' is used to refer to non-invasive neoplastic epithelium. Although we recognise adenomas of the gut as dysplastic, we don't use the term 'dysplasia' in reporting them. The use of the term 'dysplasia' for pre-invasive epithelium gradually came to replace other terms in studies attempting to identify epithelial changes that were cancer precursors in surveillance biopsies of patients with chronic colitides. The two-tier system of classification, dividing dysplasias into low-grade or high-grade lesions is conceptually straightforward; however, difficulties exist in the distinction of regenerative epithelium from low-grade dysplasia, of low-grade from high-grade dysplasia, and in identifying superficially invasive carcinoma in a dysplastic mucosa. The category 'indefinite for dysplasia' is an honest recognition of the difficulties in distinguishing reactive or regenerative epithelium from low-grade dysplasia, since these epithelia share many cytological features. In surveillance biopsies in ulcerative colitis and Barrett's mucosa, for each epithelial category from non-dysplastic through indefinite, low-grade and high-grade dysplasia, there are specific management recommendations that vary from no change in surveillance to increased surveillance to definitive therapy that is often a major resection. The recommendation for referral of high-grade dysplasias to consultants reflects the concern pathologists have about making such clinically significant diagnoses with limited experience. Pathologists should use the accepted terminology, share cases to expand their experience, and seek consultation in selected cases. This paper follows the evolution of the dysplasia concept, details the difficult areas of diagnosis, and discusses the importance of interaction between clinicians and pathologists in dealing with dysplasias.

Grading and staging mucinous neoplasms of the appendix: a case series and review of the literature

The grading and staging of appendiceal mucinous neoplasms is challenging and fraught with terminology problems, but has critical prognostic and therapeutic implications. We utilized a small case series to examine the grading and staging systems of appendiceal mucinous neoplasms and outline the evidence for the new systems proposed in the upcoming 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual. We reviewed 33 cases of appendiceal mucinous neoplasms with available clinical follow-up data, 6 of which were widely disseminated in the peritoneum. An additional 4 cases with disseminated peritoneal involvement were also reviewed. A detailed review of the literature was performed with an emphasis on features associated with disease recurrence and correlation of grade with outcome. Recurrence was not seen in 64 low-grade appendiceal mucinous neoplasms (LAMNs) confined to the muscularis propria in our series (n=21) or in the literature (n=43). Of cases of LAMN with neoplastic epithelium present beyond the muscularis propria, 64% (57/89) had peritoneal disease at the time of diagnosis or follow-up. A majority of studies of disseminated appendiceal mucinous neoplasms showed significant five-year survival differences using a three-tier grading scheme. Thus, LAMNs confined to the muscularis propria are best considered as in situ tumors, as these are cured with complete excision. A three-tier system has prognostic significance and should be used for grading of disseminated appendiceal mucinous neoplasms. The conclusions of this case series and literature review provide evidence to support the changes proposed in the 8th edition of the AJCC Staging Manual.

Stromal Clusterin Expression Predicts Therapeutic Response to Neoadjuvant Chemotherapy in Triple Negative Breast Cancer

BackgroundExpression of clusterin correlates with tumor progression and therapeutic response in several human malignancies, including breast cancer. However, its predictive value in the neoadjuvant setting in breast cancer remains unexplored. The objective of this explorative study was to determine whether clusterin expression in breast cancer correlated with clinical pathologic characteristics and whether its expression was predictive of response to neoadjuvant chemotherapy (NAC). Materials and MethodsWe determined the clusterin expression pattern in 72 triple negative breast cancers (TNBC) treated with NAC before surgery. Clusterin expression was evaluated by immunohistochemistry and was correlated with pathologic characteristics and response to NAC using residual cancer burden score. ResultsImmunohistochemistry analysis revealed a differential pattern of expression between tumor and stroma. Clusterin expression in the tumor associated stroma as opposed to expression by the neoplastic epithelium was significantly associated with neoadjuvant-treated TNBC. Low stromal clusterin, low stromal content, and high tumor-infiltrating lymphocytes were associated with a significantly greater likelihood of achieving a good pathologic response as reflected by lower residual cancer burden scores (P = .002, P = .003, and P = .001, respectively). Tumor and/or stromal clusterin expression were not associated with patient age, tumor histologic grade, stage, and lymph node status. ConculsionThis study suggests a potential role for the assessment of stromal clusterin as a predictive biomarker for response of TNBC to neoadjuvant therapy. Further validation of this biomarker in a large study is needed.

Modulation of basal cell fate during productive and transforming HPV-16 infection is mediated by progressive E6-driven depletion of Notch.

In stratified epithelia such as the epidermis, homeostasis is maintained by the proliferation of cells in the lower epithelial layers and the concomitant loss of differentiated cells from the epithelial surface. These differentiating keratinocytes progressively stratify and form a self‐regenerating multi‐layered barrier that protects the underlying dermis. In such tissue, the continual loss and replacement of differentiated cells also limits the accumulation of oncogenic mutations within the tissue. Inactivating mutations in key driver genes, such as TP53 and NOTCH1, reduce the proportion of differentiating cells allowing for the long‐term persistence of expanding mutant clones in the tissue. Here we show that through the expression of E6, HPV‐16 prevents the early fate commitment of human keratinocytes towards differentiation and confers a strong growth advantage to human keratinocytes. When E6 is expressed either alone or with E7, it promotes keratinocyte proliferation at high cell densities, through the combined inactivation of p53 and Notch1. In organotypic raft culture, the activity of E6 is restricted to the basal layer of the epithelium and is enhanced during the progression from productive to abortive or transforming HPV‐16 infection. Consistent with this, the expression of p53 and cleaved Notch1 becomes progressively more disrupted, and is associated with increased basal cell density and reduced commitment to differentiation. The expression of cleaved Notch1 is similarly disrupted also in HPV‐16‐positive cervical lesions, depending on neoplastic grade. When taken together, these data depict an important role of high‐risk E6 in promoting the persistence of infected keratinocytes in the basal and parabasal layers through the inactivation of gene products that are commonly mutated in non‐HPV‐associated neoplastic squamous epithelia. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Spectroscopic characterization of oral epithelial dysplasia and squamous cell carcinoma using multiphoton autofluorescence micro-spectroscopy.

Multiphoton autofluorescence microscopy (MPAM) has shown potential in identifying features that are directly related to tissue microstructural and biochemical changes throughout epithelial neoplasia. In this study, we evaluate the autofluorescence spectral characteristics of neoplastic epithelium in dysplasia and oral squamous cell carcinoma (OSCC) using multiphoton autofluorescence spectroscopy (MPAS) in an in vivo hamster model of oral neoplasia in order to identify unique signatures that could be used to delineate normal oral mucosa from neoplasia. A 9,10-dimethyl-1,2-benzanthracene (DMBA) hamster model of oral precancer and OSCC was used for in vivo MPAM and MPAS. Multiphoton Imaging and spectroscopy were performed with 780 nm excitation while a bandpass emission 450-650 nm was used for MPAM. Autofluorescence spectra was collected in the spectral window of 400-650 nm. MPAS with fluorescence excitation at 780 nm revealed an overall red shift of a primary blue-green peak (480-520 nm) that is attributed to NADH and FAD. In the case of oral squamous cell carcinoma (OSCC) and some high-grade dysplasia an additional prominent peak at 635 nm, attributed to PpIX was observed. The fluorescence intensity at 635 nm and an intensity ratio of the primary blue-green peak versus 635 nm peak, showed statistically significant difference between control and neoplastic tissue. Neoplastic transformation in the epithelium is known to alter the intracellular homeostasis of important tissue metabolites such as NADH, FAD, and PpIX, which was observed by MPAS in their native environment. A combination of deep tissue microscopy owing to higher penetration depth of multiphoton excitation and depth resolved spectroscopy could prove to be invaluable in identification of cytologic as well as biomolecular spectral characteristic of oral epithelial neoplasia. Lasers Surg. Med. 49:866-873, 2017. © 2017 Wiley Periodicals, Inc.

Overinterpretation is common in pathological diagnosis of appendix cancer during patient referral for oncologic care.

ContextLow-grade appendiceal mucinous neoplasm (LAMN) and appendiceal adenocarcinoma are known to cause the majority of pseudomyxoma peritonei (PMP, i.e. mucinous ascites); however, recognition and proper classification of these neoplasms can be difficult despite established diagnostic criteria.ObjectiveTo determine the pathological diagnostic concordance for appendix neoplasia and related lesions during patient referral to an academic medical center specialized in treating patients with PMP.DesignThe anatomic pathology laboratory information system was searched to identify cases over a two-year period containing appendix specimens with mucinous neoplasia evaluated by an outside pathology group and by in-house slide review at a single large academic medical center during patient referral.Results161 cases containing appendix specimens were identified over this period. Forty-six of 161 cases (28.6%) contained appendiceal primary neoplasia or lesions. Of these, the originating pathologist diagnosed 23 cases (50%) as adenocarcinoma and 23 cases (50%) as LAMN; however, the reference pathologist diagnosed 29 cases (63.0%) as LAMN, 13 cases (28.3%) as adenocarcinoma, and 4 cases (8.7%) as ruptured simple mucocele. Importantly, for cases in which the originating pathologist rendered a diagnosis of adenocarcinoma, the reference pathologist rendered a diagnosis of adenocarcinoma (56.5%, 13 of 23), LAMN (39.1%, 9 of 23), or simple mucocele (4.3%, 1 of 23). The overall diagnostic concordance rate for these major classifications was 71.7% (33 of 46) with an unweighted observed kappa value of 0.48 (95% CI, 0.27–0.69), consistent with moderate interobserver agreement. All of the observed discordance (28.3%) for major classifications could be attributed to over-interpretation. In addition, the majority of LAMN cases (65.5%) had potential diagnostic deficiencies including over-interpretation as adenocarcinoma and lacking or discordant risk stratification (i.e. documentation of extra-appendiceal neoplastic epithelium).ConclusionsAppendiceal mucinous lesions remain a difficult area for appropriate pathological classification with substantial discordance due to over-interpretation in this study. The findings highlight the critical need for recognition and application of diagnostic criteria regarding these tumors. Recently published consensus guidelines and a checklist provided herein may help facilitate improvement of diagnostic concordance and thereby reduce over-interpretation and potential overtreatment. Further studies are needed to determine the extent of this phenomenon and its potential clinical impact.

Genomic Characterization of Low- and High-Grade Pancreatic Mucinous Cystic Neoplasms Reveals Recurrent KRAS Alterations in "High-Risk" Lesions.

Pancreatic ductal adenocarcinoma arises from the following 3 distinct precursor lesions: pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm (MCN). Genetic abnormalities in the first 2 precursor lesions have been well characterized, but there are limited data on progression pathways in MCNs. This study aimed to characterize genomic differences between MCNs with low-grade (LG) and high-grade (HG) dysplasia or carcinoma. Neoplastic epithelium from surgical resections of 25 MCNs, 16 with LG dysplasia and 9 with HG dysplasia or invasive carcinoma, was analyzed by targeted massively parallel sequencing. KRAS mutations were most frequent, present in 9 HG (100%) and 3 LG (19%) tumors, 2 of the latter also having discrete areas of HG tumor with the same mutation. TP53 mutations and CDKN2A loss were identified in 5 HG tumors (56%) each but not in LG tumors. The low frequency of KRAS alterations in cysts without a HG component suggests that a subset of MCNs may have a low risk for malignant progression. Novel single-nucleotide variants that occur at a lower rate may help identify this group and provide a substrate for new diagnostic, prognostic, and therapeutic targets.

PD10-06 INTRA-OPERATIVE OPTICAL IMAGING UTILIZING ANTI-PSMA (PROSTATE SPECIFIC MEMBRANE ANTIGEN) FLUORESCENT ANTIBODY DURING ROBOT ASSISTED RADICAL PROSTATECTOMY (RARP)

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy I1 Apr 2017PD10-06 INTRA-OPERATIVE OPTICAL IMAGING UTILIZING ANTI-PSMA (PROSTATE SPECIFIC MEMBRANE ANTIGEN) FLUORESCENT ANTIBODY DURING ROBOT ASSISTED RADICAL PROSTATECTOMY (RARP) Avinash Chennamsetty, William Chu, Justin Emtage, Paul Gellhaus, Jonathan Yamzon, Clayton Lau, Bertram Yuh, Tommy Tong, David Colcher, Timothy Wilson, and Ali Zhumkhawala Avinash ChennamsettyAvinash Chennamsetty More articles by this author , William ChuWilliam Chu More articles by this author , Justin EmtageJustin Emtage More articles by this author , Paul GellhausPaul Gellhaus More articles by this author , Jonathan YamzonJonathan Yamzon More articles by this author , Clayton LauClayton Lau More articles by this author , Bertram YuhBertram Yuh More articles by this author , Tommy TongTommy Tong More articles by this author , David ColcherDavid Colcher More articles by this author , Timothy WilsonTimothy Wilson More articles by this author , and Ali ZhumkhawalaAli Zhumkhawala More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.569AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Identification of prostatic tissue from non-prostatic tissue can help preserve potency, continence, as well as decrease positive margins. PSMA, a transmembrane glycoprotein expressed by neoplastic prostate epithelium, is a possible target for identification of prostate tissue. MDX1201, an investigational new drug (IND) composed of fully human IgG with conjugated fluorescent marker (AlexaTM488) with specificity against PSMA was safely administered in mice models. The antibody-fluorescent dye complex was shown to bind to cells expressing PSMA demonstrating significant staining of prostatic adenocarcinoma. We performed the first in-human FDA-approved phase I 3+3 dose finding study of intravenously (IV) administered MDX1201 in intermediate- to high-risk patients undergoing RARP and extended lymph node (LN) dissection. METHODS Patients received a single intravenous infusion of MDX1201 four days prior to RARP to allow for safety evaluation. A 488 nanometer laser was attached to the da Vinci Si surgical robot camera at the time of RARP to allow for visualization of fluorescent dye marking presence of prostatic cancerous tissue. 5 mg dose was given to the first 3 patients, and then the dose was escalated to 15 mg provided safety considerations permit. Patients with prior prostate cancer treatment were excluded. RESULTS MDX1201 was successfully administered to 5 patients, with no adverse events observed. Initial 5 mg dose failed to show visualization of fluorescent dye in first 3 patients. Of the 15 mg dose patients, patient #4 demonstrated fluorescence ex vivo within the sectioned prostate that correlated with pathological findings, while patient #5 demonstrated fluorescence in-vivo with mild prostatic fluorescence at the right apex, left apex, left mid, and also moderate fluorescence demonstrated at the right external iliac LNs. For patient #5, histopathologic examination confirmed tumor to the mid right lobe (dominant nodule), with a minor focus in anterior left lobe near the base. There was no LN metastasis in this patient (pT2cN0). In the five patients (median PSA 9.5, 80% intermediate-risk, 100% > pT2c), the median LN yield was 18 with no LN involvement in any patient. No positive margins were detected. CONCLUSIONS We demonstrate the first in human study using an anti PSMA antibody demonstrating fluorescence in the prostate. Identification of prostatic tissue using a conjugated fluorescent marker with specificity against PSMA may help guide preservation of critical structures. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e201-e202 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Avinash Chennamsetty More articles by this author William Chu More articles by this author Justin Emtage More articles by this author Paul Gellhaus More articles by this author Jonathan Yamzon More articles by this author Clayton Lau More articles by this author Bertram Yuh More articles by this author Tommy Tong More articles by this author David Colcher More articles by this author Timothy Wilson More articles by this author Ali Zhumkhawala More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Intraductal neoplasms of the bile duct. A new challenge to biliary tract tumor pathology.

Invasive biliary tract carcinomas are usually tubular adenocaricnomas with abundant desmoplastic reactions and frequent ductal and periductal invasion at the time of the diagnosis. Recently, several intraductal neoplasms of the bile duct, particularly at a pre-invasive stage, have been recognized. They include intraductal papillary neoplasm of the bile duct (IPNB), biliary intraepithelial neoplasm (BilIN), and others, such as intraductal tubulopapillary neoplasm (ITPN) of the bile duct. IPNBs are grossly visible predominantly intraductal-growing papillary neoplasms covered by well-differentiated neoplastic epithelium with fine fibrovascular cores in the dilated bile ducts. Regarding their similarities to intraductal papillary mucinous neoplasm of the pancreas (IPMN) of main pancreatic duct type, some IPNBs resemble IPMN ("pancreatic type"), while others are only somewhat similar or variably different from IPMN ("non-pancreatic type"). Some IPNBs develop via a common oncogenic signaling pathway, and others, particularly those of intestinal type, frequently show GNAS mutations, as in IPMN. BilINs are a microscopically recognizable flat or micropapillary pre-invasive neoplasm and are presumed to precede conventional nodular-sclerosing cholangiocarcinomas. ITPN of the bile duct is a rare neoplasm composed of densely packed tubular glands. These three types of neoplasms are not infrequently associated with invasive adenocarcinoma. Pre-invasive intraglandular neoplasms of the peribiliary glands, another epithelial system in the biliary tree, have been also reported. Further characterization of these intraductal and intraglandular neoplasms of the bile duct is needed to overcome devastating invasive biliary tract carcinoma.

P53 Protein Expression in Dental Follicle, Dentigerous Cyst, Odontogenic Keratocyst, and Inflammatory Subtypes of Cysts: An Immunohistochemical Study.

An odontogenic keratocyst (OKC) is a developmental odontogenic cyst with aggressive clinical behavior. This cyst shows a different growth mechanism from the more common dentigerous cyst and now has been renamed as a keratocystic odontogenic tumor (KCOT). Inflammation can assist tumor growth via different mechanisms including dysregulation of the p53 gene. This study aims to assess and compare the expression of tumor suppressor gene p53 in inflamed and non-inflamed types of OKC and dentigerous cyst. Immunohistochemical expression of p53 was assessed in 14 cases of dental follicle, 34 cases of OKC (including 18 inflamed OKCs), and 31 cases of dentigerous cyst (including 16 inflamed cysts). The mean percentage of p53 positive cells was 0.7% in dental follicles, 5.4% in non-inflamed OKCs, 17.3% in inflamed OKCs, 1.2% in non-inflamed dentigerous cysts, and 2.2% in inflamed dentigerous cysts. The differences between the groups were statistically significant (p < 0.050) except for the difference between inflamed and non-inflamed dentigerous cysts, and between dental follicle and non-inflamed dentigerous cyst. The difference in p53 expression in OKC and dentigerous cyst can explain their different growth mechanism and clinical behavior. Inflammation is responsible for the change in behavior of neoplastic epithelium of OKC via p53 overexpression.

Difference in EGFR expression and mean vascular density in normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma.

Objective: To evaluate the expression of the epidermal growth factor receptor (EGFR) and mean vascular density (MVD) in normal oral mucosa (NOM), oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Material and methods: Descriptive case study. Nineteen histological samples diagnosed with NOM, 18 diagnosed with OED, and 19 with OSCC, were analyzed with immunohistochemistry against EGFR and CD31. EGFR expression was evaluated by extent and intensity of its expression in normal, dysplastic and neoplastic epithelium. MVD was determined through the detection of blood vessels by antibodies against CD31. Results: Extension of EGFR expression was highest in OSCC followed by OED and lowest in NOM, resulting in significant different between the degrees of extension (p<0.001). Intensity of EGFR was similar in NOM, OED and OSCC, without differences in its expression (p=0.533). Differences in MVD were found between NOM and OSCC groups (p<0.01), and between OED and OSCC groups (p<0.01), with no differences between NOM and OED groups (p=0.91). MVD was 21.17 ± 4.98 in NOM, 23.40 ± 5.77 in OED and 33.92 ± 8.39 in OSCC. Conclusion: EGFR is expressed in normal, dysplastic or neoplastic oral epithelium. However, the extent of its expression is greater as malignancy increases. MVD varies according to the diagnosis.

PD-236 Defining the Signaling Pathways and Functional Role for Kynurenine Metabolites in the Normal and Neoplastic Colon Epithelium

Background:IDO1, an enzyme that initiates tryptophan metabolism along the kynurenine pathway (KP), is commonly overexpressed in IBD and colorectal cancer (CRC). We previously demonstrated that global knockout of IDO1 reduced tumorigenesis in the AOM/DSS model of colitis-associated cancer (CAC). The

Intraductal Papillary Neoplasm of the Bile Duct With Invasive Adenocarcinoma Complicating IgG4-related Sclerosing Cholangitis: Report of a Case

Although there have been many previous studies of IgG4-related SC focusing on the differential diagnosis from cholangiocarcinoma, only a few patients with cholangiocarcinoma against a background of IgG4-related SC have been reported. We herein present a case of intraductal papillary neoplasm of the bile duct (IPNB) associated with invasive carcinoma complicating IgG4-related sclerosing cholangitis. A 71-year-old female with icterus was admitted to a local hospital, where stricture of the extrahepatic bile duct were detected, and subsequently referred to our hospital for possible surgery. Abdominal multidetector-row computed tomography demonstrated marked wall thickening along the entire extrahepatic bile duct. The left lateral superior bile duct (B2) and left lateral inferior duct (B3) were individually obstructed, and percutaneous transhepatic biliary drainage catheters were placed in B2 and B3 separately. The patient was diagnosed to have diffusely spread cholangiocarcinoma and underwent right hepatic trisectionectomy with caudate lobectomy and pancreatoduodenectomy. A histological examination revealed intraductal papillary tumors composed of fibrovascular stalks covered by neoplastic epithelium. Carcinomatous invasion of the papillary tumors was observed in the fibromuscular layer, and there was abundant infiltration of inflammatory cells with fibrosis outside of the cancerous tissue. The inflammatory cells were primarily composed of plasma cells, a majority of which were positive for IgG4 (&amp;gt;30 cells/high-power field); the postoperative serum IgG4 level was 890 mg/dL. Therefore, a diagnosis of coexisting IPNB associated with invasive carcinoma and IgG4-related sclerosing cholangitis was made. To the best of our knowledge, this is the first report of IPNB complicating IgG4-related sclerosing cholangitis.

A cross-sectional study of p53 expression in patients with squamous cell carcinoma cervix: A hospital-based study

Context: Cervical cancer is the second most common cancer in women in India and the fourth most common cancer in women worldwide. The p53 is a tumor suppressor gene. Overexpression of p53 is detected by immunohistochemistry (IHC) and it indicates a worsened prognosis in some malignancies. Aims: The present study was undertaken to assess the expression of p53 by IHC in normal cervical epithelium and squamous cell carcinoma (SCC) cervix. The role of p53 as a potential biomarker by correlating p53 expression with clinico-pathological parameters was also studied. Settings and Design: Cross-sectional study. Subjects and Methods: A total of 50 cases of cervical biopsy or hysterectomy specimens of SCC cervix and fifty cases of hysterectomy specimens for other gynecologic causes were included in the study. IHC was used to study the p53 expression in normal and neoplastic cervical epithelium. The p53 positivity was assessed by using a semi quantitative method in SCC cervix. The p53 expression was correlated with various clinico-pathological parameters. Statistical Analysis Used: Data collected was analyzed using appropriate statistical test. Results: All the fifty cases (100%) of SCC cervix showed positive p53 expression. The normal cervical epithelium in 90% cases was p53 negative and 10% showed basal layer positivity. A statistically significant correlation was seen between p53 score and menopausal status ( P = 0.010). Conclusions: Overexpression of p53 is suggestive of high grade of tumor.