Atypical Glands Research Articles

Label-free monitoring of colorectal adenoma–carcinoma sequence based on multiphoton microscopy

The monitoring and evaluation of colorectal adenoma–carcinoma sequence during endoscopy are important for endoscopic resection of precursor lesions to disrupt the adenoma–carcinoma sequence and halt progression to invasive neoplastic disease. In this study, multiphoton microscopy (MPM) was used to identify different stages during the development of colorectal adenocarcinoma including adenoma with low-grade and high-grade dysplasia, and adenocarcinoma invading the submucosa. It was found that by combining two-photon excited fluorescence (TPEF) imaging and second harmonic generation (SHG) imaging, MPM can reveal the morphological changes of the epithelial cells and glands, identify the invasive position and depth of atypical glands and quantitatively describe the change of the cellular nucleus and the nuclear-to-cytoplasmic ratio during the stepwise progression of colorectal adenocarcinoma. These are important pathological findings for pathologists when diagnosing colorectal lesions. With the advancement of a compact and flexible multiphoton endoscope for in vivo imaging and clinical applications, MPM has the potential to provide immediate histological diagnosis for the monitoring and evaluation of the colorectal adenoma–carcinoma sequence during endoscopy.

MP67-08 IDENTIFICATION OF PATIENTS WHO CAN AVOID REPEAT BIOPSY USING MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING

INTRODUCTION AND OBJECTIVES: The aim of our study is to determine if multiparametric magnetic resonance imaging (MRI) and/or clinical variables can discriminate between significant cancer and others (indolent or no cancers) before repeat biopsy and to identify men who can avoid repeat biopsy with low risk of missing significant cancer. METHODS: Between 2007 and 2010, 137 consecutive men who underwent repeat biopsy because of elevated or continuous high prostate-specific antigen (PSA) level after initial biopsy (n 1⁄4 88), atypical gland or prostatic intraductal neoplasia at previous biopsy (n 1⁄4 39), positive digital rectal findings (n 1⁄4 1), or patient desire (n 1⁄4 9) were prospectively evaluated. All men underwent 1.5T MRI, including T2-weighted, diffusion-weighted, and/or dynamic contrastenhanced imaging in the prebiopsy setting. Repeat biopsy protocol was 14to 28-core biopsy, including at least 4-core anterior samplings under transrectal ultrasound. Pathological specimens were evaluated according to the 2005 modified Gleason grading. Biopsy results were categorized into biopsy no cancer (BNC), biopsy indolent cancer (BIC), and biopsy significant cancer (BSC). We defined BIC as biopsy GS 3+4, clinical stage T1-T2a based on digital rectal findings (DRE), percent positive core 20%, and maximum cancer length < 5 mm. Cancer other than BIC was defined as BSC. Frequency of biopsy results according to MRI was evaluated. We also assessed clinical variables as predictors for BSC using logistic regression analysis in men with negative MRI. Clinical variables included age, PSA, free PSA, PSA at initial biopsy, rate of increase in PSA, DRE, prostate volume, number of days since initial biopsy, and pathology at previous biopsy. RESULTS: Median age and PSA were 66 years (range: 44e80) and 8.7 ng/ml (range: 1.1e58.6), respectively. The negative and positive MRI group included 84 and 53 men, respectively. The frequency of BNC/BIC/BSC was 76/19/5% in men with negative MRI and 36/19/45% in men with positive MRI. In men with negative MRI, multivariate analysis revealed that DRE was the only significant predictor of BSC. The frequency of BSC in men with negative MRI was 25% (2/8) in abnormal DRE and 3% (2/76) in normal DRE. CONCLUSIONS: Our results suggest that in repeat prostate biopsy setting, men with prebiopsy-negative MRI and normal DRE can avoid biopsy with a very low risk of missing significant cancer.

MP56-10 BACILLUS CALMETTE-GUERIN INTRAVESICAL INSTILLATION THERAPY AFTER THE SECOND TRANSURETHRAL RESECTION SIGNIFICANTLY DECREASES INTRAVESICAL RECURRENCE IN PATIENTS WITH NEW-ONSET HIGH-GRADE T1 BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Superficial1 Apr 2014MP56-10 BACILLUS CALMETTE-GUERIN INTRAVESICAL INSTILLATION THERAPY AFTER THE SECOND TRANSURETHRAL RESECTION SIGNIFICANTLY DECREASES INTRAVESICAL RECURRENCE IN PATIENTS WITH NEW-ONSET HIGH-GRADE T1 BLADDER CANCER Keitaro Iida, Toshiki Etani, Taku Naiki, Ryosuke Ando, Noriyasu Kawai, Keiichi Tozawa, and Kenjiro Kohri Keitaro IidaKeitaro Iida More articles by this author , Toshiki EtaniToshiki Etani More articles by this author , Taku NaikiTaku Naiki More articles by this author , Ryosuke AndoRyosuke Ando More articles by this author , Noriyasu KawaiNoriyasu Kawai More articles by this author , Keiichi TozawaKeiichi Tozawa More articles by this author , and Kenjiro KohriKenjiro Kohri More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1578AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives High-grade T1 bladder cancer often results in intravesical recurrence. Bacillus Calmette-Guerin intravesical instillation therapy (BCG) after initial transurethral resection (TUR) helps prevent recurrence. Further, a second TUR is recommended to resect residual cancer. Here, we discuss the efficacy of BCG after the second TUR against new-onset high-grade T1 bladder cancer. Methods Our retrospective analysis included 157 patients with high-grade T1 bladder cancer based on an initial TUR, treated at our university and affiliated hospitals from January 2008 to December 2012. Of the 157 patients, 38 were treated with BCG after a second TUR (group 1) and 56 were only treated with BCG (group 2). Residual cancer and recurrence-free survival rates were statistically analyzed. Results The mean patient age was 69 years (range, 39-86 years), and the mean follow-up period was 25.7 months. The 2 groups did not differ in age, gender, and previous upper urinary tract cancer history. The 2 groups also did not differ in tumor size, tumor multiplicity, and concomitant carcinoma in situ based on initial TUR findings. In group 1, the second TUR revealed that 27 patients (71%) had residual cancer. Pathology of the second TUR specimen revealed pT0 in 8 patients (21%), dysplasia in 2 (5%), an atypical gland in 1 (3%), pTis/a in 9 (24%), and pT1 in 18 (47%). Two-year recurrence-free survival was 85% and 57% in groups 1 and 2, respectively, and 5-year recurrence-free survival was 85% and 46% in groups 1 and 2, respectively. The differences between these survival rates were statistically significant (p = 0.0016). Notably, recurrence within 6 months after the initial TUR occurred in 1 patient (3%) in group 1 and in 14 patients (25%) in group 2. Conclusions A high recurrence-free survival rate was achieved by BCG administration after the second TUR in patients with new-onset high-grade T1 bladder cancer. BCG alone is thought to have limited efficacy against residual cancer. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e567 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Keitaro Iida More articles by this author Toshiki Etani More articles by this author Taku Naiki More articles by this author Ryosuke Ando More articles by this author Noriyasu Kawai More articles by this author Keiichi Tozawa More articles by this author Kenjiro Kohri More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The value of TAG72 on prostate needle biopsy specimens with minimal adenocarcinoma

The study included 30 men diagnosed with minimal adenocarcinoma in needle biopsies and subsequently treated with radical prostatectomy (RP). Immunohistochemical staining for TAG 72 on the needle biopsies were semiquantitatively scored and expression levels were related to significant disease at RP. There was high TAG 72 expression in atypical glands in 9 (30%), moderate in 10 (33%), low in 5 (17%), and absent in 6 (20%). Most minimal adenocarcinomas were Gleason score 6 (n=20; 67%) and had high (9), moderate (7), low (2), absent (2) TAG 72 expression. Minimal high grade Gleason score 7-8 adenocarcinomas were diagnosed in 10 patients. In these cases TAG 72 expression was moderate (3), low (3), absent (4). Low TAG 72 expression was a predictor for prostate cancer with Gleason score ≥7 in RP specimens. A minimal amount of cancer in prostate needle core tissue equates with a small amount of carcinoma gland. The correlation of the level of TAG 72 expression in needle core tissue with the amount of cancer in the whole gland was not high. The determination of TAG 72 expression on diagnostic needle biopsies supports the selection of men with indolent prostate cancer at RP. It could improve the pretreatment risk assessment of patients with minimal adenocarcinoma.

Early over‐expression of GRP receptors in prostatic carcinogenesis

The GRP receptor shows high over-expression in prostatic adenocarcinoma and high grade PIN, but low expression in normal prostate glands. This represents the molecular basis for GRP receptor imaging of prostate cancer with radioactive compounds. However, a focal, high density GRP receptor expression can be observed in hitherto uncharacterized prostate glands. GRP receptors were quantitatively measured with in vitro receptor autoradiography using ¹²⁵I-Tyr⁴ -bombesin in samples from 115 prostates. On successive tissue sections, ¹²⁵I-Tyr⁴ -bombesin autoradiography was compared with H&E staining and MIB-1 and 34βE12 immunohistochemistry. On one hand, it was confirmed that GRP receptors were expressed in adenocarcinoma and high grade PIN in high density and high incidence (77% and 73%, respectively), but in normal prostate glands in low density and low frequency (18%). On the other hand, a novel and intriguing observation was the existence of focal non-invasive prostate glands with high GRP receptor density, characterized by low grade nuclear atypia and increased proliferation, compatible with lower grade PIN. There was a significant GRP receptor density gradient (P ≤ 0.005), increasing from normal prostate glands (mean relative optical density, ROD, of ¹²⁵I-Tyr⁴ -bombesin binding: 0.17) over atypical glands without increased MIB-1 labeling (0.28) and atypical glands with increased MIB-1 expression (0.44) to high grade PIN and adenocarcinoma (0.64 and 0.58, respectively). GRP receptor over-expression may be a novel, specific marker of early prostatic neoplastic transformation, arising in low grade PIN, and progressively increasing during malignant progression. This should be considered when interpreting in vivo GRP receptor imaging in males.

Abstract 2729: A genetically engineered mouse model of de novo pancreatic carcinogenesis .

Abstract Multistep models of PDAC development converge on both abnormalities in KRAS and E2F activation, which are part of the Rb/E2F pathway, and dysfunction of p53, which is associated with the MDM2/p53 pathway. Recent progress in the understanding of the protective roles of the Rb/E2F and MDM/p53 pathways against carcinogenesis showed that cross talk and complementary actions of these pathways are present in many types of cancers. In this study, we addressed directly questions regarding the collaborative roles of the Rb/E2F and MDM2/p53 pathways in suppressing the progression of multistep PDAC carcinogenesis by generating TKC (loxP-βgeo-STOP-loxPtemperature-sensitive SV40 T antigen (tsTAg)), loxP-STOP-loxP-KrasG12D, and Pdx1-Cre) mice which exhibit impairment of both pathways and K-rasG12D expression in pancreatic epithelial cells. The PDAC induced in TKC mice exhibited rapid development and absence of inflammation or PanIN formation, which occurred by de novo carcinogenesis. The tumors resembled human PDAC at the histological and molecular level. In in vitro study, we established PDAC cell lines from TKC mice and immortalized pancreatic ductal cell lines from TC mice, Cytokeratin 19 expression with which was applied to select cells as pancreatic ductal cell differentiation. In collagen gel 3D culture, PDAC cells formed atypical gland structures the same as in subcutaneous transplanted tumor in nude mice, while the Cytokeratin 19 positive immortalized ductal cell lines from TC mice formed ductal structures similar to either intralobular or interloblar pancreatic ducts. The results of the analysis of the highlighted molecular mechanisms suggest that the synthetic interaction among mutated Kras, uncontrolled E2f activation, and dysfunction of p53 results in de novo pancreatic carcinogenesis. This model represents an important tool to explore molecular targets for diagnostics and cancer therapy for PDAC via de novo pancreatic carcinogenesis.This work was supported by grants from the Program for Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN) and New Energy and Industrial Technology Development Organization (NEDO) of Japan, and supported in part by Grants-in-Aid for Scientific Research on Priority Area (21590454, 24590498, and 24108006 to Y. I.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Citation Format: Takashi Yamaguchi, Sanae K. Ikehara, Yuzuru Ikehara. A genetically engineered mouse model of de novo pancreatic carcinogenesis . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2729. doi:10.1158/1538-7445.AM2013-2729

Minimal deviation adenocarcinoma of the cervix and tumorlets of sex-cord stromal tumor with annular tubules of the ovary in Peutz-Jeghers syndrome

We report 2 cases of minimal deviation adenocarcinoma of the cervix and tumorlets of sex cord tumor with annular tubules (SCTATs) of the ovaries, accompanied by Peutz-Jeghers syndrome. Case 1 is a 36-year-old woman and case 2 is a 35-year-old woman. Grossly, the cervix of both cases showed markedly barrel shaped enlargement with an infiltrating tumor. Microscopically, well-differentiated atypical glands were infiltrating into the entire thickness of the cervix. The ovarian masses in case 1 were diagnosed as metastatic carcinoma in mucinous cystadenoma with tumorlets of SCTATs of the ovaries. Multiple scattered tumorlets of SCTATs were also found in the ovary of case 2. By direct DNA sequencing analysis, a frame shift mutation of the STK11/LKB1 gene was identified in case 1. Case 1 represented the more aggressive clinical course, and although the patient received additional combined chemo-radiation therapy, she expired 1 year later. In general, mutation of the STK11/LKB1 gene is associated with poor clinical outcome in malignant tumors accompanied by Peutz-Jeghers syndrome.

Use of Immunohistochemistry in Routine Workup of Prostate Needle Biopsies: A Tertiary Academic Institution Experience

Diagnostic use of immunohistochemistry has been extensively studied in prostate needle biopsy, but its use in routine practice and the quality assurance and associated cost have not been previously addressed. To examine the routine use of immunohistochemistry in prostate biopsies in a tertiary academic institution. We reviewed reports of 748 consecutive prostate biopsies and we evaluated the turnaround times, the final diagnosis on individual specimens, the intradepartmental consultation rates, and the associated costs. Immunohistochemistry evaluation was required for 39.4% of biopsies and 12% of blocks (average 1.8 blocks/case). The biopsies with immunohistochemistry were signed out 1.7 workdays later (8.6 versus 6.9 days). The diagnostic breakdown for individual blocks evaluated by immunohistochemistry was Cancer 47.7%; Atypical, Suspicious 10.8%; Small Atypical Glands Adjacent to High-Grade Prostatic Intraepithelial Neoplasia 6.9%; High-Grade Prostatic Intraepithelial Neoplasia 12.4%; and Benign 22.2%. Diagnoses of Cancer or Atypical, Suspicious (Atypical, Suspicious + Small Atypical Glands Adjacent to High-Grade Prostatic Intraepithelial Neoplasia) were rendered in 65.4% of individual blocks assessed by immunohistochemistry. Immunohistochemistry aided in establishing limited cancer (≤10% of core) in 69.3% of cases and in 74% of single-core-positive biopsies. Departmental consultation was performed in 18.3% of biopsies and immunohistochemistry was used in 68% of these cases. Both immunohistochemistry and consultation were performed in 55.8% of Atypical, Suspicious cases. The average immunohistochemistry cost per biopsy was $22.34 and the estimated annual cost for prostate biopsy immunohistochemistry in our laboratory was $33 420.64. Immunohistochemistry is frequently used in our prostate biopsy practice to establish or confirm a limited Cancer diagnosis, to better resolve diagnostic ambiguity, or for quality assurance. The data provided herein can be used for comparisons with other prostate biopsy practices.

The diagnostic use of ERG in resolving an “atypical glands suspicious for cancer” diagnosis in prostate biopsies beyond that provided by basal cell and α-methylacyl-CoA-racemase markers

Immunohistochemical (IHC) staining for ERG is used as a surrogate for TMPRSS2-ERG gene fusion, a specific molecular event seen in ~50% of prostate carcinomas (PCas) and ~20% of high-grade prostatic intraepithelial neoplasia (HGPIN) intermingled with adjacent PCa demonstrating identical gene fusions. We studied 84 "atypical glands suspicious for cancer (ATYP)" cases using multiplex ERG/α-methylacyl-CoA-racemase (AMACR)/high-molecular-weight cytokeratin/p63 IHC to determine how often ERG contributes to resolving an ATYP diagnosis beyond that provided by AMACR and basal markers. Final diagnoses of benign, ATYP, and cancer were rendered after review of morphology and all markers in 3, 30, and 51 cases, respectively. Of 51 cancer diagnoses, 45% and 94% were positive for ERG and AMACR, respectively. Of 30 atypical diagnoses, 10% and 67% were positive for ERG and AMACR, respectively. Of 3 benign diagnoses, none and 83% were positive for ERG and AMACR, respectively. Three ERG-positive atypical cases were classified as "HGPIN with adjacent ATYP." ERG was expressed in adjacent noncancer glands of 20% of PCas, whereas AMACR was expressed in noncancer glands in all diagnostic categories in 40% of cases. Positive ERG staining helped establish the initial ATYP diagnosis to PCa in 28% cases whose diagnoses would otherwise remain ATYP based on AMACR and basal markers. ERG positivity in small atypical glands where HGPIN diagnosis is excluded helps establish a definitive cancer diagnosis in a small proportion of additional ATYP cases. We recommend judicious use of ERG, preferably as a component of multiplex IHC, in evaluation of difficult prostate biopsies.

Expression of ERG protein, a prostate cancer specific marker, in high grade prostatic intraepithelial neoplasia (HGPIN): lack of utility to stratify cancer risks associated with HGPIN

What's known on the subject? and What does the study add? High grade prostatic intraepithelial neoplasia is a pre-malignant lesion to prostate cancer and is associated with 20%-25% risk of prostate cancer in subsequent repeat biopsies. ERG is a highly prostate-cancer-specific marker. Expression of ERG is rare in isolated high grade prostatic intraepithelial neoplasia diagnosed in prostate biopsy and is not associated with cancer risk in subsequent repeat biopsies. • To evaluate how often ERG, a highly prostate-cancer-specific marker, is expressed in isolated high grade prostatic intraepithelial neoplasia (HGPIN) by immunohistochemistry. • To study whether a positive ERG immunostain in HGPIN correlates with prostate cancer (PCa) detection in subsequent repeat biopsies. • Patients with initial HGPIN in biopsies and at least one follow-up prostate biopsy were included. • Biopsies with HGPIN were immunostained for ERG. • The ERG staining results were then correlated with the PCa risk in subsequent biopsies. • The mean age of 94 patients was 63 years (range 48-78). A mean of 1.8 (range 1-5) repeat biopsy sessions were carried out at a mean interval of 27.4 months (range 1.5-140). The repeat biopsies showed PCa and non-cancer lesions (benign, HGPIN, atypical glands suspicious for cancer) in 36 patients (38%) and 58 patients (62%) respectively. • ERG immunostain was positive in five (5.3%) biopsies with HGPIN, in which PCa was found in two (40%) subsequent biopsies. Of 89 biopsies with negative ERG staining, PCa was found in 34 (38%) repeat biopsies. The cancer detection rate was not different between ERG positive and negative cases (P= 0.299). • This is the first study to investigate the ERG protein expression in prostate biopsy containing HGPIN only and its use to stratify the cancer risk associated with HGPIN. We found that ERG expression is distinctly uncommon in isolated HGPIN (5.3%). • Positive ERG expression is not associated with increased cancer detection in subsequent repeat biopsies. The use of ERG immunostain in the evaluation and cancer risk stratification of HGPIN is of limited value.

Histopathologic features of atypical glands on prostate biopsy: Nucleolar size is a predictor of subsequent detection of prostatic adenocarcinoma

Patients whose prostate biopsy reveals the presence of atypical glands suspicious for carcinoma (AGSC) are subject to close monitoring and repeat biopsies, perhaps unnecessarily, as clinicians do not have a clear basis for understanding and stratifying the significance of these findings. In a retrospective, blinded manner, we histopathologically examined initial biopsies reported as AGSC (82 patients, 93 foci). On subsequent biopsies, 31 (38%)/5 (6%) patients were found to have prostate cancer (PCA)/AGSC, respectively, while no carcinoma (NOCA) was identified in the remainder (56%) of cases. Nucleolar grade (on a scale of 1-4 with "1" denoting small, inconspicuous nucleoli and "4" denoting macronucleoli) was significantly higher in PCA cases than in NOCA cases whether comparing all AGSC foci (P = 0.006) or when considering the highest grade in each patient (P = 0.009). However, the number of AGSC per focus was similar (P = 0.926) between PCA (mean ± SD: 7.03 ± 5.35) and NOCA (mean ± SD: 7.13 ± 4.44). Adjacent (P = 0.117) and separate (P = 0.457) high-grade prostatic intraepithelial neoplasia was found in 8/37 (22%) foci and 12/31 (39%) cases in PCA, respectively, and in 4/48 (8%) foci and 13/46 (28%) cases in NOCA, respectively. The presence of intraluminal dense secretion, crystalloid, or mucin in AGSC did not show a statistically significant correlation between PCA [5/37 (14%)] and NOCA [10/48 (21%)] (P = 0.567). Our study may thus clarify the significance of AGSC on prostate biopsy and suggests that the size of nucleoli in AGSC is a positive predictor of subsequent detection of prostatic adenocarcinoma.

Multiple atypical polypoid adenomyoma of the uterus

Atypical polypoid adenomyoma (APA) of the uterus is a rare neoplasm that predominantly occurs in premenopausal woman. It typically appears as a polypoid mass with a mixture of hyperintensity and hypointensity on T2-weighted MRI. We report a case of a 45-year-old woman with multiple APAs (33 and 22 mm). She underwent hysteroscopic resection. The diagnosis of APAs was histologically made by irregularly proliferating atypical endometrial glands that were admixed with a stroma. This is the first case of multiple APAs with radiological findings. It is important to recognize the possible multiplicity of APA for proper diagnosis.

Atypical polypoid adenomyomas progressed to endometrial endometrioid adenocarcinomas

Atypical polypoid adenomyoma (APA) is an uncommon uterine tumor which is composed of atypical endometrial glands and cellular smooth-muscle stroma. At present APA is categorized as a benign lesion and treated conservatively in the literatures. However, there are also several cases reported that progressed to endometrial endometrioid adenocarcinoma (EEC) till now. Here, we present two more rare cases of APA that may have undergone progression to EEC. Two patients who had APA 6 and 4 years ago, respectively, and had ECC were reported. The history of the two patients and the literatures were retrospectively reviewed. The truth that APA may have a chance to progress to carcinoma suggests that APA is at least an indicator lesion for the development of EEC, and highlights that clinicians should carefully monitor the patients, and a meticulous follow-up examination is mandatory.

Abstract 4434: Development of pancreatic ductal adenocarcinoma (PDAC) by the expression of temperature-sensitive SV40 large T antigen (tsTAg) and K-ras G12D on pancreatic epithelial linage cells

Abstract Based on studies using genetically engineered mouse (GEM) models producing pancreatic ductal adenocarcinoma (PDAC), pancreatic intraepithelial neoplasia (PanIN) - PDAC linear pathway has been proposed. Whereas the positive association between the carcinogenesis and the engineered genetic abnormalities K-ras, Ink4a/Arf, Trp53, and Smad4, it has been pointed out the oversimplification on the postulated carcinogenesis steps. Indeed, there should be various routes leading to PDAC on the etiological heterogeneity, and it remains controversial whether PanIN-1 lesions are required for development of PDAC in view of the pathogenesis. In order to increase knowledge about the routes leading to PDAC, we generated GEM harboring loxP-μgeo-stop-loxP-tsTAg (LbsL-tsTAg); loxP-stop-loxP-K-rasG12D; Pdx1-Cre (TKC) alleles that express temperature-sensitive SV40 T antigen (tsTAg) and K-rasG12D on epithelial cells in pancreas. The tsTAg has been widely used to generate immortalized cells by inhibiting tumor suppressor molecules, P53 and Rbs (Rb1, Rbl1, Rbl2), and we previously reported the generation of GEM with LbsL-tsTAg and the success to establish the immortalized lymphatic endothelial cells using this mice (Yamaguchi T. et al, FEBS J. Vol.275: p1988-1998, 2008). In TKC mice, PDAC foci appeared at 5th days after birth without PanIN-1 lesions, and showed rapid progression and invasion into duodenum, resulting in death within 3 weeks. On the contrary, though tsTAg-expressing TC mice develop neither PDAC nor PanIN, dysplastic feature appeared on acinar cells at 15-20 weeks after birth. In in vitro assay, the characteristics of the established PDAC cell lines from TKC mice was compared with the immortalized cell lines expressing Cytokeratin 19 (Ck19, pancreatic ductal cell marker) from TC mice. PDAC cells were positive for Ck19 and formed atypical gland structures in collagen gel 3D culture the same as in subcutaneous transplanted tumor in nude mice, while the Ck19 positive immortalized cell lines from TC mice formed ductal structures in collagen gel similar to either intralobular or interloblar pancreatic ducts. The expression of Tacstd2, SerpinB2, and microRNA-200 group genes were upregulated in PDAC cells more than the Ck19 positive immortalized cell lines, which were commonly in human PDAC. These results suggest that PDAC can develop without PanIN-1 lesion under the given conditions as TKC mice, and that constitutive active mutation of K-ras plays an important role for lineage addiction to show ductal phenotype. Our newly established mice models and in vitro assay systems are feasible not only to establish molecular taxonomy of PDAC, but also to develop biomarkers for early detection, and help to discover the therapeutic target molecules. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4434. doi:1538-7445.AM2012-4434

1922 FEATURES OF ATYPICAL GLANDS ON INITIAL PROSTATE BIOPSY AS POSITIVE OR NEGATIVE PREDICTORS OF MALIGNANCY ON SUBSEQUENT PROSTATE BIOPSY

You have accessJournal of UrologyProstate Cancer: Detection and Screening III1 Apr 20121922 FEATURES OF ATYPICAL GLANDS ON INITIAL PROSTATE BIOPSY AS POSITIVE OR NEGATIVE PREDICTORS OF MALIGNANCY ON SUBSEQUENT PROSTATE BIOPSY Sriram Venigalla, Chen Zhao, and Hiroshi Miyamoto Sriram VenigallaSriram Venigalla Rochester, NY More articles by this author , Chen ZhaoChen Zhao Rochester, NY More articles by this author , and Hiroshi MiyamotoHiroshi Miyamoto Rochester, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2079AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients whose prostate biopsy reveals the presence of atypical glands suspicious for prostatic carcinoma (AGSC) are subject to close monitoring and repeat biopsies, perhaps unnecessarily, as clinicians do not have a clear basis for understanding and stratifying the significance of these findings. The value of histologic atypia on an initial prostate biopsy in predicting the detection of prostate cancer on subsequent biopsies should thus be further studied. METHODS In a retrospective, blinded manner, we examined the initial biopsies of 82 patients (93 foci) reported as AGSC. Five factors assessed in these biopsies include the size of the nucleoli of cells composing AGSC (graded on a scale of 1-4 with “1” denoting small, inconspicuous nucleoli and “4” denoting macronucleoli), the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) adjacent to or separate from AGSC, the number of AGSC, the presence of intraluminal crystalloid, mucin, or dense secretions within AGSC, and the presence of basal cells in AGSC highlighted by immunohistochemical staining. RESULTS On subsequent biopsies, 31 (38%) patients were found to have prostate cancer (PCA) while no carcinoma was identified in the remainder (62%) of cases (NOCA). Nucleolar grade was significantly higher (p=0.010) in PCA cases (mean ± SD: 2.43 ± 0.80) than in NOCA cases (mean ± SD: 1.98 ± 0.70). Adjacent (p=0.235) and separate (p=0.132) HGPINs were found in 8/37 (22%) foci and 8/31 (26%) cases in PCA, respectively, and in 6/56 (11%) foci and 6/51 (12%) cases in NOCA, respectively. The number of atypical glands was similar (p=0.950) between PCA (mean ± SD: 7.03 ± 5.35) and NOCA (mean ± SD: 7.09 ± 4.18). The presence of intraluminal crystalloid, mucin, or dense secretions in AGSC did not show a statistically significant correlation between PCA [5/37 (14%)] and NOCA [13/56 (23%)] (p=0.293). Immunohistochemical stains demonstrated patchy basal cells in 17/39 (44%) of NOCA whereas basal cells were absent in 24/27 (89%) PCA (p=0.006). CONCLUSIONS On an atypical initial prostate biopsy, the size of nucleoli in AGSC is a positive predictor of prostate cancer on subsequent biopsy. On the other hand, as expected, even patchy staining of basal cells in AGSC represents a negative predictor of prostate cancer. However, HGPIN adjacent to or separate from AGSC, the total number of AGSC, and intraluminal materials do not reliably predict the subsequent diagnosis of prostate cancer. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e775-e776 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sriram Venigalla Rochester, NY More articles by this author Chen Zhao Rochester, NY More articles by this author Hiroshi Miyamoto Rochester, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Primary Vaginal Mucinous Adenocarcinoma of Gastric Type Arising in Adenosis

We report 2 cases of primary vaginal mucinous adenocarcinoma arising in adenosis in nondiethylstilbestrol-exposed women, 1 with uterus didelphys. Both tumors exhibited morphologic and immunohistochemical features (MUC6 and/or HIK 1083 positivity) identical to the recently described cervical gastric-type adenocarcinoma, a subtype of mucinous adenocarcinoma that is non-human papillomavirus related and possibly related to adenoma malignum. Both neoplasms were intensely p53 positive, suggesting that TP53 mutation may be implicated in their development. We believe that the vaginal tumors arose from adenosis through atypical adenosis, as benign and atypical glands were present at the periphery of the neoplasms. In reporting these cases, we discuss atypical adenosis and other types of non-diethylstilbestrol-associated vaginal adenocarcinomas. At least 9 other examples of primary vaginal, or more uncommonly cervical, adenocarcinomas arising in non-diethylstilbestrol-exposed women with congenital genitourinary malformations have been reported, suggesting a probable causal association between congenital malformation, vaginal adenosis, and vaginal adenocarcinoma.

Atypical presentation of colon adenocarcinoma: a case report

IntroductionAdenocarcinoma of the colon is the most common histopathological type of colorectal cancer. In Western Europe and the United States, it is the third most common type and accounts for 98% of cancers of the large intestine. In Uganda, as elsewhere in Africa, the majority of patients are elderly (at least 60 years old). However, more recently, it has been observed that younger patients (less than 40 years of age) are presenting with the disease. There is also an increase in its incidence and most patients present late, possibly because of the lack of a comprehensive national screening and preventive health-care program. We describe the clinicopathological features of colorectal carcinoma in the case of a young man in Kampala, Uganda.Case presentationA 27-year-old man from Kampala, Uganda, presented with gross abdominal distension, progressive loss of weight, and fever. He was initially screened for tuberculosis, hepatitis, and lymphoma, and human immunodeficiency virus/acquired immunodeficiency syndrome infection. After a battery of tests, a diagnosis of colorectal carcinoma was finally established with hematoxylin and eosin staining of a cell block made from the sediment of a liter of cytospun ascitic fluid, which showed atypical glands floating in abundant extracellular mucin, suggestive of adenocarcinoma. Ancillary tests with alcian blue/periodic acid Schiff and mucicarmine staining revealed that it was a mucinous adenocarcinoma. Immunohistochemistry showed strong positivity with CDX2, confirming that the origin of the tumor was the colon.ConclusionsColorectal carcinoma has been noted to occur with increasing frequency in young adults in Africa. Most patients have mucinous adenocarcinoma, present late, and have rapid disease progression and poor outcome. Therefore, colorectal malignancy should no longer be excluded from consideration only on the basis of a patient's age. A high index of suspicion is important in the diagnosis of colorectal malignancy in young African patients.

Immunohistochemical pitfalls in prostate pathology

The diagnosis of prostatic adenocarcinoma relies on a constellation of architectural, cytological, and immunohistochemical features. Although the diagnosis of prostatic adenocarcinoma is straightforward in most cases, due to earlier detection of the disease in the modern era, pathologists have become increasingly challenged in diagnosing small foci of cancer when only a few atypical glands are present in needle biopsies. Immunohistochemistry has therefore become an essential tool in the evaluation of such foci to confirm the absence of basal cells. In this context, the 2 most commonly used basal cell markers are anti-keratin 34BE12 and p63. Furthermore, α-methylacyl-CoA racemase, a marker found to be overexpressed in the cytoplasm of prostatic adenocarcinoma glands, is also commonly used in routine practice. Another diagnostic role of immunohistochemistry is to confirm the prostatic origin of the tumor in the primary or metastatic setting of high-grade prostatic adenocarcinoma, which may be confused with nonprostatic carcinomas. We herein review the utility as well as the limitations of immunohistochemistry in the diagnosis of prostatic adenocarcinoma, and we describe the most important pitfalls in the interpretation of various immunostains that pathologists should be aware of to minimize misdiagnoses.

The value of triple antibody (34βE12 + p63 + AMACR) cocktail stain in radical prostatectomy specimens with crushed surgical margins

BackgroundTriple antibody cocktail immunohistochemical staining is routinely used as an ancillary method to establish a diagnosis of prostate cancer in biopsies with small foci of atypical glands. Crush artefact can...

Case report: parotid basal cell adenoma, membranous type

A52-year-old female withbackgroundofnon-Hodgkin's lymphoma and polymyositis presented with a 4 year history of slow growing, left parotid mass. There were no other associated symptoms. Fine needle aspirate of the mass was performed and the diagnosis of an atypical primary salivary gland neoplasm was made. Subsequent left parotidectomy was performed and the diagnosis of parotid basal cell adenoma, membranous type was made. Basal cell adenoma is a benign epithelial neoplasm of the salivary gland which is characterised by uniform proliferation of basaloid cells. Basal cell adenoma often occurs in the parotid gland followed by the submandibular gland and the upper lip region. Basal cell adenoma accounts for 1–3% of all benign parotid tumours, and the peak incidence is in the 6th to 7th decades of life. There are various subtypes based on morphological features which include solid, trabecular, tubular, and membranous types. The membranous subtype has been associated with the dermal cyclindromas which have similar incidence of chromosomal alteration at 16q12– 13. The membranous subtype is characterised by tumour cells arranged in a jig-saw like pattern with prominent PAS+ eosino-philic, basement-membrane type material. The main differential diagnosis is basal cell adenocarcinoma, and it can be difficult to distinguish between the two. Basal cell adeno-carcinoma is characterised by increased number of mitotic figures, increased nuclear pleomorphism, infiltrative growth, and peri-neural and intravascular invasion. In our case, the proliferative index Ki-67 is low, and there is no significant nuclear pleomor-phism, infiltrative growth pattern, or perineural invasion. However, the lesion extends to the diathermied margin, which is associated with a higher rate of recurrence of approximately 25%.