Subsequent Surgical Specimens Research Articles

Concordance between core needle biopsy and surgical specimen for oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status in breast cancer.

This study aimed to analyse the concordance rate, sensitivity, specificity, positive predictive value (PPV) and negative predictive value of core needle biopsy (CNB) and subsequent surgical specimen (SS) in assessing levels of oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2/neu). It also evaluated the revised American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for ER/PgR positivity. We analysed the breast cancer database of KK Women's and Children's Hospital, Singapore, from 1 June 2005 to 30 December 2012. Invasive breast cancer patients who had CNB and subsequent SS were included. A total of 560 patients were included. The concordance of ER, PgR and HER2/neu positivity between CNB and SS was 96.1%, 89.1% and 96.8%, respectively. When the 'ER ≥ 10% positive' group was compared with the 'ER ≥ 1% positive' group, specificity increased from 79.7% to 92.5% and PPV increased from 93.9% to 97.5%. When the 'PgR ≥ 10% positive' group was compared with the 'PgR ≥ 1% positive' group, specificity increased from 84.2% to 89.3% and PPV improved from 89.7% to 92.9%. The revised ASCO/CAP guidelines decreased discordant results by > 50% for ER and by 18.2% for PgR. CNB has high concordance with SS in the evaluation of the molecular profile of invasive breast cancer. Thus, molecular evaluation does not need to be repeated with SS except for ER-, PgR- and HER2/neu-negative CNB results. The revised ASCO/CAP guidelines resulted in more precise ER and PgR status on CNB.

Abstract P3-07-58: CD44v as a potential predictive biomarker for pathologic complete response in primary HER2+ breast cancer: Utility of adaptive response biopsy in preoperative therapy

Abstract Background: Preoperative dual anti-HER2 therapy with lapatinib and trastuzumab in combination with conventional chemotherapy demonstrates a higher pathologic complete response rate (pCR) than trastuzumab with chemotherapy in patients with HER2+ breast cancer. Preoperative chemotherapy has been reported to increase the fraction of cancer stem-like cells (CSCs) in breast cancer, but this effect has not been well validated in clinical setting. Cancer cells with the epithelial-mesenchymal transition (EMT) phenotype also exhibit stem cell–like properties with drug resistance. Our goal was to determine the quantitative values of various biomarkers in baseline and adaptive response biopsy specimens and in subsequent surgical specimens to predict pCR in patients treated with dual anti-HER2 therapy as demonstrated by reduction of CSCs, phosphorylated receptors and signaling kinases, and circulating tumor cells (CTC) with the EMT phenotype. Methods: Eighteen patients with operable primary HER2+ invasive breast cancer (≥T2 excluding inflammatory breast cancer, any N) were eligible. Patients received lapatinib (1000 mg PO daily) + trastuzumab (4 mg/kg at loading, then 2 mg/kg IV weekly) for the first 6 weeks, then lapatinib (750 mg daily) + trastuzumab (2 mg/kg IV weekly) + paclitaxel (80 mg/m2 IV weekly) for 12 weeks, followed by surgery (ClinicalTrials.gov Identifier: NCT01688609). Tumor and blood specimens were collected before (baseline), after the 6 weeks of dual anti-HER2 therapy (adaptive response biopsy), and at 18 weeks, after 12 weeks of dual anti-HER2 therapy + paclitaxel (surgical specimens). We measured CSC biomarkers CD44 variant (CD44v) and aldehyde dehydrogenase-1 in tumor tissues, EMT markers in CTCs (TWIST1, SNAIL1, SLUG, ZEB1, and FOXC2) in blood samples by quantitative RT-PCR, and the ratios of phosphorylated EGFR (pEGFR)/EGFR, pHER2/HER2, pERK/ERK, and pAkt/Akt in tumor tissues. All tissue and CTC biomarker levels at all three time points were evaluated for their association with response via Fisher's exact test, McNemar's test, and Wilcoxon rank sum test according to the variables. Results: Eight of 18 patients (44.4%) achieved pCR after dual anti-HER2 therapy + concurrent paclitaxel. All patients who achieved pCR showed reduction or disappearance of CD44v+ cells over the treatment course. Five of the 10 non-pCR patients showed consistent CD44v expression or enrichment after dual anti-HER2 therapy in both the adaptive response biopsy and the surgical specimens. None of the eight pCR patients had detectable CD44v in the 7-week adaptive response biopsy specimen (Fisher exact test, two-tailed, P = 0.0359). None of the other markers significantly predicted pCR. Conclusion: Persistent expression or enrichment of CD44v was suggested to be predictive for non-pCR in breast cancer patients treated with preoperative dual anti-HER2 therapy plus concurrent cytotoxic chemotherapy. A single evaluation of biomarkers before therapy is insufficient for prediction of clinical response. Application of the adaptive response biopsy during the course of preoperative therapy might play a significant role in the success of therapeutic strategies that target CSCs. Citation Format: Yamauchi T, Imamura CK, Yamauchi H, Jinno H, Takahashi M, Kitagawa Y, Nakamura S, Lim B, Krishnamurthy S, Reuben JM, Liu D, Tripathy D, Zujewski JA, Chen H, Takebe N, Saya H, Ueno NT. CD44v as a potential predictive biomarker for pathologic complete response in primary HER2+ breast cancer: Utility of adaptive response biopsy in preoperative therapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-58.

The outcomes of "atypical" and "suspicious" bile duct brushings in the identification of pancreaticobiliary tumors: Follow-up analysis of surgical resection specimens.

Bile duct brushing cytology is frequently used to investigate suspected pancreaticobiliary tumors, but it is associated with low diagnostic sensitivity. As recently proposed by the Papanicolaou Society of Cytopathology in its new classification scheme for pancreaticobiliary cytology, the use of "atypical" and "suspicious (for malignancy)" categories may give a better prediction of malignancy and improve patient management. A series of 65 "atypical" and "suspicious" results initially diagnosed at the University of Washington and Harborview Medical Centers between 2005 and 2012 were analyzed to determine outcomes based on the review of subsequent surgical resection specimens. Seven of 15 (47%) "atypical" cases demonstrated malignant outcomes, whereas 49 of 50 (98%) "suspicious" cases showed documented malignancy within a mean follow-up of 4 months (P < 0.0001 from Pearson's chi-squared test). The analysis of surgical resection specimens demonstrates that 59% of "atypical" and "suspicious" bile duct brushings with malignant outcomes were pancreatic adenocarcinoma (95% confidence interval (CI): 46-71%), 97% of pancreatic adenocarcinomas caused strictures in the head of the pancreas (95% CI: 86-100%), and that 86% of pancreatic adenocarcinomas were moderate to poorly differentiated (95% CI: 73-99%). Fifty-three of the 60 (88%) patients in the presence of prior stenting had a histologically confirmed malignancy. The use of "atypical" and "suspicious" categories may allow more accurate surveillance and/or more rapid surgical exploration of pancreaticobiliary tumors.

Use of BRAF v600e immunocytochemistry on FNA direct smears of papillary thyroid carcinoma.

Mutations of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) are identified in almost half of all papillary thyroid carcinomas (PTCs). These mutations are specific for PTC and may confer a worse prognosis. An immunohistochemical (IHC) stain for BRAF is commercially available and has been validated in surgical specimens. Fine-needle aspiration (FNA) is frequently used as a diagnostic tool for risk stratification of thyroid nodules. Therefore, the authors evaluated the performance of immunostaining with the anti-BRAF antibody VE1 on FNA direct smears. The authors identified 51 FNA specimens that had subsequent surgical resection specimens with a diagnosis of PTC. BRAF VE1 IHC was performed on the surgical specimens to determine their mutation status. The corresponding direct smears were then stained using the same VE1 stain to assess correlation. Twenty-two of the 46 included surgical specimens were positive for BRAF mutations (47.8%) by IHC, consistent with the published rates. The paired cytologic smears from these cases revealed 65.3% concordance. The overall sensitivity of BRAF staining on cytologic smears was 63.6%, and the specificity was 58.3%. Concordance rates were highest in specimens that were diagnosed as malignant or suspicious for malignancy (75% and 85.7%, respectively). The negative predictive value increased to 77.8% when suspicious for follicular neoplasm/suspicious cases were combined. Specimens that were malignant or suspicious on FNA were most likely to be BRAF concordant. Limitations to the interpretation of smears included low cellularity and obscuring blood, macrophages, or colloid. With further refinement, it is possible that BRAF immunocytochemistry can be applied prospectively to thyroid FNAs for risk stratification and to reduce false-negative rates.

Tu1672 Final Cytopathologic Diagnosis of Initially “Indeterminate” Pancreatic Mass Lesions

Tu1672 Final Cytopathologic Diagnosis of Initially “Indeterminate” Pancreatic Mass Lesions Nigeen F. Hessami, Stuart R. Gordon, Timothy B. Gardner* Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH Background & Aims: Endoscopic Ultrasound (EUS)-guided Fine Needle Aspiration (FNA) of pancreatic masses is generally very accurate; occassionally however, cytology is classified as atypical or suspicious. These “indeterminate” results often lead to repeat procedures along with patient and provider uneasiness. We aimed to determine the final pathologic diagnosis in patients with pancreatic masses undergoing EUS-FNA whose initial cytology report was characterized as “atypical” or “suspicious”. Methods: A retrospective chart review was performed on patients referred for EUS-FNA of a pancreatic mass at our medical center from 2000-11. Initial cytology results were characterized as “benign”, “atypical”, “suspicious”, or ”malignant”. Reports were then compared to the final pathology of the pancreatic mass which was obtained from a repeat EUS-FNA or a subsequent surgical specimen. The following lesions were considered malignant: lymphoma, adenocarcinoma, islet cell tumor, and metastatic disease. Results: 619 patients met the inclusion criteria. On initial EUS-FNA, 448 had a “malignant” cytology, 26 had “suspicious” cytology, 29 were “atypical”, and 88 were “benign”. Of the 26 with “suspicious” cytology, 92.3% eventually were found to have a malignant diagnosis. In the 29 patients with “atypical” cytology, 65.5% eventually were eventually deemed malignant. In the 448 patients with an initial “malignant” report, 99.3% had the malignancy subsequently confirmed. The probability of an initial “suspicious” diagnosis being negative and an initial “malignant” diagnosis being negative were equivalent (pZ0.23). Linear regression demonstrated that a “suspicious” cytology was most likely in lesions from the neck (OR Z 2.01, 95% CI 1.23-2.79) and body (OR Z 2.23, 95% CI 1.78-2.67) and “atypical” cytology from the uncinate (OR Z 3.05, 95% CI 2.47-3.64). Conclusion: EUS-FNA of pancreas masses with an initial “suspicious” cytology are almost always found eventually to be malignant. These findings suggest that “suspicious” cytology may be treated as if the result were malignant. Probability that a Pancreatic Mass was Malignant given the EUSguided FNA Cytology Results

Tu1673 Cytology With Rapid on-Site Examination (ROSE) Does Not Improve Diagnostic Yield of EUS-FNA of Pancreatic Cystic Lesions

Tu1672 Final Cytopathologic Diagnosis of Initially “Indeterminate” Pancreatic Mass Lesions Nigeen F. Hessami, Stuart R. Gordon, Timothy B. Gardner* Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH Background & Aims: Endoscopic Ultrasound (EUS)-guided Fine Needle Aspiration (FNA) of pancreatic masses is generally very accurate; occassionally however, cytology is classified as atypical or suspicious. These “indeterminate” results often lead to repeat procedures along with patient and provider uneasiness. We aimed to determine the final pathologic diagnosis in patients with pancreatic masses undergoing EUS-FNA whose initial cytology report was characterized as “atypical” or “suspicious”. Methods: A retrospective chart review was performed on patients referred for EUS-FNA of a pancreatic mass at our medical center from 2000-11. Initial cytology results were characterized as “benign”, “atypical”, “suspicious”, or ”malignant”. Reports were then compared to the final pathology of the pancreatic mass which was obtained from a repeat EUS-FNA or a subsequent surgical specimen. The following lesions were considered malignant: lymphoma, adenocarcinoma, islet cell tumor, and metastatic disease. Results: 619 patients met the inclusion criteria. On initial EUS-FNA, 448 had a “malignant” cytology, 26 had “suspicious” cytology, 29 were “atypical”, and 88 were “benign”. Of the 26 with “suspicious” cytology, 92.3% eventually were found to have a malignant diagnosis. In the 29 patients with “atypical” cytology, 65.5% eventually were eventually deemed malignant. In the 448 patients with an initial “malignant” report, 99.3% had the malignancy subsequently confirmed. The probability of an initial “suspicious” diagnosis being negative and an initial “malignant” diagnosis being negative were equivalent (pZ0.23). Linear regression demonstrated that a “suspicious” cytology was most likely in lesions from the neck (OR Z 2.01, 95% CI 1.23-2.79) and body (OR Z 2.23, 95% CI 1.78-2.67) and “atypical” cytology from the uncinate (OR Z 3.05, 95% CI 2.47-3.64). Conclusion: EUS-FNA of pancreas masses with an initial “suspicious” cytology are almost always found eventually to be malignant. These findings suggest that “suspicious” cytology may be treated as if the result were malignant. Probability that a Pancreatic Mass was Malignant given the EUSguided FNA Cytology Results

Atypical urothelial tissue fragments in noninstrumented voided urine specimens are associated with low but significantly higher rates of urothelial neoplasia than benign-appearing urothelial tissue fragments.

The interpretation of urothelial tissue fragments (UTF) in voided urine (VU) specimens is controversial. If UTF contain cytomorphologically atypical cells, the diagnosis often becomes more challenging. The authors previously analyzed the outcome of patients with benign-appearing UTF in 274 noninstrumented VU specimens. In this retrospective study, noninstrumented VU specimens containing UTF with atypical cytomorphological features (AUTF) were evaluated and compared with the previous results. The Johns Hopkins Hospital electronic pathology database was searched for VU cases containing UTF over a 5-year period. A total of 170 noninstrumented VU specimens containing AUTF were identified. Twenty-four specimens had subsequent or coincidental surgical pathology specimens with the following overall rates of neoplasia: high-grade urothelial carcinoma: 8.8% (15 specimens), low-grade urothelial neoplasia: 1.2% (2 specimens), and prostate carcinoma invading the bladder: 0.6% (1 specimen). A total of 49 specimens (28.8%) were diagnosed with urolithiasis on follow-up. Twenty-five cases had follow-up cytology specimens, all of which were negative for malignancy. Of 72 cases without histopathologic, radiologic, or cytopathologic follow-up, 62 (86.1%) had a mean clinical follow-up of 22.5 months and 10 cases did not have clinical follow-up. The presence of AUTF in noninstrumented VU is associated with low rates of urothelial neoplasia but a statistically higher risk of urothelial neoplasia than the presence of BUTF (10.0% vs 4.4%; P<.05). In particular, the rate of high-grade urothelial carcinoma is significantly higher in noninstrumented VU specimens containing AUTF than those containing BUTF (8.8% vs 0.7%; P<.0001). In addition, urolithiasis is associated with AUTF in a substantial percentage of noninstrumented VU specimens.

The Role of Endorectal Ultrasound and Magnetic Resonance Imaging in the Management of Early Rectal Lesions in a Tertiary Center

BackgroundIn early rectal cancer, ERUS has a vital role in determining radical or local excision based on identification of T-stage. Transanal endoscopic microsurgery (TEMs) has a reduced morbidity and mortality compared with radical surgery. Correct identification of lesions that can be managed with TEMs is therefore imperative. Our aim was to assess the accuracy of ERUS in identifying mucosal/submucosal lesions and thus their suitability for TEMs. Patients and MethodsA retrospective analysis of a prospectively maintained database of patients who underwent ERUS was carried out over an initial 25-month period at a tertiary colorectal center. Our main outcome measures were T-stage measured using ERUS or magnetic resonance imaging (MRI) (indicating suitability for local excision, ie, ≤ T1) with correlation with that of the subsequent surgical specimen and improvement in accuracy over time. After data analysis and review, the study was repeated over the subsequent 12 months to establish whether there was a learning curve with the use of ERUS. ResultsOver the initial period, 52 patients who met the inclusion criteria underwent ERUS. T-staging was accurate in 73.1% (38/52) with identification of ≤ T1 lesions having a sensitivity of 70.8% and a specificity 100%. The accuracy, sensitivity, and specificity of MRI was similar to that of ERUS (72.7%, 70.0%, and 100% respectively). Over the subsequent period, 23 patients underwent ERUS with T-staging accuracy improving to 78.3% (18/23) (P = .777). ConclusionIn our experience, ERUS is a useful adjunct to clinical assessment and pelvic MRI in determining suitability for local excision. Its 100% specificity in determining that a lesion is limited to the mucosa or submucosa aids in the assessment of lesions that are being considered for submucosal resection. Over the time periods assessed, improvement in T-staging accuracy was demonstrated, which might be due to the presence of a learning curve.

Residual disease following conization of women with stage IA-IB1 cervical carcinoma in a high incidence region.

To determine rates of residual disease along with influencing factors in women with stage IA to IB1 cervical carcinoma after conization. A retrospective study was conducted of medical records of 198 stage IA to IB1 cervical carcinoma patients who had undergoing cervical conization followed by primary surgical treatment during 2006-2013. Independent factors correlating with residual carcinoma in subsequent surgical specimens were analyzed by stepwise regression analysis. Mean age was 48.9 years. Cone specimens demonstrated free margins in 36 women (18.8%). In case of having disease at margin, high-grade cervical intraepithelial neoplasia (CIN) and carcinoma were evidenced in 58 and 97 women, respectively. Pathology of subsequent specimens revealed residual carcinoma in 78 women (39.4%), high-grade CIN or adenocarcinoma in situ (AIS) in 45 (22.7%), and no residual pathology in 75 (37.9%). Age more than 35 years, postmenopausal status, having symptoms, diseases or invasive lesions at conization margins or disease on endocervical aspect, and higher stage were significantly correlated with residual cancer in surgical treatment specimens. On regression analysis, postmenopause and stage were independent factors associated with residual carcinoma. Patient and tumor characteristics are predictive factors for residual cancer in the studied group of women.

Comparison of the Yield of Different Diagnostic Procedures for Cellular Differentiation and Genetic Profiling of Non–Small-Cell Lung Cancer

As treatments for non-small-cell lung cancer (NSCLC) become personalized, cellular and molecular differentiation of the tumor is becoming the standard of care. Our objective is to compare the yield of different diagnostic procedures for cellular differentiation of NSCLC and analysis of epidermal growth factor receptor (EGFR) mutation. We evaluated all patients diagnosed with NSCLC from January 2004 to September 2010 at the Jewish General Hospital, Montreal. Diagnostic procedures included surgical biopsies, nonsurgical histologic biopsies (endobronchial and core needle), transbronchial needle aspirate (TBNA) and transthoracic needle aspirate (TTNA), bronchoalveolar lavage (BAL), and pleural fluid samples. We included 702 subjects investigated for histopathologic differentiation of NSCLC. Of these, 269 were also investigated for EGFR mutation. Failure to ascertain the cellular subtype and EGFR mutation status was least likely with surgical specimens (0% and 1.8%, respectively); followed by TTNA (14% and 10%, respectively) and histologic biopsy (18% for both); and was frequent with TBNA (39% and 30%, respectively). Although BAL and pleural fluid specimens provided reasonable yield for cellular differentiation (20 % and 11%, respectively), their results were not accurate in 6% of their samples when compared with concurrent or subsequent surgical specimens (reference standard) performed in a subgroup of patients. Radiologically guided TTNA and histologic biopsies provided high yield for both molecular and histologic analyses. The yield of unguided TBNA was relatively low. Further studies are needed to assess the adequacy of BAL and pleural fluid samples for EGFR mutation analysis and accurate characterization of cellular subtypes of NSCLC.

Prospective analysis of sensitivity and specificity of urinary cytology and other urinary biomarkers for bladder cancer

IntroductionAlthough urinary cytology (C) is the most widely used noninvasive test for the detection and surveillance of bladder cancer (BC), it has poor sensitivity especially for low-grade tumors. We prospectively tested the performance of urine markers on patients with BC using C and 4 commercially available urinary marker tests: Hemoglobin Dipstick (H), BTA Stat (B), NMP22 BladderChek (N), and ImmunoCyt (I). MethodsUrinary samples from 109 consecutive patients with BC were prospectively collected. All samples were tested using conventional C and available biomarkers. Prior and subsequent surgical specimen reports were examined, and sensitivity and specificity were calculated for each. Collected variables included patient demographics, date of urinary collection, type of specimen (voided, washing, or catheterized), surgical pathology, recurrence, and follow-up. ResultsSensitivity values for each marker were as follows: C, 48% (16% for low-grade tumors and 84% for high-grade [HG] tumors); B, 61% (36% and 91%); H, 51% (38% and 66%); N, 58% (25% and 92%); and I, 62% (47% and 83%). Specificity results for each marker were as follows: C, 86%; B, 78%; H, 58%; N, 85%; and I, 79%. On multivariate analysis, higher stage (C and N) and HG disease (C, H, B, N, and I) were independent prognostic factors for improved test performance. When urinary markers were combined with C, sensitivity/specificity values for HG disease were as follows: C+H, 85%/57%; C+B, 91%/78%; C+N, 94%/84%; and C+I, 90%/78%. ConclusionsBased on these data, C seems to yield the highest specificity and N the highest sensitivity for HG tumors. The combination “C+N” seems to be the better approach to improve the sensitivity for HG tumors compared with single markers and other combinations.

Concordance between Core Needle Biopsy and Surgical Excision Specimens for Tumour Hormone Receptor Profiling According to the 2011 St. Gallen Classification, in Clinical Practice

To focus on and compare the tumor hormone receptor profiles on core needle biopsy (CNB) and subsequent surgical excision specimens in a large clinical series of invasive breast carcinoma patients, with regard to guidelines proposed at the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. A total of 993 consecutive patients who had hormone receptors (HR) assays performed on both CNB and subsequent surgical excision specimens of invasive carcinomas were included (1,110 tumors). Concordant tumor HR profiles between CNB and surgical excision specimens were noted in 1,085 of 1,110 tumors (97.75%). Among 138 tumors considered negative on CNB (both HR assays <1%), 10 cases (7.2%) displayed an HR profile positive on surgical excision specimen. Discrepancies between CNBs and surgical excision specimens are very seldom noted. HR assay evaluation on surgical excision specimens should only be considered in patients when both HR assays are negative on CNBs.

Cytologic Appearance of Atypical Endometrial Cells in Pap Tests: Is There Correlation with Subsequent Surgical Pathology Specimens?

Cytologic Appearance of Atypical Endometrial Cells in Pap Tests: Is There Correlation with Subsequent Surgical Pathology Specimens?

The accuracy of preoperative U.S.-guided vacuum-assisted breast biopsy (VABB) in determining ER, PgR, HER2, and Ki67 status in early breast cancer.

37 Background: The intrinsic subtypes are important in the management of patients with early breast carcinoma; however, there have been only a few reports about the accuracy of preoperative subtyping by the preoperative ultrasonography guided vacuum-assisted breast biopsy (U.S.-guided VABB). The aim of this study was to evaluate concordance of the status of ER, PgR, HER2, and Ki67 between U.S.-guided VABB and subsequent surgical specimen. Methods: We retrospectively assessed the concordance of ER, PgR, HER2 and Ki67 status between U.S.-guided VABB and surgical specimen. The patients (n=228) underwent surgical treatment without neoadjuvant chemotherapy at the institute of Japan Association of Breast and Thyroid Sonology (JABTS) Interventional study Group from 2009 to 2012. All the US-guided VABB were performed using 8 or 11-gauge Mammotome or 10-gauge VACORA. The ER and PgR status were determined by IHC and HER2 expression status was tested by both IHC and FISH. The agreement on ER, PgR, HER2 and Ki67 status were evaluated by the absolute concordance rate and the kappa statistic values. Results: The concordance rate of ER, PgR, and HER2 status between U.S.-guided VABB and surgical specimens were 96.4% (134/139), 89.2% (124/139), and 96.3% (130/135), respectively (kappa statistic value of 0.90, 0.77, and 0.84), and the agreement of Ki67 level was 89.6% (112/125) with a Kappa statistic value of 0.79. The concordance rate of the intrinsic subtypes was 84.0% (105 of 125 cases). Conclusions: The judgment of ER status, and HER2 status by preoperative U.S.-guided VABB can be used with confidence to determine the treatment strategies based on molecular subtypes.

Is the performance of urinary cytology as high as reported historically? A contemporary analysis in the detection and surveillance of bladder cancer

ObjectivesThe goal of this study was to evaluate sensitivity and specificity of urine cytology during a contemporary period at our institution in comparison with historical analysis and other reported urinary biomarkers. Materials and methodsData from 1,114 consecutive patients corresponding to 3,251 specimens (2,979 cytologic and 272 histologic specimens) between January 2006 and July 2006 were retrieved. Subsequent cytologic and surgical specimen reports were examined with a minimum 2-year follow-up period. Collected parameters included the date of collection, reason for urinary evaluation, type of specimen, and tumor grade. Atypical diagnosis was considered negative. ResultsOn cytologic examination, 71% of specimens were benign, 23% atypical, and 6% suspicious or positive for urothelial carcinoma. Reason for collection was surveillance in 61% and new symptoms in 28%. Depending on the tumor grade, sensitivity results ranged from 10% for low-grade to 51% for high-grade tumors. Importantly, specificity of urine cytology ranged from 83% to 88% (depending on the type of urine collection and type of clinical presentation). Anticipatory positive rate was 44% after a median time of 15 months. Specificity of other reported urinary markers ranges from 40% to 90%. ConclusionOur institution's experience with regard to specificity of urine cytology is lower than reported historically. Whether this is a consequence of heterogeneous study designs and parameters is open to debate. As the anticipatory positive rate was high, close surveillance remains recommended in patients with positive urine cytology and negative workup. Other institutions are encouraged to evaluate whether there remains a significant advantage for urine cytology over other urinary marker assays within their own clinical setting.

Immunohistochemical Expression of HBME-1, E-cadherin, and CD56 in the Differential Diagnosis of Thyroid Nodules

Distinction between benign and malignant thyroid tumors is essential for proper clinical management. The aim of this study was to evaluate the diagnostic potential of a set of 3 molecular markers in the differential diagnosis of thyroid tumors. Immunohistochemistry for HBME-1, E-cadherin (E-CAD), and CD56 was carried out in 36 follicular adenomas, 77 colloid goiters, 36 papillary thyroid carcinomas, and 14 follicular carcinomas. Sixty-eight thyroid fine needle aspiration (FNA) cases confirmed by subsequent surgical resection specimens were selected. Immunocytochemistry for HBME-1, E-CAD, and CD56 was performed in these cases, including 25 papillary thyroid carcinomas, 1 follicular carcinoma, 22 follicular adenomas, and 20 colloid goiters. PTC was characterized by a decreased expression of E-CAD and CD56 contrary to the surrounding benign thyroid tissues. There was no HBME-1 expression in benign thyroid tissues, but it was high in papillary thyroid carcinomas and weak in follicular adenomas. The expression of E-CAD and CD56 was significantly higher in follicular adenomas than in the surrounding thyroid tissues. Analyzing the FNA material, HBME-1 expression was documented in 96% of papillary thyroid carcinomas, but there was no expression in the benign lesions. E-CAD and CD56 expression was significantly weakened in papillary thyroid carcinomas, but enhanced in follicular adenomas. HBME-1 was found only in malignant lesions and can be considered the most sensitive, specific single marker in papillary thyroid carcinomas. CD56 and E-CAD can assist in the decision-making on the benign and malignant nature of the nodule. Immunocytochemistry is of value as an ancillary test to enhance the diagnostic accuracy of thyroid FNA samples.

Implications of diagnosing ductal carcinoma in situ in core needle biopsies of the breast

Objective: To study the implications of Ductal Carcinoma In Situ (DCIS) diagnosis in Core Needle Biopsies (CNBs) of the breast. Method: The histology slides of 59 CNBs and BCS (Breast conserving surgery) /Mastectomy were reviewed for the presence and percentage of DCIS and 63 BCS were reviewed for positivity of the surgical margins. SPSS -13 and appropriate statistical tests were used for analysis. Results: The sensitivity of CNB to predict DCIS in the surgical specimen was 45.65%. A positive relationship was established between DCIS positivity in CNB and DCIS percentage in the subsequent surgical specimen (p=0.002). A positive correlation exists between the number of positive margins and percentage of DCIS (p Conclusion: DCIS in CNB is often associated with DCIS in BCS/mastectomy in a higher percentage of the same. A higher percentage of DCIS frequently has positive BCS margins, thus wider excisions are indicated for women with DCIS positive CNB's. Sensitivity of identifying DCIS in the CNB increases with number of CNB cores. DOI: http://dx.doi.org/10.4038/jdp.v6i1.4419 Journal of Diagnostic Pathology 2011(6); 1: 28-33

Immunohistochemical detection of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 in formalin‐fixed breast carcinoma cell block preparations: Correlation of results to corresponding tissue block (needle core and excision) samples

Evaluation of ER, PR and Her 2 are routinely performed on breast carcinomas. For accurate detection of these markers, compliance with the ASCO/CAP guidelines is recommended. Our previous study showed that alcohol fixation did not affect ER results when alcohol-fixed cell block (CB) sections were compared to formalin-fixed tissue sections, while PR and Her2 showed less concordance. The aim of this study was to evaluate and to compare ER, PR and Her2 IHC results on formalin-fixed CB sections to those observed on subsequent surgical (needle core or resection) specimens (SS). Fifty cases of formalin fixed CB samples obtained from primary (18%) and metastatic (82%) breast carcinomas were studied, all of which had subsequent SS available. ER, PR, and Her2 IHC studies were done on all samples and results were compared. ER results on formalin-fixed CB samples showed excellent correlation with SS (correlation coefficient cc = 0.82). While there was minimal improvement in PR results (cc = 0.433), Her2 detection did not improve by formalin fixation (cc = 0.439). Formalin fixation for CB preparations does not significantly improve the already good detection of ER positive breast tumors. The concordance rate in PR and IHC results between formalin-fixed CB and SS samples showed improvement as compared with the alcohol-fixed CB results. However, there was no improvement in detection of Her2 overexpression by using formalin fixation on cytology specimens.

A case of verrucous carcinoma of the esophagus associated with difficult histopathological diagnosis of endoscopic biopsy specimens

Verrucous carcinoma of the esophagus (VCE) is a rare, slow-growing, well-differentiated squamous cell carcinoma. Histologically, superficial layers of this cancer tend to have less atypical epithelium with non-specific inflammatory change, which therefore makes diagnosis of malignancy extremely difficult unless a surgical specimen is obtained. We recently encountered a case in which a malignant tumor was suspected on initial endoscopic evaluation, but two biopsies revealed no carcinoma cells. Analysis of a third biopsy finally suggested the possibility of squamous cell carcinoma. A subsequent surgical specimen revealed the tumor as VCE. In addition, immunohistochemical examination revealed that Ki67 immunopositive cells were distributed along the basal layer of the VCE, regarded as a pattern unique to this type of cancer. It is important to know of the existence of VCE. In cases in which this tumor is endoscopically suspected, repeated deep biopsy is strongly recommended and the only curative treatment for this type of cancer is resection.

Neuropathology in patients with multiple surgeries for medically intractable epilepsy

Outcomes following surgery for chronic epilepsy are generally good; however, seizures persist/recur following initial surgery in some patients. We hypothesize that in patients who require multiple surgeries for intractable epilepsy, an identifiable pathologic substrate can be found in the subsequent surgical specimen, which accounts for the recurrent seizures. We retrospectively studied 102 patients (56 females) with medically intractable epilepsy who have had at least 2 surgeries more than 60 days apart from 1990-2010. Patient age at time of 1st surgery ranged from 3 months-60 years (mean 18.1 years). Mean duration of seizures prior to 1st surgery was 9.7 years. Time between the 1st and 2nd surgeries ranged from 0.28-15.3 years (mean 4.3 years). The most common pathologies at initial resection included focal cortical dysplasia (45%), tumor (19%), hippocampal sclerosis (16%), and non-specific changes (13%); 10% of patients had multiple significant pathologies. Of the 89 patients that had a significant initial surgical finding, 74 (83.1%) had a significant pathology at 2nd surgery; the same pathology was identified in 49 (66.2%) of these cases. The most commonly identified pathologies at 2nd surgery included remote infarcts (likely postoperative) (N=51) and focal cortical dysplasia (N=29). Three out of the 13 patients with initially non-specific findings had a significant finding at 2nd surgery, excluding postoperative infarct. Follow-up after last surgery ranged from 0.5-190 months (mean 48 months); 83% of patients were on anti-convulsive medication and 57% were seizure-free at last known follow-up. In the majority of cases of recurrent epilepsy with at least 2 surgeries (84%), pathologic findings accounting for seizures were found at the 2nd surgery. In most cases with significant initial pathology, a similar pathology was present at 2nd surgery (55%). Post-operative contusional damage may account for persistent seizures following initial surgery in a subset of patients.