Search

Claudin-4 is a sensitive and specific marker for carcinoma in effusion cytology. The authors examined the diagnostic use of claudin-4 versus MOC-31 and Ber-EP4 by comparing their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in differentiating carcinoma from mesothelioma and benign/mesothelial hyperplasia in effusion specimens.This retrospective study comprised a cohort of 229 cytology specimens, including 211 effusion fluid and 18 fine-needle aspiration specimens. Cytologic categories included 134 carcinoma, 28 mesothelioma, 46 indefinite (suspicious and atypical), and 21 benign. Cell block sections were stained for claudin-4 and compared with those previously stained for MOC-31 and Ber-EP4. Indefinite cases were further reclassified based on clinical and pathologic findings into benign (26 cases), mesothelioma (11 cases), and carcinoma (nine cases).None of the mesotheliomas (0/39) or benign effusions (0/47) were positive for claudin-4, whereas 134 of the 143 carcinoma specimens were positive. Compared to MOC-31 and Ber-EP4, claudin-4 had the highest specificity and PPV (100% for each), followed by Ber-EP4. Claudin-4 showed high sensitivity (93.7%), albeit lower than MOC-31. MOC-31 had the lowest specificity and PPV but the highest sensitivity and NPV. Ber-EP4 had the lowest sensitivity (91.6%).Claudin-4 can be used as a single marker for carcinoma with high sensitivity and superior specificity compared with MOC-31 and Ber-EP4. Mesothelial lineage can be ruled out when claudin-4 is positive. In equivocal cytology samples with few scattered cells of interest, a panel of claudin-4 and Ber-EP4 results in the highest combined sensitivity and specificity.

PURPOSE To our knowledge, NRG/RTOG 9804 is the only randomized trial to assess the impact of whole breast irradiation (radiation therapy [RT]) versus observation (OBS) in women with good-risk ductal carcinoma in situ (DCIS), following lumpectomy. Long-term results focusing on ipsilateral breast recurrence (IBR), the primary outcome, are presented here. PATIENTS AND METHODS Eligible patients underwent lumpectomy for DCIS that was mammogram detected, size ≤ 2.5 cm, final margins ≥ 3 mm, and low or intermediate nuclear grade. Consented patients were randomly assigned to RT or OBS. Tamoxifen use was optional. Cumulative incidence was used to estimate IBR, log-rank test and Gray's test to compare treatments, and Fine-Gray regression for hazard ratios (HRs). RESULTS A total of six hundred thirty-six women were randomly assigned from 1999 to 2006. Median age was 58 years and mean pathologic DCIS size was 0.60 cm. Intention to use tamoxifen was balanced between arms (69%); however, actual receipt of tamoxifen varied, 58% RT versus 66% OBS ( P = .05). At 13.9 years' median follow-up, the 15-year cumulative incidence of IBR was 7.1% (95% CI, 4.0 to 11.5) with RT versus 15.1% (95% CI, 10.8 to 20.2) OBS ( P = .0007; HR = 0.36; 95% CI, 0.20 to 0.66); and for invasive LR was 5.4% (95% CI, 2.7 to 9.5) RT versus 9.5% (95% CI, 6.0 to 13.9) OBS ( P = .027; HR = 0.44; 95% CI, 0.21 to 0.91). On multivariable analysis, only RT (HR = 0.34; 95% CI, 0.19 to 0.64; P = .0007) and tamoxifen use (HR = 0.45; 95% CI, 0.25 to 0.78; P = .0047) were associated with reduced IBR. CONCLUSION RT significantly reduced all and invasive IBR for good-risk DCIS with durable results at 15 years. These results are not an absolute indication for RT but rather should inform shared patient-physician treatment decisions about ipsilateral breast risk reduction in the long term following lumpectomy.

Mucocele-like lesions of the breast identified on core biopsy are rare high-risk lesions associated with variable upgrade rates to carcinoma on excision. We aimed to identify the clinicoradiopathological features that can help optimize management of this lesion. We evaluated 50 mucocele-like lesions identified on core biopsies from two institutions, including 36 with no atypia and 14 with limited atypia. Outcome data from excision or clinicoradiological follow-up were reviewed with core biopsy results. Radiological targets were calcifications in 74% of cases, calcifications with associated mass or density in 16%, and mass in 10%. One of the 16 excised lesions without atypia on core biopsy, which was a mass lesion, was upgraded to mucinous carcinoma on excision. Of the 12 excised lesions with limited atypia, none were upgraded on excision. Among the lesions not excised, 20 without atypia had a median follow-up of 61 months, and 2 with limited atypia had follow-up of 97 and 109 months. None of these 22 patients had new development of their lesions on follow-up. The upgrade rate was 2% in our entire cohort, 3% for lesions without atypia, and 0% for lesions with limited atypia. Clinicoradiological surveillance can be appropriate when a mucocele-like lesion without atypia is identified on core biopsy for a non-mass lesion with pathological-radiological concordance. For mucocele-like lesions with limited atypia, a nonsurgical approach could be considered if the atypia by itself does not warrant excision. The latter recommendation requires careful clinicopathological correlation and support from additional studies.

HER2 overexpression and gene amplification are routinely tested by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. In addition, HER2 mRNA expression is also tested by the Oncotype DX assay. Discordance between laboratories among the different assays remains a problem. To improve the routine HER2 reporting, the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) updated their guidelines in 2018. Our study will compare concordance of HER2 status by IHC and FISH using ASCO/CAP 2013 and 2018 guidelines with Oncotype DX. We retrospectively reviewed 657 estrogen receptor positive primary breast cancer cases with available Oncotype DX tests between 2011 and 2018. Medical records were reviewed for HER2 results by IHC, FISH, and Oncotype DX. The HER2 results by different assays and between 2013 and 2018 guidelines were compared. Of the 657 cases, 280 were tested by IHC, FISH, and Oncotype DX. HER2-equivocal cases by IHC 2013 guidelines were all negative (67/67, 100%) by FISH 2018 guidelines and by Oncotype DX. HER2-equivocal cases by FISH 2013 guidelines were all negative (16/16, 100%) by FISH 2018 guidelines, while 15/16 (93.8%) negative and 1/16 (6.2%) equivocal by Oncotype DX. The HER2-equivocal and HER2-negative groups were similar in age, gender, histology, grade, and Ki67 score. HER2 concordance was highest between Oncotype DX (99.6%) and FISH per 2018 guidelines. This suggests that the ASCO/CAP 2018 guidelines improved the accurate stratification of HER2-equivocal cases.

In preclinical studies, celecoxib has been associated with reduced risk of breast cancer. In this study, the aim was to assess the biomodulatory effect of celecoxib on blood and benign breast tissue biomarkers in women at increased risk for breast cancer. Women at increased risk for breast cancer [5-year Gail risk score of >1.67%, history of atypical hyperplasia, lobular carcinoma in situ, or previous estrogen receptor (ER)-negative breast cancer] were treated with celecoxib at 400 mg orally twice daily for 6 months. Participants underwent random periareolar fine needle aspiration and blood draw at baseline and at 6 months for analysis of biomarkers: serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1 (IGFBP-1), and IGFBP-3; tissue expression of Ki-67 and ER; as well as cytology. Forty-nine patients were eligible for analysis. Median IGFBP-1 levels increased significantly from 6.05 ng/mL at baseline to 6.93 ng/mL at 6 months (P = 0.04), and median IGFBP-3 levels decreased significantly from 3,593 ng/mL to 3,420 ng/mL (P = 0.01). We also detected favorable changes in cytology of 52% of tested sites after 6 months of celecoxib therapy. No changes in tissue Ki-67 and ER expression levels were observed. No grade 3 or 4 toxicity was recorded. Celecoxib was well tolerated and induced favorable changes in serum biomarkers as well as cytology in this pilot phase II trial. A phase IIb placebo-controlled study with celecoxib could be considered for women at increased risk for breast cancer.

BACKGROUND Papanicolaou (Pap) cytology and high-risk human papillomavirus (HPV) DNA cotesting for women aged ≥30 years are recommended for the prevention of cervical cancer. The objective of the current study was to evaluate the efficacy of this cotesting for predicting the risk of high-grade cervical intraepithelial neoplasia 3 (CIN3) during a 3-year follow-up period. METHODS A retrospective database search identified women aged ≥30 years who had baseline HPV and Pap cytology cotesting results in 2007 or 2008 and for whom 3-year follow-up results were available. The cumulative 3-year risks of developing CIN-3 were calculated. RESULTS The 3-year follow-up data after baseline Pap/HPV cotesting were available for 1986 women (mean age, 53 years). Of the 1668 women who had a baseline Pap-negative (Pap-)/HPV- cotesting result, 1561 (93.6%) had a follow-up Pap cytology result that was negative for intraepithelial lesions or malignancy. Of the 1530 women who had follow-up Pap/HPV cotesting, 1504 (98.3%) had a Pap-/HPV- result. The 3-year cumulative risk of developing CIN-3 was found to be highest for women with a baseline Pap-positive (Pap+)/HPV+ cotesting result (12.5%); the risk of CIN-3 was lower in those with a Pap-/HPV+ result (1.5%; P = .0032) or a Pap-/HPV- result (0.06%; P

The Uniform Approach to Breast Fine Needle Aspiration Biopsy was put forward by a learned group of breast physicians in 1997. This landmark manuscript focused predominantly on diagnosis and reporting of mammary epithelial lesions. Today, most American practitioners turn initially to core biopsy rather than aspiration biopsy for the first line diagnosis of solid breast lesions; however, recent efforts from the International Academy of Cytology have produced a system called the Standardized Reporting of Breast Fine Needle Aspiration Biopsy Cytology (colloquially labeled in 2017 as the "Yokohama System"), suggesting a new interest in breast fine needle aspiration (FNA), especially in resource limited settings or clinical practice settings with experienced breast cytopathologists. Fibroepithelial lesions of the breast comprise a heterogeneous group of biphasic tumors with epithelial and stromal elements. Mesenchymal lesions of the breast include a variety of neoplasms of fibroblastic, myofibroblastic, endothelial, neural, adipocytic, muscular, and osteo-cartilaginous derivations. The cytology of mesenchymal breast lesions is infrequently described in the literature and is mainly limited to case reports and small series. This illustrated review highlights the cytologic features of fibroepithelial and mesenchymal mammary proliferations and discusses differential diagnoses and histomorphologic correlates.

BACKGROUND The 2013 testing guidelines for determining the human epidermal growth factor receptor 2 (HER2) status include new cutoff points for the HER2/chromosome enumeration probe 17 (CEP17) ratio and the average HER2 copy number per cell, and they recommend using a reflex test with alternative chromosome 17 probes (Ch17Ps) to resolve equivocal HER2 results. This study sought to determine the clinical utility of alternative Ch17Ps in equivocal cases and the effects of equivocal results and/or a change in the HER2 status on patients' outcomes. METHODS The University of Texas MD Anderson Cancer Center database of HER2 dual-probe fluorescence in situ hybridization results from 2000 to 2010 was searched for cases of invasive breast cancer with HER2/CEP17 ratios

To compare the diagnostic accuracy of ultrasound (US)-guided core needle biopsy (CNB) of breast masses performed with 14-gauge, 16-gauge and 18-gauge needles. We retrospectively reviewed the charts of 1,112 patients who underwent US-guided breast CNB with 14-gauge, 16-gauge and 18-gauge needles. Cases with surgical excision or a minimum of 2 years of imaging follow-up were included. Rates of sample inadequacy, discordance with surgical or imaging findings and upgrade of DCIS to invasive cancer or high-risk lesion to in situ or invasive cancer were computed for each needle size. The study included 703 CNBs: 203 performed with 14-gauge, 235 with 16-gauge and 265 with 18-gauge needles. There were no significant differences between 14-gauge, 16-gauge and 18-gauge needles in rates of specimen inadequacy (0 %, 0.4 % and 1.9 %, respectively) (p = 0.084); surgical discordance (2.6 %, 2.9 % and 3.8 %) (p = 0.76); imaging discordance (0 %, 0 % and 2 %) (p = 1.0); DCIS upgrade (43 %, 43 % and 36 %) (p = 1.00) or high-risk lesion upgrade (38 %, 25 % and 55 %) (p = 0.49). There was no statistically significant difference in diagnostic accuracy of US-guided CNB of breast masses performed with 14-gauge, 16-gauge and 18-gauge needles. • Percutaneous image-guided breast core needle biopsy (CNB) is the standard of care. • Breast CNB with 14-gauge, 16-gauge and 18-gauge needles has similar diagnostic accuracy. • Smaller gauge needles can be confidently used for ultrasound-guided breast CNB.

Intraluminal crystalloids have rarely been described in the breast, particularly in cases with ductal carcinoma in situ (DCIS). We recently encountered a case of DCIS of the breast associated with numerous intraluminal crystalloids. The patient presented with a mass in the right breast, and microcalcifications were detected on screening and diagnostic mammograms; the patient underwent needle biopsies, lumpectomy, and skin-sparing mastectomy. Invasive ductal carcinoma associated with extensive DCIS was diagnosed. Multiple refractile, eosinophilic crystalloids, with variable morphologies including rectangular, triangular and needle-like with sharp borders, were observed within the lumina of DCIS, besides calcium phosphate microcalcifications. We report this case together with a literature review on crystalloid-containing lesions in breast and non-breast tissues. We also studied radiologic findings of these crystalloids using a specimen radiograph.

Background Peritoneal metastases (PM) in patients with gastric adenocarcinoma (GAC) may be identified by diagnostic laparoscopy (DL) or imaging (I). Although prognosis is poor, some patients have excellent outcome. We compared the overall survival (OS) of patients in 3 groups: those with positive cytology (CY+) by DL (DL-CY+), those with gross PM (GPM) by DL (DL-GPM+) and with GPM obvious on I (I-GPM+). Methods 146 GAC patients were identified. The Kaplan–Meier analysis, univariate, and multivariate Cox proportional hazards regression models were employed. Results Patients were primarily men (67%), with good ECOG scores (0–1; 89%), had DL (84%), had poorly differentiated GAC (92%), and had received chemotherapy (89%). The median OS for all patients was 15 months (5%CI, 12.9–18.2 months). The DL-CY+ group had median OS of 22.5 months (95%CI, 15–29.3 months). Patients with I-GPM+ had four times the risk of death than those with DL-CY+ (P

Purpose The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation. Patients and Methods This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method. Results Median follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients. Conclusion In this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted.

Background Acurrate assessment of HER2 status in patients with breast cancer is critical in selecting patients for targeted therapy. In 2013, the American Society of Clinical Oncology-/College of American Pathologists (ASCO/CAP) released new guidelines for HER2 testing in an attempt to more acurately identify all breast cancer patients who are eligible for HER2 targeted therapy; these guidelines included new cutoff points for HER2/CEP17 ratio by in situ hybridization (ISH) or average HER2 copy number/cell and recommended the use of a reflex test with alternative ISH chromosome 17 probe for resolving cases with equivocal HER2 ISH results. We sought to determine the clinical utility of alternative chromosome 17 probes in such equivocal cases. Patients and Methods Our institution's database of HER2 dual- probe ISH results was searched for cases of invasive breast cancer with a HER2/CEP17 ratio of 4 and Results Of 5489 cases of invasive breast cancer tested by dual-probe ISH for HER2 gene status, 316 (5.7%) cases were found to have equivocal results according to the 2013 ASCO/CAP guidelines. Further analysis of the 30 equivocal consecutive cases using the alternative chromosome 17 probes (SMS/RARA), 17 cases were upgraded from equivocal to positive HER2 status, and 13 cases remained unchanged. Conclusion The use of alternative chromosome 17 probes effectively determines true HER2 status in most equivocal HER2 ISH cases. Equivocal results are common; therefore, we advocate testing for alternative chromosome 17 genes to better categorize equivocal cases under the new ASCO/CAP guidelines. Additional analysis of the remaining equivocal cases and their relation to disease progression is underway and will be presented at the meeting. Citation Format: Sneige N, Gong Y, Multani AS, Ibrahim NK. The clinical utility of alternative chromosome 17 probes in equivocal HER2 results. [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 P5-07-08.

The aim of this study was to analyze the clinicopathological features of patients with flat epithelial atypia, diagnosed in directional vacuum-assisted biopsy targeting microcalcifications, to identify upgrade rate to in situ ductal or invasive breast carcinoma, and determine factors predicting carcinoma in the subsequent excision. We retrospectively evaluated the histological, clinical, and mammographic features of 69 cases from 65 women, with directional vacuum-assisted biopsy-diagnosed flat epithelial atypia with or without atypical ductal hyperplasia or atypical lobular hyperplasia, which underwent subsequent surgical excision. The extent and percentage of microcalcifications sampled by directional vacuum-assisted biopsy were evaluated by mammography. All biopsy and surgical excision slides were reviewed. The age of the women ranged from 40 to 85 years (mean 57 years). All patients presented with mammographically detected microcalcifications only, except in one case that had associated architectural distortion. Extent of calcifications ranged from1 cm (n = 47), 1-3 cm (n = 15) to 3 cm (n = 6), and no measurement (n = 1). A mean of 11 cores (range 6-25) was obtained from each lesion. Post-biopsy mammogram revealed90% removal of calcifications in 81% of cases. Pure flat epithelial atypia represented nearly two-thirds of directional vacuum-assisted biopsy specimens (n = 43, 62%), while flat epithelial atypia coexisted with atypical ductal hyperplasia (18 cases, 26%), or atypical lobular hyperplasia (8 cases, 12%). Upon excision, none of the cases were upgraded to in situ ductal or invasive breast cancer. In one case, however, an incidental, tubular carcinoma (4 mm) was found away from biopsy site. Excluding this case, the upgrade rate was 0%. Our study adds to the growing evidence that diagnosis of flat epithelial atypia on directional vacuum-assisted biopsy for microcalcifications as the only imaging finding is not associated with a significant upgrade to carcinoma on excision, and therefore, excision may not be necessary. Additionally, excision may not be necessary for flat epithelial atypia with atypical ductal hyperplasia limited to ≤2 terminal duct-lobular units, if at least 90% of calcifications have been removed on biopsy.

// Yusuke Shimodaira 1 , Rebecca S. Slack 2 , Kazuto Harada 1 , Manoop S. Bhutani 3 , Elena Elimova 1 , Gregg A. Staerkel 4 , Nour Sneige 5 , Jeremy Erasmus 6 , Hironori Shiozaki 1 , Nikolaos Charalampakis 1 , Venkatram Planjery 1 , Dilsa Mizrak Kaya 1 , Fatemeh G. Amlashi 1 , Mariela A. Blum 1 , Heath D. Skinner 7 , Bruce D. Minsky 7 , Dipen M. Maru 5 , Wayne L. Hofstetter 8 , Stephen G. Swisher 8 , Jeannette E. Mares 1 , Jane E. Rogers 9 , Quan D. Lin 1 , William A. Ross 3 , Brian Weston 3 , Jeffrey H. Lee 3 and Jaffer A. Ajani 1 1 Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA 2 Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA 3 Department of Gastroenterology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA 4 Department of Anatomic Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA 5 Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA 6 Department of Diagnostic Radiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA 7 Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA 8 Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA 9 Department of Pharmacy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA Correspondence to: Jaffer A. Ajani, email: // Keywords : esophageal carcinoma, fine-needle aspiration, endoscopic ultrasound, upper mediastinal lymph nodes, positron emission tomography Received : March 15, 2017 Accepted : April 17, 2017 Published : May 23, 2017 Abstract Implications of assessing the proximal and far para-tracheal or sub-carinal nodes (para-tracheal [PTN] or sub-carinal [SCN]) associated with lower primary esophageal carcinomas (ECs) are unclear. To evaluate the value of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) for PTN and SCN, we analyzed results by positron emission tomography (PET) avidity, 4 EUS node malignancy features, and EUS-FNA results in all patients with Siewert’s I or II EC. Of 133 patients (PTN, n =102; SCN, n =31) with EUS-FNA, 47 (35%) patients had malignant node, leading to treatment modifications. EUS-FNA diagnosed significantly more patients with malignant nodes ( p =0.02) even when PET and EUS features were combined. Among 94 PET-negative and EUS-negative patients, 9 (10%) had malignant EUS-FNA. At a minimum follow-up of 1 year, only 3 (5%) of 62 patients with benign EUS-FNA had evidence of malignancy in the nodal area of prior EUS-FNA. Patients with malignant EUS-FNA independently had a much shorter overall survival (OS) than those with benign EUS-FNA ( p

OBJECTIVE. The objective of our study was to describe our technique and preliminary results of ultrasound-guided fine-needle aspiration (FNA) of indeterminate internal mammary (IM) lymph nodes in patients with a history of breast cancer. CONCLUSION. Ultrasound-guided FNA of IM nodes is feasible and is particularly useful in the staging of breast cancer.

Introduction Microbiology culture is the "gold standard" for diagnosis of fungal infections; however, culture has a lengthy turnaround time. A more timely assessment is possible with cytology and Gomori-methamine silver (GMS) staining. Materials and methods A total of 100 respiratory tract specimens with a positive fungal Gomori-methamine silver stain and corresponding culture were selected. The cytology slides were reviewed for factors contributing to discrepant results. Specimens were classified as 2 types of variances: interpretative and sampling. Concordant diagnoses were also evaluated. Results Eighty-two cases had fungal organisms that grew in culture. The remaining 18 cases were composed solely of fungal organisms that did not grow in culture (17 cases with Pneumocystis jirovecii ; 1 case with Pityrosporum ovale ). These 18 cases were excluded from the variance analysis. Thirty-three of 82 cases (40%) had concordant cytology and microbiology results, whereas 49 cases were discrepant. Variances were both sampling (41 cases) and interpretive (8 cases). Interpretive variances were predominantly Aspergillus species misinterpreted as Candida . Difficulty identifying true septate hyphae was the major contributing factor for misinterpretation. Conclusions Cytologic evaluation of respiratory specimens remains a useful preemptive diagnostic tool in the rapid diagnosis of fungal infection. Cytology samples significantly contribute to the diagnosis of respiratory fungi. However, interpretive variances between Aspergillus and Candida organisms are common. Awareness of the characteristic features that distinguish fungal organisms can further improve the diagnostic utility of cytology.

BackgroundObservational and experimental data support a potential breast cancer chemopreventive effect of green tea.MethodsWe conducted an ancillary study using archived blood/urine from a phase IB randomised, placebo-controlled dose escalation trial of an oral green tea extract, Polyphenon E (Poly E), in breast cancer patients. Using an adaptive trial design, women with stage I-III breast cancer who completed adjuvant treatment were randomised to Poly E 400mg (n=16), 600mg (n=11) and 800mg (n=3) twice daily or matching placebo (n=10) for 6months. Blood and urine collection occurred at baseline, and at 2, 4 and 6months. Biological endpoints included growth factor [serum hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], lipid (serum cholesterol, triglycerides), oxidative damage and inflammatory biomarkers.ResultsFrom July 2007-August 2009, 40 women were enrolled and 34 (26 Poly E, eight placebo) were evaluable for biomarker endpoints. At 2months, the Poly E group (all dose levels combined) compared to placebo had a significant decrease in mean serum HGF levels (-12.7% versus +6.3%, P=0.04). This trend persisted at 4 and 6months but was no longer statistically significant. For the Poly E group, serum VEGF decreased by 11.5% at 2months (P=0.02) and 13.9% at 4months (P=0.05) but did not differ compared to placebo. At 2months, there was a trend toward a decrease in serum cholesterol with Poly E (P=0.08). No significant differences were observed for other biomarkers.ConclusionsOur findings suggest potential mechanistic actions of tea polyphenols in growth factor signalling, angiogenesis and lipid metabolism.

We evaluated the efficacy of using standard radiologic and histologic criteria to guide the follow-up of patients with lobular carcinoma in situ (LCIS), lobular neoplasia (LN), or atypical lobular hyperplasia (ALH). Patients with high-risk benign lesions diagnosed on biopsy were presented and reviewed in a multidisciplinary clinical management conference from 1 November 2003 through September 2011. Associations between patient characteristics and rates of upgrade were determined by univariate and multivariate logistic models, and times to diagnosis carcinoma were calculated. Of 853 cases reviewed, 124 (14.5%) were lobular neoplasms. In all, 104 patients were clinically and/or radiographically monitored. In 20 patients, who were found to have LN on core biopsy and were recommended to have immediate surgical excision, a more significant lesion was identified in 8 (40%) of the excised specimens. Factors associated with a more significant lesion on excisional biopsy included whether the lobular lesion had been targeted for biopsy and whether the extent of disease involved three or more terminal duct lobular units. Of the 104 patients radiographically and clinically monitored, the median follow-up time was 3.4 years with a range of 0.44-8.6 years. Five patients under surveillance were subsequently diagnosed with breast malignancy (three of the five at a site unrelated to the initial biopsy). Patients with incidental lobular lesions identified on percutaneous core needle biopsy have a small risk of upgrade and may not require an excisional biopsy. Clinical management of low-volume lobular lesions in a multidisciplinary setting is an efficacious alternative to surgical excision when radiologic and histologic characteristics are well-defined.

Determining whether a pancreatic mass is a primary or secondary neoplasm is necessary for appropriate treatment. We reviewed our experience using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for diagnosis of pancreatic tumors to identify clinical and cytopathologic characteristics of metastatic disease. We reviewed all cases of tumors metastatic to the pancreas evaluated at The University of Texas MD Anderson Cancer Center and The Methodist Hospital in Houston, Texas during the period from 2002 to 2012. The review included cytologic specimens, clinical history, radiologic findings, primary tumor type, and clinical follow-up. We identified 66 patients with disease metastatic to the pancreas for which cytologic material was available: 38 (58%) men and 28 (42%) women, with an average age of 63 years (range, 40–89 years). Most metastases (98%) were single lesions, and nearly half were located in the head of the pancreas (30/66). The most common site of origin for these metastases was kidney (27 [41%] cases). Follow-up information was available for 65 (98%) patients, and duration of follow-up ranged from

Background The management of benign papilloma (BP) without atypia identified on breast core needle biopsy (CNB) is controversial. In this study, we determined the upgrade rate to malignancy for BPs without atypia diagnosed on CNB and whether there are factors associated with upgrade. Methods Through our pathology database search, we studied 80 BPs without atypia identified on CNB from 80 patients from 1997 to 2010, including 30 lesions that had undergone excision and 50 lesions that had undergone ≥ 2 years of radiologic follow-up. Associations between surgery or upgrade to malignancy and clinical, radiologic, and pathologic features were analyzed. Results Mass lesions, lesions sampled by ultrasound-guided CNB, and palpable lesions were associated with surgical excision. All 3 upgraded cases were mass lesions sampled by ultrasound-guided CNB. None of the lesions with radiologic follow-up only were upgraded to malignancy. The overall upgrade rate was 3.8%. None of the clinical, radiologic, or histologic features were predictive of upgrade. Conclusion Because the majority of patients can be safely managed with radiologic surveillance, a selective approach for surgical excision is recommended. Our proposed criteria for excision include pathologic/radiologic discordance or sampling by ultrasound-guided CNB without vacuum assistance when the patient is symptomatic or lesion size is ≥ 1.5 cm.

National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31 suggested the efficacy of adjuvant trastuzumab, even in HER2-negative breast cancer. This finding prompted us to develop a predictive model for degree of benefit from trastuzumab using archived tumor blocks from B-31.Case subjects with tumor blocks were randomly divided into discovery (n = 588) and confirmation cohorts (n = 991). A predictive model was built from the discovery cohort through gene expression profiling of 462 genes with nCounter assay. A predefined cut point for the predictive model was tested in the confirmation cohort. Gene-by-treatment interaction was tested with Cox models, and correlations between variables were assessed with Spearman correlation. Principal component analysis was performed on the final set of selected genes. All statistical tests were two-sided.Eight predictive genes associated with HER2 (ERBB2, c17orf37, GRB7) or ER (ESR1, NAT1, GATA3, CA12, IGF1R) were selected for model building. Three-dimensional subset treatment effect pattern plot using two principal components of these genes was used to identify a subset with no benefit from trastuzumab, characterized by intermediate-level ERBB2 and high-level ESR1 mRNA expression. In the confirmation set, the predefined cut points for this model classified patients into three subsets with differential benefit from trastuzumab with hazard ratios of 1.58 (95% confidence interval [CI] = 0.67 to 3.69; P = .29; n = 100), 0.60 (95% CI = 0.41 to 0.89; P = .01; n = 449), and 0.28 (95% CI = 0.20 to 0.41; P.001; n = 442; P(interaction) between the model and trastuzumab.001).We developed a gene expression-based predictive model for degree of benefit from trastuzumab and demonstrated that HER2-negative tumors belong to the moderate benefit group, thus providing justification for testing trastuzumab in HER2-negative patients (NSABP B-47).

BACKGROUND: The authors compared the predictive value of type 16 and/or 18 human papillomavirus (HPV) versus non-16/18 HPV types for high-grade (grade ≥2) cervical neoplasm/vaginal intraepithelial neoplasm and carcinoma (CIN/VAIN2+) in women with mildly abnormal Papanicolaou (Pap) results (ie, atypical squamous cells of undetermined significance [ASCUS] or low-grade squamous epithelial lesion [LSIL]). METHODS: The authors retrospectively selected Pap specimens with HPV testing results obtained from 243 women (155 with ASCUS and 88 with LSIL Pap results) in their Department of Pathology. HPV genotyping was performed using the EasyChip HPV blot assay. The Pap specimens with HPV16/18 and non-16/18 HPV types were compared with follow-up biopsy results. Follow-up duration ranged from 1 month to 58 months (mean, 26 months). RESULTS: In total, 58 of 155 specimens (37%) that had ASCUS and 29 of 88 specimens (33%) that had LSIL were positive for HPV16/18. CIN/VAIN2+ biopsies were identified in 43 of 155 women (28%) with ASCUS and in 28 of 88 women (32%) with LSIL. Women with ASCUS and HPV16/18 had a significantly higher rate (43%) of CIN/VAIN2+ than women with ASCUS and non-16/18 HPV types (19%; P = .003; odds ratio, 3.10; 95% confidence interval, 1.48-6.53). There was no statistically significant difference in the rate of CIN/VAIN2+ between women who had LSIL and HPV16/18 (45%) and those who had LSIL and non-16/18 HPV types (29%; P = .16; odds ratio, 1.96; 95% confidence interval, 0.77-4.97). CONCLUSIONS: HPV genotyping for HPV16/18 improved risk assessment for women with ASCUS Pap results and may be used to predict the risk of CIN/VAIN2+ to better guide follow-up management. Cancer (Cancer Cytopathol) 2013. © 2012 American Cancer Society.

Selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene that reduce the risk of breast cancer are limited to only estrogen receptor-positive (ER(+)) breast cancer. In addition, patient acceptance of SERMs is low due to toxicity and intolerability. New agents with improved toxicity profile that reduce risk of ER-negative breast cancer are urgently needed. Observational studies show that statins can reduce breast cancer incidence and recurrence. The objective of this prospective short-term prevention study was to evaluate the effect of a lipophilic statin, atorvastatin, on biomarkers in breast tissue and serum of women at increased risk. Eligible participants included women with previous history of carcinoma in situ, or atypical hyperplasia, or 5year breast cancer projected Gail risk >1.67%, or lifetime breast cancer risk >20% calculated by models including Claus, Tyrer-Cuzick, Boadicea, or BRCAPRO. Patients underwent baseline fine needle aspiration (FNA) of the breast, blood collection for biomarker analysis, and were randomized to either no treatment or atorvastatin at 10, 20, or 40mg/day dose for 3months. At 3months, blood collection and breast FNA were repeated. Biomarkers included C-reactive protein (CRP), lipid profile, atorvastatin, and its metabolites, Ki-67, bcl-2, EGFR, and pEGFR. Baseline genotype for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) was also measured. Among 60 patients evaluated, a significant reduction in serum CRP, cholesterol and low-density lipoprotein (LDL), and increase in atorvastatin metabolites in serum and breast FNAs was demonstrated. No changes were observed in other tissue biomarkers. This study shows that atorvastatin and its metabolites are detectable in breast samples and may lower serum CRP among women without hyperlipidemia.

Introduction EasyChip HPV blot is a human papillomavirus (HPV) genotyping assay that can be potentially used for HPV assay validation or clinical HPV research. To evaluate its genotyping accuracy, we compared EasyChip HPV blot with quantitative real-time polymerase chain reaction (qRT-PCR)/type-specific PCR assays in the detection of 8 high-risk HPV genotypes. Materials and methods Archival SurePath Papanicolaou specimens with abnormal results and follow-up biopsy (n = 154) were selected retrospectively for HPV genotyping by EasyChip HPV blot. To determine the accuracy of the assay, qRT-PCR and type-specific PCR also were performed and results for 8 high-risk HPV genotypes were compared (HPV16, 18, 31, 33, 35, 45, 52, and 58). Results A total of 95 Papanicolaou specimens were qualified for data analysis. Concordance between EasyChip HPV blot and qRT-PCR/type-specific PCR assays was high, with a very good agreement for the 8 high-risk HPV genotypes (95%; kappa value: 0.894, 95% CI: 0.805-0.984) and for HPV16 and HPV18 (96%; kappa value: 0.899, 95% CI: 0.802-0.996). HPV16 was the most frequent HPV genotype by EasyChip HPV blot. The odds ratio of HPV16/18 for high-grade cervical intraepithelial neoplasia was 11.25 (95% CI: 3.93-32.31). Conclusions EasyChip HPV blot is a reliable HPV genotyping assay that can be used for HPV assay validation or clinical HPV studies.

Mammary Paget disease (MPD) is considered an intraepidermal manifestation of an underlying mammary carcinoma. In contrast to extramammary Paget disease, invasion of mammary Paget cells into the dermis (invMPD) has not been reported, except for 2 cases described in Rosen's textbook. Our study was designed to identify the presence of dermal invasion of mammary Paget cells and characterize the associated clinicopathologic features. Slides from 146 MPD patients were retrieved. Six cases of invMPD were identified. One case of invMPD was not associated with an underlying breast cancer, 1 was associated with invasive ductal carcinoma (IDC), 1 with ductal carcinoma in situ (DCIS) with microinvasion, and 3 with DCIS only. The underlying breast carcinomas was separate from the area of invMPD. The depth of invasion, measured from the dermal-epidermal junction to the focus of deepest invasion, ranged from 0.02 to 0.9 mm. The horizontal extent ranged from 0.01 to 4.0 mm. Lymph node with isolated tumor clusters was present in case 1, which had no underlying carcinoma but had the greatest extent of invasion, and in case 3, which had DCIS with microinvasion. One patient (case 1) died of unrelated causes 2 years later, and the remaining patients were alive without disease at last follow-up. In summary, we describe 6 cases of MPD with invasion of Paget cells into the dermis and provide histopathologic criteria for the diagnosis of this rare and underrecognized entity. Further studies are required to determine whether invasion in MPD has clinical significance.

BACKGROUND: Patients with ovarian serous tumors of low malignant potential (OSLMP) who have peritoneal implants, especially invasive implants, are at an increased risk of developing tumor recurrence. To the best of the authors' knowledge, the ability of peritoneal washing (PW) cytology to detect the presence and type of peritoneal implants has not been adequately investigated, and its prognostic significance is unknown. METHODS: Records and PW specimens of 101 patients diagnosed with and treated for OSLMP between 1996 and 2010 at The University of Texas MD Anderson Cancer Center were retrospectively reviewed. Patients' staging biopsy findings were compared with the results of the authors' review of the PWs. Follow-up data were also analyzed. RESULTS: Of the 96 patients for whom staging biopsy results were available, 26 (27%) had peritoneal implants (17 noninvasive and 9 invasive), 19 (20%) had endosalpingiosis, and 51 (53%) had negative findings. The PW specimens of 18 of the 26 patients (69%) with peritoneal implants were positive for serous neoplasm, and a correlation was found between cytologic and histologic findings (P < .0001). The sensitivity, specificity, positive predictive value, and negative predictive value were 69%, 84%, 62%, and 88%, respectively. Four of 101 patients had disease recurrence; 3 of these patients had invasive implants and 1 patient had noninvasive implants. None of the patients who had negative staging biopsy findings or endosalpingiosis but did have PW specimens that were positive for serous neoplasm developed disease recurrence. CONCLUSIONS: PW cytology detects the presence of peritoneal implants with moderate accuracy. However, long-term studies are needed to determine whether positive PW cytologic findings are an independent predictor of tumor recurrence. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society.

Aims: Microglandular adenosis (MGA) is a proliferative breast lesion, which has been proposed to be a potential precursor of triple-negative breast cancers. The aims of this study were to determine whether MGAs harbour genetic alterations and if any such genetic aberrations found in MGAs are similar to those found in matched invasive carcinomas. Methods and results: Twelve cases of MGA and/or atypical MGA (AMGA), 10 of which were associated with invasive carcinoma, were evaluated. Immunohistochemical profiling revealed that all invasive carcinomas were of triple-negative phenotype and expressed S100, cytokeratins 8/18 and basal markers. The morphologically distinct components of each case (MGA, AMGA and/or invasive carcinoma) were microdissected and subjected to microarray comparative genomic hybridization. Apart from three typical MGAs, all samples harboured genetic alterations. The percentage of the genome affected by copy number aberrations in MGA/AMGA ranged from 0.5 to 61.9%, indicating varying levels of genetic instability. In three cases, MGA/AMGA displayed copy number aberrations similar to those found in matched invasive components, providing strong circumstantial evidence that MGA may constitute the substrate for the invasive carcinoma development. Conclusions: Our results support the contention that MGA can be a clonal lesion and non-obligate precursor of triple-negative breast cancer.

BACKGROUND: Enhancer of zeste homolog 2 (EZH2), a member of polycomb group proteins, is involved in the regulation of cell cycle progression and has been implicated in various human malignancies, including breast cancer, and also has been associated with aggressive tumor behavior. However, the clinical significance of EZH2 expression in inflammatory breast cancer (IBC), a rare but aggressive type of breast carcinoma, has not been explored. In this retrospective study, the authors examined EZH2 expression in IBC tumors and evaluated the relation between EZH2 expression and patient survival. METHODS: Tissue microarrays of 88 surgically resected IBC tumors were stained immunohistochemically for EZH2, and the authors evaluated the association of EZH2 expression status with clinicopathologic factors and clinical outcome. RESULTS: The median follow-up for the entire cohort was 45.7 months, and the 5-year overall survival (OS) rate was 45%. EZH2 was expressed frequently in IBC tumors (75.7%) and was associated significantly with unfavorable prognostic factors, such as higher tumor grade, negative estrogen receptor status, and triple-negative status (ie, negative for the estrogen, progesterone, and human epidermal growth factor 2 receptors). Univariate survival analysis indicated that patients who had EZH2-positive IBC had a significantly lower 5-year OS rate than patients who had EZH2-negative IBC (P = .01). In multivariate analysis, only positive EZH2 status remained an independent predictor of worse OS. CONCLUSIONS: EZH2 was expressed frequently in IBC tumors. The current results indicated that EZH2 expression status may be used to identify a subset of patients with IBC who have a relatively worse prognosis. Targeting EZH2 also may provide a novel strategy for improving the clinical outcome of patients with IBC. Cancer 2011;. © 2011 American Cancer Society.

Prominent coarse eosinophilic cytoplasmic granules reminiscent of those in intestinal Paneth cells are rarely identified in breast carcinomas. In the literature, this phenomenon seems to be associated with acinic cell carcinoma of the breast or microglandular adenosis-related lesions. In this study, we report 3 breast carcinoma cases with such granules. Two of the cases were carcinomas arising in microglandular adenosis, one of which contained areas of acinic carcinoma-like features. The other case was a mammary carcinoma with prominent microglandular adenosis and also acinic cell carcinoma growth patterns. In the latter case, the patient had a history of neoadjuvant chemotherapy; and cells with coarse granules were found in both the pretreatment and posttreatment specimens. Although all 3 tumors were negative for HER2/neu, 2 tumors were estrogen receptor/progesterone receptor negative and one was estrogen receptor/progesterone receptor positive. Follow-up for 2 patients at 12 months and 3 years showed no evidence of disease, and the other patient died of her disease at 34 months. We provide a review of the literature and conclude that prominent coarse eosinophilic granules are a rare and nonspecific feature in breast epithelium. The clinical significance remains to be investigated, given the limited experience.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy is routinely used to stage lung cancer; however, its usefulness in diagnosing lymphoproliferative disorders has not been well established. In this retrospective study, we determined the utility of EBUS-TBNA in evaluating mediastinal lymphadenopathy in patients with suspected lymphoproliferative disorders. METHODS: The authors searched the pathology database at their institution to identify all patients who had undergone EBUS-TBNA biopsy for possible lymphoproliferative disorders. The cytologic diagnoses were correlated with concurrent and subsequent biopsy findings and clinical follow-up data. RESULTS: Of 886 lymph nodes evaluated by EBUS-TBNA biopsy, 91 nodes from 33 patients (23 men and 10 women) were eligible. Fourteen patients had a history of lymphoma. Adequate material for diagnosis was obtained in 31 of 34 procedures (1 patient had 2 procedures). The cytologic diagnoses of the 31 adequate procedures included 19 with benign disease (8 reactive lymph nodes and 11 granulomatous inflammation), 8 with lymphoma (2 large B-cell, 2 small lymphocytic, 2 Hodgkin, 1 mantle cell, and 1 T-cell lymphoblastic), 2 with cells suspicious for Hodgkin lymphoma, and 2 cases with atypical cells. CONCLUSIONS: EBUS-TBNA proved to be useful for evaluating mediastinal lymphadenopathy in patients with suspected lymphoproliferative disorders. Its use may decrease the need for invasive diagnostic procedures. Immediate assessment is valuable in these cases because of the need to triage material for immunophenotyping or other studies to determine optimal and clinically meaningful diagnoses. Cancer (Cancer Cytopathol) 2011. © 2011 American Cancer Society

This study specifically addressed the performance of chromogenic in situ hybridization (CISH) on HER2 testing in 66 breast carcinomas with chromosome 17 polysomy and 49 carcinomas with an equivocal HercepTest (DakoCytomation, Carpinteria, CA) score by comparing CISH with corresponding FISH results at 2 test sites and evaluating intersite agreement of CISH results. For tumors with chromosome 17 polysomy, when using the manufacturers’ criteria, the concordance values between CISH and FISH at site A, site B, and intersite CISH agreement were 95.8%, 95.5%, and 93.5%, respectively; when using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, the values were 100.0%, 100.0%, and 100.0%, respectively. For tumors with an equivocal HercepTest score, when using the manufacturers’ criteria, the concordance values between the 2 methods at site A, site B, and intersite CISH agreement were 88.2%, 95.1%, and 91.1%, respectively; when using the ASCO/CAP criteria, the values were 96.7%, 97.3%, and 97.4%, respectively. These results indicate that CISH is reliable for testing these 2 types of tumors, especially when the ASCO/CAP criteria are used.

Chromogenic in situ hybridization (CISH) has shown the potential to replace fluorescence in situ hybridization (FISH) to determine HER2 gene status. To validate the reliability of CISH, we used 226 consecutive breast carcinomas from 2 institutions and tested CISH and FISH on the same tumor set simultaneously at different test sites. Besides manufacturers' scoring criteria, the new American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines were used to interpret HER2 status. The concordance between CISH and FISH for positive and negative results was 98.5% at site A and 98.6% at site B using the manufacturers' criteria, and 99.0% at site A and 99.1% at site B using the ASCO/CAP criteria. Reproducibility of CISH results was more than 98.0% among 3 sites using the manufacturers' criteria and 100.0% between 2 sites using the ASCO/CAP criteria. Our results confirm that CISH is reliable for HER2 testing per ASCO/CAP guidelines.

Aims: Ductal carcinoma in situ (DCIS) associated with invasive mucinous carcinoma (IMC) has not been well characterized. The aim was to characterize mucinous DCIS (mDCIS) of the breast and to describe, to our knowledge for the first time, neovascularization in mucin. Methods and results: The pathology reports and slides were reviewed from 44 patients treated between 2003 and 2006 at The University of Texas M. D. Anderson Cancer Center, whose diagnosis fulfilled the criteria of IMC or DCIS with mucin production. The patients, all female, had a mean age of 62 years. DCIS was present in 93% of cases and the predominant histological types were solid, cribriform and micropapillary. The DCIS was grade 1 in 12 of 41 cases (29.3%), grade 2 in 25 of 41 cases (61%) and grade 3 in four of 41 cases (9.8%). Mucin was seen in the lumen of the ducts involved by DCIS in 88% of cases, mucin and vessels in 63.4% of cases and neither mucin nor vessels in 12.2%. The DCIS was vascular endothelial growth factor-positive, platelet-derived growth factor receptor-beta-positive and CDX-2-negative (100%). Occasional luminal cells within the DCIS were immunopositive for CD68. Conclusions: A significant number of mDCIS showed neovascularization in intraluminal mucin. When identified on core needle biopsy, the presence of vascularized mucin should not be used alone to discriminate between invasive and in situ carcinoma. A hypothesis proposed for the source of recruitment of vessels in the mucin is that mucin can promote neovascularization and that tumour cells invade not into the adjacent fibroconnective tissue, but rather into the mucinous, richly vascularized stroma that they have induced. Alternatively, it is possible that both cells and their secretory product invade together. To our knowledge, this is the first study to characterize neovascularization within the mucinous component of DCIS associated with and without IMC.

Purpose. To describe the sonographic characteristics of intramammary lymph node metastasis (ILNM) in patients with breast cancer and to assess the value of sonography and sonographically guided fine needle aspiration biopsy (FNAB) in their diagnosis. Methods. We retrospectively reviewed the charts and films of 19 women with biopsy-documented ILNM who were seen in our breast diagnostic center between December 1999 and July 2003. The sonographic appearance of the nodes was analyzed and correlated with clinical and mammographic findings and with biopsy results. Results. The ILNMs were clinically and mammographically occult in 7 (37%) of the 19 women. The diameter of the ILNMs was less than 1 cm in 15 (79%) cases. The volume of the central echogenic hilum was less than 50% of the total volume of the node in each of the patients. There was marked decrease in cortical echogenicity of the ILN in all cases. Metastatic involvement was established via sonographically guided FNAB in each of the 19 suspicious intramammary lymph nodes. Conclusion. Sonography and sonographically guided FNAB are valuable methods of assessment for ILNM in patients with known or suspected breast cancer. The most consistent sonographic features associated with ILNM were reduction in the volume of the central echogenic hilum and marked hypoechogenicity of the node's cortex. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008.

To evaluate a commercialized in situ hybridization (ISH) assay for detecting human papillomavirus (HPV) DNA, we compared the ability of a new ISH probe, Inform HPV III (Ventana Medical Systems, Tucson, AZ), to that of PCR assays to detect HPV DNA in cervical tissue specimens with normal cervix (20 cases), cervical intraepithelial neoplasia (CIN; CIN 1, 27 cases; CIN 2, 28 cases; and CIN 3, 33 cases), and cervical carcinoma (29 cases). General HPV DNA was detected using consensus primer-mediated PCR assays. HPV genotyping was performed by using EasyChip HPV blot (King Car Yuan Shan Institute, I-Lan, Taiwan). HPV16 integration status (E2/E6 ratio) was determined by using quantitative real-time PCR. Our findings showed that the ISH and PCR had fair to good agreements in detecting HPV DNA across all CIN categories without significant differences (Kappa coefficient, 0.34 to 0.63; P = 0.13 to 1.0). However, ISH detected significantly fewer HPV-positive cases in carcinoma than PCR did (Kappa coefficient, 0.2; P = 0.03). Eleven cases with ISH − PCR + results had HPV types that can be detected by Inform HPV III. Five carcinoma cases with ISH − PCR + results showed a significantly higher level of integrated HPV16 ( P = 0.008) than did the ISH + cases. As a consequence, lower copy numbers of episomal HPV16 in carcinoma might be the cause for the false-negative ISH results. Although the punctate signal pattern of HPV significantly increased with the severity of disease ( P trend = 0.01), no significant difference in the HPV16 integration status was observed between the cases with a punctate signal only and the cases with mixed punctate and diffuse signals ( P = 0.4). In conclusion, ISH using the Inform HPV III probe seems comparable to PCR for detecting HPV DNA in cervical tissue with CINs. False-negative ISH results appear to be associated with the lower copy numbers of the episomal HPV16 but not with the ability of the Inform HPV III probe to detect specific HPV types. In addition, signal patterns, especially a mixed punctate and diffuse pattern of HPV, cannot be reliably used to predict viral integration status.

The purpose of this study was to compare the imaging features of metaplastic breast carcinoma with those of invasive ductal carcinoma.Women diagnosed on preoperative mammography or sonography with metaplastic breast carcinoma and T-stage matched invasive ductal carcinoma of the breast from a single pathology database were included in the study. Clinical and pathologic information on all metaplastic cancers was documented. Mammography and sonography variables were recorded using the BI-RADS lexicon. Groups were compared using Fisher's exact test, the chi-square test, or Wilcoxon's rank sum test, as appropriate.Forty-three patients diagnosed with metaplastic carcinoma were matched to 43 patients with ductal carcinoma by tumor T stage. Patients with metaplastic carcinoma were younger (median, 46 vs 53 years, p = 0.048) than those with ductal carcinoma. Mammographically, metaplastic carcinomas were less frequently irregular in shape (16% vs 74%, p0.0001) and less frequently showed microlobulated or spiculated margins (19% vs 56%, p = 0.0008) and calcifications (25% vs 51%, p = 0.02) when compared with ductal carcinomas. Sonographically, metaplastic carcinomas were less frequently irregular in shape (27% vs 69%, p = 0.001) and less frequently showed angular margins (9% vs 49%) and posterior acoustic shadowing (9% vs 49%, p0.0001).Characteristic malignant imaging features, including irregular shape, spiculated margins, segmentally distributed pleomorphic calcifications, and posterior acoustic shadowing, are uncommon in metaplastic carcinomas. These carcinomas tend to show more benign imaging features, such as round or oval shape with circumscribed margins, when compared with ductal carcinomas.

Triple negative breast carcinomas (TNBCs) are a group of primary breast tumors with aggressive clinical behavior. Most TNBCs possess a basal phenotype (BP) and show varying degrees of basal cytokeratin and myoepithelial marker expression. The importance of recognizing these tumors came to light largely as the result of gene expression profiling studies that categorized breast cancer into 3 major groups. Two of these groups are defined by their respective expression of estrogen receptor and HER2. TNBCs represent a third group and are defined by negativity for hormone receptors and HER2. TNBCs currently lack effective targeted therapies and are frequently resistant to standard chemotherapeutic regimens. These tumors tend to occur in premenopausal women and members of specific ethnic groups and a subset are associated with heritable BRCA1 mutations. For patients with sporadic TNBCs and BP tumors, BRCA1 dysfunction seems to play a major role in the development and progression of disease. The pathologist's role in the diagnosis and characterization of TNBCs and BP tumors is currently being defined as we are acquiring knowledge of the biologic and genetic underpinnings that drive this heterogeneous group of diseases. This review will provide a historical prospective on TNBCs and tumors that express basal cytokeratins and myoepithelial makers. Additionally, we will discuss the molecular biologic, genetic and pathologic aspects of these tumors. Guidelines will be provided on how to best approach the diagnosis of these cases and on what input pathologists should provide clinicians to help develop optimal therapeutic and preventative strategies against this aggressive group of breast cancers.

Purpose: Short-term phase I and phase II breast cancer prevention trials require tissue acquisition at baseline and after intervention to evaluate modulation of potential biomarkers. Currently used tissue acquisition methods include ductal lavage (DL), random periareolar fine needle aspiration (RPFNA), and core needle biopsy. The optimum method to retrieve adequate samples and the most accepted method by study participants is not known. Experimental Design: We compared RPFNA and DL as breast tissue acquisition methods for short-term breast cancer prevention trials by evaluating sample adequacy and tolerability in subjects who participated in two prospective phase II breast cancer prevention trials. Eighty-six women at increased risk for breast cancer were included in this study and underwent baseline DL and RPFNA. High risk was defined as having a 5-year Gail score of >1.67% or a history of atypical hyperplasia (AH), lobular carcinoma, or breast cancer. Results: Median age was 54.5 years (range, 39-75 years); 75% of the women were postmenopausal. About 51% of the women yielded nipple aspiration fluid, and breast fluid samples via DL were retrieved in 73% of these subjects. Of these samples, 71% were adequate samples (greater than 10 epithelial cells). However, when the entire cohort was considered, only 31% of the subjects had adequate samples. RPFNA was also attempted in all subjects, and sample retrieval rate was 100%. Out of these, 96% of the subjects had adequate samples. In DL samples, AH rate was 3.7% was and hyperplasia (H) rate was 11.1%. In RPFNA samples, AH rate was 12.9%, and H rate was 24.7%. Cytology findings in RPFNA samples correlated with age, menopausal status, and breast cancer risk category (previous history of lobular carcinoma in situ). Both procedures were well tolerated, and no complications occurred among participants. Conclusions: Considering that the main end point for short-term prevention trials is the modulation of biomarkers, it is important to optimize adequate sample acquisition; therefore, RPFNA is a more practical option for future phase I and II breast cancer prevention trials compared with DL.

Purpose: Recent studies have indicated that expression of chemokine receptors CXCR4 and CCR7 could be an indicator of the metastatic potential of breast cancer. Expression of CXCR4 and CCR7 along with the biomarkers HER2-neu and epidermal growth factor receptor (EGFR) was investigated in inflammatory breast cancer (IBC) to evaluate their prognostic implications. Experimental design: CXCR4, CCR7, and EGFR were evaluated by immunohistochemical staining (IHC) of paraffin-embedded tissue sections. HER2-neu amplification was assessed by FISH and/or IHC. All patients received chemotherapy, surgery, and radiation. Results: Forty-four cases diagnosed with IBC from 1994 to 2002 were included in the study. In all, 18 (40.9%) patients had positive CXCR4, 10 (22.7%) had positive CCR7, 21 (47.7%) had positive HER2-neu, and EGFR was positive in 12 of 40 patients (30%). The 5-year overall survival (OS) was 24.8% for CXCR4-positive disease versus 42.3% for CXCR4-negative patients (P = 0.53) and 20.0% for CCR7-positive disease versus 41.9% for CCR7-negative patients (P = 0.24). EGFR-positive disease had significantly worse OS compared with EGFR-negative disease (P = 0.01). Conclusions: These data demonstrate the expression of growth factor and chemokine receptors in IBC. The expression of these receptors is associated with increased risk of recurrence and death, and thus, they may represent potential therapeutic targets in IBC.

Current human papillomavirus (HPV) DNA testing using pooled probes, although sensitive, lacks specificity in predicting the risk of high-grade cervical intraepithelial neoplasia (CIN 2/3) progression. To evaluate selected HPV genotyping, viral load, and viral integration status as potential predictive markers for CIN progression, we performed HPV genotyping in formalin-fixed, paraffin-embedded cervical tissue with cervical carcinoma (29 cases) and CINs (CIN 1, 27 cases; CIN 2, 28 cases; CIN 3, 33 cases). General HPVs were screened using consensus primers GP5+/GP6+ and PGMY09/11. HPV genotyping and viral load measurement were performed using quantitative real-time PCR for eight oncogenic HPV types (16, 18, 31, 33, 35, 45, 52, and 58). HPV 16 viral integration status was evaluated by measuring HPV 16 E2/E6 ratio. We observed that HPV DNA positivity increased in parallel with the severity of CINs and carcinoma, with 59% positivity in CIN 1, 68% in CIN 2, 76% in CIN 3, and 97% in carcinoma (P trend=0.004). The eight oncogenic HPV types were significantly associated with CIN 2/3 (81%) and carcinoma (93%) (odds ratio (OR), 15.0; 95% confidence interval (CI), 5.67-39.76; P

Objective To evaluate the efficacy of INFORM HPV using the SurePath collection method in women whose Pap tests indicated abnormal results. Study Design Ninety-two women from the gynecology clinics at The University of Texas M. D. Anderson Cancer Center who had Pap tests and underwent follow-up biopsies were selected for the study. This included 51 women with atypical squamous cells of undetermined significance (ASCUS), 23 women with low-grade squamous intraepithelial lesion (LSIL), 15 women with high-grade squamous intraepithelial lesion (HSIL) and 3 women with negative Pap results. The INFORM HPV, an in situ hybridization assay, testing for oncogenic types of HPV was performed, and the results were compared with follow-up biopsies. Results The positive rate of the INFORM HPV increased with higher grades of cytology diagnoses. The sensitivity of the INFORM HPV testing for predicting high-grade cervical intraepithelial neoplasia (CIN 2/3) also increased with higher grades of cytology diagnoses. A negative predictive value (NPV) of 94.9% and a specificity of 80.4% for predicting CIN 2/3 were observed in the ASCUS group. Conclusion Using SurePath Pap specimens, the INFORM HPV lacks sufficient sensitivity and NPV for predicting CIN 2/3 in women with ASCUS. Therefore, use of the test as a triage tool is limited.

Peritoneal metastases (PM) in patients with gastric adenocarcinoma (GAC) may be identified by diagnostic laparoscopy (DL) or imaging (I). Although prognosis is poor, some patients have excellent outcome. We compared the overall survival (OS) of patients in 3 groups: those with positive cytology (CY+) by DL (DL-CY+), those with gross PM (GPM) by DL (DL-GPM+) and with GPM obvious on I (I-GPM+).146 GAC patients were identified. The Kaplan-Meier analysis, univariate, and multivariate Cox proportional hazards regression models were employed.Patients were primarily men (67%), with good ECOG scores (0-1; 89%), had DL (84%), had poorly differentiated GAC (92%), and had received chemotherapy (89%). The median OS for all patients was 15 months (5% CI, 12.9-18.2 months). The DL-CY+ group had median OS of 22.5 months (95% CI, 15-29.3 months). Patients with I-GPM+ had four times the risk of death than those with DL-CY+ (P 0.001) and patients with DL-GPM+ had two times the risk of death than those with DL-CY+ (P = 0.001). At 36 months, all DL-GPM+ and I-GPM+ had died but 8 patients with DL-CY+ remained alive.Some GAC patients with DL-CY+ have long OS; therefore, novel strategies to further prolong their OS are needed.

Purpose The objective of this study was to evaluate whether p27 kip1 downregulation is a prognostic factor in patients with inflammatory breast carcinoma (IBC). Patients and Methods Fifty-eight patients with IBC were treated between January 1994 and July 2002. Median age was 49 years. Thirty-eight patients had baseline biopsy specimens. Patients received preoperative chemotherapy with FAC (5-fluorouracil/doxorubicin/cyclophosphamide; 34%) or FAC followed by a taxane (66%). All patients underwent mastectomies. All patients received radiation therapy and hormonal treatment when indicated. Expression level of p27 kip1 was evaluated by indirect immunoperoxidase procedure. The p27 kip1 was considered downregulated if nuclear staining was present in > 50% of the neoplastic cells. Results Thirty-two patients (84%) had p27 kip1 -downregulated tumors, and 6 patients (17%) had p27 kip1 -normal tumors. Six patients (16%) exhibited a pathologic complete response. At a median follow-up of 43 months, 25 recurrences (66%) and 27 deaths (71%) occurred. Patients with p27 kip1 -downregulated tumors had fewer pathologic complete responses (9% vs. 50%; P = 0.03) and had lower 4-year recurrence-free survival (23% vs. 83%; P = 0.03) and overall survival rates (36% vs. 83%; P = 0.01). Conclusion The p27 kip1 deregulation manifested by low protein cellular concentration might represent an adverse prognostic marker in IBC and could provide a valuable tool for selecting treatment for this aggressive disease.