BACKGROUND: This study assessed BRCA1 and BRCA2 mutation prevalence in an unselected cohort of patients with triple-negative breast cancer (BC). METHODS: One hundred ninety-nine patients were enrolled. Triple negativity was defined as <1% estrogen and progesterone staining by immunohistochemistry and HER-2/neu not overexpressed by fluorescence in situ hybridization. Having given consent, patients had BRCA1 and BRCA2 full sequencing and large rearrangement analysis. Mutation prevalence was assessed among the triple-negative BC patients and the subset of patients without a family history of breast/ovarian cancer. Independent pathological review was completed on 50 patients. RESULTS: Twenty-one deleterious BRCA mutations were identified-13 in BRCA1 and 8 in BRCA2 (prevalence, 10.6%). In 153 patients (76.9%) without significant family history (first-degree or second-degree relatives with BC aged <50 years or ovarian cancer at any age), 8 (5.2%) mutations were found. By using prior National Comprehensive Cancer Network (NCCN) guidelines recommending testing for triple-negative BC patients aged <45 years, 4 of 21 mutations (19%) would have been missed. Two of 21 mutations (10%) would have been missed using updated NCCN guidelines recommending testing for triple-negative BC patients aged <60 years. CONCLUSIONS: The observed mutation rate was significantly higher (P ¼ .0005) than expected based on previously established prevalence tables among patients unselected for pathology. BRCA1 mutation prevalence was lower, and BRCA2 mutation prevalence was higher, than previously described. Additional mutation carriers would have met new NCCN testing guidelines, underscoring the value of the updated criteria. Study data suggest that by increasing the age limit to 65 years, all carriers would have been identified. Cancer 2012;118:2787-

We studied flow cytometry in 156 fine-needle aspirations (FNAs) of lymph nodes performed between June 1993 and September 1998. Information from flow cytometry was combined with cytomorphologic evaluation, and the diagnosis determined by using combined modalities was compared with tissue biopsy results or clinical follow-up. In 74 cases, a combined cytopathologic-flow cytometric diagnosis of lymphoma was made; histologic material was available for 52 patients; in no case was a benign process found. The lymphoma grade assigned agreed with histopathologic findings in 45 of 48 cases with a specific cytologic diagnosis. Treatment was initiated on the basis of the FNA alone for 17 of 52 patients with a history of lymphoma and in 22 additional patients with no follow-up biopsy. Among 71 cases in which the diagnosis using both modalities was benign, the only false-negative was 1 case of Hodgkin disease. Of the 156 cases, 11 were considered atypical or suggestive of lymphoma; biopsies from 8 of 10 patients revealed lymphoma. A combination of flow cytometry and cytomorphology of cells obtained by FNA of lymph nodes can distinguish between benign and malignant lymphoid infiltrates and support a diagnosis of lymphoma that permits definitive therapy in most cases.

prostate carcinomas with stage at radical prostatectomy (RP) and progression after RP. For the former group, 109 RP specimens with Gleason sums of 6 and 7 were 1 Department of Pathology, The Johns Hopkins studied: 34 organ-confined tumors, 37 with capsular penetration, 21 with seminal Medical Institutions, Baltimore, Maryland.vesicle involvement, and 17 with pelvic lymph node metastasis. For the latter 2 Department of Urology, The Johns Hopkins group, 87 RP specimens were studied that had a Gleason sum of 5 to 7 for which Medical Institutions, Baltimore, Maryland.the patients underwent follow-up of at least 7 years or until progression. Thirty-3 UroCor, Oklahoma City, Oklahoma.seven patients (43%) progressed at a mean of 3.5 years (range, 1-8 years). Representative sections of each tumor were stained for CD31 and ''hot spot'' microvessels were quantitated in a 3.14-mm 2 area. RESULTS.In the first arm, there was no relationship between MVD and stage at RP. In the second arm, the mean MVD in tumors that progressed was significantly higher than in nonprogressors (43.0 { 26.1 vs. 29.0 { 13.1; P õ 0.0001 by WilcoxonGehan statistic). MVD and Gleason sum were independent statistically significant predictors of progression (MVD, P õ 0.0001; Gleason sum, P õ 0.0001 by Cox proportional hazards model). CONCLUSIONS.MVD is an independent significant predictor of progression after RP for tumors with a Gleason sum of 5 to 7. Because these comprise the majority of RP specimens, it is this group for which discrimination of biologic potential is most needed. Angiogenesis may be useful in the prognostic stratification of patients beyond that possible using stage and grade alone. prostate carcinomas do not progress after diagnosis or therapy. And yet a subpopulation of men exists in which the carcinoma will behave

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Breast implant-associated anaplastic large cell lymphoma (ALCL) is a T-cell neoplasm arising around textured breast implants that was recognized recently as a distinct entity by the World Health Organization. Rarely, other types of lymphoma have been reported in patients with breast implants, raising the possibility of a pathogenetic relationship between breast implants and other types of lymphoma. We report 8 cases of Epstein-Barr virus (EBV)-positive large B-cell lymphoma associated with breast implants. One of these cases was invasive, and the other seven neoplasms were non-invasive and showed morphologic overlap with breast implant ALCL. All eight cases expressed B-cell markers, had a non-germinal center B-cell immunophenotype, and were EBV+ with a latency type III pattern of infection. We compared the non-invasive EBV+ large B-cell lymphoma cases with a cohort of breast implant ALCL cases matched for clinical and pathologic stage. The EBV+ large B-cell lymphoma cases more frequently showed a thicker capsule, and more often were associated with calcification and prominent lymphoid aggregates outside of the capsule. The EBV+ B-cell lymphoma cells were more often arranged within necrotic fibrinoid material in a layered pattern. We believe this case series highlights many morphologic similarities between EBV+ large B-cell lymphoma and breast implant ALCL. The data presented suggest a pathogenetic role for breast implants (as well as EBV) in the pathogenesis of EBV+ large B-cell lymphoma. We also provide some histologic findings useful for distinguishing EBV+ large B-cell lymphoma from breast implant ALCL in this clinical setting.

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The presence of normal anatomic structures may be a source of confusion to the pathologist examining prostatic needle biopsies. The morphologic features of Cowper's (bulbourethral) glands incidentally biopsied during transrectal sampling of the prostate have not been described. We reviewed seven cases of Cowper's glands found in prostatic core biopsy specimens. Sections containing Cowper's glands were stained with hematoxylin-eosin, mucicarmine, periodic acid-Schiff's-digest (PAS-D), and antibodies directed at high-molecular-weight cytokeratin (HMWCK), prostate-specific acid phosphatase (PSAP), prostate-specific antigen (PSA), Ulex europaeus agglutinin, and muscle-specific actin. Histologically, Cowper's glands resemble mucinous minor salivary glands entrapped within fascicles of muscle. Lobules of acini composed of cells distended with mucin (mucicarmine and PAS-D positive) were admixed with ducts and ductules composed of hybrid cells with both mucinous and ductular epithelial features. The HMWCK was strongly reactive with the ductular epithelium and demonstrated an attenuated cell lining at the periphery of lobules. The mucinous cytoplasm reacted with U. europaeus, whereas the ductal elements failed to stain. PSAP stains were negative, with PSA positive in most cases. Muscle-specific actin was positive in three cases. Cowper's glands occasionally may be sampled by transrectal needle biopsy. Recognition of this anatomic structure will allow discrimination from low-grade prostatic adenocarcinoma, foamy gland carcinoma, mucinous metaplasia of prostate glands, and atypical glands of undetermined significance.

A web-based tutorial improves the accuracy of Gleason grading of practicing pathologists. To the authors' knowledge the current study is the first large scale, international study that has evaluated and validated the use of a web-based program to educate a population of widely dispersed physicians.