Débora Balabram

Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast

BackgroundThis study aimed to assess inter-observer variability between the original diagnostic reports and later review by a specialist in breast pathology considering lobular neoplasias (LN), columnar cell lesions (CCL), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) of the breast.MethodsA retrospective, observational, cross-sectional study was conducted. A total of 610 breast specimens that had been formally sent for consultation and/or second opinions to the Breast Pathology Laboratory of Federal University of Minas Gerais were analysed between January 2005 and December 2010. The inter-observer variability between the original report and later review was compared regarding the diagnoses of LN, CCL, ADH, and DCIS. Statistical analyses were conducted using the Kappa index.ResultsWeak correlations were observed for the diagnoses of columnar cell change (CCC; Kappa = 0.38), columnar cell hyperplasia (CCH; Kappa = 0.32), while a moderate agreement (Kappa = 0.47) was observed for the diagnoses of flat epithelial atypia (FEA). Good agreement was observed in the diagnoses of atypical lobular hyperplasia (ALH; Kappa = 0.62) and lobular carcinoma in situ (LCIS; Kappa = 0.66). However, poor agreement was observed for the diagnoses of pleomorphic LCIS (Kappa = 0.22). Moderate agreement was observed for the diagnoses of ADH (Kappa = 0.44), low-grade DCIS (Kappa = 0.47), intermediate-grade DCIS (Kappa = 0.45), and DCIS with microinvasion (Kappa = 0.56). Good agreement was observed between the diagnoses of high-grade DCIS (Kappa = 0.68).ConclusionsAccording to our data, the best diagnostic agreements were observed for high-grade DCIS, ALH, and LCIS. CCL without atypia and pleomorphic LCIS had the worst agreement indices.Virtual SlidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1640072350119725.AbstractIntroduçãoO objetivo do estudo foi avaliar a variabilidade interobservador entre os diagnósticos do laudo original e após revisão por especialista em patologia mamária considerando as neoplasias lobulares (NL), lesões células colunares (LCC), hiperplasia ductal atípica (HAD) e carcinoma ductal in situ (CDIS) em biopsias mamárias.MétodosEstudo retrospectivo, observacional, do tipo transversal. Um total de 610 casos de espécimes mamários que foram enviados formalmente para consultoria e/ou segunda opinião ao Laboratório de Patologia Mamária da Universidade Federal de Minas Gerais foram analisados entre janeiro de 2005 e dezembro de 2010. A variabilidade interobservador entre o laudo original e o laudo de revisão foi comparada entre os diagnósticos de NL, LCC, HDA e CDIS. A análise estatística foi realizada pelo índice de Kappa.ResultadosObservamos uma concordância fraca para os diagnósticos de alterações de células colunares (ACC; Kappa = 0,38), e hiperplasia de células colunares (HCC; Kappa = 0,32), enquanto uma concordância moderada (Kappa = 0,47) foi observada para o diagnóstico de atipia epitelial plana (AEP). A concordância foi considerada boa para os diagnósticos de hiperplasia lobular atípica (Kappa = 0,62) e carcinoma lobular in situ (CLIS; Kappa = 0,66). Entretanto, a concordância foi considerado baixa para o diagnóstico de CLIS pleomórfico (Kappa = 0,22). Concordância moderada foi observada para os diagnósticos de HLA (Kappa = 0,44), CDIS de baixo grau (Kappa = 0,47), CDIS de grau intermediário (Kappa = 0,45) e CDIS microinvasor (Kappa = 0,56). Boa concordância foi observada para o diagnóstico de CDIS de alto grau (Kappa = 0,68).ConclusãoDe acordo com nossos dados, as melhores concordâncias diagnósticas foram observadas entre CDIS de alto grau, HLA e CLIS. As LCC sem atipias e o CLIS pleomórfico tiveram os piores índices de concordância.

Co-Expression of p16, Ki67 and COX-2 Is Associated with Basal Phenotype in High-Grade Ductal Carcinoma In Situ of the Breast.

We assessed the co-expression of cell cycle-related biomarkers in a series of 121 consecutive cases of high-grade ductal carcinoma in situ (DCIS), pure or associated with invasive carcinoma, and their associations with the different immunoprofiles of DCIS. Cases were identified from the histopathology files of the Breast Pathology Laboratory, Federal University of Minas Gerais, Brazil, from 2003 to 2008. The expression of estrogen receptor, progesterone receptor, HER2 overexpression, cytokeratin 5, epidermal growth factor receptor 1, cyclooxygenase-2, p16 and Ki67 were assessed. Tumors were placed into five subgroups according to their immunohistochemical profile: luminal A, luminal B, HER2, basal-like and “not classified”. We found that the basal phenotype was associated with a higher frequency of p16-positive cases (83%) and the luminal A phenotype showed a higher frequency of p16-negative cases (93%; p=0.000). The association of biomarkers p16+/Ki67+/COX2+ was expressed in 02/06 cases (33.3%) of the basal phenotype but in only 01/70 cases (1.4%) of the luminal A phenotype (p=0.01). The co-expression of p16+/Ki67+/COX2- was associated with a basal phenotype (p=0.004). P16 expression, p16+/Ki67+/COX2+ and p16+/Ki67+/COX2- co-expression showed significant associations with the basal phenotype and these profiles could be used to guide more aggressive treatment strategies in patients with high-grade DCIS.

Survival of patients with operable breast cancer (Stages I-III) at a Brazilian public hospital--a closer look into cause-specific mortality.

BackgroundBreast cancer incidence is increasing. The survival rate varies and is longer in high-income countries. In Brazil, lower-income populations rely on the Unified Public Health System (Sistema Único de Saude, SUS) for breast cancer care. The goal of our study is to evaluate the survival of patients with operable breast cancer stages I-III at a Brazilian public hospital that treats mostly patients from the SUS.MethodsA cohort study of patients who underwent surgery for breast cancer treatment at the Clinical Hospital of the Federal University of Minas Gerais from 2001 to 2008 was performed, with a population of 897 cases. Information on tumor pathology and staging, as well as patients’ age and type of health coverage (SUS or private system) was collected. A probabilistic record linkage was performed with the database of the Mortality Information System to identify patients who died by December 31th, 2011. The basic cause of death was retrieved, and breast cancer-specific survival rates were estimated with the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis of factors related to survival.ResultsA total of 282 deaths occurred during the study’s period, 228 of them due to breast cancer. Five-year breast cancer-specific survival rates were 95.5% for stage I, 85.1% for stage II and 62.1% for stage III disease. Patients from the SUS had higher stages at diagnosis (42% was in stage III, and from the private system only 17.6% was in this stage), and in the univariate but not multivariate analysis, being treated by the SUS was associated with shorter survival (hazard ratio, HR = 2.22, 95% CI 1.24-3.98). In the multivariate analysis, larger tumor size, higher histologic grade, higher number of positive nodes and age older than 70 years were associated with a shorter breast cancer-specific survival.ConclusionsFive-year breast cancer survival was comparable to other Brazilian cohorts. Patients treated by the SUS, rather than by the private system, had shorter survival times, mostly due to higher initial stage of the disease.

False positivity in HER2 testing of breast cancer: novel paths for approaching an old dilemma

Aims Variability in determining HER2 status has been reported, especially, differences in sensitivity and specificity among commercially available antibodies, with false positive and false negative results. We compared the sensitivity and specificity of five anti-HER2 antibodies by immunohistochemistry (IHC), using the new dual colour brightfield in situ hybridisation (DDISH) as the gold standard, on invasive breast carcinomas (IBC) arrays. Material and methods Serial sections from tissue microarrays (TMA) containing 200 preselected primary IBC were submitted to DDISH (VENTANA INFORM HER2 Dual ISH assay), and immunohistochemistry, using Dako A0485 and HercepTest (polyclonal), Novocastra CB11 (mouse monoclonal), NeoMarkers SP3 and Ventana 4B5 (rabbit monoclonal). Results From the initial 200 cases, 184 were assessed by DDISH and IHC. The concordance among the antibodies was considered very good (kappa statistics varied from 0.82 to 0.9). The overall concordance between IHC and DDISH ranged from 94.1% for CB11 to 96.6% for A0485. The antibodies A0485, HercepTest, SP3 and 4B5 were over 95% sensitive and specific. CB11 was the most specific antibody (97.1%). 60% (CB11) to 83.3% (SP3) of the 2+ cases showed no gene amplification by DDISH. False negative cases varied from 0.5% (A0485) to 3.8% (CB11) of the cases, and false positive from 1.6% (CB11) to 2.7% (HercepTest, SP3 and 4B5) of the 184 cases. Conclusions There was very good agreement among the five anti-HER2 antibodies. CB11 was the most specific antibody, but showed more false negative cases. A0485, SP3, 4B5 and HercepTest were highly sensitive and specific, but showed more false positive cases.

Consultoria em patologia cirúrgica mamária: variabilidade interobservador no diagnóstico de lesões proliferativas intraductais atípicas

PURPOSE To evaluate the agreement about the histopathological diagnosis of intraductal proliferative breast lesions between general pathologists and a specialist in breast pathology. METHODS This was an observational, cross-sectional study of 209 lesions received in consultation at the Breast Pathology Laboratory of the School of Medicine, Federal University of Minas Gerais, from 2007 to 2011, comparing the original diagnosis and the review. We included only cases with a formal request for review and cases in which the original diagnosis or reviewers diagnosis showed proliferative lesions, pure ductal carcinoma in situ, ductal carcinoma in situ associated with microinvasion or associated with invasive carcinoma. The kappa index and percent concordance were used in the statistical analyses. RESULTS A moderate agreement was observed between the original histopathological diagnosis and the second opinion (kappa=0.5; percentual concordance=83%). After the review, the diagnosis of malignancy was confirmed in 140/163 cases (86%) and the diagnosis of benign lesions was confirmed in 34/46 cases (74%). Regarding specific diagnosis, we observed moderate agreement between the original diagnosis and the reviewers diagnosis (136/209 cases; kappa=0.5; percent concordance=65%). The highest disagreement was observed in cases of ductal carcinoma in situ with microinvasion (6/6 cases; 100%). Important discordance was observed in cases of atypical ductal hyperplasia (16/30 cases; 53%) and ductal carcinoma in situ (25/75 cases; 33%). Regarding the histological grade of ductal carcinoma in situ, we observed good agreement between the original diagnosis and the review (29/39 cases; kappa=0.6, percent agreement=74%). CONCLUSION Our data confirm that intraductal proliferative breast lesions, especially atypical ductal hyperplasia, ductal carcinoma in situ and ductal carcinoma in situ with microinvasion show relevant discrepancies in the histopathological diagnoses, which may induce errors in therapeutic decisions.

Intramuscular lipoma of the subscapularis muscle

CONTEXT Intramuscular lipomas are benign tumors that infiltrate the muscles. CASE REPORT We describe the case of a 58-year-old female patient with an axillary lump. The lump was a lipoma inside the subscapularis muscle. It is important to differentiate these lesions from liposarcomas and from other diseases that may present as axillary lumps. The most accurate imaging method for differentiating benign lipomatous tumors from liposarcomas is magnetic resonance imaging, but surgical removal of these intramuscular lesions to confirm the diagnosis is recommended. CONCLUSION Intramuscular lipomas are a rare cause of benign axillary lumps and should be considered in making differential diagnoses on axillary masses.

High agreement between whole slide imaging and optical microscopy for assessment of HER2 expression in breast cancer: Whole slide imaging for the assessment of HER2 expression

UNLABELLED Whole slide imaging (WSI) technology has been used for training, teaching, researching, and remote consultation. Few studies compared HER2 expression using optical microscopy (OM) and WSI evaluations in breast carcinomas. However, no consensus has been achieved comparing both assessments. MATERIAL AND METHODS Sections from tissue microarray containing 200 preselected invasive breast carcinomas were submitted to immunohistochemistry applying three anti-HER2 antibodies (HercepTest™, CB11, SP3) and in situ hybridization (DDISH). Slides were evaluated using OM and WSI (Pannoramic MIDI and Viewer, 3DHISTECH). Sensitivity and specificity were calculated comparing the anti-HER2 antibodies and DDISH. RESULTS WSI and OM HER2 evaluations agreement was considered good (SP3, k=0.80) to very good (CB11 and HercepTest™, k=0.81). WSI evaluation led to higher sensitivity (ranging from 100 of SP3 and HercepTest™ to 97 of CB11) and lower specificity (ranging from 86.4 of SP3 to 89.4 of HercepTest™) compared to OM evaluation (sensitivity ranged from 92.1 of CB11 to 98 of SP3 and specificity ranged from 95.2 of SP3 and HercepTest™ to 97.1 of CB11 and SP3). CONCLUSION High agreement was achieved between WSI and OM evaluations. All three antibodies were highly sensitive and specific using both evaluations. WSI can be considered a useful tool for HER2 immunohistochemical assessment.

Immunohistochemical profile of high-grade ductal carcinoma in situ of the breast

OBJECTIVE: To determine the frequency of the immunohistochemical profiles of a series of high-grade ductal carcinoma in situ of the breast. METHODS: One hundred and twenty-one cases of high-grade ductal carcinoma in situ, pure or associated with invasive mammary carcinoma, were identified from 2003 to 2008 and examined with immunohistochemistry for estrogen receptor, human epidermal growth factor receptor 2, cytokeratin 5, and epidermal growth factor receptor. The tumors were placed into five subgroups: luminal A, luminal B, HER2, basal-like, and “not classified”. RESULTS: The frequencies of the immunophenotypes of pure ductal carcinoma in situ were the following: luminal A (24/42 cases; 57.1%), luminal B (05/42 cases; 11.9%), HER2 (07/42 cases; 16.7%), basal-like phenotype (00/42 cases; 0%), and “not classified” (06/42 cases; 14.3%). The immunophenotypes of ductal carcinoma in situ associated with invasive carcinoma were the following: luminal A (46/79 cases; 58.2%), luminal B (10/79 cases; 12.7%), HER2 (06/79 cases; 7.6%), basal-like (06/79 cases; 7.6%), and “not classified” (11/79 cases; 13.9%). There was no significant difference in the immunophenotype frequencies between pure ductal carcinoma in situ and ductal carcinoma in situ associated with invasive carcinoma (p>0.05). High agreement was observed in immunophenotypes between both components (kappa = 0.867). CONCLUSION: The most common immunophenotype of pure ductal carcinoma in situ was luminal A, followed by HER2. The basal-like phenotype was observed only in ductal carcinoma in situ associated with invasive carcinoma, which had a similar phenotype.

Ductal carcinoma in situ of the breast: correlation between histopathological features and age of patients

BackgroundThe histopathological subtype, nuclear grade and presence or absence of comedonecrosis are established as critical elements in the reporting of ductal carcinoma in situ (DCIS) of the breast. The aims of this study were to determine the frequencies of morphological subtypes of DCIS, nuclear grade and comedonecrosis; to compare the age of patients with the histopathological characteristics of DCIS, and to assess the agreement of grade between in situ and invasive components in DCIS cases that were associated with invasive carcinoma.MethodsWe evaluated a series of 403 cases of DCIS, pure or associated with invasive mammary carcinoma, consecutively identified from the histopathology files of the Breast Pathology Laboratory, Federal University of Minas Gerais, Brazil, from 2003 to 2008.ResultsDCIS displayed a single growth pattern in most cases (55.1%) and the solid subtype was the most common morphology (42.2% of the total). High-grade DCIS was identified in 293/403 cases (72.7%) and comedonecrosis was present in 222/403 cases (55%). Among DCIS with a single architectural pattern, high grade was more common in the solid subtype (151/168 cases, 89.9%; p < 0.001). Only 32% of tumours with a cribriform pattern had high nuclear grade. Comedonecrosis was more common in the solid morphology than in the cribriform, papillary and micropapillary subtypes (p < 0.001). Patients with high-grade DCIS were younger in relation to patients with low-grade DCIS (p = 0.027) and patients with tumours with comedonecrosis were also younger in comparison to patients with tumours without comedonecrosis (p = 0.003). Fair agreement was observed between in situ and invasive components with regard to grade (weighted kappa = 0.23).ConclusionsThe high nuclear grade and the presence of comedonecrosis were identified more frequently in younger patients and more often correlated with the solid pattern of DCIS.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_227

Association between age and survival in a cohort of Brazilian patients with operable breast cancer

Whether age is an independent prognostic factor in breast cancer is a matter of debate. This is a retrospective cohort study of 767 breast cancer patients, stages I-III, treated at the Hospital das Clínicas, Minas Gerais Federal University, Belo Horizonte, Minas Gerais State, Brazil, from 2001 to 2008, aiming to study the relationship between age and survival. We included variables related to patients, tumors, and types of treatment. Different sets of Cox models were used for survival analysis. Hazard ratios (HR) and 95%CI were calculated. The relationship between age and breast cancer survival did not change substantially in any of them. In the model that accounted for all variables, women aged 70 and older (HR = 1.51, 95%CI: 1.04-2.18), and 35 or younger (HR = 1.78, 95%CI: 1.05-3.01) had shorter cancer specific survival than patients aged between 36 and 69. In addition, older age, having at least one comorbidity, and being white were associated with a higher risk of dying from other causes. In conclusion, shorter breast cancer survival is expected among the youngest and oldest patients.E discutivel se idade e um fator prognostico independente para câncer de mama. Conduzimos uma coorte retrospectiva de 767 pacientes com câncer de mama, estadios I-III, tratadas no Hospital das Clinicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil, de 2001 a 2008, para estudar a relacao entre idade e sobrevida. Incluimos variaveis relacionadas as pacientes, aos tumores e ao tratamento. Diferentes conjuntos de modelos de Cox foram construidos. As razoes de risco (RR) e IC95% foram calculados. A relacao entre idade e sobrevida por câncer de mama nao foi alterada substancialmente entre os modelos de Cox. No modelo com todas as variaveis explicativas, as mulheres de 70 anos ou mais (RR = 1,51; IC95%: 1,04-2,18) e ate 35 anos (RR = 1,78; IC95%: 1,05-3,01) tiveram sobrevida causa-especifica mais curta que as de 36-69 anos. Idades a partir de 70 anos, ter ao menos uma comorbidade e ser branca foram associadas a risco maior de obito por outras causas. Em conclusao, as pacientes mais jovens e as mais idosas parecem ter sobrevida mais curta por câncer de mama.