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Adenoid cystic carcinoma (AdCC) is an uncommon type of invasive breast carcinoma with a favorable prognosis. However, some cases are aggressive. The study aims to define the clinicopathologic predictors of outcome. Clinical, radiological, and pathologic variables were recorded for 76 AdCC cases from 11 institutions. The following histologic characteristics were evaluated by the breast pathologist in each respective institution, including Nottingham grade (NG), percentages of various growth patterns (solid, cribriform, trabecular-tubular), percentage of basaloid component, tumor borders (pushing, infiltrative), perineural invasion, lymphovascular invasion, necrosis, and distance from the closest margin. Various grading systems were evaluated, including NG, salivary gland-type grading systems, and a new proposed grading system. The new grading system incorporated the growth pattern (percent solid, percent cribriform), percent basaloid morphology, and mitotic count using the Youden index criterion. All variables were correlated with recurrence-free survival. Nineteen (25%) women developed local and/or distant recurrence. Basaloid morphology (≥25% of the tumor) was identified in 20 (26.3%) cases and a solid growth pattern (using ≥60% cutoff) in 22 (28.9%) cases. In the univariate analysis, the following variables were significantly correlated with worse recurrence-free survival: solid growth pattern, basaloid morphology, lymphovascular invasion, necrosis, perineural invasion, and pN-stage. In the multivariate analysis including basaloid morphology, pN-stage, lymphovascular invasion, and perineural invasion, basaloid morphology was statistically significant, with a hazard ratio of 3.872 (95% CI, 1.077; 13.924; P =.038). The NG and the new grading system both correlated with recurrence-free survival. However, grade 2 had a similar risk as grade 3 in the NG system and a similar risk as grade 1 in the new grading system. For solid growth patterns and basaloid morphology, using a 2-tier system with 1 cutoff was better than a 3-tier system with 2 cutoffs. Basaloid morphology and solid growth pattern have prognostic values for AdCC, with a 2-tier grading system performing better than a 3-tier system.
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Neoplasias da Mama , Carcinoma Adenoide Cístico , Feminino , Humanos , Masculino , Carcinoma Adenoide Cístico/terapia , Mama , Ciclo Celular , NecroseRESUMO
PURPOSE: Estrogen-receptor (ER) and progesterone-receptor (PR) expression levels in breast cancer, which have been principally compared via binomial descriptors, can vary widely across tumors. We sought to characterize ER and PR expression levels using semi-quantitative analyses of receptor staining in germline pathogenic variant (PV) carriers of cancer predisposition genes. METHODS: We conducted a retrospective chart review of patients who underwent germline genetic testing for cancer predisposition genes at a tertiary cancer center genetics clinic. We performed comparisons of semi-quantitative ER and PR percentage staining levels across carriers and non-carriers of cancer predisposition genes. RESULTS: Breast cancers from BRCA1 PV carriers expressed significantly lower ER (15.2% vs 78.2%, p < 0.001) and lower PR (6.8% vs 41.1%, p < 0.001) staining compared to non-PV carriers. Similarly, breast cancers of BRCA2 (66.7% vs 78.2%, p = 0.005) and TP53 (50.6% vs 78.2%, p = 0.015) PV tumors also displayed moderate decreases in ER staining. Conversely, CHEK2 tumors displayed higher ER (93.1% vs 78.2%, p = 0.005) and PR (72% vs 48.8%, p = 0.001) staining when compared to non-PV carriers. We observed a wide range of dispersion across the ER and PR staining levels of the carriers and noncarriers. ER and PR ranges of dispersion of CHEK2 tumors were uniquely narrower than all other groups. CONCLUSION: The findings of our study suggest that precise expression levels of ER and PR in breast cancers can vary widely. These differences are further augmented when comparing expression staining across PV and non-PV carriers, suggesting potentially unique tumorigenesis and progression pathways influenced by germline cancer predisposition genes.
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Neoplasias da Mama , Neoplasias da Mama/patologia , Quinase do Ponto de Checagem 2/genética , Feminino , Predisposição Genética para Doença , Células Germinativas/metabolismo , Mutação em Linhagem Germinativa , Hormônios , Humanos , Mutação , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Estudos RetrospectivosRESUMO
Diagnostic errors occur in the preanalytic, analytic, and postanalytic phases of specimen processing. Correlating clinical and imaging information with gross and microscopic findings is crucial to limit errors and unnecessary treatment. Herein, we report the case of a 54-year-old woman who presented with left breast bloody nipple discharge and subsequently underwent central duct excision. Pathology revealed a high-grade sarcoma. The patient presented to our institution for further management. Upon secondary pathology review and DNA fingerprinting analysis, the correct interpretation was rendered. Our case demonstrates the importance of clinical correlation and review of pathology slides prior to definitive therapy.
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Neoplasias da Mama , Fibrossarcoma , Glândulas Mamárias Humanas , Derrame Papilar , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , MamilosRESUMO
CONTEXT: Accurate assessment of clinical and pathological tumor stage is crucial for patient treatment and prognosis. OBJECTIVE: The aim of this study was to assess the concordance between the tumor size and focality between radiological studies and pathology and to evaluate the impact of discrepancies on staging. DESIGN: Patients who underwent surgery for invasive breast carcinoma from January 1, 2014, to December 31, 2015, were identified. RESULTS: Three imaging modalities (mammogram, ultrasound and MRI) were compared with gross examination and final pathology. 1152 preoperative radiological studies were evaluated for focality and 1019 were evaluated for tumor size. For all 3 radiographic modalities, there was a statistically significant difference between the mean tumor size on radiology and the final pathology report (mammogram, P < .001; ultrasound, P = .004; MRI, P < .001). In 29% of radiology studies, there was a discrepancy in stage. The error rate for determining focality was 28% for mammograms, 27% for ultrasounds, and 29% for MRIs. Tumor size from gross examination correlated with microscopic tumor size in 57% of cases, but gross examination had 88% concordance with the final pathology report in determining focality. CONCLUSION: Our study revealed statistically significant differences in mean tumor size reported across all 3 imaging modalities when compared to the final pathology report. MRI had the highest error rate, with a tendency to overestimate tumor size and number of foci. Among all diagnoses, cases of invasive carcinoma with an extensive intraductal component were most prone to discrepancies with imaging.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Imagem Multimodal/métodos , Radiologia/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Neoplasias da Mama/ultraestrutura , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Mamografia/métodos , Mamografia/estatística & dados numéricos , Pessoa de Meia-Idade , Imagem Multimodal/estatística & dados numéricos , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos , Carga Tumoral , Ultrassonografia/métodos , Ultrassonografia/estatística & dados numéricosRESUMO
BACKGROUND: Triple-negative breast carcinoma (TNBC) patients do not benefit from hormone- or human epidermal growth factor receptor 2- (HER2-) targeted therapies. Accurate testing is pivotal for these patients. METHODS: TNBC cases that were retested at our institution during a 3-year period were evaluated for concordance rates in estrogen (ER) and progesterone (PR) receptor and HER2 results. RESULTS: We found 19 (22%) discrepancies (13 major/6 minor) among 86 cases. Minor discrepancies were in HER2 changes by immunohistochemistry, and all cases were demonstrated to be negative by and dual in situ hybridization. All major discrepancies were in ER/PR expression changes. In only 2 cases the treatment changed based on repeated results and/or patient history. CONCLUSIONS: Discrepancies in prognostic/predictive testing continue to be frequent despite rigorous regulations. However, since for the majority of patients in our setting, the treatment plan did not change, reflex retesting for TNBC has been deemed unnecessary in our institution.
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Core needle biopsy (CNB) is the most common sampling technique for the histologic evaluation of breast abnormalities. Diagnosing benign proliferative, borderline and some in-situ lesions in CNB is challenging and subject to a significant degree of interobserver variability. In addition, due to the inherent limitations of CNB, "upgrading" to a more significant pathology at excision is an important consideration for some lesions. Pathologists carry a major responsibility in patient diagnosis, risk stratification and management. Familiarity with the histologic features and the clinical significance of these common and problematic lesions encountered in CNB is necessary for adequate treatment and patient follow-up. This review will focus on benign, atypical and in-situ epithelial proliferations, papillary lesions, radial sclerosing lesions, adenosis and cellular fibroepithelial lesions. Highlights of histologic features, useful strategies for accurate diagnosis, basic immunohistochemistry and management will be presented.
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Biópsia com Agulha de Grande Calibre/normas , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Mama/patologia , Imuno-Histoquímica/métodos , Adulto , Assistência ao Convalescente , Idoso , Idoso de 80 Anos ou mais , Mama/ultraestrutura , Doenças Mamárias/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/ultraestrutura , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Diagnóstico Diferencial , Feminino , Doença da Mama Fibrocística/patologia , Indicadores Básicos de Saúde , Humanos , Hiperplasia/patologia , Pessoa de Meia-Idade , Variações Dependentes do Observador , Patologistas/ética , PrognósticoRESUMO
Determination of human epidermal receptor protein-2 (HER2) is a crucial step in the treatment of patients diagnosed with invasive breast carcinoma. HER2 status is an independent clinical prognostic factor and a predictive factor of tumor response to chemotherapeutic agents such as trastuzumab. Accurate testing is necessary to offer adequate therapy to patients. To evaluate the variation in HER2 testing results, we analyzed our data from review cases in which HER2 testing was repeated at our institution from January 2013 to December 2014. For the study, the reason for repeating the test, the testing methodology used, and the tests results were collected. Concordance between outside and in-house HER2 results was compared. Discrepancies were classified as major and minor. A total of 173 cases were retested during this period. One-hundred and twenty-eight cases met the inclusion criteria. Sixteen cases were originally tested at large reference laboratories and two in international laboratories. In the 110 remaining cases, the test was performed at small community laboratories or the testing facility was not available. Forty-one (32%) discrepancies were identified. Of these, 15 (12% of 128 total) were major and 26 (20% of 128 total) were considered minor discrepancies. Our study confirms that significant discrepancies in HER2 results persist even after stricter and well-developed testing guidelines have been embraced.
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Neoplasias da Mama/química , Neoplasias da Mama/diagnóstico , Laboratórios/normas , Receptor ErbB-2/análise , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/química , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/tratamento farmacológico , Feminino , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Trastuzumab/uso terapêuticoRESUMO
BACKGROUND: Breast cancer is a heterogeneous disease that encompasses a wide range of clinical behaviors and histological and molecular variants. It is the most common type of cancer affecting women worldwide and is the second leading cause of cancer death. METHODS: A comprehensive literature search was performed to explore the advances in molecular medicine related to the diagnosis and treatment of breast cancer. RESULTS: During the last few decades, advances in molecular medicine have changed the landscape of cancer treatment as new molecular tests complement and, in many instances, exceed traditional methods for determining patient prognosis and response to treatment options. Personalized medicine is becoming the standard of care around the world. Developments in molecular profiling, genomic analysis, and the discovery of targeted drug therapies have significantly improved patient survival rates and quality of life. CONCLUSIONS: This review highlights what pathologists need to know about current molecular tests for classification and prognostic/ predictive assessment of breast carcinoma as well as their role as part of the medical team.
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Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Perfilação da Expressão Gênica/métodos , Medicina de Precisão/métodos , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Prognóstico , Análise Serial de Proteínas , Receptor ErbB-2/genética , Receptores de Estrogênio/biossíntese , Receptores de Progesterona/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
BACKGROUND: During the last few decades, immunohistochemistry (IHC) has become an integral part of pathology. Although hematoxylin and eosin (H & E) stain remains the fundamental basis for diagnostic pathology of the breast, IHC stains provide useful and sometimes vital information. Moreover, considering the role of hormonal therapy in hormone receptor-positive breast tumors, as well as the availability of targeted chemotherapeutic agents for HER2-positive cases, IHC studies represent a major part of workups. METHODS: A literature search was performed to explore the uses of IHC stains related to the diagnoses of breast lesions and prognostic/predictive information. RESULTS: Selective use of IHC stains in conjunction with H & E examination helps resolve most diagnostic issues encountered by surgical pathologists during their day-to-day practice. Pathologists should be familiar with the use of each immunostain and its limitations to avoid interpretative errors. CONCLUSIONS: IHC stains help guide the differential diagnosis of challenging epithelial lesions of the breast. They should be selectively and judiciously used and their findings must be interpreted with the differential diagnoses in mind and with an understanding of possible pitfalls.
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Adenocarcinoma/patologia , Neoplasias da Mama/patologia , Biomarcadores Tumorais , Neoplasias da Mama/secundário , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Receptor ErbB-2/genética , Receptores de Estrogênio/biossíntese , Receptores de Progesterona/biossíntese , Sarcoma/patologiaRESUMO
BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a rare variant of colorectal cancer with an adverse prognosis. "Retraction artifact" around tumor cells is a feature of IMPC. The aim of this study was to assess the nature of the retractions around the tumor cells and to describe the histopathological features of a group of 18 cases of IMPC. METHODS: A pathology review of 128 consecutive colorectal cancers identified 18 cases of histologically proven IMPC using 5% of the total tumor volume comprised of a micropapillary component as the diagnostic criterion. Immunostains for D2-40, CD31, CD34, vascular endothelial growth factor A (VEGF-A), and mucin 1 (MUC-1) were performed using the avidin-biotin complex method. RESULTS: Cases of IMPC were characterized by pseudomicropapillae surrounded by lacunar-like clear spaces. These structures exhibited the inside-out growth pattern as highlighted by MUC-1 staining. The lining of the lacunar spaces was immunoreactive to CD31 but not CD34 or D2-40, indicating that they are neovascular structures. Furthermore, the tumor cells strongly and diffusely expressed VEGF-A. CONCLUSIONS: The strong coexpression of VEGF-A and CD31 suggests a prominent role of neoangiogenesis in these tumors.
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Neoplasias Colorretais/patologia , Neoplasias Colorretais/fisiopatologia , Mucina-1/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/biossíntese , Antígenos CD34/biossíntese , Antígenos de Neoplasias/biossíntese , Biomarcadores Tumorais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Molécula-1 de Adesão Celular Endotelial a Plaquetas/biossíntese , Prognóstico , Estudos RetrospectivosRESUMO
A woman aged 48 years presented with fevers, chills, weight loss, and night sweats. She had significant lymphadenopathy of the left neck as well as the left axilla. Her history was significant for bilateral breast augmentation with textured silicone implants more than 25 years ago. Excisional biopsy of a cervical lymph node revealed large, atypical cells positive for CD4 and CD30 and negative for Epstein-Barr virus-encoded ribonucleic acid, CD2, CD3, CD5, CD7, CD8, CD15, CD20, pan-keratin, S100, anaplastic lymphoma kinase (ALK), and paired box 5. These findings were consistent with Ann Arbor stage IIIB ALK-anaplastic large cell lymphoma (ALCL). The patient was started on 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone. She initially had no signs or symptoms of breast involvement; however, after developing seroma during the clinical course, the patient underwent capsulectomy and removal of the intact, textured silicone implants. Pathological evaluation demonstrated ALK-ALCL in the left breast capsule with cells displaying a significant degree of pleomorphism with binucleated forms and numerous mitoses. Fluorescence in situ hybridization confirmed the tumor was negative for t(2;5). She presented 8 weeks later showing evidence of recurrent systemic disease.
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Implantes de Mama/efeitos adversos , Linfoma Anaplásico de Células Grandes/diagnóstico , Quinase do Linfoma Anaplásico , Diagnóstico Diferencial , Feminino , Humanos , Linfonodos/patologia , Linfoma Anaplásico de Células Grandes/enzimologia , Linfoma Anaplásico de Células Grandes/patologia , Pessoa de Meia-Idade , Receptores Proteína Tirosina Quinases/metabolismoRESUMO
Angiosarcoma of the breast represent <1% of breast malignancies. It can arise de novo (primary) or following treatment for breast carcinoma (secondary). Primary breast angiosarcoma usually affects young women and is extremely rare in the male patient population. Imaging features can have a nonspecific appearance. Histologically, the diagnosis can be challenging, especially in small core needle biopsies. Mastectomy or wide local excision is the usual treatment for both forms of angiosarcoma. Prognosis and recurrence is worse with increasing grade of tumor. Herein, we discuss the rare occurrence of primary breast angiosarcoma in a man with history of immunodeficiency. Clinical, radiological and pathologic findings will be discussed.
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Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Humanos , Masculino , Mastectomia Simples/métodos , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do TratamentoRESUMO
CONTEXT.: Breast pathology (BP) is considered to be subject to interobserver variability among pathologists, emphasizing the need for adequate training. However, specifics of BP residency training have not been elucidated. OBJECTIVE.: To assess the characteristics of BP residency training in the United States. DESIGN.: A Qualtrics-managed online survey was emailed to program directors of all US pathology residency programs, requesting them to forward the survey link to their pathology residents. RESULTS.: One hundred seventeen residents' survey responses were evaluable. Most responses (92; 79%) came from residents in university hospital-based programs. Thirty-five respondents (30%) had a dedicated BP rotation in their program. Most respondents believed that BP was an important part of training (96 of 100; 96%) and pathology practice (95 of 100; 95%). Seventy-one respondents believed that their BP training was adequate overall (71 of 100; 71%). Forty-one percent of respondents indicated that they would not like BP to be a significant part of their future practice. The main reasons given were that they had a different preferred area of interest, that they lacked interest in BP, or that breast cases were time-consuming to sign out. CONCLUSIONS.: Our results show that in the United States, most programs do not offer a dedicated BP rotation, but breast cases are signed out by subspecialized or experienced breast pathologists. In addition, most respondents believed that they received adequate training and would be competent to independently sign out BP in the future. Additional studies addressing new-in-practice pathologists' proficiency in BP will further help elucidate the quality of BP training in the United States.
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Internato e Residência , Humanos , Estados Unidos , Inquéritos e Questionários , PatologistasRESUMO
The reaction-diffusion equation is widely used in mathematical models of cancer. The calibration of model parameters based on limited clinical data is critical to using reaction-diffusion equation simulations for reliable predictions on a per-patient basis. Here, we focus on cell-level data as routinely available from tissue biopsies used for clinical cancer diagnosis. We analyze the spatial architecture in biopsy tissues stained with multiplex immunofluorescence. We derive a two-point correlation function and the corresponding spatial power spectral distribution. We show that this data-deduced power spectral distribution can fit the power spectrum of the solution of reaction-diffusion equations that can then identify patient-specific tumor growth and invasion rates. This approach allows the measurement of patient-specific critical tumor dynamical properties from routinely available biopsy material at a single snapshot in time.
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Invasividade Neoplásica , Neoplasias , Humanos , Biópsia/métodos , Neoplasias/patologia , Calibragem , Análise Espacial , Modelos Biológicos , Simulação por ComputadorRESUMO
Lupus mastitis (LM) is a rare benign inflammatory condition characterized by inflammation of the deep subcutaneous adipose tissues of the breast. It can be seen in patients with a known history of systemic lupus erythematous or discoid lupus or rarely can be the initial presentation of these diseases. Histologically, the most common findings are the presence of a dense lymphoplasmacytic infiltration of lobules and hyaline fat necrosis. Radiologic characteristics of LM can mimic a malignant lesion. However, because histologic features of this lesion have been well defined, correlation with clinical history is important to arrive at an accurate diagnosis and, therefore, deliver appropriate patient management. Herein, we present a review of LM with emphasis on clinicopathologic findings and differential diagnosis.
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Lúpus Eritematoso Sistêmico/complicações , Mastite/etiologia , Mastite/patologia , Feminino , HumanosRESUMO
Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance triple-negative breast cancer (TNBC) responses to neoadjuvant chemotherapy (NAC). This article describes the phase 2 trial of T-VEC plus NAC (ClinicalTrials.gov ID: NCT02779855 ). Patients with stage 2-3 TNBC received five intratumoral T-VEC injections with paclitaxel followed by doxorubicin and cyclophosphamide and surgery to assess residual cancer burden index (RCB). The primary end point was RCB0 rate. Secondary end points were RCB0-1 rate, recurrence rate, toxicity and immune correlates. Thirty-seven patients were evaluated. Common T-VEC toxicities were fevers, chills, headache, fatigue and injection site pain. NAC toxicities were as expected. Four thromboembolic events occurred. The primary end point was met with an estimated RCB0 rate = 45.9% and RCB0-1 descriptive rate = 65%. The 2-year disease-free rate is equal to 89% with no recurrences in RCB0-1 patients. Immune activation during treatment correlated with response. T-VEC plus NAC in TNBC may increase RCB0-1 rates. These results support continued investigation of T-VEC plus NAC for TNBC.
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Melanoma , Terapia Viral Oncolítica , Neoplasias de Mama Triplo Negativas , Humanos , Terapia Viral Oncolítica/métodos , Melanoma/patologia , Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Adenomyoepithelioma comprises a spectrum of lesions with variable morphology and clinical behavior, presenting at a wide age range. The most common presenting symptom is palpable abnormality. Mammographic abnormalities include focal asymmetries, masses and microcalcifications. Adenomyoepithelioma is a biphasic neoplasm characterized by proliferation of epithelial and myoepithelial cells. Adenomyoepitheliomas can be benign, atypical and malignant (adenomyoepithelioma with carcinoma). Malignant transformation occurs in either one or both cellular components leading to the development of invasive carcinoma. Invasive carcinoma types include invasive breast carcinoma of no special type, invasive lobular carcinoma, invasive carcinoma of special types, myoepithelial carcinoma, metaplastic carcinoma and biphasic carcinoma such as epithelial-myoepithelial carcinoma. While the majority of classic adenomyoepitheliomas have a benign clinical course and can be treated by local excision, local recurrence and distant metastasis have been reported. In malignant cases, treatment is determined by the associated carcinoma to include radiotherapy after breast conserving surgery and sentinel lymph node biopsy or axillary lymph node dissection, as indicated. Herein we report a case of a 62 year old woman who was found to have focal asymmetry on screening mammogram. She underwent a core biopsy of the lesion which showed atypical epithelial-myoepithelial neoplasm and excision was recommended. Upon excision, a diagnosis of malignant adenomyoepithelioma with associated epithelial-myoepithelial carcinoma was rendered with negative margins. The patient declined additional surgery for sentinel lymph node biopsy and declined adjuvant therapy. Six months after surgery, the patient is doing well with no complains. A follow-up mammogram and ultrasound of the axilla showed no abnormalities.
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Adenomioepitelioma , Neoplasias da Mama , Carcinoma , Mioepitelioma , Adenomioepitelioma/patologia , Adenomioepitelioma/cirurgia , Mama/patologia , Neoplasias da Mama/patologia , Carcinoma/patologia , Feminino , Humanos , Mamografia , Mastectomia Segmentar , Pessoa de Meia-Idade , Mioepitelioma/patologia , Mioepitelioma/cirurgiaRESUMO
Molecular epidemiology evidence indicates racial and ethnic differences in the aggressiveness and survival of breast cancer. Hispanics/Latinas (H/Ls) and non-Hispanic Black women (NHB) are at higher risk of breast cancer (BC)-related death relative to non-Hispanic white (NHW) women in part because they are diagnosed with hormone receptor-negative (HR) subtype and at higher stages. Since the cell cycle is one of the most commonly deregulated cellular processes in cancer, we propose that the mitotic kinases TTK (or Mps1), TBK1, and Nek2 could be novel targets to prevent breast cancer progression among NHBs and H/Ls. In this study, we calculated levels of TTK, p-TBK1, epithelial (E-cadherin), mesenchymal (Vimentin), and proliferation (Ki67) markers through immunohistochemical (IHC) staining of breast cancer tissue microarrays (TMAs) that includes samples from 6 regions in the Southeast of the United States and Puerto Rico -regions enriched with NHB and H/L breast cancer patients. IHC analysis showed that TTK, Ki67, and Vimentin were significantly expressed in triple-negative (TNBC) tumors relative to other subtypes, while E-cadherin showed decreased expression. TTK correlated with all of the clinical variables but p-TBK1 did not correlate with any of them. TCGA analysis revealed that the mRNA levels of multiple mitotic kinases, including TTK, Nek2, Plk1, Bub1, and Aurora kinases A and B, and transcription factors that are known to control the expression of these kinases (e.g. FoxM1 and E2F1-3) were upregulated in NHBs versus NHWs and correlated with higher aneuploidy indexes in NHB, suggesting that these mitotic kinases may be future novel targets for breast cancer treatment in NHB women.
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Objective: To quantitatively evaluate intratumoral habitats on dynamic contrast-enhanced (DCE) breast MRI to predict pathologic breast cancer response to stereotactic ablative body radiotherapy (SABR). Methods: Participants underwent SABR treatment (28.5 Gy x3), baseline and post-SABR MRI, and breast-conserving surgery for ER/PR+ HER2- breast cancer. MRI analysis was performed on DCE T1-weighted images. MRI voxels were assigned eight habitats based on high (H) or low (L) maximum enhancement and the sequentially numbered dynamic sequence of maximum enhancement (H1-4, L1-4). MRI response was analyzed by percent tumor volume remaining (%VR = volume post-SABR/volume pre-SABR), and percent habitat makeup (%HM of habitat X = habitat X voxels/total voxels in the segmented volume). These were correlated with percent tumor bed cellularity (%TC) for pathologic response. Results: Sixteen patients completed the trial. The %TC ranged 20%-80%. MRI %VR demonstrated strong correlations with %TC (Pearson R = 0.7-0.89). Pre-SABR tumor %HMs differed significantly from whole breasts (P = 0.005 to <0.00001). Post-SABR %HM of tumor habitat H4 demonstrated the largest change, increasing 13% (P = 0.039). Conversely, combined %HM for H1-3 decreased 17% (P = 0.006). This change correlated with %TC (P < 0.00001) and distinguished pathologic partial responders (≤70 %TC) from nonresponders with 94% accuracy, 93% sensitivity, 100% specificity, 100% positive predictive value, and 67% negative predictive value. Conclusion: In patients undergoing preoperative SABR treatment for ER/PR+ HER2- breast cancer, quantitative MRI habitat analysis of %VR and %HM change correlates with pathologic response.
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OBJECTIVE: This study evaluates breast MRI response of ER/PR+ HER2- breast tumors to pre-operative SABR with pathologic response correlation. METHODS: Women enrolled in a phase 2 single institution trial of SABR for ER/PR+ HER2- breast cancer were retrospectively evaluated for radiologic-pathologic correlation of tumor response. These patients underwent baseline breast MRI, SABR (28.5 Gy in 3 fractions), follow-up MRI 5 to 6 weeks post-SABR, and lumpectomy. Tumor size and BI-RADS descriptors on pre and post-SABR breast MRIs were compared to determine correlation with surgical specimen % tumor cellularity (%TC). Reported MRI tumor dimensions were used to calculate percent cubic volume remaining (%VR). Partial MRI response was defined as a BI-RADs descriptor change or %VR ≤ 70%, while partial pathologic response (pPR) was defined as %TC ≤ 70%. RESULTS: Nineteen patients completed the trial, and %TC ranged 10% to 80%. For BI-RADS descriptor analysis, 12 of 19 (63%) showed change in lesion or kinetic enhancement descriptors post-SABR. This was associated with lower %TC (29% vs. 47%, P = .042). BI-RADS descriptor change analysis also demonstrated high PPV (100%) and specificity (100%) for predicting pPR to treatment (sensitivity 71%, accuracy 74%), but low NPV (29%). MRI %VR demonstrated strong linear correlation with %TC (R = 0.70, P < .001, Pearson's Correlation) and high accuracy (89%) for predicting pPR (sensitivity 88%, specificity 100%, PPV 100%, and NPV 50%). CONCLUSION: Evaluating breast cancer response on MRI using %VR after pre-operative SABR treatment can help identify patients benefiting the most from neoadjuvant radiation treatment of their ER/PR+ HER2- tumors, a group in which pCR to neoadjuvant therapy is rare.