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A subset of patients with ductal carcinoma in situ (DCIS) of the breast develop ipsilateral invasive breast cancer after breast-conserving surgery with or without adjuvant radiotherapy. Risk assessment and prediction of adverse outcomes for individual patients based on traditional clinical and pathological parameters are limited. The Oncotype DCIS Score is a commercially available multigene assay that has been independently validated in a prospective clinical trial and a population-based cohort. The score helps to identify a subset of women >50 years old with unifocal disease that carries <10% risk of any local recurrence after breast-conserving surgery alone. In this population, individual patients and physicians may consider omitting adjuvant radiotherapy. In this article, we review the literature and summarize the evidence regarding the role of the Oncotype DCIS Score in estimating the risk of ipsilateral local recurrence and ipsilateral invasive breast cancer recurrence. The available data on clinical utility and cost-effective analysis for optimizing decisions on adjuvant treatments are discussed.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Perfilação da Expressão Gênica , Neoplasias da Mama/genética , Carcinoma Intraductal não Infiltrante/genética , Estudos de Avaliação como Assunto , Feminino , Humanos , Invasividade Neoplásica , PrognósticoRESUMO
PURPOSE: The impact of Ductal Carcinoma in Situ (DCIS) with multiple foci of microinvasion (MI) (≤ 1 mm) on the risks of local recurrence (LR) and invasive LR is unknown, leading to uncertainty if DCIS with multiple foci of MI requires more aggressive treatment. We report a population-based analysis of the impact of multiple foci of MI, confirmed by pathology review, on the 15-year risks of LR and invasive LR treated with breast-conserving surgery (BCS) ± radiotherapy (RT). METHODS: Cohort includes all women diagnosed with DCIS ± MI from 1994 to 2003 treated with BCS ± RT. Cox proportional hazards model was used to evaluate the impact of multiple foci of MI on the risks of LR and invasive LR, adjusting for covariates. The 15-year local and invasive local recurrence-free survival rates were calculated using the Kaplan-Meier method with differences compared by log-rank test. RESULTS: The cohort includes 2988 women treated by BCS; 2721 had pure DCIS (51% received RT), 267 had DCIS with one or more foci of MI (58% had RT). Median follow-up was 13 years. Median age at diagnosis was 58 years. On multivariable analyses, the presence of multiple foci of MI was associated with an increased risk of invasive LR (HR = 1.59, 95% CI 1.01-2.49, p = 0.04) but not DCIS LR (HR = 0.89, 95% CI 0.46, 1.76, p = 0.7). The 15-year invasive LRFS risks for cases with pure DCIS, with 1 focus or multiple foci of MI were 85.7%, 85.6%, 74.7% following treatment by BCS alone, 87.2%, 89.9%, and 77% for those treated with BCS + RT without boost and 89.2%, 91.3%, and 95% for women treated with BCS + RT and boost. CONCLUSIONS: The presence of multiple foci of MI in DCIS is associated with higher 15-year risks of invasive LR after breast-conserving therapy compared to women with pure DCIS but treatment with whole breast and boost RT can mitigate this risk.
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Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Mastectomia Segmentar/métodos , Recidiva Local de Neoplasia/epidemiologia , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/radioterapia , Carcinoma Intraductal não Infiltrante/epidemiologia , Carcinoma Intraductal não Infiltrante/radioterapia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Medição de Risco , Análise de SobrevidaRESUMO
Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of mammary ductal epithelial cells confined to the ductal-lobular system, and a non-obligate precursor of invasive disease. While there has been a significant increase in the diagnosis of DCIS in recent years due to uptake of mammography screening, there has been little change in the rate of invasive recurrence, indicating that a large proportion of patients diagnosed with DCIS will never develop invasive disease. The main issue for clinicians is how to reliably predict the prognosis of DCIS in order to individualize patient treatment, especially as treatment ranges from surveillance only, breast-conserving surgery only, to breast-conserving surgery plus radiotherapy and/or hormonal therapy, and mastectomy with or without radiotherapy. We conducted a semi-structured literature review to address the above issues relating to "pure" DCIS. Here we discuss the pathology of DCIS, risk factors for recurrence, biomarkers and molecular signatures, and disease management. Potential mechanisms of progression from DCIS to invasive cancer and problems faced by clinicians and pathologists in diagnosing and treating this disease are also discussed. Despite the tremendous research efforts to identify accurate risk stratification predictors of invasive recurrence and response to radiotherapy and endocrine therapy, to date there is no simple, well-validated marker or group of variables for risk estimation, particularly in the setting of adjuvant treatment after breast-conserving surgery. Thus, the standard of care to date remains breast-conserving surgery plus radiotherapy, with or without hormonal therapy. Emerging tools, such as pathologic or biologic markers, may soon change such practice. Our review also includes recent advances towards innovative treatment strategies, including targeted therapies, immune modulators, and vaccines.
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Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Feminino , Humanos , Mamografia , Medição de RiscoRESUMO
BACKGROUND: Although the rate of carcinoma upgrade for atypical ductal hyperplasia (ADH) diagnosed on core needle biopsy (CNB) is variable, current standard treatment consists of surgical excision (SE) for all ADH CNB diagnoses. Our objective was to identify features of ADH on CNB that may stratify carcinoma upgrade risk on SE. METHODS: We retrospectively analyzed cases diagnosed as ADH on CNB. An independent slide review and detailed analysis of radiological and clinical data was performed. Statistical analyses were used to identify predictors for upgrade. Using variables predictive of upgrade, a model to stratify the probability of upgrade of ADH diagnosed on CNB was constructed. RESULTS: We identified 124 ADH cases with subsequent SE. Of these, 62 cases (50%) were upgraded to carcinoma. Features predictive of upgrade were as follows: diagnosis of "At least ADH", percentage of cores involved by ADH, radiologic lesion size, presence of ipsilateral carcinoma, and patient age. A 4-tiered predictive model using percentage of cores involved by ADH, histologic extent of ADH, radiologic lesion size, and patient age was constructed. This predictive model has a fair accuracy, with an area under the ROC curve of 0.76. CONCLUSION: We have identified several predictors of carcinoma upgrade for ADH diagnosed on CNB. Our predictive model may be used to stratify the risk of carcinoma upgrade on SE.
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Biópsia com Agulha de Grande Calibre/métodos , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Estudos RetrospectivosRESUMO
Mammary fibroepithelial lesions encompass a wide spectrum of tumors ranging from an indolent fibroadenoma to potentially fatal malignant phyllodes tumor. The criteria used for their classification based on morphological assessment are often challenging to apply and there is no consensus as to what constitutes an adequate resection margin. We studied a retrospective cohort of 213 fibroepithelial lesions in 178 patients (80 fibroadenomas with unusual features and 133 phyllodes tumors: 63 benign, 41 borderline, and 29 malignant) in order to describe the spectrum of changes within each group, with special emphasis on margin evaluation. Outcome data were available for 153 fibroepithelial lesions in 139 patients (median 56 months, range 3-249 months). Positive final margin (tumor transected), age < 50 years and a predominantly myxoid stroma were statistically significant predictors of local recurrence, while age > 50, stromal overgrowth, diffuse marked atypia, necrosis and mitotic index of ≥ 10 per 10 HPF were predictive of distant metastases. Tumors with satellite/bulging nodules were at a significantly higher risk to have a final positive resection margin. Our findings highlight important aspects of the interpretation and reporting of fibroepithelial lesions: the amount of myxoid stroma and the presence of satellite nodules are clinically relevant and should be routinely assessed and reported; infiltrative border might not be a prerequisite for the diagnosis of malignant phyllodes tumor, while the presence of tumor necrosis, massive stromal overgrowth or mitotic index of ≥ 25 per 10 HPF is diagnostic of malignant phyllodes tumor. On the other hand, increased mitotic index outside of the range of the World Health Organization guidelines in the absence of other worrisome features should be treated with caution, as it can be found in benign tumors.
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Neoplasias da Mama/patologia , Fibroadenoma/patologia , Recidiva Local de Neoplasia/patologia , Tumor Filoide/patologia , Adulto , Idoso , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Fibroadenoma/mortalidade , Humanos , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Tumor Filoide/mortalidade , Estudos RetrospectivosRESUMO
Cutaneous malakoplakia is a rare infection-related granulomatous disease frequently associated with immunocompromised states. Foamy macrophages containing basophilic granules, called the Michaelis-Gutman bodies, are pathognomonic. We report a case of cutaneous malakoplakia in a 77-year-old male with pyoderma gangrenosum and a 2-year history of a non-healing malleolar ulcer treated successfully with cotrimoxazole.
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Hospedeiro Imunocomprometido , Malacoplasia/tratamento farmacológico , Malacoplasia/etiologia , Pioderma Gangrenoso/complicações , Pioderma Gangrenoso/tratamento farmacológico , Administração Cutânea , Idoso , Humanos , Masculino , Resultado do TratamentoRESUMO
Validated biomarkers are needed to improve risk assessment and treatment decision-making for women with ductal carcinoma in situ (DCIS) of the breast. The Oncotype DX DCIS Score (DS) was shown to predict the risk of local recurrence (LR) in individuals with low-risk DCIS treated by breast-conserving surgery (BCS) alone. Our objective was to confirm these results in a larger population-based cohort of individuals. We used an established population-based cohort of individuals diagnosed with DCIS treated with BCS alone from 1994 to 2003 with validation of treatment and outcomes. Central pathology assessment excluded cases with invasive cancer, DCIS < 2 mm or positive margins. Cox model was used to determine the relationship between independent covariates, the DS (hazard ratio (HR)/50 Cp units (U)) and LR. Tumor blocks were collected for 828 patients. Final evaluable population includes 718 cases, of whom 571 had negative margins. Median follow-up was 9.6 years. 100 cases developed LR following BCS alone (DCIS, N = 44; invasive, N = 57). In the primary pre-specified analysis, the DS was associated with any LR (DCIS or invasive) in ER+ patients (HR 2.26; P < 0.001) and in all patients regardless of ER status (HR 2.15; P < 0.001). DCIS Score provided independent information on LR risk beyond clinical and pathologic variables including size, age, grade, necrosis, multifocality, and subtype (adjusted HR 1.68; P = 0.02). DCIS was associated with invasive LR (HR 1.78; P = 0.04) and DCIS LR (HR 2.43; P = 0.005). The DCIS Score independently predicts and quantifies individualized recurrence risk in a population of patients with pure DCIS treated by BCS alone.
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Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Mastectomia Segmentar , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Carcinoma Intraductal não Infiltrante/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Ontário/epidemiologia , Vigilância da População , Medição de RiscoRESUMO
Trastuzumab-containing therapy is a standard of care for patients with HER2+ breast cancer. HER2 status is routinely assigned using in situ hybridization to assess HER2 gene amplification, but interpretation of in situ hybridization results may be challenging in tumors with chromosome 17 polysomy or intratumoral genetic heterogeneity. Apparent chromosome 17 polysomy, defined by increased chromosome enumeration probe 17 (CEP17) signal number, is a common genetic aberration in breast cancer and represents an alternative mechanism for increasing HER2 copy number. Some studies have linked elevated CEP17 count ('polysomy') with adverse clinicopathologic features and HER2 overexpression, although there are numerous discrepancies in the literature. There is evidence that elevated CEP17 ('polysomy') count might account for trastuzumab response in tumors with normal HER2:CEP17 ratios. Nonetheless, recent studies establish that apparent 'polysomy' (CEP17 increase) is usually related to focal pericentromeric gains rather than true polysomy. Assigning HER2 status may also be complex where multiple cell subclones with distinct HER2 amplification characteristics coexist within the same tumor. Such genetic heterogeneity affects up to 40% of breast cancers when assessed according to a College of American Pathologists guideline, although other definitions have been proposed. Recent data have associated heterogeneity with unfavorable clinicopathologic variables and poor prognosis. Genetically heterogeneous tumors harboring HER2-amplified subclones have the potential to benefit from trastuzumab, but this has yet to be evaluated in clinical studies. In this review, we discuss the implications of apparent polysomy 17 and genetic heterogeneity for assigning HER2 status in clinical practice. Among our recommendations, we support the use of mean HER2 copy number rather than HER2:CEP17 ratio to define HER2 positivity in cases where coamplification of the centromere might mask HER2 amplification. We also highlight a need to harmonize in situ hybridization scoring methodology to support accurate HER2 status determination, particularly where there is evidence of heterogeneity.
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Neoplasias da Mama/genética , Cromossomos Humanos Par 17 , Amplificação de Genes , Dosagem de Genes , Heterogeneidade Genética , Hibridização In Situ , Receptor ErbB-2/genética , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Centrômero , Feminino , Predisposição Genética para Doença , Humanos , Seleção de Pacientes , Fenótipo , Medicina de Precisão , Valor Preditivo dos Testes , Inibidores de Proteínas Quinases/uso terapêutico , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , TrastuzumabRESUMO
AIMS: Cystic neutrophilic granulomatous mastitis (CNGM) is a subtype of granulomatous mastitis (GM) associated with Corynebacterium spp infection. We aimed to analyse the prevalence of Corynebacteria in CNGM and non-CNGM cases. METHODS: Breast specimens diagnosed as granulomatous inflammation between 2010 and 2020 were reviewed to identify a CNGM cohort and a non-CNGM cohort. Polymerase chain reaction-based identification of Corynebacteria by 16S ribosomal RNA (16S rRNA) primers, followed by confirmatory Sanger sequencing (SS), was performed on all cases. Clinical, radiological and microbiology data were retrieved from the electronic patient records. RESULTS: Twenty-eight CNGM cases and 19 non-CNGM cases were identified. Compared with the non-CNGM cohort, patients in the CNGM cohort were more likely to be multiparous (p=0.01), breast feeding (p=0.01) and presenting with a larger breast mass (p<0.01), spontaneous drainage (p=0.05) and skin irritation (p<0.01). No significant difference in the prevalence of Corynebacteria between the cohorts (7% vs 11%, p=0.68) by microbiological culture was identified. Compared with microbiology culture, the sensitivity and specificity of each Corynebacterial detection method were 50% and 81% for Gram stain, and 25% and 100% for 16S rRNA combined with SS. Regardless of the diagnosis, patients positive for Corynebacteria were more likely to have a persistent disease (p<0.01). CONCLUSION: CNGM presents as a large symptomatic breast mass in multiparous breastfeeding women. The importance of adequate sampling and repeated microbiology culture in conjunction with sequencing on all GM cases with persistent disease is paramount.
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Ductal carcinoma in situ (DCIS), a non-invasive breast cancer, is usually treated by breast-conserving surgery (BCS). Randomized trials prove that the addition of radiotherapy (XRT) leads to lower rates of recurrence. Despite the evidence, half of women do not receive XRT after BCS. It is unknown how well clinicians identify women with low risk DCIS for treatment by BCS alone or to what extent women with DCIS develop recurrent cancer due to the omission of radiotherapy. We report the outcomes of a population of women with DCIS treated with BCS, alone or with radiotherapy, and evaluate the effectiveness of each therapeutic approach. All women diagnosed with DCIS and treated with BCS, alone or with radiotherapy in Ontario from 1994 to 2003 were identified. Treatments and outcomes were validated by chart review. Survival analyses were used to study the development of local recurrence (LR) in relation to patient and tumor characteristics and the use of radiotherapy. The cohort included 3,762 women treated with breast-conserving therapy; 1,895 of whom (50 %) also received radiation. At 10 years median follow-up, LR developed in 233 (12 %) women who received radiotherapy and in 363 (19 %) of women who did not (p < 0.0001). The 10-year actuarial LR rate for women who did and did not receive radiotherapy was 12.7 and 20.0 % (p < 0.0001). Differences were significant for both for invasive LR (7.0 vs. 10.0 %, p < 0.0001) and for DCIS recurrence (6.1 vs. 10.8 %, p < 0.0001). We estimate that 22 % of recurrences diagnosed in Ontario women treated for DCIS between 1994 and 2003 would have been prevented if all patients had received radiotherapy. The omission of radiotherapy after BCS for DCIS resulted in substantive recurrences that might have been avoided with treatment. Additional markers are needed to identify a low risk group in whom radiation can be safely omitted.
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Neoplasias da Mama/epidemiologia , Carcinoma Intraductal não Infiltrante/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/radioterapia , Carcinoma Intraductal não Infiltrante/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Ontário/epidemiologia , População , Risco , Resultado do Tratamento , Adulto JovemRESUMO
Trastuzumab in combination with capecitabine or 5-fluorouracil and cisplatin is approved by the European Medicines Agency for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive (immunohistochemistry 3+ or immunohistochemistry 2+/fluorescence in situ hybridization-positive or immunohistochemistry 2+/silver in situ hybridization-positive) metastatic adenocarcinoma of the stomach or gastro-esophageal junction. Approvals are underway in other countries, with recent approvals granted in the United States and Japan. Experience and data from trastuzumab use in breast cancer have highlighted the importance of quality HER2 testing and scoring to ensure accurate identification of patients eligible for treatment. HER2 testing in gastric cancer differs from testing in breast cancer due to inherent differences in tumor biology; gastric cancer more frequently shows HER2 heterogeneity (focal staining) and incomplete membrane staining. Consequently, gastric cancer-specific HER2 testing protocols have been developed and standardized and it is imperative that these recommendations be adhered to. Given the predictive value of HER2 protein levels with response in the trastuzumab for GAstric cancer study (ToGA), immunohistochemistry should be the initial testing methodology and fluorescence in situ hybridization or silver in situ hybridization should be used to retest immunohistochemistry 2+ samples. Wherever possible, bright-field methodologies should be used as these are considered to be superior to fluorescent methodologies at identifying heterogeneous staining. Specific training is required before embarking on HER2 testing in gastric cancer, irrespective of the experience of HER2 testing in breast cancer. This paper provides the most up-to-date practical guidance on HER2 testing and scoring in patients with gastric and gastro-esophageal junction cancer, as agreed by a panel of expert pathologists with extensive experience of HER2 testing particularly reflecting the European Medicines Agency-approved indication. It is anticipated that these recommendations should ensure accurate and consistent HER2 testing, which will allow appropriate selection of patients eligible for treatment with trastuzumab.
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Adenocarcinoma/diagnóstico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Esofágicas/diagnóstico , Junção Esofagogástrica/patologia , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/normas , Hibridização In Situ/métodos , Hibridização In Situ/normas , Guias de Prática Clínica como Assunto , Receptor ErbB-2/genética , Coloração pela Prata , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , TrastuzumabRESUMO
A 62-year-old man presented with a 2-year history of a 2-cm cystic mass involving his occiput. There had been recent enlargement, and the clinical impression was that of a pilar cyst. Histopathological sections showed a partially dermal solid and cystic proliferation. The tumor contained areas of glandular differentiation with cuboidal to columnar cells lining luminal and cystic spaces. A concurrent spindle cell proliferation was seen interspersed between glands and also formed broad, cellular sheets of cells. The stroma was sclerotic and without chondroid or myxoid elements. Immunohistochemistry showed that the spindled cells expressed S100 protein, cytokeratin and smooth muscle myosin. The immunohistochemical profile and the relationship with ductal elements supported myoepithelial differentiation. The proliferation warranted the diagnosis of myoepithelioma arising from a hidradenoma, which to our knowledge has not been previously described. In addition to discussing this case, we provide a brief review of epithelial-myoepithelial neoplasms encountered in the skin.
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Acrospiroma , Neoplasias de Cabeça e Pescoço , Mioepitelioma , Segunda Neoplasia Primária , Couro Cabeludo , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Acrospiroma/metabolismo , Acrospiroma/patologia , Proliferação de Células , Derme/metabolismo , Derme/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mioepitelioma/metabolismo , Mioepitelioma/patologia , Proteínas de Neoplasias/metabolismo , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/patologia , Couro Cabeludo/metabolismo , Couro Cabeludo/patologia , Neoplasias das Glândulas Sudoríparas/metabolismo , Neoplasias das Glândulas Sudoríparas/patologiaRESUMO
BACKGROUND: The inability to identify individuals with ductal carcinoma in situ (DCIS) who are at risk of breast cancer (BC) mortality have hampered efforts to reduce the overtreatment of DCIS. The 21-gene recurrence score (RS) predicts distant metastases for individuals with invasive BC, but its prognostic utility in DCIS is unknown. METHODS: We performed a population-based analysis of 1362 individuals of DCIS aged 75 years or younger at diagnosis treated with breast-conserving therapy. We examined the association between a high RS (defined a priori as >25) and the risk of BC mortality by using a propensity score-adjusted model accounting for the competing risk of death from other causes, testing for interactions. All statistical tests were 2-sided. RESULTS: With 16 years median follow-up, 36 (2.6%) died of BC, and 200 (14.7%) died of other causes. The median value of the RS was 15 (range = 0-84); 29.6% of individuals had a high RS. A high RS was associated with an 11-fold increased risk of BC mortality (hazard ratio = 11.27, 95% confidence interval [CI] = 3.00 to 42.33; P < .001) in women aged 50 years or younger at diagnosis treated with breast-conserving surgery alone, culminating in a 9.4% (95% CI = 2.3% to 22.5%) 20-year risk of BC death. For women with a high RS, treatment with radiotherapy was associated with a 71% (hazard ratio = 0.29, 95% CI = 0.10 to 0.89; P = .03) relative and a 5% absolute reduction in the 20-year cumulative risk of death from BC. CONCLUSION: The 21-gene RS predicts BC mortality in DCIS and combined with age (50 years or younger) at diagnosis can identify individuals for whom radiotherapy reduces the risk of death from BC.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/terapia , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Sentinel lymph node biopsy (SLNB) has been widely accepted as the lymph node sampling procedure of choice for melanoma patients. Current standards of practice suggest completion lymph node dissection (CLND) for patients with a positive SLNB result. The rationale for SLNB+/-CLND is for staging and prognosis as well as local control and possibly survival improvement. CLND, however, entails significant morbidity. In addition, most patients (approximately 80%) will have no further melanoma metastases in non-sentinel nodes and these patients may not benefit from the additional dissection. We had previously developed a score (based on patient age and the total size of metastasis within the SLN) that predicted which SLN-positive patients would have a positive CLND. Utilization of this scoring system would spare a significant number of melanoma patients the risks associated with CLND. The purpose of this study was to validate this score using different melanoma populations. METHODS: A retrospective chart review of all patients that had undergone SLNB for melanoma at four different Canadian centers was undertaken. Data from the Calgary Foothills Medical Center, the Winnipeg Health Sciences Center, and the Toronto Sunnybrook Health Sciences Center from January 1999 to present was collected. In addition, we identified all patients from April 2007 to present at the Misericordia Hospital in Edmonton for this study. This patient information had not been utilized when we were developing this score. The collected variables included patient age, Breslow thickness, result of SLNB, total size of SLN metastasis, largest size of SLN metastasis, and results of CLND. Logistic regression was used to test the significance of a score system's correlation (based on cutoff age of 55 years and cutoff total SLN metastasis of 5 mm) with the CLND results. We also used logistic regression to test the correlation of cutoff values of total SLN metastasis with non-sentinel lymph node (NSLN) metastasis. RESULTS: Data were collected on 599 patients across the four centers. Breslow thickness significantly correlated with SLN metastasis. The risk score system (based on patient age and total SLN metastasis) was significantly predictive of the CLND result in SLNB-positive patients. However, the age became non-significant on multivariate analysis. Total SLN metastasis emerged as the variable that is most predictive of NSLN metastasis. Patients with total SLN metastasis less than 2 mm had a 3.6% risk of NSLN metastasis, those with SLN metastasis from 2-5 mm had a 12.5% risk of NSLN metastasis, whereas those with total SLN metastasis of 5 mm or greater had a 30% risk of NSLN metastasis. CONCLUSION: Using cutoff values of 2 and 5 mm for total SLN metastasis, prediction of NSLN metastasis can be made in melanoma patients. Patients with less than 2 mm of total SLN metastasis are unlikely (<3.67% likelihood) to harbor NSLN metastasis; these patients may not benefit from additional nodal dissection beyond SLNB.
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Melanoma/patologia , Humanos , Metástase Linfática , Melanoma/secundário , Pessoa de Meia-Idade , Estudos Retrospectivos , Biópsia de Linfonodo SentinelaAssuntos
Artrite/complicações , Cútis Laxa/complicações , Dermatoses da Mão/complicações , Adulto , Feminino , Dedos , HumanosRESUMO
CONTEXT.: The use of neoadjuvant therapy in the management of early-stage invasive breast cancer is increasing. Residual Cancer Burden and other similar tools use pathologic characteristics of post-neoadjuvant therapy breast tumors to determine long-term outcome. However, there are no standardized guidelines for the pathologic evaluation of these specimens in the routine clinical setting. OBJECTIVE.: To assess current practices among Canadian pathologists and pathology assistants with regard to the processing and reporting of post-neoadjuvant therapy breast specimens. DESIGN.: An electronic survey was distributed to pathologists and pathology assistants across Canada. RESULTS.: Sixty-three responses were obtained. A total of 48% (15 of 31) of surveyed pathologists reported familiarity with the Residual Cancer Burden tool. A total of 40% (25 of 63) of respondents reported a lack of routine use of specimen photography, and 35% (22 of 63) reported a lack of routine use of grossing diagrams. There was significant variation with respect to tumor bed sampling; the most common method was to submit 1 block per centimeter of tumor (20 of 63; 32%). There was also significant variation in the method of measuring residual tumor; the most common method was to measure the largest cross-section of residual tumor (16 of 32; 50%). CONCLUSIONS.: There is a need for standardization of the evaluation of post-neoadjuvant therapy breast specimens in the routine clinical setting in Canada. We recommend the routine use of specimen mapping, submitting the largest cross section of tumor bed in toto, reporting tumor size as per American Joint Committee on Cancer and Residual Cancer Burden guidelines, and routinely including measurements of residual tumor cellularity and in situ disease in the final pathology report as per Residual Cancer Burden guidelines.
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Neoplasias da Mama/patologia , Mama/patologia , Patologia Cirúrgica/normas , Manejo de Espécimes/normas , Neoplasias da Mama/tratamento farmacológico , Canadá , Quimioterapia Adjuvante , Feminino , Humanos , Terapia Neoadjuvante/métodosRESUMO
PURPOSE: The prognosis of women with triple-negative breast cancers (defined as cancers that are estrogen receptor-negative, progesterone receptor-negative and HER2/neu negative) is poor, compared to women with other subtypes of breast cancer. It is proposed that the underlying difference in recurrence rates may be explained in part by different routes of metastatic spread. EXPERIMENTAL DESIGN: We studied a cohort of 1608 patients diagnosed with breast cancer, diagnosed between January 1987 and December 1997 at Women's College Hospital in Toronto. Triple-negative breast cancers were defined as those that were estrogen receptor-negative, progesterone receptor-negative and HER2/neu-negative. We compared the incidence rates of metastatic spread to bone and to other (non-bone) organs in women with triple-negative and other forms of breast cancer. RESULTS: Of the 1,608 patients, 180 (11.2%) had triple-negative breast cancer. The 1608 women were followed for a median of 9.0 years (range 0.1-19 years). Compared to other patients, those with triple-negative breast cancer had an increased likelihood of distant recurrence over the study period (adjusted hazard ratio (HR) 1.9; 95% CI: 1.5-2.5, P < 0.0001). The relatively poor prognosis was apparent in the five years after diagnosis (HR 2.9; 95% CI: 2.1-3.9; P = 0.0001) but not thereafter (HR 0.5; 95% CI: 0.2-1.1; P = 0.07). In particular, women with triple-negative breast cancer were four times more likely to experience a visceral metastasis within five years of diagnosis than those with other types of cancer (HR 4.0; 95% CI: 2.7-5.9; P < 0.0001). The rates of bone metastases were comparable for triple-negative and for other forms of cancer in this time period (HR 0.8; 95% CI: 0.4-1.6 P = 0.5). CONCLUSIONS: The excess risk of distant recurrence in triple-negative breast cancers, versus other forms of cancer, is attributable in large part to an excess of visceral metastases in the first five years following diagnosis.
Assuntos
Neoplasias da Mama/patologia , Metástase Neoplásica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/secundário , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Vísceras/patologiaRESUMO
Traditional prognostic markers for breast cancer include estrogen receptor (ER), progesterone receptor (ER) and HER2/neu. Negative staining for these three markers defines the 'triple-negative' phenotype. By adding markers for cytokeratin 5/6 and EGFR, triple-negative breast cancers can be divided into 'basal-like' and 'normal-like' subgroups. We conducted immuno-staining on a panel of 958 patients with breast cancer, using all five markers and we followed the patients for distal recurrence and death. We compared rates of distal recurrence in the basal-like and normal-like subgroups with that of women with ER-positive breast cancer. Only 16 of 958 women had normal-like breast cancers. These cancers resembled basal-like cancers in that they had a high proliferative index, but the women with normal-like breast cancers resembled ER-positive women in terms of distant recurrence. The addition of CK5/6 and EGFR to the standard panel (ER/PR/HER2/neu) defines a small subgroup of women with normal-like breast cancer. The prognosis of these women may be superior to that of basal-like breast cancers but firm conclusions cannot be made.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Proteínas de Neoplasias/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/química , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Divisão Celular , Intervalo Livre de Doença , Receptores ErbB/análise , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Queratina-5/análise , Queratina-6/análise , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto JovemRESUMO
Toker cells are inconspicuous cytokeratin 7 positive cells that should be distinguished from intraepidermal involvement by malignant cells seen in Paget's disease (PD) of the nipple. The aim of our study was to quantitatively assess the number and pattern of distribution of Toker cells in nipples without PD in mastectomy specimens. Sequential sections from the nipple of 173 mastectomies were evaluated using HE and immunohistochemistry. Two breast pathologists reviewed the stains and recorded the number and pattern of distribution of CK7 positive cells (CK7+) and their HER2/neu, ER and PR status. There were 152/173 (88.4%) cases with CK7+ cells. The mean number of CK7+ cells per section was 22 (range 0-200) and the mean number of CK7+ cells per field at 10x was 10 (range 0-106). 10/37 (27%) of nipples from prophylactic mastectomies and 15/136 (11.1%) of mastectomies for cancer displayed over 10 CK7+ cells in an area of 10x. In 32/173 (18.5%) CK7+ cells formed small groups or clusters. Notably these cells were not restricted to the basal part of the epidermis. None of the groups/clusters of Toker cells were appreciated on HE stain and all were HER2/neu, ER and PR negative. The absence of any CK7+ cells in 20 cases occurred in hyperpigmented epidermis, possibly obscuring rare positive cells. Toker cells are frequently present in the epidermis of the nipple and are more prevalent than appreciated on routine HE stain. These cells can be present in clusters and can have pagetoid pattern of distribution. They occur in nipples of cancer patients with or without PD and in prophylactic mastectomies performed for high risk patients. The substantial number and the clustering of Toker cells should not be mistaken for PD of the nipple. Unlike PD, Toker cells have small bland nuclei and are characterized by CK7+ and HER2/neu ER and PR negative immunoprofile.