RESUMO
Accurate pathological diagnosis is the cornerstone of optimal clinical management for patients with breast disease. As non-operative diagnosis has now become the standard of care, histopathologists encounter the daily challenge of making definitive diagnoses on limited breast core needle biopsy (CNB) material. CNB samples are carefully evaluated using microscopic examination of haematoxylin and eosin (H&E)-stained slides and supportive immunohistochemistry (IHC), providing the necessary information to inform the next steps in the patient care pathway. Some entities may be difficult to distinguish on small tissue samples, and if there is uncertainty a diagnostic excision biopsy should be recommended. This review discusses (1) benign breast lesions that may mimic malignancy, (2) malignant conditions that may be misinterpreted as benign, (3) malignant conditions that may be incorrectly diagnosed as primary breast carcinoma, and (4) some IHC pitfalls. The aim of the review is to raise awareness of potential pitfalls in the interpretation of breast lesions that may lead to underdiagnosis, overdiagnosis, or incorrect classification of malignancy with potential adverse outcomes for individual patients.
Assuntos
Microscopia , HumanosRESUMO
HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma-adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15-3.15) and adjacent non-neoplastic epithelium (n = 152, p < 0.001, HR 2.7, 95% CI 1.59-4.66), but not stroma. In stage II cases, however, the prognostic value of HLA-DR expression was significant only in adjacent non-neoplastic tissues, for both epithelium (n = 63, p = 0.015, HR 3.6, 95% CI 1.279-10.25) and stroma (n = 63, p = 0.018, HR 5.07, 95% CI 1.32-19.49). HLA-DR was lower in carcinoma tissue compared to matched adenomas (n = 35), in epithelium (p < 0.01) and stroma (p < 0.001). HLA-DR was further reduced in late-stage carcinoma (n = 101) compared to early stage (n = 105), in epithelium (p < 0.001) and stroma (p < 0.01). HLA-DR expression was lower (p < 0.05) in the adjacent non-neoplastic epithelium of patients with cancer recurrence. We demonstrate a progressive loss of HLA-DR in epithelial and stromal tissue compartments during CRC development and show prognostic ability in carcinoma-adjacent non-neoplastic tissues, highlighting the importance of this molecule in the anti-cancer immune response. These findings may have wider implications for immunotherapeutic interventions.
Assuntos
Adenocarcinoma/patologia , Adenoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Antígenos HLA-DR/metabolismo , Recidiva Local de Neoplasia/patologia , Células Estromais/metabolismo , Adenocarcinoma/metabolismo , Adenoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
INTRODUCTION: Breast cancer patients respond differently to neoadjuvant chemotherapy(NAC) based on receptor subtype. The aim of this study was to assess the impact of progesterone receptor (PgR) status on response to neoadjuvant chemotherapy (NAC) in estrogen receptor (ER)+, human epidermal growth factor receptor (HER)- breast cancer patients. METHODS: ER+ and HER- patients receiving NAC over a 7-year period (2011-2017) were identified. The primary outcome was breast complete pathological response (pCR) rate. Secondary outcomes included axillary pCR, axillary/breast pCR and complete radiological response (cRR). RESULTS: A total of 203 patients were identified (149 in the ER+, PgR+, and HER- group and 54 in the ER+, PgR-, and HER- group). Compared with the PgR+ group, PgR- patients were significantly associated with breast pCR (31.5% vs 7.4%; χ² test; P < .01). In multivariable analysis, PgR- status (odds ratio [OR], 4.58; 95% confidence interval [CI]: 1.58,13.28; P = .005), radiological size >50 mm (OR, 5.38; 95% CI: 1.07,27.04; P = .04) and grade (OR, 3.52;95% CI: 1.21,10.23;P = .02) were significant predictors of breast pCR. Only PgR- status was a significant predictor of cRR (OR, 6.234; 95% CI: 2.531, 15.355; P < .001). In node positive patients, PgR negativity was associated with a trend towards breast/axillary nodal pCR (22% vs 12.7%; χ² test; P = .055). CONCLUSION: Over 30% of ER+, PgR-, and HER- patients will have a breast pCR after NAC. PgR- is the only significant predictor of breast pCR/cRR in this tumor subtype. ER+, PgR-, and HER- patients should be considered for NAC.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Metástase Linfática , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Estudos RetrospectivosRESUMO
Wnt pathway deregulation is a common characteristic of many cancers. Only colorectal cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of the pancreas) have activating mutations in ß-catenin (CTNNB1). We have compared the dynamics and the potency of ß-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of ß-catenin took much longer to achieve Wnt deregulation and acquire a crypt-progenitor cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of ß-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of ß-catenin mutation to differentially transform the SI versus the colon correlated with higher expression of E-cadherin and a higher number of E-cadherin:ß-catenin complexes at the membrane. Reduction in E-cadherin synergised with an activating mutation of ß-catenin resulting in a rapid CPC phenotype within the SI and colon. Thus, there is a threshold of ß-catenin that is required to drive transformation, and E-cadherin can act as a buffer to sequester mutated ß-catenin.
Assuntos
Caderinas/metabolismo , Transformação Celular Neoplásica , Neoplasias do Colo , Mutação , Proteínas de Neoplasias , Via de Sinalização Wnt , beta Catenina , Animais , Caderinas/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Camundongos , Camundongos Transgênicos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMO
The fundamental mechanisms underlying erosive oesophagitis and subsequent development of Barrett's oesophagus (BO) are poorly understood. Here, we investigated the contribution of specific components of the gastric refluxate on adhesion molecules involved in epithelial barrier maintenance. Cell line models of squamous epithelium (HET-1A) and BO (QH) were used to examine the effects of bile acids on cell adhesion to extracellular matrix proteins (Collagen, laminin, vitronectin, fibronectin) and expression of integrin ligands (α3 , α4, α5 , α6 and αν ). Experimental findings were validated in human explant oesophageal biopsies, a rat model of gastroesophageal reflux disease (GORD) and in patient tissue microarrays. The bile acid deoxycholic acid (DCA) specifically reduced adhesion of HET-1A cells to vitronectin and reduced cell-surface expression of integrin-αν via effects on endocytic recycling processes. Increased expression of integrin-αv was observed in ulcerated tissue in a rat model of GORD and in oesophagitis and Barrett's intestinal metaplasia patient tissue compared to normal squamous epithelium. Increased expression of integrin-αν was observed in QH BO cells compared to HET-1A cells. QH cells were resistant to DCA-mediated loss of adhesion and reduction in cell-surface expression of integrin-αν . We demonstrated that a specific component of the gastric refluxate, DCA, affects the epithelial barrier through modulation of integrin αν expression, providing a novel mechanism for bile acid-mediated erosion of oesophageal squamous epithelium and promotion of BO. Strategies aimed at preventing bile acid-mediated erosion should be considered in the clinical management of patients with GORD.
Assuntos
Esôfago de Barrett/metabolismo , Ácido Desoxicólico/farmacologia , Células Epiteliais/efeitos dos fármacos , Esofagite/metabolismo , Refluxo Gastroesofágico/metabolismo , Integrina alfaV/genética , Animais , Esôfago de Barrett/genética , Esôfago de Barrett/patologia , Adesão Celular , Linhagem Celular , Colágeno/química , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Esofagite/genética , Esofagite/patologia , Fibronectinas/química , Refluxo Gastroesofágico/genética , Refluxo Gastroesofágico/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Integrina alfaV/metabolismo , Integrinas/genética , Integrinas/metabolismo , Laminina/química , Permeabilidade/efeitos dos fármacos , Transporte Proteico , Ratos , Análise Serial de Tecidos , Vitronectina/químicaRESUMO
AIMS: Breast myxoid fibroadenomas (MFAs) are characterized by a distinctive hypocellular myxoid stroma, and occur sporadically or in the context of Carney complex, an inheritable condition caused by PRKAR1A-inactivating germline mutations. Conventional fibroadenomas (FAs) are underpinned by recurrent MED12 mutations in the stromal components of the lesions. The aim of this study was to investigate the genomic landscape of MFAs and compare it with that of conventional FAs. METHODS AND RESULTS: Eleven MFAs from patients without clinical and/or genetic evidence of Carney complex were retrieved. DNA samples of tumour and matching normal tissue were subjected to massively parallel sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay, an assay targeting 410 cancer genes. Genetic alterations detected by MSK-IMPACT were tested in samples in which the stromal and epithelial components were separately laser capture-microdissected. Sequencing revealed no germline PRKAR1A mutations and non-synonymous mutations in six MFAs. Interestingly, in three of the MFAs in which the stromal and epithelial components were separately microdissected, the mutations were found to be restricted to the epithelial rather than the stromal component. The sole exception was a lesion harbouring a somatic truncating PRKAR1A mutation. Upon histological re-review, this case was reclassified as a breast myxoma, consistent with the spectrum of tumous observed in Carney complex patients. In this case, the PRKAR1A somatic mutation was restricted to the stromal component. CONCLUSION: MFAs lack MED12 mutations, and their stromal components seem not to harbour mutations in the 410 cancer genes tested. Whole-exome and/or whole-genome analyses of MFAs are required to elucidate their genetic drivers.
Assuntos
Neoplasias da Mama/genética , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Fibroadenoma/genética , Adulto , Mama/patologia , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Fibroadenoma/classificação , Fibroadenoma/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Complexo Mediador/genética , Microdissecção , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNARESUMO
Sentinel lymph node (SLN) biopsy has been established as the standard of care for axillary staging in patients with invasive breast carcinoma and clinically negative lymph nodes (cN0). Historically, all patients with a positive SLN underwent axillary lymph node dissection (ALND). The ACOSOG Z0011 trial showed that women with T1-T2 disease and cN0 who undergo breast-conserving surgery and whole-breast radiotherapy can safely avoid ALND. The main goal of SLN examination should be to detect all macrometastases (>2 mm). Gross sectioning of SLNs at 2-mm intervals and microscopic examination of one haematoxylin and eosin-stained section from each SLN block is the preferred method for pathological evaluation of SLNs. The role and timing of SLN biopsy for patients who have received neoadjuvant chemotherapy is controversial, and continues to be explored in clinical trials. SLN biopsies from patients with invasive breast carcinoma who have received neoadjuvant chemotherapy pose particular challenges for pathologists.
Assuntos
Neoplasias da Mama/patologia , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela/métodos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Terapia Neoadjuvante , Padrões de Prática MédicaRESUMO
We describe an unexpected finding of diffuse large B-cell lymphoma associated with mature cystic teratoma of the ovary. A 68-yr-old woman with a complex left ovarian cystic mass on imaging underwent bilateral salpingo-oophorectomy, lymphadenectomy, appendicectomy, and omentectomy. Histopathologic examination revealed nodules of malignant non-Hodgkin lymphoma within the teratoma. A diagnosis of diffuse large B-cell lymphoma, germinal center cell subtype by Hans criteria was made after immunostaining and molecular studies. The patient was treated with R-CHOP chemotherapy and remains disease-free at 14-mo follow-up.
Assuntos
Linfoma Difuso de Grandes Células B/patologia , Neoplasias Ovarianas/patologia , Teratoma/patologia , Idoso , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica , Apendicectomia , Ciclofosfamida , Doxorrubicina , Feminino , Rearranjo Gênico , Humanos , Imunoglobulinas/genética , Imuno-Histoquímica , Excisão de Linfonodo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/cirurgia , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/cirurgia , Omento/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Ovariectomia , Prednisona , Rituximab , Salpingectomia , Teratoma/tratamento farmacológico , Teratoma/cirurgia , VincristinaRESUMO
Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict paclitaxel responses in women presenting with high-grade serous EOC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ciclo Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Císticas, Mucinosas e Serosas/metabolismo , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Proteínas Repressoras/metabolismo , Regiões 3' não Traduzidas , Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio/genética , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Proteínas Mad2 , MicroRNAs/metabolismo , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Císticas, Mucinosas e Serosas/mortalidade , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Císticas, Mucinosas e Serosas/terapia , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Inclusão em Parafina , Modelos de Riscos Proporcionais , Interferência de RNA , Proteínas Repressoras/genética , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Transfecção , Resultado do TratamentoRESUMO
Endoscopic oesophageal biopsies are common in daily pathology practice. Inflammation and damage of the oesophageal mucosa is known as oesophagitis and is common worldwide. A variety of physical, chemical and infectious agents cause oesophagitis. The oesophagus has a limited range of responses to a wide variety of injuries, and so histopathological features of different diseases often overlap. The pathologist is reliant on the endoscopist for the 'macroscopic description' of the oesophagus. Access to the endoscopic images enhances the pathologist's overall interpretation of the case. Correlating clinical, endoscopic and microscopic findings may be crucial in arriving at the correct diagnosis. In this review, we present clinicopathological descriptions of the major types of oesophagitis.
Assuntos
Endoscopia Gastrointestinal/métodos , Esofagite/patologia , Esôfago/patologia , Biópsia , Doenças Transmissíveis/complicações , Doenças Transmissíveis/patologia , Esofagite Eosinofílica/etiologia , Esofagite Eosinofílica/patologia , Esofagite/etiologia , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/patologia , Humanos , Doença Iatrogênica , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , MucosaRESUMO
Sentinel lymph node biopsy (SLNB) has become the preferred method of surgical pathological nodal staging of early breast cancer by the end of the nineties. As the most likely sites of metastasis, the SLNs allow a more precise staging, and indeed gross sectioning, step sectioning, immunohistochemistry, and molecular staging methods have been used to disclose metastatic involvement of these lymph nodes. This review summarizes the backgrounds of SLNB, trends in related surgery and pathology. It also gives an insight into European National recommendations related to SLN and divergent daily practices in European pathology departments, on the basis of replies to questionnaires from 84 pathologists from 38 European countries. The questionnaires revealed the post-neoadjuvant setting as an area where a significant minority of pathologists report less confidence in classifying residual nodal involvement into TNM categories. The review also summarizes the neoadjuvant therapy-related aspects of SLNB.
Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Axila/patologia , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Linfonodo Sentinela/patologia , Biópsia de Linfonodo SentinelaRESUMO
Clinical trials have shown that many patients with breast cancer with limited sentinel lymph node (SLN) metastatic disease can safely avoid axillary lymph node dissection. Ultra-staging of initially negative SLNs may not confer additional clinical benefit. Despite this, protocols of 'enhanced pathological examination' (EPE) are still widely used. We evaluated the impact of our EPE protocol. If initial SLN H&Es are negative, we cut three additional H&E levels at 500 µm intervals with two spare sections at each level, to allow for immunohistochemistry if necessary. Occult micrometastases or isolated tumour cells were identified, using this protocol, in 3.4%, resulting in change of N stage in 3%. 1% of patients had further axillary surgery based on these findings. Our SLN-EPE protocol provided additional information in a small number of cases and changed axillary management in a minority. It represented a significant workload for scientists and pathologists, and had time and cost implications. We concluded that emphasising careful gross examination along with judicious use of additional levels and immunohistochemistry may be more beneficial than our current protocol.
Assuntos
Neoplasias da Mama/patologia , Metástase Linfática/patologia , Linfonodo Sentinela/patologia , Axila/cirurgia , Neoplasias da Mama/terapia , Humanos , Imuno-Histoquímica , Metástase Linfática/diagnóstico , Estadiamento de Neoplasias , Biópsia de Linfonodo SentinelaRESUMO
Raman spectroscopy can provide a rapid, label-free, nondestructive measurement of the chemical fingerprint of a sample and has shown potential for cancer screening and diagnosis. Here we report a protocol for Raman microspectroscopic analysis of different exfoliative cytology samples (cervical, oral and lung), covering sample preparation, spectral acquisition, preprocessing and data analysis. The protocol takes 2 h 20 min for sample preparation, measurement and data preprocessing and up to 8 h for a complete analysis. A key feature of the protocol is that it uses the same sample preparation procedure as commonly used in diagnostic cytology laboratories (i.e., liquid-based cytology on glass slides), ensuring compatibility with clinical workflows. Our protocol also covers methods to correct for the spectral contribution of glass and sample pretreatment methods to remove contaminants (such as blood and mucus) that can obscure spectral features in the exfoliated cells and lead to variability. The protocol establishes a standardized clinical routine allowing the collection of highly reproducible data for Raman spectral cytopathology for cancer diagnostic applications for cervical and lung cancer and for monitoring suspicious lesions for oral cancer.
Assuntos
Detecção Precoce de Câncer , Neoplasias/diagnóstico , Neoplasias/patologia , Análise Espectral Raman/métodos , Algoritmos , Colo do Útero/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Pulmão/patologiaRESUMO
BACKGROUND: Breast fibromatosis is a rare clinical entity, but poses significant diagnostic and therapeutic challenges. In light of recent changes in management practices, the aim was to review our institutional experience of breast fibromatosis and provide a review of current available literature on such management. METHODS: A search of pathological databases within two tertiary institutions for all patients diagnosed with fibromatosis of the breast over a 10-year period (2007-2016) was performed. Clinicopathological characteristics and modes of treatment were recorded for each patient. Concurrently a comprehensive literature search was performed and studies relating to breast fibromatosis and its management were identified and reviewed. RESULTS: Sixteen patients were identified. Median age at diagnosis was 42 (range 21-70) and all patients were diagnosed with core biopsy. The most useful imaging modality in diagnosis was ultrasonography and magnetic resonance imaging. 13/16 were treated surgically whilst 3/16 were treated using a watch-and-wait approach. 6/13 (46%) required re-excision of margins and 2/13 (15%) had recurrence after surgery. On review of the literature, there is no dedicated guideline in place for the management of breast fibromatosis. Currently a 'watch and wait' approach is favoured over surgical intervention due to high levels of recurrence and associated surgical morbidity. All cases should be discussed at a sarcoma multidisciplinary team meeting and tyrosine kinase inhibitors should be considered in advanced cases. CONCLUSIONS: Breast fibromatosis is rare but affects young patients. Active surveillance is now favoured over surgical resection due to high recurrence rates and extensive morbidity. Dedicated guidelines are required to ensure best outcomes.
Assuntos
Neoplasias da Mama/terapia , Fibroma/terapia , Mastectomia/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Conduta Expectante/estatística & dados numéricos , Adulto , Idoso , Biópsia com Agulha de Grande Calibre , Mama/diagnóstico por imagem , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Fibroma/diagnóstico , Fibroma/epidemiologia , Fibroma/patologia , Humanos , Imageamento por Ressonância Magnética , Mastectomia/efeitos adversos , Mastectomia/normas , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Guias de Prática Clínica como Assunto , Reoperação/estatística & dados numéricos , Ultrassonografia Mamária , Conduta Expectante/normas , Adulto JovemRESUMO
The small intestine represents 75% of the length and 90% of the absorptive surface area of the gastrointestinal tract (GIT), yet only 2% of digestive system cancers occur at this site. Adenocarcinoma accounts for half of small bowel malignancies. There have been a number of important recent advances in our understanding, classification and treatment of small bowel tumours. Over recent years, ampullary tumours have become recognised as a form of small bowel carcinoma, distinct from head of pancreas and lower biliary tract tumours. This is reflected in separate TNM systems and increasing interest in separating intestinal from pancreatobiliary subtypes. The recognition of the importance of microsatellite (MSI) status and the advent of molecular pathology has also changed our approach to these neoplasms.
Assuntos
Adenocarcinoma/patologia , Neoplasias do Ducto Colédoco/patologia , Neoplasias Duodenais/patologia , Neoplasias Intestinais/patologia , Adenoma/patologia , Humanos , Neoplasias Pancreáticas/patologiaRESUMO
Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC.
RESUMO
Oncotype DX® is a gene expression assay that quantifies the risk of distant recurrence in patients with hormone receptor positive early breast cancer, publicly funded in Ireland since 2011. The aim of this study was to correlate Oncotype DX® risk groupings with traditional histopathological parameters and the results of other risk assessment tools including Recurrence Score-Pathology-Clinical (RSPC), Adjuvant Risk Index (Adj RI), Nottingham Prognostic Index (NPI) and the Adjuvant! Online 10-year score (AO). Patients were retrospectively identified from the histopathology databases of two Irish hospitals and patient and tumour characteristics collated. Associations between categorical variables were evaluated with Pearson's chi-square test. Correlations were calculated using Spearman's correlation coefficient and concordance using Lin's concordance correlation coefficient. Statistical analysis was performed using SPSS software, version 22.0.In our 300 patient cohort, Oncotype DX® classified 59.7% (n = 179) as low, 30% (n = 90) as intermediate, and 10.3% (n = 31) as high risk. Overall concordance between the RS and RSPC, Adj RI, NPI, and AO was 67.3% (n = 202), 56.3% (n = 169), 59% (n = 177), and 36.3% (n = 109), respectively. All risk assessment tools classified the majority of patients as low risk apart from the AO 10-year score, with RSPC classifying the highest number of patients as low risk. This study demonstrates that there is good correlation between the RS and scores obtained using alternative risk tools. Concordance with NPI is strong, particularly in the low-risk group. NPI, calculated from traditional clinicopathological characteristics, is a reliable alternative to Oncotype DX® in the identification of low-risk patients who may avoid adjuvant chemotherapy.
Assuntos
Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Medição de Risco/métodos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , RiscoRESUMO
CONTEXT: -Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes. OBJECTIVE: -To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes. DATA SOURCES: -Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. CONCLUSIONS: -The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin-stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non-sentinel lymph node involvement. This information is important to decide on further axillary treatment.
Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Mama/cirurgia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Reprodutibilidade dos Testes , Linfonodo Sentinela/cirurgiaRESUMO
Colorectal cancer (CRC) is a leading cause of cancer deaths. Molecularly targeted therapies (e.g. bevacizumab) have improved survival rates but drug resistance ultimately develops and newer therapies are required. We identified quininib as a small molecule drug with anti-angiogenic activity using in vitro, ex vivo and in vivo screening models. Quininib (2-[(E)-2-(Quinolin-2-yl) vinyl] phenol), is a small molecule drug (molecular weight 283.75 g/mol), which significantly inhibited blood vessel development in zebrafish embryos (p < 0.001). In vitro, quininib reduced endothelial tubule formation (p < 0.001), cell migration was unaffected by quininib and cell survival was reduced by quininib (p < 0.001). Using ex vivo human CRC explants, quininib significantly reduced the secretions of IL-6, IL-8, VEGF, ENA-78, GRO-α, TNF, IL-1ß and MCP-1 ex vivo (all values p < 0.01). Quininib is well tolerated in mice when administered at 50 mg/kg intraperitoneally every 3 days and significantly reduced tumour growth of HT-29-luc2 CRC tumour xenografts compared to vehicle control. In addition, quininib reduced the signal from a αvß3 integrin fluorescence probe in tumours 10 days after treatment initiation, indicative of angiogenic inhibition. Furthermore, quininib reduced the expression of angiogenic genes in xenografted tumours. Collectively, these findings support further development of quininib as a novel therapeutic agent for CRC.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neovascularização Patológica/metabolismo , Fenóis/uso terapêutico , Quinolinas/uso terapêutico , Animais , Vasos Sanguíneos/efeitos dos fármacos , Linhagem Celular , Neoplasias Colorretais/complicações , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Células Endoteliais/efeitos dos fármacos , Expressão Gênica , Células HT29 , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Camundongos Endogâmicos BALB C , Neovascularização Patológica/complicações , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-ZebraRESUMO
Pathologic assessment of colorectal cancer specimens plays an essential role in patient management, informing prognosis and contributing to therapeutic decision making. The tumor-node-metastasis (TNM) staging system is a key component of the colorectal cancer pathology report and provides important prognostic information. However there is significant variation in outcome of patients within the same tumor stage. Many other histological features such as tumor budding, vascular invasion, perineural invasion, tumor grade and rectal tumor regression grade that may be of prognostic value are not part of TNM staging. Assessment of extramural tumor deposits and peritoneal involvement contributes to TNM staging but there are some difficulties with the definition of both of these features. Controversies in colorectal cancer pathology reporting include the subjective nature of some of the elements assessed, poor reporting rates and reproducibility and the need for standardized examination protocols and reporting. Molecular pathology is becoming increasingly important in prognostication and prediction of response to targeted therapies but accurate morphology still has a key role to play in colorectal cancer pathology reporting.