RESUMO
Accurate characterisation of gastrointestinal stromal tumours (GIST) is important for prognosis and the choice of targeted therapies. Histologically the diagnosis relies on positive immunostaining of tumours for KIT (CD117) and DOG1. Here we report that GISTs also abundantly express the type 3 Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA3). SERCA enzymes transport calcium ions from the cytosol into the endoplasmic reticulum and play an important role in regulating the intensity and the periodicity of calcium-induced cell activation. GISTs from various localisations, histological and molecular subtypes or risk categories were intensely immunopositive for SERCA3 with the exception of PDGFRA-mutated cases where expression was high or moderate. Strong SERCA3 expression was observed also in normal and hyperplastic interstitial cells of Cajal. Decreased SERCA3 expression in GIST was exceptionally observed in a zonal pattern, where CD117 staining was similarly decreased, reflecting clonal heterogeneity. In contrast to GIST, SERCA3 immunostaining of spindle cell tumours and other gastrointestinal tumours resembling GIST was negative or weak. In conclusion, SERCA3 immunohistochemistry may be useful for the diagnosis of GIST with high confidence, when used as a third marker in parallel with KIT and DOG1. Moreover, SERCA3 immunopositivity may be particularly helpful in cases with negative or weak KIT or DOG1 staining, a situation that may be encountered de novo, or during the spontaneous or therapy-induced clonal evolution of GIST.
Assuntos
Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Cálcio , Retículo Endoplasmático/metabolismo , Imuno-Histoquímica , Proteínas Proto-Oncogênicas c-kit/metabolismoRESUMO
BACKGROUND: Microsatellite instability (MSI) is a negative predictive factor for neoadjuvant chemotherapy in resectable oesogastric adenocarcinoma and a crucial determinant for immunotherapy. We aimed to evaluate reliability of dMMR/MSI status screening performed on preoperative endoscopic biopsies. METHODS: Paired pathological samples from biopsies and surgical specimen of oesogastric adenocarcinoma were retrospectively collected between 2009 and 2019. We compared dMMR status obtained by immunohistochemistry (IHC) and MSI status by PCR. dMMR/MSI status on surgical specimen was considered as reference. RESULTS: PCR and IHC were conclusive on biopsies respectively for 53 (96.4%) and 47 (85.5%) of the 55 patients enrolled. IHC was not contributive for 1 surgical specimen. A third reading of IHC was carried out for 3 biopsies. MSI status was observed in 7 (12.5%) surgical specimens. When analyses were contributive, sensitivity and specificity of biopsies for dMMR/MSI were respectively 85% and 98% for PCR vs. 86% and 98% for IHC. Concordance rate between biopsies and surgical specimen was 96.2% for PCR and 97.8% for IHC. CONCLUSIONS: Endoscopic biopsies are a suitable source of tissue for dMMR/MSI status determination in oesogastric adenocarcinoma which should be routinely performed at diagnosis to better adapt neoadjuvant treatment. MINIABSTRACT: By comparison of dMMR phenotype obtained by immunohistochemistry and MSI status by PCR between match-paired samples of oesogastric cancer's endoscopic biopsies and surgical specimen, we observed that biopsies are a suitable source of tissue for dMMR/MSI status determination.
Assuntos
Adenocarcinoma , Neoplasias Colorretais , Neoplasias Gástricas , Humanos , Instabilidade de Microssatélites , Estudos Retrospectivos , Reprodutibilidade dos Testes , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Neoplasias Gástricas/genética , Biópsia , Esôfago/patologia , Reparo de Erro de Pareamento de DNARESUMO
Branchial cyst of the second pouch is the most common lesion of the nasopharyngeal lateral wall, generally localized between the pharyngeal wall and internal carotid artery. Cases consistent with such lesion, were collected. Symptomatic patients were treated with endoscopic trans-nasal marsupialisation, asymptomatic cases were followed-up. Among the 10 patients included, 4 were symptomatic and accordingly treated. In the literature, 36 cases were found, all of which were treated, most commonly with a total excision. Considering the benign nature of branchial nasopharyngeal cyst, its treatment should be tailored to each patient: endoscopic marsupialization in symptomatic lesion, follow-up in asymptomatic one. Laryngoscope, 132:1904-1908, 2022.
Assuntos
Branquioma , Neoplasias de Cabeça e Pescoço , Região Branquial/cirurgia , Branquioma/cirurgia , Endoscopia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Nasofaringe/patologia , Nasofaringe/cirurgiaRESUMO
The role of the proangiogenic factor olfactomedin-like 3 (OLFML3) in cancer is unclear. To characterize OLFML3 expression in human cancer and its role during tumor development, we undertook tissue expression studies, gene expression analyses of patient tumor samples, in vivo studies in mouse cancer models, and in vitro coculture experiments. OLFML3 was expressed at high levels, mainly in blood vessels, in multiple human cancers. We focused on colorectal cancer (CRC), as elevated expression of OLFML3 mRNA correlated with shorter relapse-free survival, higher tumor grade, and angiogenic microsatellite stable consensus molecular subtype 4 (CMS4). Treatment of multiple in vivo tumor models with OLFML3-blocking antibodies and deletion of the Olfml3 gene from mice decreased lymphangiogenesis, pericyte coverage, and tumor growth. Antibody-mediated blockade of OLFML3 and deletion of host Olfml3 decreased the recruitment of tumor-promoting tumor-associated macrophages and increased infiltration of the tumor microenvironment by NKT cells. Importantly, targeting OLFML3 increased the antitumor efficacy of anti-PD-1 checkpoint inhibitor therapy. Taken together, the results demonstrate that OLFML3 is a promising candidate therapeutic target for CRC.
RESUMO
BACKGROUND: The prevalence and prognosis association of microsatellite instability (MSI) in oesogastric junction and gastric adenocarcinoma (OGC) have been reported with conflicting results. METHODS: Patients with OGC from 2010 to 2015 were enrolled in this retrospective multicenter study. MSI was determined by genotyping. MLH1 promoter methylation and BRAFV600E mutation were screened in the MSI tumors. RESULTS: Among 315 tumors analyzed, 39 (12.4%) were of the MSI phenotype. Compared to MSS tumors, MSI tumors were more frequent in patients >70 years (17% vs 9%, p=0.048) and in gastric antral primary (20% versus 5% in junction tumor and 12% in fundus tumor. Among 29 MSI tumors analyzed, 28 had a loss of MLH1 protein expression and 27 had MLH1 promotor hypermethylation. None had a BRAF V600E mutation. The 4-year cumulative incidence of recurrence for patients with resected tumor was significantly lower in dMMR tumors versus pMMR tumors (17% versus 47%, p=0.01). For the patients with unresectable tumor the median overall survival was 11 months in MSS group and 14 months in MSI group (p=0.24). CONCLUSION: MSI prevalence in OGC was 12.4%, associated with antral localization and advanced age. Patients with MSI tumors had a lower cumulative incidence of recurrence after surgery. MSI phenotype was mainly associated with loss of MLH1 protein expression, MLH1 promotor hypermethylation and had no BRAFV600E mutation.
Assuntos
Adenocarcinoma , Instabilidade de Microssatélites , Neoplasias Gástricas , Adenocarcinoma/genética , Humanos , Proteína 1 Homóloga a MutL/genética , Prevalência , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/genéticaRESUMO
PURPOSE: To describe and analyse functional treatment of temporal bone chondroblastoma (TBCh). METHODS: From January 2000 to June 2019, at the Department of Otorhinolaryngology, Hôpital Lariboisière, Paris, France, patients with TBCh were enrolled in this study. All cases routinely performed pre-operatory work-up including evaluation of performance status, audio-vestibular function test, ear endoscopy, contrasted CT scan and MRI of head and neck region; in one case we also performed an angio-CT scan. All patients underwent resection of the tumour with a "functional" approach RESULTS: Three male patients (mean age 46,6 years)-two primary tumours and one recurrence-were treated. In all three cases the tumour invaded the middle ear with a variable degree of hearing loss and infiltration of temporal bone structures. All surgeries were performed with a microscopic approach associated with open/endoscopic approach when necessary. Inner ear and facial nerve were speared in all cases and the TMJ was partially resected in 2 cases due to its moderate involvement. At present, after a mean follow-up of 103 months (range 40-225 months), only one case presented recurrence which has been successfully treated with radiotherapy. CONCLUSIONS: Our results of treatment suggest that functional surgery can be relevant in the management of TBCh since it is focused on both treatment of this pathology and maintenance of a good quality of life.
Assuntos
Neoplasias Ósseas , Condroblastoma , Condroblastoma/diagnóstico por imagem , Condroblastoma/cirurgia , França , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paris , Qualidade de Vida , Estudos Retrospectivos , Osso Temporal/diagnóstico por imagem , Osso Temporal/cirurgiaRESUMO
The goal of the work described here was to assess the performance of Doppler ultrasound (US) of the superior mesenteric artery (SMA) and celiac trunk (CT) in the evaluation of tumor response in female mice with ovarian peritoneal carcinomatosis treated either with bevacizumab or with carboplatin. Compared with untreated mice, carboplatin-treated mice had a lower weight (23.3 ± 2.0 vs. 27.9 ± 2.9 g, p < 0.001), peritoneal carcinomatosis index (PCI, 11 ± 3 vs. 28 ± 6, p < 0.001), Ki67-positive staining surfaces (p < 0.001), vascular density (p < 0.001), mean blood flow velocity (mBFVel) in the SMA (7.0 ± 1.4 vs. 10.9 ± 1.8 cm/s, p < 0.001) and CT (8.0 ± 1.8 vs. 14.3 ± 4.6 cm/s, p < 0.001) and no ascites. Weight and mBFVel were similar in bevacizumab-treated and untreated mice. The mBFVels in the SMA and CT correlated with the PCI used as an estimation of the tumor burden, Râ¯=â¯0.70 (p < 0.0001) and Râ¯=â¯0.65 (p < 0.0001), respectively. Doppler US allows non-invasive assessment of the effects of anticancer therapy in ovarian peritoneal carcinomatosis-induced mice.
Assuntos
Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Carboplatina/uso terapêutico , Artéria Celíaca/diagnóstico por imagem , Artéria Mesentérica Superior/diagnóstico por imagem , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/irrigação sanguínea , Neoplasias Peritoneais/tratamento farmacológico , Ultrassonografia Doppler , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Resultado do Tratamento , Células Tumorais CultivadasRESUMO
BACKGROUND: This study evaluated the histologic response after preoperative systemic therapy (pST) using the Peritoneal Regression Grading Score (PRGS) and tumor regression grade (TRG) classifications for patients with peritoneal metastases (PM) from colorectal cancer (CRC). METHODS: Twenty-three patients were selected from a prospective database of 196 patients who underwent CRS followed by HIPEC for synchronous PM from CRC. In all study patients, biopsies of the PM obtained before pST (during the first laparoscopy) and after pST (during cytoreductive surgery) were compared. RESULTS: Complete (PRGS 1), Major (PRGS 2), Minor (PRGS 3) and no histological responses (PRGS 4) were obtained in 17,5%, 52% and 13% and 17,5% of patients, respectively. Major (TRG 1-2), partial (TRG3), and no (TRG4-5) histological tumor regression were observed in 61%, 9% and 30% of patients, respectively. Regardless of the classification applied, median OS was significantly higher in patients with a "complete or major" response than in those with a "minor/partial or no" response (54 vs. 26 months, p < 0.05). CONCLUSIONS: The PRGS and TRG can be used in clinical practice to evaluate the histological response after pST. This study demonstrated that a complete histologic response of PM from CRC can be obtained after pST.
Assuntos
Adenocarcinoma Mucinoso/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Terapia Neoadjuvante , Neoplasias Peritoneais/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adenocarcinoma Mucinoso/secundário , Antineoplásicos Imunológicos/administração & dosagem , Bevacizumab/administração & dosagem , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Cetuximab/administração & dosagem , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Compostos Organoplatínicos/uso terapêutico , Neoplasias Peritoneais/secundário , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: It may be impossible to perform cancer surgery with free margins in the presence of an unresectable structure. Local drug treatment after surgery has been proposed to increase the rate of tumor control. METHODS: Multi-nanolayers (10-330 nm) were generated by a low-pressure (375mTorr) inductively coupled plasma (13.56 MHz) reactor for anticancer drug delivery by the deposition of polycaprolactone-polyethylene glycol multistack barrier on the collagen membrane (100 µm thickness). Carboplatin (300 µg/cm2) was used for the in vitro and in vivo investigations. Energy-dispersive X-ray spectroscopy (15 keV), scanning electron microscopy and inductively coupled plasma mass spectrometry were used to detect the presence of carboplatin in the nanolayer, the tumor sample and the culture medium. Preclinical studies were performed on ovarian (OVCAR-3NIH) and colon (CT26) cancer cell lines as xenografts (45 days) and allografts (23 days) in Swiss-nude (n = 6) and immunocompetent BALB/cByJ mice (n = 24), respectively. RESULTS: The loading of carboplatin or other drugs between the nanofilm on the collagen membrane did not modify the mesh complex architecture or the drug properties. Drugs were detectable on the membrane for more than 2 weeks in the in vitro analysis and more than 10 days in the in vivo analysis. Cytotoxic mesh decreased cell adherence (down 5.42-fold) and induced cancer cell destruction (up to 7.87-fold). Implantation of the mesh on the mouse tumor nodule modified the cell architecture and decreased the tumor size (50.26%) compared to the control by inducing cell apoptosis. CONCLUSION: Plasma technology allows a mesh to be built with multi-nanolayer anticancer drug delivery on collagen membranes.
Assuntos
Antineoplásicos/administração & dosagem , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Gases em Plasma , Animais , Apoptose/efeitos dos fármacos , Carboplatina/administração & dosagem , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Nanomedicina/métodos , Nanoestruturas , Neoplasias/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A tumor contains special types of cells that have characteristics similar to stem cells that aid in tumor initiation, evasion and proliferation and are often resistant to chemotherapy. These cancer stem cells can be differentiated to eradicate their stemness and proliferative capacity by differentiating agents. This study investigated the effect of differentiation on the expression of two immune checkpoint inhibitors, human leukocyte antigenG (HLAG) and programmed death ligand1 (PDL1). Two cancer cell lines (OVCAR3NIH and KATOIII) were treated with adipocyte and neurocyte differentiation media for 14 days. Bonemarrow derived mesenchymal stem cells (BMMSCs) were used as control healthy stem cells. We found that the cancer cell lines (OVCAR3NIH and KATOIII) when subjected to differentiation lost their proliferation ability. BMMSC proliferation was not halted but was decreased in the adipocyte differentiation media. There was no decrease in the CD90 stem cell marker in the BMMSCs; however, both cancer cell lines showed decreased CD90 stem cell marker. A significant increase in HLAG was noted for both the cancer cell lines following adipocyte differentiation. No effect was found for BMMSCs. Moreover, an increase in PDL1 in cancer cell lines was found following neurocyte differentiation. Moreover, we found that differentiation resulted in decreased PDL1 expression in BMMSCs. Differentiation therapy of cancer stem cells may result in increased immunosuppression ability, hence causing hindrance in the removal of cancer cells. Moreover, the differentiation of healthy stem cells can result in increased immunogenic reactivity owing to a decrease in PDL1 expression.
Assuntos
Antígeno B7-H1/genética , Antígenos HLA-G/genética , Células-Tronco Mesenquimais/citologia , Neoplasias/genética , Antígeno B7-H1/metabolismo , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Meios de Cultura/química , Regulação Neoplásica da Expressão Gênica , Antígenos HLA-G/metabolismo , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Neoplasias/metabolismo , Antígenos Thy-1/metabolismoRESUMO
This experimental study evaluated the histological response of peritoneal metastases (PM) from colorectal cancer (CRC) after preoperative systemic chemotherapy (pCT). The results demonstrated that the Peritoneal Regression Grade Score could be used in medical practice. AIM: The aim was to evaluate the histological criteria used by the tumour regression grade (TRG) and Peritoneal Regression Grade Score (PRGS) for determining the response to chemotherapy (CT), in a mouse model of peritoneal metastases (PM) from colorectal cancer (CRC). METHODS: Twenty immunocompetent BALB/c mice were randomized into four groups at day (D) 10 after intraperitoneal (ip) injection with bioluminescent CRC tumour cells (CT26-luc). A histology before treatment group was obtained by sacrifice on D10; the other groups all received one of the following ip treatments over 15 days: 5% glucose (control, G5); 5-fluorouracil (5FU, 0.03â¯mg/g); or 5FU with oxaliplatin (Ox, 0.006â¯mg/g). The histological response (HR) was analysed by comparing the histology of PM before and after treatment, using both scores: TRG and PRGS. RESULTS: All mice showed limited PM as visualised by bioluminescence and confirmed at the time of sacrifice in the histology before treatment group. The mean peritoneal carcinomatosis index (PCI) wasâ¯=â¯8 [6-10], The rate of complete HR was significantly higher in the Ox-5FU group (83.3%) than 5FU group (0%) and G5 group (0%) (pâ¯=â¯0.016). Fibrosis was present only in CT-treated groups (pâ¯=â¯0.05). PCI, ascites volume and haemorrhagic ascites were significantly higher in the G5 group than CT groups (pâ¯<â¯0.05). CONCLUSIONS: The TRG score can be used in practice when we want to compare the HR between the primary tumour and the PMs. The PRGS is a good measure of HR and is correlated with the efficacy of CT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Colorretais/patologia , Gradação de Tumores/métodos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Animais , Modelos Animais de Doenças , Fluoruracila/farmacologia , Medições Luminescentes , Camundongos , Camundongos Endogâmicos BALB C , Oxaliplatina/farmacologiaRESUMO
The present study focuses on the influence of the tumor microenvironment on the expression of HLA-G in ovarian cancer and its impact on immune cells. We used carcinomatosis fluids (nâ¯=â¯16) collected from patients diagnosed with epithelial ovarian cancer, detected by an increase in CA125 levels. Our results indicate that HLA-G is expressed by 1) ascitic cell clusters, 2) stromal cells (hospicells) extracted from cancer cell clusters, and 3) cancer cell lines and tumor cells. The origin of HLA-G was linked to inflammatory cytokines present in the cancer microenvironment. In parallel, the ascitic fluid of patients with ovarian cancer contains soluble HLA-G (sHLA-G). The mesothelial cell layer and submesothelial tissues, as well as the immune cell infiltrate, do not secrete HLA-G. In contrast, sHLA-G is absorbed by peritoneal tissues along with mesothelial layers as well as immune cell infiltrates. We demonstrated that interleukin-1ß along with TGF-ß can be a major HLA-G-inducing factor that upregulates HLA-G expression through the NF-κB pathway. The level of HLA-G in ascites correlated positively with the expression of T regulatory (T-regs) cells, while it negatively correlated with the expression of natural killer and memory cells in tumor-infiltrating immune cells. In conclusion, the production of HLA-G is associated with the presence of inflammatory cytokines and is strongly correlated with microenvironment tolerant cells such as T-regs and diminution of NK and memory T cells.
Assuntos
Carcinoma/genética , Regulação Neoplásica da Expressão Gênica , Antígenos HLA-G/genética , Neoplasias Ovarianas/genética , Biomarcadores , Carcinoma/imunologia , Carcinoma/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Antígenos HLA-G/imunologia , Antígenos HLA-G/metabolismo , Humanos , Imuno-Histoquímica , Interleucina-1beta/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismo , Ligação ProteicaAssuntos
Linfoma , Síndrome de Sjogren , Biópsia , Centro Germinativo , Humanos , Glândulas Salivares MenoresRESUMO
IMPORTANCE: Primary resistance to immune checkpoint inhibitors is observed in 10% to 40% of patients with metastatic colorectal cancer (mCRC) displaying microsatellite instability (MSI) or defective mismatch repair (dMMR). OBJECTIVE: To investigate possible mechanisms underlying primary resistance to immune checkpoint inhibitors of mCRC displaying MSI or dMMR. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of a single-center, prospective cohort included 38 patients with mCRC diagnosed as MSI or dMMR by local laboratories and entered into trials of immune checkpoint inhibitors between January 1, 2015, and December 31, 2016. The accuracy of MSI or dMMR status was also assessed in a retrospective cohort comprising 93 cases of mCRC that were diagnosed as MSI or dMMR between January 1, 1998, and December 31, 2016, in 6 French hospitals. Primary resistance of mCRC was defined as progressive disease according to Response Evaluation Criteria in Solid Tumors criteria, 6 to 8 weeks after initiation of immune checkpoint inhibitors, without pseudo-progression. All tumor samples were reassessed for dMMR status using immunohistochemistry with antibodies directed against MLH1, MSH2, MSH6, and PMS2, and for MSI using polymerase chain reaction with pentaplex markers and with the HSP110 T17 (HT17) repeat. MAIN OUTCOMES AND MEASURES: The primary outcome was positive predictive value. RESULTS: Among the 38 patients (15 women and 23 men; mean [SD] age, 55.6 [13.7] years) in the study with mCRC displaying MSI or dMMR, primary resistance to immune checkpoint inhibitors was observed in 5 individuals (13%). Reassessment of the status of MSI or dMMR revealed that 3 (60%) of these 5 resistant tumors were microsatellite stable or displayed proficient mismatch repair. The positive predictive value of MSI or dMMR status assessed by local laboratories was therefore 92.1% (95% CI, 78.5%-98.0%). In the retrospective cohort of 93 patients (44 women and 49 men; mean [SD] age, 56.8 [18.3] years) without immune checkpoint inhibitor treatment, misdiagnosis of the MSI or dMMR status by local assessment was 10% (n = 9), with a positive predictive value of 90.3% (95% CI, 82.4%-95.0%). Testing for MSI with the HT17 assay confirmed the MSI or dMMR status in 2 of 4 cases showing discrepant results between immunohistochemistry and pentaplex polymerase chain reaction (ie, dMMR but microsatellite stable). CONCLUSIONS AND RELEVANCE: Primary resistance of mCRC displaying MSI or dMMR to immune checkpoint inhibitors is due mainly to misdiagnosis of their MSI or dMMR status. Larger studies are required to confirm these findings. Microsatellite instability or dMMR status should be tested routinely using both immunohistochemistry and polymerase chain reaction methods prior to treatment with immune checkpoint inhibitors.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA , Erros de Diagnóstico , Resistencia a Medicamentos Antineoplásicos , Instabilidade de Microssatélites , Adulto , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos RetrospectivosRESUMO
OBJECTIVE: To determine risk factors for primary Sjögren's syndrome (SS)-associated lymphoma in a multicenter cohort of patients, with analysis of the predictive power of previously reported risk factors, including the presence of ectopic germinal center (GC)-like structures in minor salivary gland (MSG) biopsy tissue. METHODS: One hundred fifteen patients with primary SS were included, and MSG biopsy tissue from these patients was retrospectively examined, focusing on the presence of ectopic GC-like structures. Epidemiologic, clinical, biologic, immunologic, and histologic data were collected at the time of diagnosis of primary SS. Patients with non-Hodgkin's lymphoma (NHL) were compared with those without NHL during the follow-up period, using a Cox proportional hazards multiple regression model. RESULTS: NHL was diagnosed in 8 patients (6.96%), and ectopic GC-like structures in 19 patients (16.5%). The presence of ectopic GC-like structures was associated with a 7.8-fold increased risk of lymphoma occurrence (95% confidence interval [95% CI] 1.73-34.86 [P = 0.0075]). Other independent predictors included a positive cryoglobulin test result (hazard ratio [HR] 7.10, 95% CI 1.74-28.92 [P = 0.006]), male sex (HR 28.73, 95% CI 4.46-144.87 [P = 0.0004]), sensorimotor neuropathy (HR 35.48, 95% CI 5.79-217.39 [P = 0.0001]), and splenomegaly (HR 19.9, 95% CI 4.4-90 [P = 0.0001]). CONCLUSION: The presence of ectopic GC-like structures in MSG biopsy tissue is associated with the risk of lymphoma in patients with primary SS. These data reinforce the major role of MSG biopsy tissue in primary SS, for the identification a priori of a subgroup of patients with the highest risk of lymphoma.
Assuntos
Coristoma/complicações , Centro Germinativo , Linfoma não Hodgkin/etiologia , Doenças das Glândulas Salivares/complicações , Síndrome de Sjogren/patologia , Biópsia , Coristoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Doenças das Glândulas Salivares/patologia , Glândulas Salivares Menores/patologia , Síndrome de Sjogren/complicaçõesRESUMO
BACKGROUND: Curative surgery of synchronous peritoneal metastases (PM) and colorectal liver metastases (LM) has been recently investigated as feasible option. When synchronous peritoneal and liver resection is not achievable, the sequence of the surgery remains unknown. Our hypothesis was that liver resection (LR) promotes peritoneal growth resulting in a non-resectable PM. We sought to analyse the effects of major LR and liver regeneration after hepatectomy in a murine model of PM and the associated angiogenesis. METHODS: Murine model of colorectal PM in Balb/C mice was developed by intraperitoneal injection of different CT-26 tumour cell concentrations. Five days after the injection, mice were randomized into three groups: 68% hepatectomy group, sham laparotomy and control group without surgery. On post-operative days 1, 5 and 20, PM was evaluated macroscopically, tumour growth and liver regeneration by immunohistochemistry, and angiogenesis by immunofluorescence. Circulating progenitor cells, plasmatic cytokines and digestive arterial blood flow velocity measurements were also analysed. RESULTS: Reproducible murine model of limited colorectal PM was obtained. Surgery induced PM increases and promoted neo-angiogenesis. Major hepatectomy influence the tumour growth in the late phase after surgery, the extent of extra-peritoneal metastasis and the increase of Ki-67 expression in the remnant liver. CONCLUSIONS: This animal model confirms the pro-tumoural and pro-angiogenic role of surgery, laparotomy and major LR, which promotes the increase of angiogenic factors and their participation in PM growth. These results suggest that peritoneal resection should be first step in the case of two-step liver and peritoneal surgery for patients with colorectal PM and LM.
Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/efeitos adversos , Hospedeiro Imunocomprometido , Neoplasias Hepáticas/cirurgia , Transplante de Neoplasias/patologia , Neoplasias Experimentais , Neoplasias Peritoneais/secundário , Animais , Progressão da Doença , Feminino , Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Regeneração Hepática , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Peritoneais/diagnóstico , Prognóstico , Células Tumorais CultivadasRESUMO
BACKGROUND: The interval between surgery and adjuvant chemotherapy (AC) is a predictive factor of survival in high-risk colon cancer (CC). This study aimed to evaluate the impact of intraoperative sentinel lymph node (SLN) analysis using the one-step nucleic acid amplification (OSNA) technique on the time interval between surgery and AC. METHODS: We performed a prospective study analyzing 56 consecutive patients who had surgery for CC between July 2012 and October 2014, including 20 patients needing AC. SLN status was determined intraoperatively in 17 patients in the OSNA group; when positive, a portacath (PAC) was placed during the procedure for upcoming AC. In the remaining patients, we proceeded without SLN status determination and the PAC was installed after definitive histopathological analysis of the specimen if needed. RESULTS: There was no difference between the groups regarding cancer staging, duration of hospitalization (7.5days in the OSNA group and 10days in the control group, p=0.43) and major complications (20% vs 30% respectively, p=0.55). The time interval between surgery and adjuvant chemotherapy was significantly shorter in the OSNA group at 35 (±8) days vs 67 (±36) days (p=0.021). CONCLUSION: SLN status determination by the OSNA technique is safe, feasible and could significantly reduce time between surgery and adjuvant chemotherapy in a pilot study.
Assuntos
Carcinoma/genética , Neoplasias do Colo/genética , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Quimioterapia Adjuvante , Colo/patologia , Neoplasias do Colo/patologia , Feminino , França , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Técnicas de Amplificação de Ácido Nucleico , Projetos Piloto , Estudos Prospectivos , Tempo para o TratamentoRESUMO
Cryptococcosis is a serious infection, possibly lethal, of worldwide distribution. It mainly affects immunosuppressed patients resulting with pulmonary and/or meningeal involvements or disseminated infections. Due to the rarity of visceral and osseous infections, and to the absence of specific clinical symptoms, this diagnosis is often deferred. Resulting of diagnostic errors, samples are often directed to the department of pathology and more rarely to the department of mycology. Histopathological examination appears crucial, highlighting encapsulated yeasts with alcian blue staining. Once the diagnosis is performed, an appropriate antifungal therapy must be quickly introduced because these infections are associated with a high mortality rate. The aim of our work was to report five extra-cerebral and extra-pulmonary cryptococcosis cases, to describe their histopathological features, to evoke diagnostic techniques and to discuss the differential diagnoses.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/patologia , Criptococose/patologia , Dermatomicoses/patologia , Discite/patologia , Abscesso Hepático/patologia , Doenças Linfáticas/patologia , Sacro/patologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Biópsia , Criptococose/complicações , Cryptococcus/isolamento & purificação , Dermatomicoses/microbiologia , Discite/microbiologia , Hepatite B Crônica/complicações , Humanos , Abscesso Hepático/microbiologia , Doenças Linfáticas/microbiologia , Masculino , Meningite Criptocócica/complicações , Especificidade de Órgãos , Estudos Retrospectivos , Sacro/microbiologiaRESUMO
Vertebral Paget's disease produces a large panel of radiologic appearances sometimes atypical and pseudotumoral. Classical classifications of bone alterations based on pathophysiological hypotheses do not always match the imaging findings. This article will review the computed tomography (CT) and magnetic resonance imaging (MRI) features of Paget's disease of the spine with special emphasis on morphological findings that differentiate Paget's disease from tumors. Combined CT and MRI analyses usually provide the diagnosis of Paget's disease.
Assuntos
Osteíte Deformante/diagnóstico , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Osteíte Deformante/classificação , Osteíte Deformante/epidemiologia , Osteíte Deformante/fisiopatologia , Tomografia Computadorizada por Raios XRESUMO
The periosteum covers most bone structures. It has an outer fibrous layer and an inner cambial layer that exhibits osteogenic activity. The periosteum is a dynamic structure that plays a major role in bone modeling and remodeling under normal conditions. In several disorders such as infections, benign and malignant tumors, and systemic diseases, the osteogenic potential of the periosteum is stimulated and new bone is produced. The newly formed bone added onto the surface of the cortex adopts various configurations depending on the modalities and pace of bone production. Our aim here is to describe the anatomy, histology, and physiology of the periosteum and to review the various patterns of periosteal reaction with emphasis on relations between radiological and histopathological findings. A careful evaluation of the periosteal reaction and appearance of the underlying cortex, in combination with the MRI, clinical, and laboratory data, provides valuable information on lesion duration and aggressiveness, thereby assisting in the etiological diagnosis and optimizing patient management. A solid reaction strongly suggests a benign and slow-growing process that gives the bone enough time to wall off the lesion. Single lamellar reactions occur in acute and usually benign diseases. Multilamellar reactions are associated with intermediate aggressiveness and a growth rate close to the limit of the walling-off capabilities of the bone. Spiculated, interrupted, and complex combined reactions carry the worst prognosis, as they occur in the most aggressive and fast-growing diseases: the periosteum attempts to create new bone but is overwhelmed and may be breached.