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1.
Ann Diagn Pathol ; 73: 152360, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39029301

RESUMO

Metaplastic breast carcinoma (MBC) and gynecologic carcinosarcoma (GCS) are rare, clinically aggressive cancers that demonstrate epithelial components and mesenchymal or sarcomatoid components. In this study, we assessed PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in MBC and GCS. Overall, PD-L1 positivity using the SP142 clone was seen in 50 % of MBC and 51.9 % of GCS cases, with PD-L1 expression in tumor cells significantly higher in MBC cases (p = 0.034), and PD-L1 expression in immune cells similar in MBC and GCS cases. PD-L1 expression was significantly higher in epithelial components than in mesenchymal components in both MBC and GCS cases (p = 0.0005). TILs were low in the majority of MBC and GCS cases (≥ 10 %) and generally correlated with PD-L1 expression; however, many PD-L1 positive cases with low TILs were seen. PD-L1 expression using the 22C3 clone was additionally assessed, with positivity seen in 62.9 % of MBC cases and 30 % of GCS cases. Concordance between SP142 and 22C3 results was seen in 62.5 % of MBC cases and 80 % of GCS cases. Overall, our findings suggest that a subset of MBC and GCS cases may benefit from immune checkpoint inhibitor therapy. Our findings also illustrate unique aspects of PD-L1 expression patterns in these tumors which may harbor additional prognostic and therapeutic significance.

2.
Histopathology ; 65(3): 309-18, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24548339

RESUMO

AIMS: The study of haemangiomas in end-stage renal disease (ESRD). METHODS AND RESULTS: Twenty ESRD nephrectomies from 16 patients (aged 9 months-68 years) were due to hypertension (four), focal segmental glomerulosclerosis (four), lupus nephritis (three), diabetes (one), IgA nephropathy (one), hereditary nephritis (one), congenital nephrotic syndrome (one) and unknown cause (one). Haemangiomas appeared as a single mass (15), two masses (one), three masses (one), four masses (two) and eight masses (one) per kidney. Tumours measured 0.2-3.5 cm. Four patients had bilateral haemangiomas. All tumours were in the medulla and often abutted renal sinus fat. All except one of the tumours were anastomosing haemangiomas, showing isolated or interconnected sinusoidal capillary-sized vascular channels lined by a single layer of benign cuboidal CD34(+) , CD31(+) , D2-40(-) endothelial cells, separated by loose stroma with spindle cells. One tumour was a cellular capillary haemangioma. Intravascular growth was seen in nine specimens. All haemangiomas had extramedullary haematopoiesis. Acquired cystic kidney disease (ACKD) was seen in 11 kidneys (nine patients), renal cell carcinoma (RCC) in five, ACKD-associated RCC precursors in three, Wilms' tumour in one and papillary adenomas in five. CONCLUSIONS: Anastomosing haemangioma appears as a distinctive clinicopathological entity developing in kidneys with ESRD, with or without ACKD.


Assuntos
Hemangioma/complicações , Hemangioma/patologia , Falência Renal Crônica/complicações , Falência Renal Crônica/patologia , Neoplasias Renais/complicações , Neoplasias Renais/patologia , Adenoma/complicações , Adenoma/patologia , Adolescente , Adulto , Idoso , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/patologia , Feminino , Hemangioma/irrigação sanguínea , Hemangioma Capilar/irrigação sanguínea , Hemangioma Capilar/complicações , Hemangioma Capilar/patologia , Hematopoese Extramedular , Humanos , Lactente , Doenças Renais Císticas/complicações , Doenças Renais Císticas/patologia , Neoplasias Renais/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tumor de Wilms/complicações , Tumor de Wilms/patologia
4.
J Obstet Gynaecol Can ; 34(2): 129-135, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22340061

RESUMO

OBJECTIVE: We hypothesized that differences in models of care between health care providers would result in variations in patients' reports of counselling. Our objective was to compare what women reported being advised about weight gain during pregnancy and the risks of inappropriate weight gain according to their type of health care provider. METHODS: A cross-sectional survey was conducted using a self-administered questionnaire at obstetric, midwifery, and family medicine clinics in Hamilton, Ontario. Women were eligible to participate if they had had at least one prenatal visit, could read English, and had a live, singleton pregnancy. RESULTS: Three hundred and eight women completed the survey, a 93% response rate. Care for 90% of the group was divided approximately evenly between midwives, family physicians, and obstetricians. A minority of women looked after by any of the types of care providers reported being counselled correctly about how much weight to gain during pregnancy (16.3%, 10.3%, 9.2%, and 5.7% of patients of midwives, family physicians, obstetricians, or other types of care providers, respectively, P = 0.349). A minority of women with any category of care provider was planning to gain an amount of weight that fell within the guidelines or reported being told that there were risks to themselves or their babies with inappropriate gain. CONCLUSION: In this study comparing reported counselling between patients of obstetricians, midwives, family physicians, and other health care providers, low rates of counselling about gestational weight gain were universally reported. There is a common need for more effective counselling.


Assuntos
Aconselhamento/métodos , Medicina de Família e Comunidade , Tocologia , Obstetrícia , Cuidado Pré-Natal/métodos , Aumento de Peso , Adulto , Estudos Transversais , Feminino , Humanos , Bem-Estar Materno , Ontário , Gravidez , Inquéritos e Questionários
5.
Ann Thorac Surg ; 113(3): e167-e170, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34111385

RESUMO

We describe a 26-year-old woman presenting with chest pain and evidence of coronary ischemia. Echocardiography revealed a large left ventricular mass initially deemed unresectable at her initial institution. Investigation revealed a dopamine-secreting primary cardiac paraganglioma encompassing vital cardiac architecture. This case discusses our heart team approach to complex cardiac masses and illustrates the feasibility of surgical resection in complex cases of hormonally active primary cardiac paragangliomas.


Assuntos
Neoplasias Cardíacas , Paraganglioma Extrassuprarrenal , Paraganglioma , Adulto , Dor no Peito , Feminino , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/cirurgia , Humanos , Paraganglioma/diagnóstico por imagem , Paraganglioma/cirurgia , Tomografia Computadorizada por Raios X
6.
Methodist Debakey Cardiovasc J ; 18(1): 102-107, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304791

RESUMO

Cardiac tumors in adults are exceedingly rare and usually benign. We describe a 29-year-old man with a previous diagnosis of interventricular septal hypertrophy who presented with increasing severity of dyspnea and fatigue. Work-up revealed a 4.9 × 3.7 cm mass at the base of the interventricular septum. Biopsy revealed a benign cardiac hamartoma atypically located in the right ventricle, and the mass was resected via right ventriculotomy.


Assuntos
Hamartoma , Neoplasias Cardíacas , Comunicação Interventricular , Septo Interventricular , Masculino , Adulto , Humanos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Ventrículos do Coração/patologia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Septo Interventricular/diagnóstico por imagem , Septo Interventricular/cirurgia , Septo Interventricular/patologia , Hamartoma/diagnóstico , Hamartoma/diagnóstico por imagem
7.
J Am Soc Cytopathol ; 11(1): 3-12, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34583894

RESUMO

INTRODUCTION: The objectives of our study were to identify factors contributing to false-negative Papanicolaou (Pap) tests in patients with endocervical adenocarcinoma (EA) or adenocarcinoma in situ (AIS), and to analyze the impact of educational instruction on interobserver agreement in these cases. MATERIALS AND METHODS: False-negative Pap tests from patients with EA/AIS were reviewed by a consensus group and by 12 individual reviewers in 2 rounds, with an educational session on glandular neoplasia in Pap tests conducted between the 2 rounds. RESULTS: Of 79 Pap tests from patients with EA/AIS, 57 (72.2%) were diagnosed as abnormal and 22 (27.8%) as negative. Of the 22 false-negative cases, 10 remained negative on consensus review, with false-negative diagnoses attributed to sampling variance. The other 12 cases were upgraded to epithelial abnormalities (including 8 to glandular lesions). The false-negative diagnoses were attributed to screening variance in 2 cases and interpretive variance in 10 cases. On individual review, abnormal cells were misinterpreted as reactive glandular cells or endometrial cells in 7 of 8 and 5 of 8 cases upgraded to glandular abnormalities, respectively. With education, the proportion of individual reviewers demonstrating at least moderate agreement with the consensus diagnosis (Cohen's kappa >0.4) increased from 33% (4 of 12) to 75% (9 of 12). CONCLUSIONS: Sampling and interpretive variance each accounted for nearly one-half of the false-negative Pap tests, with underclassification as reactive glandular or endometrial cells the main source of the interpretive variances. Educational instruction significantly decreased the interpretive variance and interobserver variability in the diagnosis of glandular abnormalities.


Assuntos
Adenocarcinoma in Situ/diagnóstico , Adenocarcinoma/diagnóstico , Teste de Papanicolaou/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma in Situ/patologia , Adulto , Biópsia , Colo do Útero/patologia , Reações Falso-Negativas , Feminino , Humanos , Variações Dependentes do Observador , Teste de Papanicolaou/normas , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia
8.
Clin Cancer Res ; 28(20): 4392-4401, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-35877117

RESUMO

PURPOSE: A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy and stereotactic body radiotherapy (SBRT) in patients with mTNBC. PATIENTS AND METHODS: In this single-arm, open-label Phase 2 trial, patients with mTNBC were treated with ADV/HSV-tk [5 × 1011 virus particles (vp)] intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab (200 mg, every 3 weeks). The primary endpoint was clinical benefit rate [CBR; complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks per RECIST version1.1 at non-irradiated site]. Secondary endpoints included duration on treatment (DoT), overall survival (OS), and safety. Exploratory endpoints included immune response to treatment assessed by correlative tissue and blood-based biomarkers. RESULTS: Twenty-eight patients were enrolled and treated. CBR was seen in 6 patients (21.4%), including 2 CR (7.1%), 1 PR (3.6%), and 3 SD (10.7%). Patients with clinical benefit had durable responses, with median DoT of 9.6 months and OS of 14.7 months. The median OS was 6.6 months in the total population. The combination was well tolerated. Correlative studies with Cytometry by Time of Flight (CyTOF) and imaging mass cytometry (IMC) revealed a significant increase of CD8 T cells in responders and of myeloid cells in non-responders. CONCLUSIONS: The median OS increased by more than 2-fold in patients with clinical benefit. The therapy is a well-tolerated treatment in heavily pretreated patients with mTNBC. Early detection of increased effector and effector memory CD8 T cells and myeloids correlate with response and non-response, respectively.


Assuntos
Radiocirurgia , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Genética , Humanos , Inibidores de Checkpoint Imunológico , Timidina/uso terapêutico , Timidina Quinase/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Valaciclovir/uso terapêutico
9.
Ann Diagn Pathol ; 15(6): 402-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21855381

RESUMO

Endometrial epithelial cytoplasmic change (EECC) is an adaptive cytoplasmic change commonly seen in the endometrium. Previously considered "metaplasia," EECC is now the preferred term because it offers a descriptive designation without implying a specific mechanism of development. There are 5 types of EECC: squamous, ciliated cell, eosinophilic, mucinous, and secretory (clear cell and hobmail cell) changes. Eosinophilic syncytial change (ESC) is a similar but unrelated degenerative change seen in endometrial breakdown. Some cases of ESC show atypical cytologic features that may resemble endometrial adenocarcinoma. Thirteen endometrial biopsy and curettage specimens with atypical ESCs (AESCs) were compared against 10 hysterectomy specimens with endometrial serous carcinoma. Clinical information and immunohistochemical staining profiles for markers phosphatase and tensin homologue deleted on chromosome 10 (PTEN), p53, and Ki-67 were evaluated in each case. All 13 cases of AESC (100%) showed moderate-to-strong staining for PTEN, whereas PTEN expression was absent in all endometrial serous carcinomas (P < .001). Seven cases of AESC (54%) showed focal, weak positivity for p53, whereas all cases of serous carcinoma (100%) showed strong staining (P < .001). The Ki-67 index was low (3%-15%) and found in only 3 cases in AESC (32%) but was high (60%-90%) in all cases of endometrial serous carcinoma (100%) (P < .001). Atypical ESC and serous carcinoma share several morphological features on hematoxylin and eosin-stained sections that may complicate accurate diagnosis. The PTEN, p53, and Ki-67 staining profile can effectively distinguish between AESC and malignancy in difficult cases, providing an invaluable tool for a challenging diagnostic dilemma.


Assuntos
Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Neoplasias do Endométrio/metabolismo , Endométrio/patologia , Antígeno Ki-67/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Cistadenocarcinoma Seroso/diagnóstico , Diagnóstico Diferencial , Neoplasias do Endométrio/diagnóstico , Endométrio/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Metaplasia/metabolismo , Pessoa de Meia-Idade
10.
A A Pract ; 12(3): 79-81, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30052531

RESUMO

Type 3 von Willebrand disease is a rare and severe inherited bleeding disorder that carries an elevated risk for epidural and spinal hematoma as well as pregnancy-associated complications. Neuraxial anesthesia in these patients is controversial but may be considered if the parturient has received appropriate factor replacement. We present the case of a woman with type 3 von Willebrand disease and a severe bleeding history that underwent successful spinal anesthesia during successive cesarean deliveries. Our case highlights the importance of early multidisciplinary consultation and advance planning in the care of these rare events.


Assuntos
Raquianestesia/métodos , Cesárea/métodos , Doenças de von Willebrand/complicações , Adulto , Feminino , Humanos , Gravidez , Resultado do Tratamento
12.
N Engl J Med ; 349(2): 146-53, 2003 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-12853587

RESUMO

BACKGROUND: Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer. METHODS: Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months). RESULTS: During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group. CONCLUSIONS: In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.


Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Neoplasias/complicações , Embolia Pulmonar/prevenção & controle , Trombose Venosa/prevenção & controle , Acenocumarol/uso terapêutico , Administração Oral , Anticoagulantes/efeitos adversos , Dalteparina/efeitos adversos , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Embolia Pulmonar/mortalidade , Prevenção Secundária , Análise de Sobrevida , Tromboembolia/prevenção & controle , Varfarina/uso terapêutico
14.
Thromb Res ; 130(3): 381-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22658414

RESUMO

BACKGROUND: The assessment of patients with suspected deep vein thrombosis (DVT) remains challenging despite current diagnostic algorithms. (99m)Tc-labelled DI-DD3B6/22-80B3 Fab´ fragments ((99m)Tc-DI-80B3, ThromboView®) is a novel diagnostic test that uses a radiolabelled humanized monoclonal antibody fragment specific for the D-dimer region of cross-linked fibrin to detect DVT. This test has an anatomic component to locate DVT and a functional component to differentiate acute (newly formed) thrombus from inactive (old) thrombus. METHODS: In a multi-centre prospective cohort trial we investigated the diagnostic accuracy and safety of (99m)Tc-DI-80B3 in consecutive patients with suspected DVT who had the diagnosis confirmed or excluded by venography. RESULTS: We enrolled 94 patients with suspected DVT of whom 12 did not have (99m)Tc-DI-80B3 imaging, leaving 82 patients for the safety analysis. Of these patients, there were 16 with non-evaluable imaging (11 venography, 7 (99m)Tc-DI-80B3, both in two patients) leaving 66 patients for the accuracy analysis. (99m)Tc-DI-80B3 imaging was well-tolerated: 2 patients developed urticaria; none developed serious adverse events. For proximal DVT, the sensitivity (84.2%; 95% confidence interval [CI]: 62.4-94.5) and specificity (97.6%; CI: 83.3-99.4) were highest when the combined 0.25-hour and 3-hour (99m)Tc-DI-80B3 images were used. The accuracy was lower for distal DVT, irrespective of the images used. There were insufficient patients to comment on the accuracy of (99m)Tc-DI-80B3 imaging for suspected recurrent DVT. CONCLUSIONS: (99m)Tc-DI-80B3 (ThromboView®) is a novel diagnostic modality for patients with suspected DVT with a promising accuracy and safety profile that justifies additional clinical development in diagnostic accuracy and clinical management studies.


Assuntos
Anticorpos Monoclonais , Produtos de Degradação da Fibrina e do Fibrinogênio/imunologia , Interpretação de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons/métodos , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Estudos de Coortes , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fragmentos Fab das Imunoglobulinas/imunologia , Marcação por Isótopo , Masculino , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/imunologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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