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1.
Integr Cancer Ther ; 19: 1534735419890017, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31906724

RESUMO

The purpose of this essay is to inform others that it is possible to survive breast cancer with brain metastases. The second author is the subject patient and a long-term survivor of systemic metastatic breast cancer with numerous brain metastases (corresponding to 8% survivor group). We credit her survival to a combination of (1) medicine as practiced by an excellent oncologist with whom we developed a partnership to manage the patient's health, (2) our informed exploration of the available scientific knowledge including a review of scientific research articles that go beyond conventional care, and (3) the patient's supplementation with numerous repurposed drugs and other substances reported to have antitumor properties. Alongside her conventional treatment (the medical standard of care), it seems likely that this supplementation has been a key factor in the patient's long-term survival. We also point out that the lack of follow-up magnetic resonance imaging brain scans for early detection of brain metastases poses substantial risks for patients with HER2+ metastatic breast cancer in non-central nervous system locations. Thus, we suggest that research be conducted on such early detection for possible inclusion in the recommendations for the medical standard of care. Finally, medical doctors and also patients with backgrounds in biological science may wish to consider potential options and advantages of repurposed drugs and other substances reported in scientific publications when the medical standard of care has limited options for advanced cancer and other severe chronic health conditions. However, any efforts along this line by patients should be in collaboration with their medical doctors.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias da Mama/terapia , Carcinoma Ductal/terapia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Sobreviventes de Câncer , Carcinoma Ductal/patologia , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/patologia , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Induzidas por Radiação , Tomografia por Emissão de Pósitrons , Receptor ErbB-2 , Fatores de Tempo
2.
Medicine (Baltimore) ; 99(1): e18298, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895768

RESUMO

INTRODUCTION: Leptomeningeal dissemination due to HER2-overexpressing breast cancer is a rare and hard to treat complication with short-term dismal prognosis. PATIENT CONCERNS: A 34-year-old female previously treated because of HER2+ breast cancer is admitted to the Neurology Department in December 2016 due to sensory-motor neurological semiology. DIAGNOSIS: A wide set of diagnostic tests is performed and finally cytologic findings after repeated CSF confirm leptomeningeal infiltration by breast carcinoma (panCK+, GATA3+). INTERVENTIONS: Weekly intrathecal triple therapy with methotrexate, cytarabine and hydrocortisone plus trastuzumab is carried out during 4 months. OUTCOMES: Clinical and pathological response that lasts more than 24 months. CONCLUSION: Leptomeningeal carcinomatosis is an oncological situation where conventional therapies have limited activity. In HER2+ advanced breast cancer patients, intrathecal therapy with anti-HER2 therapy (trastuzumab) is feasible and may reach long-term disease control, especially in cases of low-tumor burden.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma Ductal/patologia , Carcinomatose Meníngea/tratamento farmacológico , Carcinomatose Meníngea/secundário , Trastuzumab/uso terapêutico , Adulto , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal/tratamento farmacológico , Feminino , Humanos , Carcinomatose Meníngea/patologia , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/patologia , Receptor ErbB-2
3.
PLoS One ; 15(1): e0227404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31945087

RESUMO

BACKGROUND: Breast cancer is the fifth most prevalent cause of death among women worldwide. It is also one of the most common types of cancer among Malaysian women. This study aimed to characterize and differentiate the proteomics profiles of different stages of breast cancer and its matched adjacent normal tissues in Malaysian breast cancer patients. Also, this study aimed to construct a pertinent protein pathway involved in each stage of cancer. METHODS: In total, 80 samples of tumor and matched adjacent normal tissues were collected from breast cancer patients at Seberang Jaya Hospital (SJH) and Kepala Batas Hospital (KBH), both in Penang, Malaysia. The protein expression profiles of breast cancer and normal tissues were mapped by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The Gel-Eluted Liquid Fractionation Entrapment Electrophoresis (GELFREE) Technology System was used for the separation and fractionation of extracted proteins, which also were analyzed to maximize protein detection. The protein fractions were then analyzed by tandem mass spectrometry (LC-MS/MS) analysis using LC/MS LTQ-Orbitrap Fusion and Elite. This study identified the proteins contained within the tissue samples using de novo sequencing and database matching via PEAKS software. We performed two different pathway analyses, DAVID and STRING, in the sets of proteins from stage 2 and stage 3 breast cancer samples. The lists of molecules were generated by the REACTOME-FI plugin, part of the CYTOSCAPE tool, and linker nodes were added in order to generate a connected network. Then, pathway enrichment was obtained, and a graphical model was created to depict the participation of the input proteins as well as the linker nodes. RESULTS: This study identified 12 proteins that were detected in stage 2 tumor tissues, and 17 proteins that were detected in stage 3 tumor tissues, related to their normal counterparts. It also identified some proteins that were present in stage 2 but not stage 3 and vice versa. Based on these results, this study clarified unique proteins pathways involved in carcinogenesis within stage 2 and stage 3 breast cancers. CONCLUSIONS: This study provided some useful insights about the proteins associated with breast cancer carcinogenesis and could establish an important foundation for future cancer-related discoveries using differential proteomics profiling. Beyond protein identification, this study considered the interaction, function, network, signaling pathway, and protein pathway involved in each profile. These results suggest that knowledge of protein expression, especially in stage 2 and stage 3 breast cancer, can provide important clues that may enable the discovery of novel biomarkers in carcinogenesis.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama , Carcinogênese/metabolismo , Carcinoma Ductal , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal/metabolismo , Carcinoma Ductal/patologia , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Malásia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Proteoma/metabolismo , Proteômica , Espectrometria de Massas em Tandem
4.
Cancer Radiother ; 24(2): 135-137, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-31992517

RESUMO

We report a rare case of salivary duct carcinoma and we study its clinical and evolutionary features. A 64-year-old patient was referred for right peripheral facial paralysis. MRI showed suspected formation of the right parotid gland. Treatment included total parotidectomy and ipsilateral neck lymph node dissection. The histology concluded to a ductal carcinoma of the parotid with lymph node metastasis. Radiation therapy has been indicated. Salivary duct carcinoma of the parotid gland is a highly aggressive and uncommon tumor. Treatment of localized forms is based on surgery and radiotherapy.


Assuntos
Carcinoma Ductal , Neoplasias Parotídeas , Carcinoma Ductal/complicações , Carcinoma Ductal/diagnóstico por imagem , Carcinoma Ductal/patologia , Carcinoma Ductal/terapia , Paralisia Facial/etiologia , Humanos , Excisão de Linfonodo , Metástase Linfática , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Parotídeas/complicações , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/terapia
5.
Urology ; 137: 108-114, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31711982

RESUMO

OBJECTIVE: To study if prostatic ductal adenocarcinoma (PDA) controlled by Grade Group (GG), PSA, and tumor volume (TV) is an independent predictor of adverse radical prostatectomy (RP) outcomes. MATERIALS: One-hundred and twenty-eight PDA and 1141 acinar continuous RPs were studied. Each tumor nodule (TN) was individually graded, staged, and its TV measured. Univariate analysis (UVA) identified features associated with lymph node metastasis (LN+), extraprostatic extension (EPE), positive surgical margins (SM+), and seminal vesicle invasion (SV+). We then assessed PDA effect on RP outcomes in a multivariate analysis (MVA). RESULTS: In 127 cases PDA was present in 1 TN and no TN was pure PDA. One-hundred and twenty-three cases had PDA in TNs with highest grade, stage, and TV. Patients with PDA were older (65 vs 63 years, P < 0.001), had higher GG (P < 0.001), and LN+ (6.3% vs 2.7%, P = 0.049). Controlling these variables by GG eliminated statistical significance. Overall, there were 3249 separate TNs (129 PDA and 3120 acinar). In UVA, PDA predicted EPE (92/124 vs 517/3045), SV+ (28/1129 vs 116/3,120), and SM+ (51/129 vs 296/3120), all P < 0.001. In MVA, PDA lost its effect on EPE (OR = 0.88, P = 0.64), SM+ (OR = 0.86, P = 0.5), and SV+ (OR = 0.99, P = 0.98). CONCLUSION: Controlled for grade and TV, PDA was not an independent predictor of adverse RP outcomes, but former 2 were. Hence, higher GG and TV associated with PDA TNs may be predictive of adverse RP outcomes rather than PDA by itself. These conclusions may be used in preoperative risk stratification and definitive therapy planning when PDA is identified on needle biopsy.


Assuntos
Carcinoma de Células Acinares , Carcinoma Ductal , Complicações Pós-Operatórias , Próstata/patologia , Prostatectomia , Neoplasias da Próstata , Idoso , Biópsia por Agulha , Carcinoma de Células Acinares/patologia , Carcinoma de Células Acinares/cirurgia , Carcinoma Ductal/patologia , Carcinoma Ductal/cirurgia , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Medição de Risco/métodos , Carga Tumoral
6.
Prostate ; 80(2): 146-152, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31737920

RESUMO

BACKGROUND: The Decipher test measures expression of 22 RNA biomarkers associated with aggressive prostate cancer used to improve risk stratification of patients to help guide management. To date, Decipher's genomic classification has not been extensively correlated with specific histologic growth patterns in prostatic adenocarcinoma. With a growing understanding of the clinical aggressiveness associated with cribriform growth pattern (CF), intraductal carcinoma (IDC), and percent Gleason pattern 4 (G4%), we sought to determine if their presence was associated with an increased genomic risk as measured by the Decipher assay. DESIGN: Clinical use of the Decipher assay was performed on the highest Gleason score (GS) tumor nodule of prostatectomy specimens from a prospective cohort of 48 patients, with GS varying from 7 through 9 to help guide clinical risk stratification. The tumors were reviewed for CF, IDC, and G4%, which were then compared to the Decipher score (0-1) and risk stratification (high vs not high). RESULTS: The presence of CF/IDC was significantly associated with Decipher risk score (P = .007), with a high-risk Decipher score in 22% vs 56% of patients without or with CF/IDC. On binary logistic regression analysis, G4% (odds ratio [OR] 1.04 per percent increase [95% confidence interval [CI], 1.02-1.06]; P = .0004) and CF predominant (OR, 9.60 [95%CI, 1.48-62.16]; P = .02) were significantly associated with a high-risk GC score. IDC did not reach significance (OR, 1.92 [95%CI, 0.65-5.67]; P = .24). CONCLUSIONS: Our findings add to an expanding knowledge base that supports G4% and CF/IDC as molecularly unique and clinically relevant features in prostatic adenocarcinoma. These histologic features should be standardly reported as they are associated with more aggressive prostate cancer. Future work should determine the independent information of these histologic findings that are relative to genomic assessment on long-term outcomes.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Carcinoma Ductal/genética , Carcinoma Ductal/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Neoplásico/genética , Idoso , Biomarcadores Tumorais/genética , Processos de Crescimento Celular/genética , Estudos de Coortes , Predisposição Genética para Doença , Genômica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores
7.
Am J Surg Pathol ; 44(5): 673-680, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31876580

RESUMO

Intraductal carcinoma of the prostate (IDC-P) has been recently recognized by the World Health Organization classification of prostatic tumors as a distinct entity, most often occurring concurrently with invasive prostatic adenocarcinoma (PCa). Whether documented admixed with PCa or in its rare pure form, numerous studies associate this entity with clinical aggressiveness. Despite increasing clinical experience and requirement of IDC-P documentation in protocols for synoptic reporting, the specifics of its potential contribution to assessment of grade group (GG) and cancer quantitation of PCa in both needle biopsies (NBx) and radical prostatectomy (RP) specimens remain unclear. Moreover, there are no standard guidelines for incorporating basal cell marker immunohistochemistry (IHC) in the diagnosis of IDC-P, either alone or as part of a cocktail with AMACR/racemase. An online survey containing 26 questions regarding diagnosis, reporting practices, and IHC resource utilization, focusing on IDC-P, was undertaken by 42 genitourinary subspecialists from 9 countries. The degree of agreement or disagreement regarding approaches to individual questions was classified as significant majority (>75%), majority (51% to 75%), minority (26% to 50%) and significant minority (≤25%). IDC-P with or without invasive cancer is considered a contraindication for active surveillance by the significant majority (95%) of respondents, although a majority (66%) also agreed that the clinical significance/behavior of IDC-P on NBx or RP with PCa required further study. The majority do not upgrade PCa based on comedonecrosis seen only in the intraductal component in NBx (62%) or RP (69%) specimens. Similarly, recognizable IDC-P with GG1 PCa was not a factor in upgrading in NBx (78%) or RP (71%) specimens. The majority (60%) of respondents include readily recognizable IDC-P in assessment of linear extent of PCa at NBx. A significant majority (78%) would use IHC to confirm or exclude intraductal carcinoma if other biopsies showed no PCa, while 60% would use it to confirm IDC-P with invasive PCa in NBx if it would change the overall GG assignment. Nearly half (48%, a minority) would use IHC to confirm IDC-P for accurate Gleason pattern 4 quantitation. A majority (57%) report the percentage of IDC-P when present, in RP specimens. When obvious Gleason pattern 4 or 5 PCa is present in RP or NBx, IHC is rarely to almost never used to confirm the presence of IDC-P by the significant majority (88% and 90%, respectively). Most genitourinary pathologists consider IDC-P to be an adverse prognostic feature independent of the PCa grade, although recommendations for standardization are needed to guide reporting of IDC-P vis a vis tumor quantitation and final GG assessment. The use of IHC varies widely and is performed for a multitude of indications, although it is used most frequently in scenarios where confirmation of IDC-P would impact the GG assigned. Further study and best practices recommendations are needed to provide guidance with regards to the most appropriate indications for IHC use in scenarios regarding IDC-P.


Assuntos
Carcinoma Ductal/patologia , Recursos em Saúde/tendências , Imuno-Histoquímica/tendências , Padrões de Prática Médica/tendências , Neoplasias da Próstata/patologia , Especialização/tendências , Biomarcadores Tumorais/análise , Biópsia com Agulha de Grande Calibre/tendências , Carcinoma Ductal/química , Carcinoma Ductal/terapia , Pesquisas sobre Serviços de Saúde , Humanos , Masculino , Gradação de Tumores , Valor Preditivo dos Testes , Neoplasias da Próstata/química , Neoplasias da Próstata/terapia , Reprodutibilidade dos Testes
8.
Biomed Khim ; 65(5): 424-431, 2019 Aug.
Artigo em Russo | MEDLINE | ID: mdl-31666416

RESUMO

The aim of this research was to study cytokine production by blood immune cells, tumor, and its microenvironment, and characterize extracellular matrix of patients with invasive ductal carcinoma of no special type and lymphatic metastases. Spontaneous and polyclonal activators stimulated production of cytokines by blood immune cells, tumor and its microenvironment were studied in 95 patients with invasive ductal carcinoma of no special type. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ß, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 was determined by the solid-phase enzyme-linked immunosorbent assay. The condition of fibrous component and presence of neutral glycoproteins and sulfated glycosaminoglycans were evaluated during the research of extracellular matrix. Regional lymphatic metastases were detected in 35 of 95 patients. It was shown that in the presence or absence of lymphatic metastases index of polyclonal activators influence on the production of cytokines by blood immune cells was different for IL-6, IL-8, and IL-1ß; while in the case of cytokine production by tumor and its microenvironment the index of influence was different for IL-2 and IL-17. The presence of lymphatic metastases corresponded with the rise of cytokines spontaneous production, while the absence of lymphatic metastases corresponded with the rise of cytokines production stimulated by polyclonal activators. The value of indices of polyclonal activators influence on the production of cytokines by blood immune cells pointed to the highly stimulating effect of polyclonal activators while the value of indices of polyclonal activators influence on cytokines production by tumor and its microenvironments pointed to the low and sometimes even absent effect of polyclonal activators. Basing on these data we propose a ratio of indices of polyclonal activators influence for the better evaluation of the probability of lymphatic metastases during preoperative period. After characterizing extracellular matrix we found out a point threshold, which, in 100% of cases, predicted the presence of lymphatic metastases basing on the condition of extracellular matrix. Using the data acquired, we are proposing a risk group for metastasis among women with no lymphatic metastases in the moment of check-up.


Assuntos
Neoplasias da Mama/imunologia , Carcinoma Ductal/imunologia , Citocinas/imunologia , Matriz Extracelular , Microambiente Tumoral , Feminino , Humanos , Metástase Linfática
9.
BMC Cancer ; 19(1): 1043, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690273

RESUMO

BACKGROUND: Radiological imaging plays a central role in the diagnosis of breast cancer (BC). Some studies suggest MRI techniques like diffusion weighted imaging (DWI) may provide further prognostic value by discriminating between tumors with different biologic characteristics including receptor status and molecular subtype. However, there is much contradictory reported data regarding such associations in the literature. The purpose of the present study was to provide evident data regarding relationships between quantitative apparent diffusion coefficient (ADC) values on DWI and pathologic prognostic factors in BC. METHODS: Data from 5 centers (661 female patients, mean age, 51.4 ± 10.5 years) were acquired. Invasive ductal carcinoma (IDC) was diagnosed in 625 patients (94.6%) and invasive lobular carcinoma in 36 cases (5.4%). Luminal A carcinomas were diagnosed in 177 patients (28.0%), luminal B carcinomas in 279 patients (44.1%), HER 2+ carcinomas in 66 cases (10.4%), and triple negative carcinomas in 111 patients (17.5%). The identified lesions were staged as T1 in 51.3%, T2 in 43.0%, T3 in 4.2%, and as T4 in 1.5% of the cases. N0 was found in 61.3%, N1 in 33.1%, N2 in 2.9%, and N3 in 2.7%. ADC values between different groups were compared using the Mann-Whitney U test and by the Kruskal-Wallis H test. The association between ADC and Ki 67 values was calculated by Spearman's rank correlation coefficient. RESULTS: ADC values of different tumor subtypes overlapped significantly. Luminal B carcinomas had statistically significant lower ADC values compared with luminal A (p = 0.003) and HER 2+ (p = 0.007) lesions. No significant differences of ADC values were observed between luminal A, HER 2+ and triple negative tumors. There were no statistically significant differences of ADC values between different T or N stages of the tumors. Weak statistically significant correlation between ADC and Ki 67 was observed in luminal B carcinoma (r = - 0.130, p = 0.03). In luminal A, HER 2+ and triple negative tumors there were no significant correlations between ADC and Ki 67. CONCLUSION: ADC was not able to discriminate molecular subtypes of BC, and cannot be used as a surrogate marker for disease stage or proliferation activity.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Ductal/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Linfonodos/diagnóstico por imagem , Glândulas Mamárias Humanas/diagnóstico por imagem , Adulto , Neoplasias da Mama/patologia , Carcinoma Ductal/patologia , Diagnóstico por Imagem , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Glândulas Mamárias Humanas/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Fenótipo , Prognóstico
10.
Gan To Kagaku Ryoho ; 46(11): 1775-1778, 2019 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-31748491

RESUMO

A woman in her early 60s noticed bilateral breast masses and visited a different hospital. Core needle biopsy showed diffuse large B-cell lymphoma of the right breast and invasive ductal carcinoma of the left breast. After referral to our department, PET-CT was performed. Compared with mild fluorodeoxyglucose accumulation in left breast cancer(BC), highly accumulated lesions were found on the right breast, left anterior chest wall, nasopharynx, and tonsil. The right breast lesion was the largest with a diameter of 30mm and was considered the primary lesion of malignant lymphoma(ML). The ML was classified as stage Ⅳ, pathologically proven with erythema of the left breast and nasopharynx. Three courses of R-CHOP were performed. However, due to suspicion of heart failure, chemotherapy was changed to R-CEOP(non-anthracycline-containing regimen)and 3 courses were additionally performed. The therapeutic effect of R-Chemo for ML was CR. Left BC showed a tendency of shrinkage. After intrathecal administration of anticancer drugs to prevent infiltration of ML into the central nervous system and preoperative endocrine therapy with aromatase inhibitor, left lumpectomy and sentinel lymph node biopsy were performed. BC was classified as clinical stage ⅠA and had an estrogen receptor score of 3b. Postoperative whole breast radiotherapy was completed, and the planned internal use of exemestane was more than 5 years. With multidisciplinary therapy, 3.5 years had passed since the initial treatment without recurrence.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Ductal , Linfoma Difuso de Grandes Células B , Feminino , Humanos , Mastectomia Segmentar , Recidiva Local de Neoplasia , Neoplasias Primárias Múltiplas , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
11.
Korean J Gastroenterol ; 74(4): 193-196, 2019 Oct 25.
Artigo em Coreano | MEDLINE | ID: mdl-31650794

RESUMO

Advances in diagnosis and therapeutic technologies have brought increased life expectancy for most cancers, but paradoxically it also has increased the risk of second primary malignancies. Cancer survivors have a higher risk of developing cancer than the general population. This suggests that more studies are needed to develop screen and management programs for cancer survivors, especially patients with gastrointestinal cancers, which are the most common cancers in Korea.


Assuntos
Neoplasias Gastrointestinais/patologia , Segunda Neoplasia Primária/diagnóstico , Antineoplásicos/uso terapêutico , Carcinoma Ductal/tratamento farmacológico , Carcinoma Ductal/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Segunda Neoplasia Primária/patologia , Fatores de Risco
12.
Prostate ; 79(14): 1673-1682, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31433509

RESUMO

BACKGROUND: The prognostic value of ductal adenocarcinoma of the prostate (DA) in nonmetastatic prostate cancer (PCa) has been identified in many studies. However, it remains unknown whether DA is an adverse prognostic factor in metastatic PCa (mPCa). METHOD: Data from 634 mPCa patients histopathologically documented with DA or/and acinar adenocarcinoma of the prostate in our center between 2012 and 2018 were retrospectively analyzed. Propensity score matching (PSM) was used to balance the baseline features. Data from the Surveillance, Epidemiology, and End Results (SEER) database were utilized to validate our findings. Castration-resistant PCa-free survival (CFS), overall survival (OS), and cancer-specific survival (CSS) were set as endpoints. RESULTS: DA was confirmed in 35 of 634 (5.5%) patients. Among the DA-positive patients, 7 of 35 (20%) and 28 of 35 (80%) harbored high (DA ≥ 50%) and low (DA < 50%) DA components, respectively. DA was not associated with poorer median CFS (mCFS) or median OS (mOS) either before PSM (mCFS: 16.9 vs 18.4 month, P = .814; mOS: 42.0 vs 70.1 month, P = .796) or after PSM (mCFS: 16.9 vs 16.9 month, P = .949; mOS: 42.0 vs 79.9 month, P = .960). Likewise, in the SEER data, DA-positive patients (n = 15 153) shared similar median CSS (25.0 vs 28.0 month, P = .206) and OS (26.0 vs 35.0 month, P = .095) with DA-negative patients (n = 70). No prognostic difference was found between patients with high and low DA components. CONCLUSION: We conducted the first study investigating the prognostic value of DA in de novo mPCa. DA was not associated with adverse clinical outcomes in mPCa patients. These findings are helpful for prognostic evaluation, treatment decision making and counseling in mPCa patients.


Assuntos
Carcinoma Ductal/patologia , Metástase Neoplásica/patologia , Neoplasias da Próstata/patologia , Idoso , Humanos , Masculino , Metástase Neoplásica/terapia , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida
13.
Malays J Pathol ; 41(2): 207-211, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31427558

RESUMO

INTRODUCTION: Salivary gland intraductal carcinoma (IDC) is rare. We present the second case of IDC originating from an intraparotid lymph node (LN) with a more detailed description of the histogenesis, immunohistochemistry (IHC) and updated molecular information. CASE REPORT: An 87-year-old male had a tumour nodule over the left parotid tail for about 20 years. Physical examinations revealed a 4.5 cm soft, non-tender and fixed mass. After the left parotidectomy, pathology confirmed the diagnosis of IDC arising within an intraparotid lymph node. The cystic component of the tumour was lined by single to multilayered ductal cells with micropapillary growth pattern. The solid part showed intraductal proliferation of neoplastic cells in solid, cribriform, micropapillary and Roman bridge-like structure. By immunohistochemistry (IHC), the tumour cells were positive for S-100, CK (AE1/AE3), mammaglobin, SOX10, and estrogen receptor (ER), with myoepithelial cell rimming highlighted by positive p63 and calponin IHC stains. The prognosis of this patient is excellent after complete excision. DISCUSSION: The mechanism of salivary gland tumour arising in the intra-parotid gland LN was assumed to be related to salivary duct inclusion within the intraparotid gland LN which is a normal occurrence during embryology development. Although the terminology may raise some confusion about the relationship between IDC and conventional salivary duct carcinoma (SDA), they are different in immunophenotype and clinicopathologic features. IDC is characterised by S100 (+) ER (+) with predominant intraductal growth and excellent prognosis; while SDC features S100 (-) androgen receptor (+) with predominant invasive growth and aggressive behavior. Recent discovery of recurrent RET gene rearrangement in IDC but not SDC also supports that IDC is not precursor lesion of the SDC.


Assuntos
Carcinoma Ductal/patologia , Linfonodos/patologia , Neoplasias Parotídeas/patologia , Idoso de 80 Anos ou mais , Humanos , Masculino
14.
Ophthalmic Plast Reconstr Surg ; 35(5): e118-e121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365510

RESUMO

Ductal carcinoma of the lacrimal gland is a very rare and aggressive neoplasm, with clinical and histopathologic similarities to salivary ductal carcinoma. Of the 25 previously reported cases, 2 patients had metastases to local lymph nodes confirmed on pathologic examination. The authors now report the clinical presentation, histopathologic and immunohistochemical features, and the treatment of a third patient with lacrimal gland ductal carcinoma with spread to local lymph nodes. In contrast to ductal carcinoma, lymph node involvement has not been reported in the largest series of adenoid cystic carcinoma, a much more common lacrimal gland malignancy. This case highlights the need for possible lymph node surveillance in patients with lacrimal gland ductal carcinoma.


Assuntos
Carcinoma Ductal/patologia , Neoplasias Oculares/patologia , Doenças do Aparelho Lacrimal/patologia , Metástase Linfática/patologia , Humanos , Masculino , Pessoa de Meia-Idade
15.
Curr Opin Urol ; 29(6): 587-592, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31453865

RESUMO

PURPOSE OF REVIEW: During the last 15 years several updates in the Gleason grading have been made. With the help of pertinent research results pathologists have gained a better insight into the meanings of several prostate cancer (PCa) patterns and know better how to classify them in the Gleason grade system. RECENT FINDINGS: During the last years PCa with cribriform architecture has be given much attention. Many data have also been published about the meaning of comedonecrosis and its relationship with Gleason pattern 4 and 5. The correlationship between comedonecrosis and intraductal PCa has also been highlighted in the recent literature. Intraductal PCa is one of the most described topics at the moment with implications to treatment such as radiation therapy. We also highlight several practical issues such as the differences of grading in prostate biopsies and prostatectomies and describe the problematic of reporting a minor high-grade pattern. SUMMARY: Many new and recent data have allowed to refine diagnosis in PCa and improve the patients's treatment. We show that comedonecrosis can be overgraded and insist on the implication with cribriform and intraducatal carcinomas. Furthermore, we describe the importance of these PCa types especially in the consideration of further treatment.


Assuntos
Carcinoma Ductal/patologia , Biópsia Guiada por Imagem/métodos , Gradação de Tumores/métodos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Biópsia , Humanos , Masculino , Neoplasias da Próstata/cirurgia , Ultrassonografia de Intervenção
16.
Mol Immunol ; 114: 172-178, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31357083

RESUMO

B lymphocytes with regulatory or effector functions synthesize granzyme B (GZMB). We investigated the frequency and phenotype of GZMB-producing B cells in breast tumor-draining lymph nodes (TDLNs). Mononuclear cells were isolated from 48 axillary lymph nodes and were stimulated with anti-BCR (B cell receptor), recombinant interleukin (IL)-21 and CD40 L alone or in combination. Flow cytometry was used to evaluate the expression of GZMB in B cells, and in 4 samples the phenotype of GZMB+ B cells was determined. B cells produced GZMB only when stimulated with a combination of IL-21 and anti-BCR for at least 16 h. Adding CD40 L to IL-21 and anti-BCR stimuli resulted in lower GZMB production in B cells. A small fraction of B cells was able to produce perforin in all stimulation conditions, and the majority of GZMB+ B cells were perforin-negative. Both naïve (CD24lowCD27-) and active/memory (CD24hiCD27+) B cells expressed GZMB. In patients with invasive ductal carcinoma, the frequency of GZMB+ B cells was significantly lower in metastatic compared to non-metastatic lymph nodes. The frequency of GZMB+ B cells did not significantly correlate with prognostic factors such as stage, tumor size or Her2 expression. In summary, a subpopulation of both naïve and memory B cells expressed GZMB in breast TDLNs. Our findings underscore the need to investigate the function of GZMB+ B cells in breast tumor immunity.


Assuntos
Linfócitos B/imunologia , Neoplasias da Mama/imunologia , Granzimas/imunologia , Linfonodos/imunologia , Ativação Linfocitária/imunologia , Adulto , Idoso , Ligante de CD40/imunologia , Carcinoma Ductal/imunologia , Feminino , Humanos , Interleucinas/imunologia , Pessoa de Meia-Idade , Perforina/imunologia
18.
Histopathology ; 75(5): 672-682, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31237963

RESUMO

AIMS: Salivary duct carcinoma (SDC) is an aggressive salivary malignancy that results in high mortality rates and is often resistant to chemotherapy. Anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint inhibitors have led to dramatic improvements in patients with various cancers. Other immunotherapeutic approaches, e.g. cancer vaccines, have shown promising results. Cancer testis antigens, e.g. preferentially expressed antigen in melanoma (PRAME), are regarded as promising vaccine targets because of their tumour-specific expression pattern. METHODS AND RESULTS: We analysed the immunoexpression of PD-L1, PD-1, major histocompatibility complex class I (MHC I) and PRAME in 53 SDCs. The immunoexpression levels of PD-L1 in tumour cells (TCs) and immune cells (ICs), PD-1 in ICs, PRAME in TCs and MHC I in TCs were analysed, and were correlated with outcome. PRAME expression was seen in 83% of SDCs. No PRAME staining was present in normal salivary gland tissue. With the three established diagnostic algorithms proposed for head and neck squamous cell carcinoma, the criteria being a combined positive score of ≥1, TC% ≥1%, and TC% ≥25%, 35 (66%), 17 (32%) and three cases (6%), respectively, were deemed to be positive for PD-L1. PD-1-positive ICs were seen in 35 (66%) cases. MHC I down-regulation was seen in 82% of SDCs. There was a significant correlation among PD-L1 expression in ICs, PD-1 expression in ICs, and PRAME expression in TCs. PD-L1 expression in TCs and lack of PD-1 expression in ICs were associated with decreased disease-specific survival in SDC patients. CONCLUSIONS: Alterations of the tumour immune microenvironment are common in SDCs, including expression of PD-1/PD-L1 and PRAME, which opens the way to potential novel immune therapies, such as cancer vaccination and PD-1/PD-L1 blockade, in these tumours.


Assuntos
Antígenos de Neoplasias/metabolismo , Antígeno B7-H1/metabolismo , Carcinoma Ductal/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral/imunologia , Carcinoma Ductal/metabolismo , Histocitoquímica , Humanos , Neoplasias das Glândulas Salivares
19.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 54(6): 416-419, 2019 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-31177683

RESUMO

Objective: To investigate the clinical manifestations and pathological changes of salivary duct carcinoma (SDC) and the relationship between them, so as to provide reference for the diagnosis of SDC. Methods: In this retrospective analysis 40 cases of SDC diagnosed from January 2012 to August 2018 in the Department of Pathology of the First Affiliated Hospital of Zhengzhou University were enrolled and the clinical and pathological characteristics were analyzed, 29 were male and 11 were female, the ratio of male to female was 2.64∶1, the median age was 59.0 years, the average course of disease was 3.5 years. The reported cases of SDC were reviewed and compared with patients of this study. Results: Among the 40 patients, 24 cases occurred in parotid gland, 9 cases in submandibular gland and 7 cases in small salivary glands; 24 cases had cancer cell infiltration and invasion of adjacent tissues, 11 cases had lymph node metastasis and 9 cases had distant metastasis at the time of diagnosis. Pathological results showed that 27 cases belonged to primary salivary duct carcinoma, 13 cases belonged to malignant transformation of pleomorphic adenoma; 10 cases invaded local nerve, 22 cases invaded glandular lobules and ducts. Immunohistochemical results showed that 33 cases were positive for androgen receptor, 27 cases were positive for cytokeratin-7, 22 cases were positive for human epidermal growth factor receptor-2, 8 cases were positive for gross cyst disease fluid protein 15. The proliferation index of nuclear antigen Ki-67 ranged from 10% to 90%. Among them 18 cases were over 50% and 22 cases were below 50%. Conclusions: Salivary duct carcinoma is a rare and highly malignant tumor of the salivary gland. Accurate pathological diagnosis is helpful to inhibit the early local recurrence, distant metastasis and improve survival rate of salivary duct carcinoma.


Assuntos
Adenoma Pleomorfo , Carcinoma Ductal , Neoplasias das Glândulas Salivares , Adenoma Pleomorfo/diagnóstico , Adenoma Pleomorfo/patologia , Carcinoma Ductal/diagnóstico , Carcinoma Ductal/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ductos Salivares , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia
20.
APMIS ; 127(8): 554-560, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31127651

RESUMO

This study aimed to investigate the expression of programmed death receptor ligand 1 (PD-L1) and deficient mismatch repair (dMMR) in ductal adenocarcinoma of the prostate. A tissue microarray of 32 ductal and 42 grade-matched acinar adenocarcinomas was used. Slides were stained for PD-L1, PD-L2, MMR proteins, CD4 and CD8. PD-L1 expression in tumor cells was only seen in 3% (1/34) of ductal and 5% (2/42) of acinar adenocarcinomas (p = 1.0), while PD-L1 expression in tumor-infiltrating immune cells was seen in 29% (10/34) of ductal and 14% (6/42) of acinar adenocarcinomas (p = 0.16). dMMR, as defined by loss of one or more of the MMR proteins, was identified in 5% (4/73) of cases, including 1 ductal and 3 acinar adenocarcinomas. There was a suggested association between infiltration of CD8+ lymphocytes and ductal subtype (p = 0.04) but not between CD4+ lymphocytes and tumor type (p = 0.28). The study shows that both dMMR and PD-L1 expression is uncommon in tumor cells of both ductal and acinar adenocarcinoma of the prostate, while PD-L1 expression in tumor-infiltrating immune cells is a more common finding.


Assuntos
Antígeno B7-H1/imunologia , Carcinoma Ductal/genética , Reparo de Erro de Pareamento de DNA , Neoplasias da Próstata/genética , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Carcinoma Ductal/patologia , Humanos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Instabilidade de Microssatélites , Neoplasias da Próstata/patologia , Análise Serial de Tecidos , Microambiente Tumoral
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