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BACKGROUND: Upregulation of the plasminogen activation system, including urokinase plasminogen activator (uPA), has been observed in many malignancies, suggesting that co-opting the PA system is a common method by which tumor cells accomplish extracellular matrix proteolysis. PAI-2, a serine protease inhibitor, produced from the SERPINB2 gene, inhibits circulating and extracellular matrix-tethered uPA. Decreased SERPINB2 expression has been associated with increased tumor invasiveness and metastasis for several types of cancer. PAI-2 deficiency has not been reported in humans and PAI-2-deficient (SerpinB2-/- ) mice exhibit no apparent abnormalities. OBJECTIVES: We investigated the role of PAI-2 deficiency on tumor growth and metastasis. METHODS: To explore the long-term impact of PAI-2 deficiency, a cohort of SerpinB2-/- mice were aged to >18 months, with spontaneous malignancies observed in 4/9 animals, all of apparently vascular origin. To further investigate the role of PAI-2 deficiency in malignancy, SerpinB2-/- and wild-type control mice were injected with either B16 melanoma or Lewis lung carcinoma tumor cells, with markedly accelerated tumor growth observed in SerpinB2-/- mice for both cell lines. To determine the relative contributions of PAI-2 from hematopoietic or nonhematopoietically derived sources, bone marrow transplants between wild-type C57BL/6J and SerpinB2-/- mice were performed. RESULTS AND CONCLUSIONS: Our results suggest that PAI-2 deficiency increases susceptibility to spontaneous tumorigenesis in the mouse, and demonstrate that SerpinB2 expression derived from a nonhematopoietic compartment is a key host factor in the regulation of tumor growth in both the B16 melanoma and Lewis lung carcinoma models.
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Inhibidor 2 de Activador Plasminogénico , Serpinas , Animales , Ratones , Ratones Endogámicos C57BL , Invasividad Neoplásica , Inhibidor 1 de Activador Plasminogénico , Inhibidor 2 de Activador Plasminogénico/genética , Serpinas/genética , Activador de Plasminógeno de Tipo UroquinasaRESUMEN
BACKGROUND: Hürthle cell metaplasia is common in hyperplastic nodules, particularly within the setting of lymphocytic thyroiditis (LT). The Bethesda System for Reporting Thyroid Cytopathology indicates that it is acceptable to classify Hürthle cell-predominant fine-needle aspiration (HC FNA) specimens as atypia of undetermined significance (AUS) rather than suspicious for a Hürthle cell neoplasm (HUR) within the setting of multiple nodules or known LT. The goal of the current study was to address whether this approach is justified. METHODS: HC FNA specimens were identified and correlated with ultrasound and surgical pathology reports if available. Multinodularity was determined based on findings on macroscopic examination if imaging results were unavailable. RESULTS: A total of 698 HC FNA specimens were identified, including 576 resected nodules, 455 of which (79%) were benign. The overall risk of malignancy for HUR was 27%, whereas the risk of malignancy for AUS was 10%. The mean size of the benign nodules was 2.1 cm on surgical resection specimens, with multiple nodules noted in 293 cases (64%) and histologic LT noted in 116 cases (25%). The mean size of the malignant nodules was 2.8 cm, with multiple nodules and histologic LT noted in 74 cases (61%) and 22 cases (18%), respectively. The malignancy rate did not differ between solitary or multiple nodules (P = .52) or in the presence or absence of LT (P = .12). However, size did significantly differ between malignant and benign nodules (P < 0.01). CONCLUSIONS: The malignancy rate did not differ significantly in the presence of multiple nodules or LT, although the latter demonstrated a statistical trend. A diagnosis of AUS over HUR based solely on the presence of multinodularity is not warranted.
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Adenoma Oxifílico/epidemiología , Células Oxífilas/patología , Glándula Tiroides/patología , Neoplasias de la Tiroides/epidemiología , Nódulo Tiroideo/epidemiología , Adenoma Oxifílico/diagnóstico , Adenoma Oxifílico/patología , Adenoma Oxifílico/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina/estadística & datos numéricos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Glándula Tiroides/citología , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/patología , Nódulo Tiroideo/cirugía , Tiroidectomía/estadística & datos numéricos , Adulto JovenRESUMEN
There has recently been an increased emphasis on the utilization of cytologic samples and small biopsies for not only diagnostic purposes but also for ancillary testing. In some instances, the ancillary tests contribute to the diagnosis and in other scenarios, they provide prognostic and theranostic information for the management of patients with advanced stage cancer. These ancillary tests include immunohistochemical biomarker analysis, molecular mutation analysis, and cytogenetic tests. Despite the finite nature of the cellular material procured in cytologic and small tissue biopsies, pathologists are tasked with ordering an increasing number of tests using these limited samples. This requires the pathologists to utilize and triage these samples in an optimal fashion so that as much information can be gleaned from a given specimen. This review will focus on the pre-analytic requirements for ancillary molecular and cytogenetic tests in the context of a discussion of the various preparation methods for cytologic and small biopsy specimens. The goal will be to provide the reader with the necessary concepts that can be utilized to develop optimal specimen selection and triage strategies to maximize the chances of effectively utilizing these samples for comprehensive diagnostic and relevant ancillary testing purposes.
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Biopsia , Citodiagnóstico/métodos , Técnicas de Diagnóstico Molecular , Patología Clínica , Patología Molecular , HumanosRESUMEN
Cytopathology is a subspecialty of pathology in which pathologists frequently interact directly with patients. Often this interaction is in the context of fine needle aspiration (FNA) procedures performed at the bedside by the cytopathologist or by another clinician with the cytopathologist present. Patient requests for preliminary results in such settings raise fundamental questions about professional scope of practice and communication of uncertainty that apply not merely to pathologists but to all clinicians. In certain settings, cytopathologists may share preliminary diagnostic impressions directly with patients. Essential to these conversations is the need to articulate potential uncertainty about both the diagnosis and next steps. In addition, the involvement and notification of the referring physician is obligatory, both for care coordination and to ensure that patients receive a consistent message.
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Comunicación , Revelación/ética , Ética Médica , Patología Clínica/ética , Relaciones Médico-Paciente , Incertidumbre , Humanos , MasculinoRESUMEN
Precision medicine promises to enhance patient treatment through the use of emerging molecular technologies, including genomics, transcriptomics, and proteomics. However, current tools in surgical pathology lack the capability to efficiently isolate specific cell populations in complex tissues/tumors, which can confound molecular results. Expression microdissection (xMD) is an immuno-based cell/subcellular isolation tool that procures targets of interest from a cytological or histological specimen. In this study, we demonstrate the accuracy and precision of xMD by rapidly isolating immunostained targets, including cytokeratin AE1/AE3, p53, and estrogen receptor (ER) positive cells and nuclei from tissue sections. Other targets procured included green fluorescent protein (GFP) expressing fibroblasts, in situ hybridization positive Epstein-Barr virus nuclei, and silver stained fungi. In order to assess the effect on molecular data, xMD was utilized to isolate specific targets from a mixed population of cells where the targets constituted only 5% of the sample. Target enrichment from this admixed cell population prior to next-generation sequencing (NGS) produced a minimum 13-fold increase in mutation allele frequency detection. These data suggest a role for xMD in a wide range of molecular pathology studies, as well as in the clinical workflow for samples where tumor cell enrichment is needed, or for those with a relative paucity of target cells.
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Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Microdisección/métodos , Animales , Núcleo Celular/metabolismo , Epitelio/metabolismo , Humanos , Ratones , Células 3T3 NIH , Coloración y EtiquetadoRESUMEN
OBJECTIVE: Malignant effusions due to papillary thyroid carcinoma (PTC) are rare, but portend a poor prognosis. PTC metastases, although rare, most frequently occur in the lungs and bone. Therefore, differentiating thyroid etiology of malignant effusions from other sites becomes clinically significant in patient management. This study examines morphologic and immunocytochemical findings in 5 cases of malignant effusions with PTC involvement. STUDY DESIGN: The electronic database at the University of Michigan was searched from January 1, 1995 to December 31, 2014 for malignant pleural effusions with PTC involvement. Clinicopathologic data were obtained from electronic medical records. Cytologic slides were reviewed. RESULTS: Five cases of malignant effusions due to PTC were identified. Characteristic cytologic features of PTC, including ovoid nuclei, irregular nuclear contours, and psammomatous calcifications, were seen. However, the predominant cytologic feature observed was moderate amounts of delicate to vacuolated cytoplasm within the tumor cells. A review of immunocytochemistry demonstrated that all 5 cases showed patchy to diffuse TTF-1 positivity and diffuse positivity for Pax-8. Thyroglobulin only showed focal to patchy positivity in 3 of 5 cases. CONCLUSION: Given the morphologic features found in our case series, an immunocytochemical workup for the evaluation of involvement of an effusion by a thyroid primary is crucial for accurate diagnosis and appropriate clinical treatment.
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Biomarcadores de Tumor/análisis , Carcinoma/química , Carcinoma/secundario , Inmunohistoquímica , Derrame Pleural Maligno/química , Derrame Pleural Maligno/patología , Neoplasias de la Tiroides/química , Neoplasias de la Tiroides/patología , Anciano , Biopsia , Carcinoma/cirugía , Carcinoma Papilar , Bases de Datos Factuales , Registros Electrónicos de Salud , Femenino , Humanos , Masculino , Michigan , Persona de Mediana Edad , Proteínas Nucleares/análisis , Factor de Transcripción PAX8 , Factores de Transcripción Paired Box/análisis , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tiroglobulina/análisis , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/cirugía , Factor Nuclear Tiroideo 1 , Factores de Transcripción/análisisRESUMEN
BACKGROUND: It is not uncommon to encounter challenges in the immunohistochemical confirmation of metastatic breast cancer given the limited sensitivities of mammaglobin and gross cystic disease fluid protein 15 (GCDFP-15/BRST-2) and the significant proportion of triple-negative breast carcinomas (ie, tumors that are negative for estrogen receptor [ER], and progesterone receptor [PgR], and human epidermal growth factor 2 [HER2]). GATA binding protein 3 (GATA3) has emerged as a potentially useful immunohistochemical adjunct during the evaluation of metastatic breast carcinomas in cytology specimens. The objective of the current study was to examine GATA3 expression in the context of malignant effusions secondary to both mammary and extramammary malignancies. METHODS: In total, 306 malignant effusions (from 62 metastatic breast carcinomas and 244 extramammary malignancies) were examined using GATA3 immunohistochemistry. Effusions with metastatic breast carcinoma were also examined using immunohistochemistry for additional breast markers (ER, PgR, HER2, mammaglobin, and GCDFP-15/BRST-2). RESULTS: GATA3 immunohistochemistry highlighted the tumor cells in 58 of the 62 samples (93.5%) from patients with metastatic breast carcinoma, which was higher than the observed sensitivity of immunohistochemistry for ER (63.8%), PgR (41.4%), HER2 (15.5%), mammaglobin (22.4%), and GCDFP-15/BRST-2 (5.2%). GATA3 expression also was observed in a subset of malignant effusions secondary to extramammary primaries, specifically, in 28 of 244 specimens (11.5%). CONCLUSIONS: GATA3 is a highly sensitive marker for the detection of metastatic breast carcinomas in effusion specimens. However, this marker is not entirely specific for malignancies of breast origin. Thus, GATA3 should be used in conjunction with additional immunohistochemical markers during the cytologic evaluation of malignant effusions.
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Adenocarcinoma Mucinoso/secundario , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/secundario , Factor de Transcripción GATA3/metabolismo , Derrame Pleural Maligno/patología , Adenocarcinoma Mucinoso/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Metástasis de la Neoplasia , Estadificación de Neoplasias , Derrame Pleural Maligno/metabolismo , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , InvestigadoresRESUMEN
Metastatic lesions in the pancreas are very uncommon and may be difficult to differentiate from the more commonly encountered primary neoplasms derived from the exocrine and endocrine pancreas because of the significant overlap in clinical presentation, imaging, and cytologic features. Metastasis to the pancreas may occur years after treatment of the primary neoplasm and is often not considered on initial evaluation because of the rarity of such events. The possibility of a metastasis to the pancreas should be entertained in patients with any prior history of malignancy because a proper diagnosis is essential in identifying surgical candidates, or avoiding potentially unnecessary surgery and facilitating triage to more appropriate nonoperative therapy. Herein, we describe intrapancreatic metastases secondary to renal cell carcinoma, melanoma, and lung carcinoma, as documented by cytologic examination of endoscopic ultrasound-guided fine-needle aspiration of the pancreatic masses.
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Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/secundario , Carcinoma de Células Renales/patología , Diagnóstico Diferencial , Humanos , Neoplasias Renales/patología , Neoplasias Pulmonares/patología , Melanoma/patología , Sensibilidad y EspecificidadRESUMEN
In this era of precision medicine, our understanding and knowledge of the molecular landscape associated with lung cancer pathogenesis continues to evolve. This information is being increasingly exploited to treat advanced stage lung cancer patients with tailored, targeted therapy. During the management of these patients, minimally invasive procedures to obtain samples for tissue diagnoses are desirable. Cytologic fine-needle aspirates are often utilized for this purpose and are important not only for rendering diagnoses to subtype patients' lung cancers, but also for ascertaining molecular diagnostic information for treatment purposes. Thus, cytologic fine-needle aspirates must be utilized and triaged judiciously to achieve both objectives. In this review, strategies in utilizing fine-needle aspirates will be discussed in the context of our current understanding of the clinically actionable molecular aberrations underlying non-small cell lung cancer and the molecular assays applied to these samples in order to obtain treatment-relevant molecular diagnostic information.
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Next-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP), an integrative NGS-based assay [compatible with <20 ng of DNA/RNA from formalin-fixed paraffin-embedded (FFPE) tissues], coupled with an informatics pipeline to specifically identify relevant predefined variants and created a knowledge base of related potential treatments, current practice guidelines, and open clinical trials. We validated OCP using molecular standards and more than 300 FFPE tumor samples, achieving >95% accuracy for KRAS, epidermal growth factor receptor, and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type) harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts.
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Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación/genética , Neoplasias/genética , Anciano , Quinasa de Linfoma Anaplásico , Biología Computacional/métodos , Análisis Mutacional de ADN/métodos , ADN de Neoplasias/genética , Receptores ErbB/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras) , Proteínas Tirosina Quinasas Receptoras/genética , Estudios Retrospectivos , Serina Endopeptidasas/genética , Transactivadores/genética , Regulador Transcripcional ERG , beta Catenina/genética , Proteínas ras/genéticaRESUMEN
PURPOSE: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become a preferred technique to evaluate pancreatic masses. The clinical management of a "suspicious for adenocarcinoma" cytological diagnosis is unclear in unresectable cases. We sought to determine whether a suspicious diagnosis in the setting of a high clinical suspicion of malignancy could be sufficient for initiating non-operative therapy, such as chemotherapy, in unresectable patients. METHODS: Twenty-nine solid pancreatic mass cytology specimens obtained by EUS-FNA with a diagnosis of suspicious for adenocarcinoma were identified from 2000 to 2012. Pathology, clinical, and radiologic data were analyzed. RESULTS: Additional procedures were performed in 21 of the 29 patients. Sixteen of the 21 patients had confirmation of malignancy on further tissue sampling and an additional 2 had confirmed unresectable cancers during surgical exploration. Three of the 21 patients had benign diagnoses on subsequent tissue sampling. Of the remaining eight patients who did not undergo additional diagnostic procedures, six were deemed clinically malignant and treated, one died within a year of the EUS-FNA, and one was lost to follow-up. CONCLUSIONS: Consideration of a suspicious diagnosis on EUS-FNA of solid pancreatic masses as sufficient for initiating non-operative therapy is reasonable in the setting of a high clinical suspicion of malignancy.
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Citodiagnóstico/métodos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Fine-needle aspirations (FNAs) of palpable masses are often performed by cytopathologists without ultrasound (US) guidance. Nonetheless, variations in the actual depth of palpable masses lead to occasional challenges. US guidance allows cytopathologists to visualize the mass and guide needle placement. This study retrospectively addressed the utility of US by comparing FNAs performed by cytopathologists on palpable masses with and without US guidance. MATERIALS AND METHODS: Cytopathologist-performed FNAs with and without US guidance from March 1, 2013 to July 1, 2014 were identified. The number of passes, location of lesions, and interpretations were recorded. Available slides were reviewed to determine the proportion of passes that contained diagnostic cellular material and cases in which diagnostic material was present on the first needle pass. RESULTS: In this study, 134 palpation-guided FNAs and 118 US-guided FNAs were analyzed. The percentage of nondiagnostic cases was significantly lower for US-guided FNAs (2.5%) than for palpation-guided FNAs (12.7%; P = 0.004). The average number of needle passes was significantly lower for US-guided FNAs (2.9) than for palpation-guided FNAs (3.6; P = 0.0002). Twenty-two of 118 of US-guided FNAs (18.6%) and 6 of 134 palpation-guided FNAs (4.5%) were completed after only a single pass (P = 0.0008). The percentage of passes with diagnostic material was significantly higher for US-guided FNAs (73.6% versus 60%; P = 0.0002). CONCLUSIONS: For palpable masses, US-guidance adds value to cytopathologists in obtaining diagnostic cellular material more often on the first pass and with fewer passes overall than by palpation alone. This has a potentially beneficial impact on patient care owing to the increased precision and accuracy of needle guidance with ultrasonography.
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Fine-needle aspiration has assumed an increasingly important role in the diagnosis and management of patients with advanced stage cancer. Given its predilection for metastases to distant sites and organs at the time of presentation, metastatic renal cell carcinoma (RCC) is not infrequently encountered in the setting of fine-needle aspiration for initial diagnosis. In some instances, fine-needle aspiration may be the only opportunity to obtain diagnostic tissue to diagnose and subclassify RCC. Therefore, cytopathologists and cytotechnologists should be familiar with and recognize the cytomorphology of RCC and the ancillary studies that can be used to confirm and subclassify RCC. Herein, we describe a case of metastatic RCC initially diagnosed on fine-needle aspiration, discuss the cytomorphologic features of RCC subtypes, and review pertinent ancillary immunohistochemical and cytogenetic adjuncts.
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Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Neoplasias Pulmonares/patología , Pulmón/patología , Abdomen , Anciano , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/fisiopatología , Carcinoma de Células Renales/secundario , Diagnóstico Diferencial , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Parálisis Facial/etiología , Humanos , Riñón/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/fisiopatología , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática , Masculino , Debilidad Muscular/etiología , Tomografía Computarizada por Rayos XRESUMEN
The diagnosis of metastatic prostate carcinoma frequently requires the use of immunohistochemical adjuncts. Immunohistochemistry for prostate-specific antigen (PSA) is commonly used for this purpose but can be of limited utility. Recently, prostate-specific membrane antigen (PSMA) has been shown to be a promising marker for the identification of metastatic prostate carcinoma in surgical specimens. The utility of this marker has yet to be reported for cytology specimens. We sought to compare the sensitivities of PSMA and PSA immunohistochemistry and investigate the specificity of PSMA by utilizing cell block preparations from cytologic cases of metastatic prostate carcinoma (n = 19) and carcinomas of nonprostatic origin (n = 33). The sensitivity of PSMA immunohistochemistry was higher (16/19; 84%) in detecting metastatic prostate carcinomas than that of PSA immunohistochemistry (11/19; 58%). Strong, diffuse staining for PSMA was seen in 13 (81%) of 16 PSMA-positive cases whereas strong, diffuse staining for PSA was observed in six (55%) of 11 PSA-positive cases. Positivity for either PSMA or PSA was seen in 17 of 19 cases of metastatic prostate carcinoma for a combined sensitivity of 89%. PSMA immunohistochemistry was completely negative in 32 of 33 cytology cases of nonprostatic carcinomas. Therefore, the specificity of this marker was 97% in this study. In conclusion, our results indicate that PSMA is a highly sensitive and specific immunomarker for the detection of metastatic prostate carcinoma in cytology specimens.
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Adenocarcinoma/metabolismo , Antígenos de Superficie/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Calicreínas/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundario , Citodiagnóstico , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Sensibilidad y EspecificidadRESUMEN
INTRODUCTION: The Bethesda System for Reporting Thyroid Cytology (TBSRTC) refines the definition of and provides specific diagnostic criteria for the category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). This study was conducted to review our institutional experience with thyroid nodules interpreted as FLUS using TBSRTC diagnostic criteria. MATERIALS AND METHODS: A SNOMED (Systemized Nomenclature of Medicine) search of the electronic pathology database in our institution for the period of January 2011 to June 2012 was conducted to identify thyroid aspirates previously interpreted as FLUS using TBSRTC diagnostic criteria. All cases were followed for at least 6 months. Follow-up information including clinical/imaging monitoring, repeat fine-needle aspiration, and/or subsequent surgical intervention, along with the corresponding cytologic diagnosis and/or histologic diagnosis were collected for each case. Cytology-histology concordance was evaluated for aspirates with surgical follow-up. RESULTS: We identified a total of 122 FLUS cases and follow-up information was available in 100 cases. Among the 100 cases, 31 appeared clinically stable and showed no size change on ultrasonographic imaging; 9 were reclassified as benign non-neoplastic by a repeat fine-needle aspiration; and 60 received surgical treatments. The follow-up histology revealed 26.7% (16 of 60) papillary thyroid carcinoma, 25% (15 of 60) follicular adenoma, and 48.3% (29 of 60) non-neoplastic nodules (nodular hyperplasia or lymphocytic thyroiditis). CONCLUSIONS: Compared with historical control subjects from our institution, the current study demonstrates that adhering to TBSRTC diagnostic criteria yields a higher prediction of histology-proven neoplasia (25% versus 14.9%) and malignancy (26.7% versus 9.2%) for the FLUS category.
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Myeloid-derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are important cellular components in the cancer microenvironment and may affect cancer phenotype and patient outcome. The nature of MDSCs and their interaction with CSCs in ovarian carcinoma are unclear. We examined the interaction between MDSCs and CSCs in patients with ovarian carcinoma and showed that MDSCs inhibited T cell activation and enhanced CSC gene expression, sphere formation, and cancer metastasis. MDSCs triggered miRNA101 expression in cancer cells. miRNA101 subsequently repressesed the corepressor gene C-terminal binding protein-2 (CtBP2), and CtBP2 directly targeted stem cell core genes resulting in increased cancer cell stemness and increasing metastatic and tumorigenic potential. Increased MDSC density and tumor microRNA101 expression predict poor survival, as does decreased tumor CtBP2 expression, independent of each other. Collectively, our work identifies an immune-associated cellular, molecular, and clinical network involving MDSCs-microRNA101-CtBP2-stem cell core genes, which extrinsically controls cancer stemness and impacts patient outcome.
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Oxidorreductasas de Alcohol/metabolismo , MicroARNs/metabolismo , Células Mieloides/metabolismo , Células Madre Neoplásicas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neoplasias Ováricas/inmunología , Oxidorreductasas de Alcohol/antagonistas & inhibidores , Oxidorreductasas de Alcohol/genética , Comunicación Celular , Proteínas Co-Represoras , Femenino , Humanos , Activación de Linfocitos , MicroARNs/genética , Células Mieloides/citología , Células Mieloides/inmunología , Metástasis de la Neoplasia , Células Madre Neoplásicas/inmunología , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/genética , Neoplasias Ováricas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño , Linfocitos T/inmunologíaRESUMEN
In patients with advanced-stage cancer, small biopsies including fine-needle aspirates may be the only opportunity to obtain diagnostic tissue. In the current era of precision medicine, there is an increasing emphasis on the performance of ancillary molecular tests that can provide insights into prognosis and targeted chemotherapeutic options for patient management. Cytopathologists must meet this challenge by accurately diagnosing these fine-needle aspirates and ensuring that adequate material has been obtained for anticipated molecular studies. Herein, we describe a case of a fine-needle aspiration illustrating these principles, especially focusing on the utilization of direct smears for ancillary studies.
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Biopsia con Aguja Fina/métodos , Técnicas Citológicas/métodos , Melanoma/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Cutáneas/patología , Triaje/métodos , Anciano , Servicios Técnicos en Hospital , Pabellón Auricular/patología , Humanos , Metástasis Linfática , MasculinoRESUMEN
CONTEXT: In 2006, the department of pathology at our institution established an intramural research funding mechanism to support anatomic pathology research projects for faculty and trainee development. A review committee consisting of faculty members with diverse academic interests evaluated applications; proposals were eligible for a maximum award amount of $30 000 per project with a maximum program cost of $150 000 annually. OBJECTIVE: To report our experience based on a retrospective review of the research proposals submitted to the committee since the inception of the Anatomic Pathology Research Fund and evaluate the outcomes of the funded projects. DESIGN: We retrospectively analyzed all project applications that were received by the committee. Outcome data were collected by reviewing progress reports, abstracts for national and international meetings, PubMed search results, and/or direct communication with investigators. RESULTS: To date, a total of 59 individual projects have been awarded funding, for a total amount of $349 792, with an average award amount of $5381 per project. A total of 26 faculty members have secured funding for projects through this mechanism, and 27 resident and fellow trainees have been engaged in the funded projects. Spanning 11 subspecialty disciplines in anatomic pathology, 32 abstracts (54%) have been presented at national meetings and 26 (44%) have been published in the peer-reviewed literature to date. One project generated data used to secure an extramural (R01) grant. CONCLUSIONS: Our funding mechanism could serve as a model used by other academic departments to support research activities, thereby fostering faculty development through scholarly activities.
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Patología/economía , Desarrollo de Programa/economía , Apoyo a la Investigación como Asunto/economía , Docentes Médicos , Humanos , Proyectos de Investigación/estadística & datos numéricos , Estudios Retrospectivos , Apoyo a la Formación Profesional/economíaRESUMEN
OBJECTIVES: In light of vaginal mesh safety concerns, we reviewed our institutional experience with analytic processes and pathologic findings of explanted vaginal mesh to identify problems and opportunities to facilitate improved documentation and research. METHODS: We reviewed gross and microscopic pathology reports and archival slides of explanted mesh specimens from January 2010 through February 2012. Specimen requisition clinical history, number of mesh specimens per case, and type of examination (gross or histologic) were abstracted from pathology records using the initial search word "mesh". RESULTS: One hundred two cases were reviewed. Explanted mesh specimens included tissue in 97%. Forty-eight percent of these cases were submitted for histopathologic evaluation (as opposed to gross examination only). Specimen requisitions listed clinical history as pain (28.4%), vaginal mesh erosion (24.5%), erosion (17.6%), urinary retention (5.9%), and infection (2.9%). When no history was provided (24.5%), the case was more frequently submitted for histologic examination (74% vs 41%, P = 0.05). In all but 2 cases, the mesh material was polypropylene; no requisition mentioned this information. Gross descriptions of mesh varied significantly; in 18% of the cases, mesh was inaccurately described as "metallic". No cases of neoplasm were diagnosed histologically; all tissue diagnoses described benign reactive processes. CONCLUSIONS: Our experience suggests that either gross or histopathologic examination is appropriate for mesh explants. Documentation of clinical history, mesh product, and material was frequently incomplete and associated with increased submission of tissue for histologic examination and inaccurate gross impression of material type. We recommend improved documentation to aid pathologic examination and enable future pathophysiologic study of mesh complications.