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1.
Oral Oncol ; 100: 104487, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31835136

RESUMO

OBJECTIVES: To test the performance of an oral cancer prognostic 13-gene signature for the prediction of survival of patients diagnosed with HPV-negative and p16-negative oral cavity cancer. MATERIALS AND METHODS: Diagnostic formalin-fixed paraffin-embedded oral cavity cancer tumor samples were obtained from the Fred Hutchinson Cancer Research Center/University of Washington, University of Calgary, University of Michigan, University of Utah, and seven ARCAGE study centers coordinated by the International Agency of Research on Cancer. RNA from 638 Human Papillomavirus (HPV)-negative and p16-negative samples was analyzed for the 13 genes using a NanoString assay. Ridge-penalized Cox regressions were applied to samples randomly split into discovery and validation sets to build models and evaluate the performance of the 13-gene signature in predicting 2-year oral cavity cancer-specific survival overall and separately for patients with early and late stage disease. RESULTS: Among AJCC stage I/II patients, including the 13-gene signature in the model resulted in substantial improvement in the prediction of 2-year oral cavity cancer-specific survival. For models containing age and sex with and without the 13-gene signature score, the areas under the Receiver Operating Characteristic Curve (AUC) and partial AUC were 0.700 vs. 0.537 (p < 0.001), and 0.046 vs. 0.018 (p < 0.001), respectively. Improvement in predicting prognosis for AJCC stage III/IV disease also was observed, but to a lesser extent. CONCLUSIONS: If confirmed using tumor samples from a larger number of early stage oral cavity cancer patients, the 13-gene signature may inform personalized treatment of early stage HPV-negative and p16-negative oral cavity cancer patients.

2.
Arch Pathol Lab Med ; 143(1): 81-85, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30133317

RESUMO

CONTEXT.­: Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging. OBJECTIVE.­: To determine diagnostic concordance for biopsy-proven low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Papanicolaou test slides in the College of American Pathologists PAP Education program. DESIGN.­: We analyzed 121 059 responses from 4251 LSIL and HSIL slides for the interval 2004 to 2013 using a nonlinear mixed-model fit for reference diagnosis, preparation type, and participant type. We evaluated interactions between the reference diagnosis and the other 2 factors in addition to a repeated-measures component to adjust for slide-specific performance. RESULTS.­: There was a statistically significant difference between misclassification of LSIL (2.4%; 1384 of 57 664) and HSIL (4.4%; 2762 of 63 395). There was no performance difference between pathologists and cytotechnologists for LSIL, but cytotechnologists had a significantly higher HSIL misclassification rate than pathologists (5.5%; 1437 of 27 534 versus 4.0%; 1032 of 25 630; P = .01), and both were more likely to misrepresent HSIL as LSIL ( P < .001) than the reverse. ThinPrep LSIL slides were more likely to be misclassified as HSIL (2.4%; 920 of 38 582) than SurePath LSIL slides (1.5%; 198 of 13 196), but conventional slides were the most likely to be misclassified in both categories (4.5%; 266 of 5886 for LSIL, and 6.5%; 573 of 8825 for HSIL). CONCLUSIONS.­: More participants undercalled HSIL as LSIL (false-negative) than overcalled LSIL as HSIL (false-positive) in the PAP Education program, with conventional slides more likely to be misclassified than ThinPrep or SurePath slides. Pathologists and cytotechnologists classify LSIL equally well, but cytotechnologists are significantly more likely to undercall HSIL as LSIL than are pathologists.


Assuntos
Lesões Intraepiteliais Escamosas Cervicais/classificação , American Medical Association , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Teste de Papanicolaou , Patologistas , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/patologia , Estados Unidos
3.
Appl Immunohistochem Mol Morphol ; 27(2): 107-113, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29084060

RESUMO

Interpretative criteria for programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) have been largely based on data from formalin-fixed, paraffin-embedded tissues, despite the fact that cytologic specimens, especially cell blocks, are often the only or most readily available tissue for testing. Unlike biopsy specimens, however, cytology sample processing methods can vary markedly. The purpose of this study was to evaluate the effects of several common preanalytic variables on PD-L1 IHC. Two cell lines with strong expression of PD-L1 (H441) and no expression (MCF7) were cultured in vitro. Harvested cells were collected in PreservCyt, CytoLyt, cell culture media (RPMI), saline, and formalin. Cell blocks were prepared by the plasma-thromboplastin method or Cellient automated system and stained with the FDA-approved 28-8 PD-L1 antibody per protocol. PD-L1 expression was scored manually by 3 pathologists for stain intensity and localization and compared across preparation methods. Several IHC staining patterns were observed: complete membranous, partial membranous, globular, and cytoplasmic, with some overlap. Cellient blocks had the best interobserver agreement and cytomorphology, highest proportion of strong complete membranous staining (82%), and least amount of cytoplasmic (11%) and globular staining (8%). RPMI, saline, and formalin samples demonstrated increased amounts of cytoplasmic and globular staining relative to Cellient, while CytoLyt exhibited the poorest performance overall. Interpretation of PD-L1 IHC on cell blocks is feasible for most processing methods examined, but may require recognition of increased cytoplasmic and globular staining in some sample types. Cellient cell blocks demonstrated superior performance compared with other methods.

4.
Cancer Cytopathol ; 127(4): 211-212, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30489699
5.
Immunity ; 49(4): 764-779.e9, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30332632

RESUMO

The major types of non-small-cell lung cancer (NSCLC)-squamous cell carcinoma and adenocarcinoma-have distinct immune microenvironments. We developed a genetic model of squamous NSCLC on the basis of overexpression of the transcription factor Sox2, which specifies lung basal cell fate, and loss of the tumor suppressor Lkb1 (SL mice). SL tumors recapitulated gene-expression and immune-infiltrate features of human squamous NSCLC; such features included enrichment of tumor-associated neutrophils (TANs) and decreased expression of NKX2-1, a transcriptional regulator that specifies alveolar cell fate. In Kras-driven adenocarcinomas, mis-expression of Sox2 or loss of Nkx2-1 led to TAN recruitment. TAN recruitment involved SOX2-mediated production of the chemokine CXCL5. Deletion of Nkx2-1 in SL mice (SNL) revealed that NKX2-1 suppresses SOX2-driven squamous tumorigenesis by repressing adeno-to-squamous transdifferentiation. Depletion of TANs in SNL mice reduced squamous tumors, suggesting that TANs foster squamous cell fate. Thus, lineage-defining transcription factors determine the tumor immune microenvironment, which in turn might impact the nature of the tumor.


Assuntos
Diferenciação Celular/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Fatores de Transcrição SOXB1/imunologia , Microambiente Tumoral/imunologia , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Diferenciação Celular/genética , Linhagem Celular Tumoral , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Fator Nuclear 1 de Tireoide/genética , Fator Nuclear 1 de Tireoide/metabolismo , Microambiente Tumoral/genética
6.
Endosc Ultrasound ; 7(5): 323-328, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29623910

RESUMO

Background and Objectives: EUS guided core biopsy was once rarely performed but is now entering mainstream practice. Neuroendocrine tumors often warrant core biopsy as sufficient tissue must be obtained to allow for special staining to ensure a correct diagnosis. Traditionally these lesions were sampled with FNA needles. We performed a retrospective pilot study to evaluate the clinical value and efficacy of the a new EUS core needle biopsy needle as compared to a standard EUS FNA needle in the evaluation of patients with known or suspected neuroendocrine tumors. Methods: A retrospective analysis of the first 10 patients (between January 2015 and April 2016) to undergo EUS-FNA with the SharkCore® needle at the University of Utah School of Medicine/Huntsman Cancer Center with neuroendocrine tumors. Each case was retrospectively reviewed by a board certified cytopathologist (BLW) for the following cytologic parameters on the aspirate smears or touch/squash preparations: overall cellularity [1 (low) to 3 (high)], percentage of obtained cells that were lesional/representative (<25%, 26%-50%, and >50%), relative ease of interpretation [1 (difficult) to 3 (easy)]. Pathologic material and reporting records were also reviewed for each case to confirm the number of needle passes to achieve diagnostic adequacy, the presence or absence diagnostic material on H&E slide (from cell block, if prepared), whether a definitive diagnosis was able to be rendered, and the presence or absence of a true core/core fragments (within the cell block, if prepared). Results: A total of 20 patients underwent EUS-FNA for suspected neuroendocrine lesions. Ten patients underwent either transgastric or transduodenal EUS-FNA with the 22 gauge SharkCore® needle. The comparison cohort of 10 patients underwent either transgastric or transduodenal EUS-FNA with the standard 22 gauge Echotip® needle. The SharkCore® needle required a fewer mean number of needle passes to obtain diagnostic adequacy than the Echotip® (P=0.0074). For cases with cell blocks, the SharkCore® needle produced diagnostic material in 100% of cases, whereas Echotip® produced diagnostic material in 60% of cases. There was no significant difference between specimen cellularity, percentage of lesional material, or ease of interpretation between the two needle types. Conclusion: Our pilot investigation targeting patients with known or suspected pancreatic NETs indicates that the SharkCore® needle shows promise in obtaining suitable tissue for ancillary testing that can allow for more definitive pathologic interpretations on EUS FNA specimens. Fewer passes were needed with the core needle when compared to a standard needle.

7.
Head Neck Pathol ; 12(1): 105-109, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28647794

RESUMO

Previous data has shown that the risk of nodal metastases is significantly greater for classical papillary thyroid carcinoma (PTC) as compared to the follicular variant (FVPTC). Given a recent change in diagnostic paradigm and definition of the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) we intended to investigate if there remains a significant difference in nodal involvement between classical PTC and FVPTC. A 6-year retrospective review of all cases with FVPTC in the diagnostic line from the University of Utah/ARUP Laboratories was conducted. Two pathologists reviewed the remaining cases using the recently described histologic criteria of NIFTP to determine the total number the FVPTCs fitting the new classification paradigm. Histologic and clinical follow-up was tracked for all patients to determine the rate of nodal disease for all groups. 127 cases were identified using the above listed criteria. Forty-seven cases (37%) were classified as NIFTPs. None of the 47 patients had nodal disease either at the time of surgery or on follow-up. Twenty-eight cases met the current criteria for FVPTC (21%); of these 7/28 (25%) had evidence of nodal disease. By comparison, 17/45 (38%) of patients with mixed classical and FVPTC had nodal disease. Overall, there was no statistically significant difference in the risk of nodal metastasis between the pure FVPTC and mixed classical/FVPTC groups (p = 0.43). Our data indicates that implementing new definition for FVPTC will narrow the gap in the risk of nodal metastases between the classical PTC and FVPTC histologic subtypes.


Assuntos
Adenocarcinoma Folicular/patologia , Carcinoma Papilar/patologia , Metástase Linfática/patologia , Neoplasias da Glândula Tireoide/patologia , Humanos , Estudos Retrospectivos , Risco , Câncer Papilífero da Tireoide
8.
Diagn Cytopathol ; 46(3): 234-238, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29230974

RESUMO

BACKGROUND: The sensitivity of brush cytology for biliary strictures has typically been low, usually 30%-60%. We compared the cellular yield and diagnostic accuracy using a new cytology brush (n = 16) versus standard biliary brushings (n = 16) in 32 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) with brushings for evaluation of a biliary stricture for malignancy. METHODS: We performed retrospective chart reviews of 16 consecutive ERCPs with brushings performed for the cytologic evaluation of a biliary stricture for malignancy using the new cytology brush between January 2016 and February 2017 at our institution. Our control cohort was 16 consecutive ERCP cases performed for the same indication directly preceding the availability of the new cytology brush. RESULTS: The biliary brushing cases performed using the new cytology brush demonstrated a significantly increased number of total cell clusters per representative ×20 field compared with cases using the standard brush (mean 24.6 versus 14.4, P = .03). This trend continued when assessing large (>50 cells) clusters (mean 5.8 vs. 3.3, P = .02) and medium (6-49 cells) clusters (11.1 vs. 5.8, P = .03). Nonetheless, there were no statistically significant differences with regards to diagnostic accuracy for the new cytology brush versus standard biliary brushings. CONCLUSION: We found that the Infinity brush significantly increased diagnostic yield with regards to total cell clusters, large (>50 cells) clusters, and medium (6-49 cells) clusters, however, this did not lead to increased diagnostic accuracy overall. Further studies of this and other brush designs are warranted to optimize biliary brushing specimens.


Assuntos
Sistema Biliar/patologia , Citodiagnóstico/instrumentação , Citodiagnóstico/métodos , Agregação Celular , Constrição Patológica , Demografia , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Otolaryngol Head Neck Surg ; 156(4): 671-676, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28366108

RESUMO

Objectives Skull base invasion from cutaneous squamous cell carcinoma (cSCC) via perineural spread affects survival and the rate of regional metastasis. Our objective is to investigate the factors associated with elective neck dissection (END) in this population and the survival difference with END compared with observation for patients with a cN0 neck. Study Design Case series with chart review. Setting Academic. Subjects and Methods Patients were treated surgically for head and neck cSCC with skull base invasion via perineural spread with a cN0 neck from 2004 to 2014. Clinicopathologic data were collected and analyzed. Primary outcomes were disease-free survival (DFS) and overall survival (OS). Results Fifty-nine patients met inclusion criteria: 28 underwent an END and 31 underwent neck observation. Free tissue transfer reconstruction was significantly associated with END ( P < .001). Patients treated with an END had significantly improved 5-year DFS (57% and 32%, P = .042) and OS (60% and 37%, P = .036) compared with those who were observed and a significantly reduced rate of regional recurrence (9% and 37%, P = .024). The rate of occult nodal metastasis identified with END was 36% and is approximately equal to the regional failure rate of the neck observation group (37%). Conclusion END was more commonly used in cases requiring free tissue transfer. The use of END for head and neck cSCCs that have invaded the skull base is not routinely performed but was found to be associated with a survival advantage and reduced regional recurrence rate.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Esvaziamento Cervical , Neoplasias Cutâneas/cirurgia , Base do Crânio , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Procedimentos Cirúrgicos Eletivos , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/métodos , Invasividade Neoplásica , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise de Sobrevida
10.
J Neurol Surg Rep ; 78(1): e15-e19, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28229035

RESUMO

Objectives Low-grade sinonasal sarcoma with neural and myogenic features (LGSSNMF) is a new, rare tumor. Our goal is to describe the imaging characteristics and surgical outcomes of this unique skull base malignancy. Design Retrospective case series. Setting Academic medical center. Participants There were three patients who met inclusion criteria with a confirmed LGSSNMF. Main Outcome Measures Imaging and histopathological characteristics, treatments, survival and recurrence outcomes, complications, morbidity, and mortality. Results Patients presented with diplopia, facial discomfort, a supraorbital mass, and nasal obstruction. Magnetic resonance imaging and computed tomography imaging in all cases showed an enhancing sinonasal mass with associated hyperostotic bone formation that involved the frontal sinus, invaded the lamina papyracea and anterior skull base, and had intracranial extension. One patient underwent a purely endoscopic surgical resection and the second underwent a craniofacial resection, while the last is pending treatment. All patients recovered well, without morbidity or long-term complications, and are currently without evidence of disease (mean follow-up of 2.1 years). One patient recurred after 17 months and underwent a repeat endoscopic skull base and dural resection. Conclusions The surgical outcomes and imaging of this unique, locally aggressive skull base tumor are characterized.

11.
Cancer Cell ; 31(2): 270-285, 2017 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-28089889

RESUMO

Loss of the tumor suppressors RB1 and TP53 and MYC amplification are frequent oncogenic events in small cell lung cancer (SCLC). We show that Myc expression cooperates with Rb1 and Trp53 loss in the mouse lung to promote aggressive, highly metastatic tumors, that are initially sensitive to chemotherapy followed by relapse, similar to human SCLC. Importantly, MYC drives a neuroendocrine-low "variant" subset of SCLC with high NEUROD1 expression corresponding to transcriptional profiles of human SCLC. Targeted drug screening reveals that SCLC with high MYC expression is vulnerable to Aurora kinase inhibition, which, combined with chemotherapy, strongly suppresses tumor progression and increases survival. These data identify molecular features for patient stratification and uncover a potential targeted treatment approach for MYC-driven SCLC.


Assuntos
Aurora Quinases/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-myc/fisiologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Progressão da Doença , Humanos , Neoplasias Pulmonares/etiologia , Camundongos , Carcinoma de Pequenas Células do Pulmão/etiologia
12.
Diagn Cytopathol ; 44(2): 73-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26592713

RESUMO

OBJECTIVES: To determine the accuracy and reproducibility of differentiating between squamous cell carcinoma (SCC) and adenocarcinoma (ADC) on fine-needle aspiration (FNA) specimens. METHODS: Fifty cases of NSCLC diagnosed by FNA having either concurrent core biopsies or resection as a diagnostic reference standard were selected. FNA slides were reviewed independently by five blinded observers. Two rounds of review were performed. Cases were initially categorized as SCC, favor SCC, NSCLC (type indeterminate), favor ADC, or ADC; while the indeterminate category was eliminated in the second round of review. RESULTS: The interobserver agreement was 0.22 and 0.1 with and without the indeterminate category, respectively. The overall accuracy for differentiating between SCC and ADC of the lung was 65% with the indeterminate category and 66% without. CONCLUSION: Overall, the low interobserver agreement in our study indicates that accurate subclassification between the NSCLCs often cannot be made by cytomorphology alone.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Biópsia por Agulha Fina/normas , Humanos , Variações Dependentes do Observador , Sensibilidade e Especificidade
13.
BJR Case Rep ; 2(1): 20150264, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-30364455

RESUMO

Pigmented villonodular synovitis (PVNS) is an uncommon, benign, but locally aggressive lesion characterized most commonly by synovial proliferation of the appendicular large joints, but occasionally involving a bursa or the tendon sheath. PVNS of the spine is rare, typically involving the posterior elements. The lytic radiographic appearance and fludeoxyglucose avidity of PVNS may mimic malignant bone lesions, including metastatic disease or myeloma. On T 1 and T 2 weighted, and gradient recalled echo MRI sequences, the low signal intensity may mimic giant cell tumour of the bone, gout or synovial amyloid deposits, thus posing a diagnostic dilemma for the imagers and the treating clinicians. We present a pathologically confirmed case of PVNS of the cervical spine in a 49-year-old female, detailing her imaging work-up, describing histopathological correlation and highlighting the lesion location and involvement of the joint space as useful imaging discriminators for diagnosing PVNS of the cervical spine.

14.
Diagn Cytopathol ; 43(10): 797-801, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26153872

RESUMO

BACKGROUND: The Papanicolaou Society of Cytopathology has developed a set of guidelines which include a diagnostic scheme with the categories "atypical" and "suspicious for malignancy." These intermediate categories may help stratify risk of malignancy for samples obtained from the bile and pancreatic ducts. However, the reproducibility of these intermediate categories is currently unknown. METHODS: Twenty sequential brushing specimens of bile or pancreatic ducts from each of the categories "atypical" and "suspicious for malignancy" were identified and the slides retrieved. All 40 cases were reviewed independently by four cytopathologists blinded to the original diagnoses. Resulting review diagnoses were statistically analyzed for agreement and the Kappa statistic calculated. Agreement of the observers' diagnoses with original diagnoses was also evaluated. RESULTS: Interobserver agreement was graded as slight to fair with observers agreeing in about 50% of cases. The corresponding kappa statistic for the category "atypical" was 0.21 and 0.18 for the category "suspicious for malignancy." Reviewer agreement with the original reference diagnosis occurred in approximately one half of review diagnoses. CONCLUSION: Analysis of agreement shows that interobserver agreement was only slight to fair. Despite the categories "atypical" and "suspicious for malignancy" having distinct risks of malignancy (62% versus 74%), the reproducibility of these categories is relatively poor. A single intermediate category may improve reproducibility over the scheme proposed by the Papanicolaou Society of Cytopathology while maintaining an ability to stratify risk of malignancy.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares/patologia , Carcinoma Ductal Pancreático/diagnóstico , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Biópsia , Carcinoma Ductal Pancreático/patologia , Humanos , Variações Dependentes do Observador , Neoplasias Pancreáticas/patologia , Reprodutibilidade dos Testes
15.
Diagn Cytopathol ; 43(8): 613-21, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25914403

RESUMO

BACKGROUND: Endoscopic ultrasonographic-guided fine-needle aspiration (EUS-FNA) is the procedure of choice for the investigation of pancreatic lesions. It shows good sensitivity and excellent specificity. Diagnostic criteria have been published but not statistically validated for the diagnosis of malignancy and stratification of risk for malignancy. METHODS: A training set of 57 EUS-FNAs and the validation set of 107 EUS-FNAs were selected. Slides were independently evaluated by three pathologists. Sixteen morphologic features were evaluated in the training set. Average absolute agreement, kappa scores, and association with malignancy were statistically evaluated. Recursive partitioning and multivariant analyses were performed on the features tested in the training set. Agreement data, univariate-odds ratios, and discriminatory power were calculated for the diagnostic features selected from the training set. The selected morphologic features formed a scoring rule that was then applied to the validation set. RESULTS: The average absolute agreement in the training set was 72%. Anisonucleosis, nuclear crowding, macro nucleoli, single atypical epithelial cells, and intracytoplasmic mucin showed the highest interrater reliability. Anisonucleosis, macronucleoli, single atypical epithelial cells, and intracytoplasmic mucin were most predictive of malignancy. A simple scoring rule was developed combining these morphologic features and applied to the validation set. Analysis of the area under the receiver operating characteristic (ROC) curve confirmed the statistical validity of the scoring rule. CONCLUSION: A scoring system utilizing the presence or absence of anisonucleosis, macronucleoli, single atypical epithelial cells, and mucinous metaplasia yielded good discriminatory power (area under ROC curve = 0.87).


Assuntos
Carcinoma Ductal Pancreático/diagnóstico , Células Epiteliais/patologia , Neoplasias/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Carcinoma Ductal Pancreático/patologia , Núcleo Celular/patologia , Citosol/química , Citosol/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Histocitoquímica , Humanos , Mucinas/análise , Neoplasias/patologia , Variações Dependentes do Observador , Neoplasias Pancreáticas/patologia , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco
16.
J Am Soc Cytopathol ; 4(5): 276-281, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-31051765

RESUMO

INTRODUCTION: Endobronchial ultrasonography-guided transbronchial fine-needle aspiration (EBUS-TBFNA) is used for preoperative staging of primary lung carcinomas. Published sensitivity and specificity are up to 86% and 100%, respectively. Diagnostic categories used by many cytopathologists are nondiagnostic, benign, atypical, suspicious, and malignant. Little information exists about the risk of malignancy associated with each of these categories. MATERIALS AND METHODS: Records of the Department of Pathology at the University of Utah were searched for all EBUS-TBFNAs of mediastinal and pulmonary hilar lymph nodes. Only cases with surgical follow-up were included in this study. For each diagnostic category (nondiagnostic, benign, atypical, suspicious, and malignant), the percentage of cases proven to be malignant was calculated following correlation of cytologic and surgical diagnoses. Positive and negative predictive values were calculated. For calculation of accuracy statistics, atypical cases were considered benign and suspicious cases were classified as malignant. RESULTS: For this study, 136 EBUS-TBFNAs of lymph nodes were obtained with adequate surgical follow-up. Risk of malignancy for nondiagnostic specimens was 42%, benign specimens 32%, atypical specimens 40%, suspicious specimens 83%, and malignant specimens 84%. Positive predictive value was 84%, and negative predictive value was 68%. CONCLUSIONS: The categories stratified malignancy risk ranging from a low of 32% for benign to 84% for malignant. The categories suspicious and malignant had similar malignancy risks. Atypical aspirates had a higher malignancy risk than benign aspirates did. Nondiagnostic aspirates had a malignancy risk similar to that of atypical aspirates. This scoring system may aid in treatment planning and patient counselling.

17.
Arch Pathol Lab Med ; 139(2): 184-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24694342

RESUMO

CONTEXT: Persistent high-risk human papillomavirus (hrHPV) infection is essential for the development of cervical cancer and its precursor lesions. High-risk HPV testing has a higher sensitivity than cytology does for detecting cervical epithelial lesions. However, a large study from a single institution showed 31% of patients with invasive cervical cancer had negative baseline hrHPV testing within 5 years preceding the diagnosis. OBJECTIVE: To investigate the limitation of hrHPV testing in detecting invasive cervical cancer. DESIGN: Cases from 2012 with a histologic diagnosis of invasive cervical carcinoma were retrieved from multiple institutions. From those records, prior hrHPV testing and Papanicolaou test results in the 5 years before the cancer diagnosis were recorded. RESULTS: Seventy patients with cervical carcinoma were included in the study. Negative HPV test result rates were 9% (5 of 53), 23% (6 of 26), and 25% (2 of 8) during the periods of less than 1 year, 1 to 3 years, and 3 to 5 years before the histologic diagnoses, respectively. Negative Papanicolaou testing results in the same time intervals were 3.4% (2 of 59), 33% (10 of 30), and 40% (6 of 15). Although the HPV(-) rate seemed to be different among different HPV test methods, no statistical significance was detected because of small sample size. Negative hrHPV rates in patients with adenocarcinoma were similar to those in patients with squamous cell carcinoma. CONCLUSIONS: These data expose limitations for the potential use of primary HPV testing. In addition, current screening guidelines recommending cotesting at 5-year intervals should be evaluated further with additional historic data collection because there are women with negative results for both Papanicolaou tests and hrHPV testing within the period of 3 to 5 years before an invasive carcinoma diagnosis.


Assuntos
Alphapapillomavirus/isolamento & purificação , Carcinoma/diagnóstico , Infecções por Papillomavirus/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Infecções por Papillomavirus/patologia , Estudos Retrospectivos , Risco , Estados Unidos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal
18.
Head Neck Pathol ; 9(1): 60-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24935815

RESUMO

The human papillomavirus (HPV) status of head and neck squamous cell carcinomas (SCCs) is a frequent request for Anatomic Pathology labs. However, prognostic value of HPV status is limited to identification of high risk HPV in oropharyngeal SCCs. The purpose of this study is to investigate the ordering practices of in situ hybridization (ISH) for HPV in head and neck tissues at our national reference laboratory. All testing orders for low risk, high risk, and combined low and high risk HPV-ISH tests requested at ARUP Laboratories between January 2010 and November 2013 had their results reviewed and were grouped by anatomic location of the tested tissue. The H&E and HPV-ISH slides from a sample of the most recent 123 tests were reviewed by two pathologists. A total of 1,128 HPV-ISH tests were ordered during the study period. Testing for combined low and high risk HPV was the most commonly ordered test. The positivity rate for high risk HPV was highest in oropharyngeal tissues. 49 of 123 reviewed cases had testing requested on non-malignant tissue, 11 of which were non-neoplastic. Unnecessary HPV-ISH ordering is prevalent in head and neck tissues. Dual testing for low and high risk HPV, frequent testing outside of the oropharynx, and testing non-neoplastic tissues appear to be common practices.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/virologia , Hibridização In Situ/estatística & dados numéricos , Infecções por Papillomavirus/diagnóstico , Padrões de Prática Médica/estatística & dados numéricos , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço
19.
Cell Rep ; 8(1): 40-9, 2014 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-24953650

RESUMO

Squamous cell carcinoma (SCC) of the lung is the second most common subtype of lung cancer. With limited treatment options, the 5-year survival rate of SCC is only 15%. Although genomic alterations in SCC have been characterized, identifying the alterations that drive SCC is critical for improving treatment strategies. Mouse models of SCC are currently limited. Using lentiviral delivery of Sox2 specifically to the mouse lung, we tested the ability of Sox2 to promote tumorigenesis in multiple tumor suppressor backgrounds. Expression of Sox2, frequently amplified in human SCC, specifically cooperates with loss of Lkb1 to promote squamous lung tumors. Mouse tumors exhibit characteristic histopathology and biomarker expression similar to human SCC. They also mimic human SCCs by activation of therapeutically relevant pathways including STAT and mTOR. This model may be utilized to test the contribution of additional driver alterations in SCC, as well as for preclinical drug discovery.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Animais , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Proteínas Serina-Treonina Quinases/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição STAT/metabolismo , Serina-Treonina Quinases TOR/metabolismo
20.
Diagn Cytopathol ; 42(7): 606-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24554528

RESUMO

Fine-needle aspiration (FNA) is widely utilized due to its short turnaround time (TAT), diagnostic accuracy, and low cost. Controversy exists as to what role cytotechnologists should play in evaluation of FNAs. Some authorities believe all FNAs should be screened by cytotechnologists while others believe that cytotechnologist review is unnecessary. Sixty sequentially performed FNAs without initial review by cytotechnologists were selected from the files of the University of Utah, Department of Pathology. The slides were obtained along with the associated final diagnoses. The slides were reviewed by cytotechnologists given patient history and specimen site but were blinded to the initial pathologist's diagnoses. The initial cytopathologist's diagnoses and subsequent cytotechnologists' diagnoses were recorded and correlated. TATs for these cases were calculated and compared with TATs in a second set of randomly selected FNAs where cytotechnologists had initially screened the cases. Correlation of initial cytopathologists' diagnoses with those of cytotechnologists' revealed no instances where cytotechnologists identified diagnostically significant findings not noted by the original pathologist. TAT for the FNAs reviewed only by a cytopathologist averaged 25.9 hours with a mode of 6 hours. TATs for cases with initial cytotechnologist screening averaged 44.1 hours with a mode of 25 hours. Pre-sign-out screening of FNA specimens by cytotechnologists does not appear to increase detection of cytologic abnormalities. Cytotechnologist screening does substantially increased TAT from a mean of 26 hours to approximately 44 hours. Such an extensive delay may reduce the overall clinical utility of the FNA technique.


Assuntos
Neoplasias/diagnóstico , Biópsia por Agulha Fina , Estudos de Coortes , Erros de Diagnóstico , Humanos , Pessoal de Laboratório Médico , Fatores de Tempo
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