ABSTRACT
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.
Subject(s)
Plasminogen Activator Inhibitor 2 , Serpins , Animals , Mice , Mice, Inbred C57BL , Neoplasm Invasiveness , Plasminogen Activator Inhibitor 1 , Plasminogen Activator Inhibitor 2/genetics , Serpins/genetics , Urokinase-Type Plasminogen ActivatorABSTRACT
STUDY DESIGN: A retrospective cohort review. OBJECTIVES: The objective of this study was to investigate the efficacy of liposomal bupivacaine (LB) in patients undergoing lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: Historically, posterior spinal fusion has been recognized as a particularly painful surgery. Postoperative pain limits early patient mobilization and discharge, and negatively impacts patient satisfaction. Local infiltration of anesthetic agents combined with postoperative multimodal pain management is common. On the basis of existing data, the liposomal formulation of bupivacaine might play a role in promoting faster recovery during the immediate postoperative period. The purpose of this study was to investigate the potential impact of LB on postoperative opioid requirements, ambulation, and duration of hospital stay, as well as potential health care cost savings. MATERIALS AND METHODS: A historical cohort of adult lumbar spinal fusion patients was retrospectively evaluated, in which 105 patients received nonliposomal anesthetic and 105 received LB. Both groups were managed with a standardized postoperative analgesia regimen. Demographic information, opioid consumption, length of stay, distance ambulated, and total cost of inpatient stay were collected. RESULTS: Although there was no difference in the pain scores between the 2 groups, the LB group was associated with significantly lower opioid usage throughout the postoperative period. More patients in the LB group were discharged within 2 days of surgery compared with the control group (88.6% vs. 38.1%, P<0.05). The control group was able to walk for a longer median distances (175 vs. 150 ft, P=0.02) on the first attempt, however, a significantly larger proportion of the LB group walked within the first 12 hours after surgery (61% vs. 3%, P<0.001). Also, LB usage was associated with $218 higher pharmacological cost compared with the control group but an overall $3035 lower cost for the entire hospitalization (P<0.001). CONCLUSION: Adjunctive usage of LB with lumbar fusion surgeries promotes earlier mobility, lower opioid consumption, and shorter length of stay resulting in overall lower health care cost. LEVEL OF EVIDENCE: Level III.
Subject(s)
Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Intervertebral Disc Degeneration/surgery , Lumbar Vertebrae , Pain, Postoperative/prevention & control , Spinal Fusion , Analgesics, Opioid/administration & dosage , Cohort Studies , Female , Humans , Injections, Intramuscular , Length of Stay , Male , Middle Aged , Pain Measurement , Retrospective StudiesABSTRACT
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.
Subject(s)
Adenoma, Oxyphilic/epidemiology , Oxyphil Cells/pathology , Thyroid Gland/pathology , Thyroid Neoplasms/epidemiology , Thyroid Nodule/epidemiology , Adenoma, Oxyphilic/diagnosis , Adenoma, Oxyphilic/pathology , Adenoma, Oxyphilic/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle/statistics & numerical data , Cohort Studies , Female , Humans , Male , Middle Aged , Risk Assessment , Thyroid Gland/cytology , Thyroid Gland/surgery , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology , Thyroid Nodule/diagnosis , Thyroid Nodule/pathology , Thyroid Nodule/surgery , Thyroidectomy/statistics & numerical data , Young AdultABSTRACT
BACKGROUND: Gender disparities exist in cancer care. Malignant pleural effusions (MPEs) carry a poor prognosis and are managed by different physicians. This study sought to evaluate referral patterns and gender differences for definitive treatment and outcomes of MPE patients. MATERIALS AND METHODS: Patients diagnosed with MPE from 1999 to 2015 at a quaternary care hospital were retrospectively reviewed to obtain patient history, referral to thoracic surgery for definitive management, and outcomes. Analysis was performed using chi-squared/Fisher's exact test, logistic regression models, and multivariate analysis. RESULTS: 224/686 patients (32.7%) were referred to thoracic surgery. No survival difference existed between referral and nonreferral groups or referred patients who received or did not receive pleurodesis. 405 patients (59.0%) were women. Women were statistically significantly less likely to be referred than men (27.9% versus 39.5%, P = 0.0014). This disparity persisted when comorbidities were controlled for (P = 0.0004) and when gynecologic cancers (e.g., uterine, ovarian, but not including breast; 55 female patients) were excluded from analysis (28.9% versus 39.5%, P = 0.0049). Women had statistically significantly more thoracenteses (3.34 versus 2.19, P < 0.0001) and improved survival compared with males (median survival = 136 d versus 54; P = 0.0004). CONCLUSIONS: Gender disparity exists in referral patterns for definitive management of MPE; women are less likely to be referred than men. Women have longer survival and a greater number of thoracenteses performed, despite a lower referral rate for definitive care. Further research is needed to understand the differences in referral rates and outcomes between men and women.
Subject(s)
Pleural Effusion, Malignant/therapy , Referral and Consultation , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Sex CharacteristicsABSTRACT
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.
Subject(s)
Biopsy , Cytodiagnosis/methods , Molecular Diagnostic Techniques , Pathology, Clinical , Pathology, Molecular , HumansABSTRACT
The Papanicolaou Society of Cytopathology has developed a set of guidelines for respiratory cytology including indications for sputum examination, bronchial washings and brushings, CT-guided FNA and endobronchial ultrasound guided fine needle aspiration (EBUS-FNA), as well as recommendations for classification and criteria, ancillary testing and post-cytologic diagnosis management and follow-up. All recommendation documents are based on the expertise of committee members, an extensive literature review, and feedback from presentations at national and international conferences. The guideline documents selectively present the results of these discussions. The present document summarizes recommendations for ancillary testing of cytologic samples. Ancillary testing including microbiologic, immunocytochemical, flow cytometric, and molecular testing, including next-generation sequencing are discussed. Diagn. Cytopathol. 2016;44:1000-1009. © 2016 Wiley Periodicals, Inc.
Subject(s)
Carcinoma/pathology , Practice Guidelines as Topic , Respiratory Tract Neoplasms/pathology , Biomarkers, Tumor/standards , Bronchoscopy/standards , Carcinoma/classification , Carcinoma/genetics , Carcinoma/metabolism , Endoscopic Ultrasound-Guided Fine Needle Aspiration/standards , Humans , Papanicolaou Test/standards , Pathology, Clinical/organization & administration , Respiratory Tract Neoplasms/classification , Respiratory Tract Neoplasms/genetics , Respiratory Tract Neoplasms/metabolism , Societies, Medical , Sputum/cytologyABSTRACT
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.
Subject(s)
Communication , Disclosure/ethics , Ethics, Medical , Pathology, Clinical/ethics , Physician-Patient Relations , Uncertainty , Humans , MaleABSTRACT
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.
Subject(s)
High-Throughput Nucleotide Sequencing/methods , Microdissection/methods , Animals , Cell Nucleus/metabolism , Epithelium/metabolism , Humans , Mice , NIH 3T3 Cells , Staining and LabelingABSTRACT
BACKGROUND: Similar to TTF-1, Napsin-A is recently used increasingly to differentiate between pulmonary adenocarcinoma (P-ADC) and extra-pulmonary adenocarcinoma (EP-ADC). The aim of this study was to compare the performance of TTF-1 and Napsin-A in determining the primary origin of adenocarcinoma in malignant serous effusion. METHODS: Following IRB approval, cellblocks from 139 cases of malignant serous effusions of histologically or clinically determined origin including: 26 P-ADC, 108 EP-ADC, 2 pulmonary squamous cell carcinoma (P-SQC), and 3 pulmonary small cell carcinoma (P-SCC) were retrieved. Each case was stained with Napsin-A and TTF-1 and evaluated for positivity and intensity of staining. RESULTS: Napsin-A and TTF-1 stained positive in 17/26 (65%) and 14/26 (54%) of P-ADC and in 2/108 (1.8%) and 0/108 (0%) of EP-ADC with a PPV of 89 and 100%, respectively. In combination, they positively stained 18/26 (70%) of P-ADC with a PPV of 90%. Out of 9 poorly differentiated P-ADC, 7 (78%) stained positive for Napsin-A, while 4 (45%) were reactive for TTF-1. Both Napsin-A and TTF-1 were negative in P-SQC, while P-SCC reacted positively for TTF-1 in 2/3 (66%) of cases and none for Napsin-A. CONCLUSION: Napsin-A and TTF-1 are both useful markers in distinguishing P-ADC from EP-ADC. However, Napsin-A performed better in poorly differentiated P-ADC and its mimickers. The nuclear staining of TTF-1 is crispier and much easier to interpret than Napsin-A cytoplasmic stain. An antibody panel including TTF-1 and Napsin-A or a dual stain will be very helpful in determining the origin of metastatic adenocarcinoma in serous effusion.
Subject(s)
Adenocarcinoma/diagnosis , Aspartic Acid Endopeptidases/genetics , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Squamous Cell/diagnosis , DNA-Binding Proteins/genetics , Lung Neoplasms/diagnosis , Pleural Effusion, Malignant/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adenocarcinoma of Lung , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Diagnosis, Differential , Gene Expression , Humans , Immunohistochemistry , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Pleural Effusion, Malignant/genetics , Pleural Effusion, Malignant/pathology , Pleural Effusion, Malignant/surgery , Sensitivity and Specificity , Tissue Embedding , Transcription FactorsABSTRACT
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.
Subject(s)
Biomarkers, Tumor/analysis , Carcinoma/chemistry , Carcinoma/secondary , Immunohistochemistry , Pleural Effusion, Malignant/chemistry , Pleural Effusion, Malignant/pathology , Thyroid Neoplasms/chemistry , Thyroid Neoplasms/pathology , Aged , Biopsy , Carcinoma/surgery , Carcinoma, Papillary , Databases, Factual , Electronic Health Records , Female , Humans , Male , Michigan , Middle Aged , Nuclear Proteins/analysis , PAX8 Transcription Factor , Paired Box Transcription Factors/analysis , Predictive Value of Tests , Retrospective Studies , Thyroglobulin/analysis , Thyroid Cancer, Papillary , Thyroid Neoplasms/surgery , Thyroid Nuclear Factor 1 , Transcription Factors/analysisABSTRACT
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.
Subject(s)
Adenocarcinoma, Mucinous/secondary , Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/secondary , GATA3 Transcription Factor/metabolism , Pleural Effusion, Malignant/pathology , Adenocarcinoma, Mucinous/metabolism , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Lobular/metabolism , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Neoplasm Metastasis , Neoplasm Staging , Pleural Effusion, Malignant/metabolism , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Research PersonnelABSTRACT
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.
Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Pancreas/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/secondary , Carcinoma, Renal Cell/pathology , Diagnosis, Differential , Humans , Kidney Neoplasms/pathology , Lung Neoplasms/pathology , Melanoma/pathology , Sensitivity and SpecificityABSTRACT
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.
ABSTRACT
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.
Subject(s)
High-Throughput Nucleotide Sequencing/methods , Mutation/genetics , Neoplasms/genetics , Aged , Anaplastic Lymphoma Kinase , Computational Biology/methods , DNA Mutational Analysis/methods , DNA, Neoplasm/genetics , ErbB Receptors/genetics , Female , Humans , Male , Middle Aged , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras) , Receptor Protein-Tyrosine Kinases/genetics , Retrospective Studies , Serine Endopeptidases/genetics , Trans-Activators/genetics , Transcriptional Regulator ERG , beta Catenin/genetics , ras Proteins/geneticsABSTRACT
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.
Subject(s)
Cytodiagnosis/methods , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle AgedABSTRACT
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.
ABSTRACT
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.
Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Lung Neoplasms/pathology , Lung/pathology , Abdomen , Aged , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/physiopathology , Carcinoma, Renal Cell/secondary , Diagnosis, Differential , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Facial Paralysis/etiology , Humans , Kidney/diagnostic imaging , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/physiopathology , Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/secondary , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis , Male , Muscle Weakness/etiology , Tomography, X-Ray ComputedABSTRACT
Primary clear-cell adenocarcinoma of the urethra, a rare tumor that histomorphologically resembles clear-cell carcinoma of the female genital tract, occurs predominantly in women and is associated with a relatively poor prognosis. The histogenesis of this rare urethral neoplasm has not been completely resolved, but it is thought to arise from either müllerian rests or metaplastic urothelium. Herein, we present comprehensive surgical pathological and cytopathological findings from a patient with primary urethral clear-cell adenocarcinoma and describe next-generation sequencing results for this patient's unique tumor-the first such reported characterization of molecular aberrations in urethral clear-cell adenocarcinoma at the transcriptomic and genomic levels. Transcriptome analysis revealed novel gene fusion candidates, including ANKRD28-FNDC3B. Whole-exome analysis demonstrated focal copy number loss at the SMAD4 and ARID2 loci and 38 somatic mutations, including a truncating mutation in ATM and a novel nonsynonymous mutation in ALK.
Subject(s)
Adenocarcinoma, Clear Cell/pathology , Biomarkers, Tumor/genetics , Urethral Neoplasms/pathology , Adenocarcinoma, Clear Cell/genetics , Adenocarcinoma, Clear Cell/surgery , DNA Copy Number Variations , Exome/genetics , Female , High-Throughput Nucleotide Sequencing , Humans , Middle Aged , Mutation , Pathology, Surgical , Sequence Analysis, DNA , Urethral Neoplasms/genetics , Urethral Neoplasms/surgeryABSTRACT
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.