ABSTRACT
Metastatic malignancies of unknown primary site (MUP) is the eighth most common form of malignancy, with an estimated 10-15% of oncology patients having a MUP. Fine needle aspiration cytology (FNA) and core needle biopsy (CNB) are often the first procedures utilized in the work-up of these cases and have a pivotal role for the diagnosis of metastases. There is an increasing emphasis on the precise classification of malignancy and determination of primary site of origin, utilizing smaller specimens. Recent available data suggest that there is a management benefit in identifying the primary site and/or specific cell lineage of MUP. In addition, the pathologists are asked to preserve the limited diagnostic material for potential molecular testing, as selected patients may benefit from targeted therapy. However, these tasks can become extremely challenging, especially if there is no previous history of malignancy, prior pathology is not available for review, or there is an unpredictable pattern of metastasis. In this review, we present a contemporary clinicopathologic approach to the work-up of MUP that includes cytomorphology, ancillary studies, and clinicopathologic correlation. The cytohistologic subclassification of malignancies into specific cell lineages and/or morphologic categories is presented. Knowledge of the various patterns of metastasis to common and unusual sites can help narrow down the location of a primary site. The use of ancillary studies with particular emphasis on IHC utilizing an algorithmic approach and the role of molecular analysis as a diagnostic and theranotic test are also discussed. When the cell block and/or CNB lacks sufficient material for ancillary testing, the cell transfer technique may be utilized.
Subject(s)
Biopsy, Fine-Needle/methods , Biopsy, Large-Core Needle/methods , Neoplasms, Unknown Primary/diagnosis , HumansABSTRACT
OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients. METHODS: To determine the effects of chemoradiation on resected esophageal adenocarcinomas, we examined the immune microenvironment pre- and post-chemoradiation using immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and functional analysis of tumor-infiltrating lymphocytes. Additionally, to assess the duration and dependency of radiation-induced PD-L1 upregulation, a surgical rat reflux model of esophageal adenocarcinoma is used. First, tumor-bearing animals were dosed with single-fraction 13Gy or 16Gy radiation to determine safety, dose correlation, and PD-L1 upregulation using qRT-PCR post-radiation. Next, longitudinal PD-L1 expression levels within individual animals were determined using serial endoscopic biopsies at baseline, 1, 5, and 9 weeks post 16Gy radiation. RESULTS: The majority of cancers displayed enhanced interferon γ and activated CD8+ T lymphocytes at the tumor stroma interface. These tumors also demonstrated enhanced upregulation of PD-L1 and multiple other immune checkpoints including TIM3, GITR, IDO1, LAG3, OX40, and KIR. The animal model results indicated PD-L1 upregulation is dose-dependent and transiently elevated post radiation exposure. CONCLUSIONS: Collectively, these findings provide insights into the evolving immune landscape after chemoradiation and have significant implications for neoadjuvant trial designs that will combine radiotherapy with immune checkpoint inhibitors.
Subject(s)
Adenocarcinoma/immunology , Adenocarcinoma/therapy , Chemoradiotherapy , Esophageal Neoplasms/immunology , Esophageal Neoplasms/therapy , Tumor Microenvironment/immunology , Adult , Aged , Aged, 80 and over , Animals , B7-H1 Antigen/immunology , Disease Models, Animal , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Lymphocytes, Tumor-Infiltrating/immunology , Male , Middle Aged , Rats , Reverse Transcriptase Polymerase Chain Reaction , Up-RegulationABSTRACT
OBJECTIVE: To assess the efficacy of heat-shock protein 90 (Hsp90) inhibitor, NVP-AUY922-AG (AUY922), in the treatment of esophageal adenocarcinoma (EAC) in vitro and in vivo. BACKGROUND: EAC is a leading cause of cancer death, and current treatment options are limited. Hsp90, a chaperone protein that regulates several oncoproteins, is upregulated in EAC, and may be a novel target for therapy. METHODS: In vitro, EAC cell lines were utilized to evaluate AUY922, alone and in combination with 5-fluorouracil (5-FU) and cisplatin. BrdU ELISA and flow cytometry were used to assess proliferation and measure apoptosis, respectively. Western blot and RT-PCR were performed to quantitate Hsp90 pathway expression. In vivo, esophagojejunostomy was performed on rats and treatment animals received AUY922 32 to 40 weeks postoperatively. Drug efficacy was evaluated with magnetic resonance imaging (MRI), endoscopic biopsy, gross histological evaluation, and Hsp90 pathway expression. RESULTS: In vitro, AUY922 demonstrated antiproliferative activity in both cell lines and showed enhanced efficacy with cisplatin and 5-FU. Western Blot and RT-PCR demonstrated downregulation of CDK1 and CDK4 and upregulation of Hsp72. In vivo, AUY922 showed decrease in tumor volume in 36.4% of rats (controlâ=â9.4%), increase in 9.1% (controlâ=â37.5%), and stable disease in 54.5% (controlâ=â43.7%). Necropsy confirmed the presence of EAC in 50% of treatment animals and 75% of control animals. mRNA expression, pre- and posttreatment, demonstrated significant downregulation of MIF, Hsp70, Hsp90ß, and CDK4, and upregulation of Hsp72. CONCLUSIONS: AUY922 exhibits antitumor efficacy in vitro and in vivo for EAC, suggesting the need for human clinical trials.
Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Isoxazoles/therapeutic use , Resorcinols/therapeutic use , Animals , Apoptosis/drug effects , Cell Culture Techniques , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Male , Rats , Rats, Sprague-DawleyABSTRACT
Mesothelioma is a form of cancer generally caused from previous exposure to asbestos. Although it was considered a rare neoplasm in the past, its incidence is increasing worldwide due to extensive use of asbestos. In the current practice of medicine, the gold standard for diagnosing mesothelioma is through a pleural biopsy with subsequent histologic examination of the tissue. The diagnostic tissue should demonstrate the invasion by the tumor and is obtained through thoracoscopy or open thoracotomy, both being highly invasive surgical operations. On the other hand, thoracocentesis, which is removal of effusion fluid from the pleural space, is a far less invasive procedure that can provide material for cytological examination. In this study, we aim at detecting and classifying malignant mesothelioma based on the nuclear chromatin distribution from digital images of mesothelial cells in effusion cytology specimens. Accordingly, a computerized method is developed to determine whether a set of nuclei belonging to a patient is benign or malignant. The quantification of chromatin distribution is performed by using the optimal transport-based linear embedding for segmented nuclei in combination with the modified Fisher discriminant analysis. Classification is then performed through a k-nearest neighborhood approach and a basic voting strategy. Our experiments on 34 different human cases result in 100% accurate predictions computed with blind cross validation. Experimental comparisons also show that the new method can significantly outperform standard numerical feature-type methods in terms of agreement with the clinical diagnosis gold standard. According to our results, we conclude that nuclear structure of mesothelial cells alone may contain enough information to separate malignant mesothelioma from benign mesothelial proliferations.
Subject(s)
Cell Nucleus/physiology , Cytodiagnosis/methods , Lung Neoplasms/classification , Lung Neoplasms/diagnosis , Mesothelioma/classification , Mesothelioma/diagnosis , Pleural Effusion, Malignant/cytology , Asbestos/adverse effects , Chromatin/physiology , Cytological Techniques/methods , Epithelial Cells/pathology , Humans , Image Processing, Computer-Assisted , Mesothelioma, Malignant , Pleura/cytology , Pleura/pathology , Pleural Effusion, Malignant/pathologyABSTRACT
BACKGROUND: Kaposi sarcoma (KS) is a vascular neoplasm associated with human herpesvirus 8 (HHV-8). Skin and mucous membranes are the most common sites, but other organs may be involved. Skeletal KS is rare and occurs either by direct spread of mucocutaneous lesions or through dissemination. Patients present with bone pain and lytic lesions for which they may undergo fine-needle aspiration (FNA). While there are about 70 published case reports of skeletal KS, there is limited literature specifically describing its cytomorphology. Our literature search yielded only a single prior reported case of FNA biopsy of skeletal KS in a Nigerian AIDS patient. CASE: We present a case of disseminated KS of the axial skeleton in a 45-year-old African-American man with AIDS which was diagnosed on FNA cytologic examination. The patient presented with multiple lytic lesions in the axial skeleton. The aspirate, core-needle biopsy and touch imprint cytology of a bone lesion demonstrated clusters of spindle and epithelioid cells in radial and streaming arrangement with indistinct intercytoplasmic borders, elongated nuclei, fine chromatin and inconspicuous nucleoli. Immunohistochemical studies revealed positivity for HHV-8 and vascular markers. The cytomorphologic and ancillary features of the case are presented and discussed.
Subject(s)
Acquired Immunodeficiency Syndrome/complications , Bone and Bones/pathology , Sarcoma, Kaposi/complications , Sarcoma, Kaposi/pathology , Biopsy , Biopsy, Fine-Needle , Cell Aggregation , Cell Shape , Epithelioid Cells/pathology , Humans , Male , Middle Aged , Sarcoma, Kaposi/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
Fine-needle aspiration (FNA) of pancreatic solid masses can be significantly impacted by sampling variation. Molecular analysis of tumor DNA can be an aid for more definitive diagnosis. The aim of this study was to evaluate how molecular analysis of the cell-free cytocentrifugation supernatant DNA can help reduce sampling variability and increase diagnostic yield. Twenty-three FNA smears from pancreatic solid masses were performed. Remaining aspirates were rinsed for preparation of cytocentrifuged slides or cell blocks. DNA was extracted from supernatant fluid and assessed for DNA quantity spectrophotometrically and for amplifiability by quantitative PCR (qPCR). Supernatants with adequate DNA were analyzed for mutations using PCR/capillary electrophoresis for a broad panel of markers (KRAS point mutation by sequencing, microsatellite fragment analysis for loss of heterozygosity (LOH) of 16 markers at 1p, 3p, 5q, 9p, 10q, 17p, 17q, 21q, and 22q). In selected cases, microdissection of stained cytology smears and/or cytocentrifugation cellular slides were analyzed and compared. In all, 5/23 samples cytologically confirmed as adenocarcinoma showed detectable mutations both in the microdissected slide-based cytology cells and in the cytocentrifugation supernatant. While most mutations detected were present in both microdissected slides and supernatant fluid specimens, the latter showed additional mutations supporting greater sensitivity for detecting relevant DNA damage. Clonality for individual marker mutations was higher in the supernatant fluid than in microdissected cells. Cytocentrifugation supernatant fluid contains levels of amplifiable DNA suitable for mutation detection and characterization. The finding of additional detectable mutations at higher clonality indicates that supernatant fluid may be enriched with tumor DNA. Molecular analysis of the supernatant fluid could serve as an adjunct method to reduce sampling variability and increase diagnostic yield, especially in cases with a high clinical suspicion for malignancy and limited number of atypical cells in the smears.
Subject(s)
Adenocarcinoma/genetics , Biomarkers, Tumor/genetics , Biopsy, Fine-Needle , Centrifugation , DNA Mutational Analysis , Mutation , Pancreatic Neoplasms/genetics , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Adenocarcinoma/pathology , DNA Mutational Analysis/methods , DNA, Neoplasm/genetics , DNA, Neoplasm/isolation & purification , Genetic Predisposition to Disease , Humans , Loss of Heterozygosity , Microdissection , Pancreatic Neoplasms/pathology , Polymerase Chain Reaction , Predictive Value of Tests , Proto-Oncogene Proteins p21(ras)ABSTRACT
HER2 (human epidermal growth factor receptor 2) receptor is a membrane tyrosine kinase and when activated affects cell proliferation and survival. The HER2 oncogene is located on chromosome 17q12. HER2 amplification is the primary pathway of HER2 receptor overexpression and is a major driver of tumor development and progression in a subset of breast cancers. HER2 is amplified in about 15% to 20% of breast cancers. The overexpressed HER2 receptor is a valuable therapeutic target. The 2007 ASCO guidelines mandate that HER2 should be evaluated in every invasive breast cancer, either at the time of diagnosis or recurrence to guide therapy. Currently HER2 testing is carried out by several methods. It is crucial to standardize testing techniques to accurately assess HER2 status. The aim of this review on HER2 in breast cancer is to discuss the important aspects of HER2 biology, its significance in breast cancer, and the current standards for its detection.
Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Receptor, ErbB-2 , Animals , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/analysis , Biomarkers, Tumor/antagonists & inhibitors , Biomarkers, Tumor/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/enzymology , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Drug Design , Female , Gene Amplification , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Molecular Diagnostic Techniques , Molecular Targeted Therapy/trends , Precision Medicine , Predictive Value of Tests , Protein Kinase Inhibitors/therapeutic use , Receptor, ErbB-2/analysis , Receptor, ErbB-2/antagonists & inhibitors , Receptor, ErbB-2/genetics , Signal Transduction , Treatment Outcome , Up-RegulationABSTRACT
BACKGROUND: Acinar cell cystadenoma (ACC) is a recently recognized cystic lesion of the pancreas that demonstrates acinar differentiation and is currently believed to behave in a benign fashion. ACC enters the differential diagnosis of pancreatic cystic lesions alongside better recognized entities such as mucinous cystic and intraductal papillary mucinous neoplasms. Although uncommon, patients with ACC can undergo fine needle aspiration (FNA) of the lesion. However, the diagnosis is rarely made on cytologic examination due to sparse cellularity. Furthermore, the eosinophilic amorphous material in the cyst lumen may be mistaken for mucin, resulting in an incorrect diagnosis of a mucinous cyst. To date, there is a paucity of literature on the cytomorphology of ACC, both in peer-reviewed publications and cytopathology texts. CASE: To our knowledge, we present the first detailed case report of FNA of ACC in a 22-year-old asymptomatic female. The FNA cytology specimen was hypocellular, and the presence of amorphous secretions led to the initial diagnosis of a mucinous-type neoplasm. Following surgical resection, the cytology specimen was reviewed. CONCLUSION: We discuss the cytomorphologic features of ACC along with the potential pitfalls and diagnostic implications.
Subject(s)
Acinar Cells/pathology , Biopsy, Fine-Needle , Cystadenoma/pathology , Pancreatic Neoplasms/pathology , Cytodiagnosis/methods , Female , Humans , Young AdultABSTRACT
A 55-year-old male with end-stage renal disease on hemodialysis presented with neck pain of 1 year's duration. A computed tomography (CT) scan was performed as part of his workup, and a posterior cervical neck mass was detected. CT-guided fine needle aspiration was performed with an immediate cytologic interpretation of tumoral calcinosis. On air-dried Diff-Quik and alcohol-fixed Papanicolaou-stained smears, the specimen demonstrated coarse-to-fine calcific debris. A final diagnosis of tumoral calcinosis was rendered. A literature search revealed that this diagnosis is rarely made by touch imprint cytology of core needle biopsy and/or needle aspiration cytology, although it can be a relatively easy and straightforward diagnosis.
Subject(s)
Bone Neoplasms/diagnosis , Calcinosis/diagnosis , Cytodiagnosis , Kidney Failure, Chronic/complications , Biopsy, Needle , Bone Neoplasms/etiology , Calcinosis/etiology , Humans , Male , Middle Aged , Tomography, X-Ray ComputedABSTRACT
This article reviews recent trends in nongyn cytology with an emphasis on error reduction, second opinion, and critical diagnosis. Compared with the surgical pathology literature, there is only a limited number of reports addressing these topics in nongyn cytology. Discussion of the error literature in nongyn cytology is presented with the intent to better identify error-prone cytology cases that could prompt intradepartmental consultation or an outside cytology expert's second opinion. The cytology second-opinion literature is also reviewed with the recommendation that interinstitutional second opinions add value to patient care. Last, the recent concept of critical value (critical diagnosis) in cytopathology is presented. All these initiatives promote patient safety, improve quality, decrease errors, and benefit patients.
Subject(s)
Cytological Techniques/standards , Diagnostic Errors/prevention & control , Pathology, Surgical/methods , Pathology, Surgical/standards , Pathology, Surgical/trends , Adult , Aged, 80 and over , Biopsy, Fine-Needle , Diagnostic Errors/trends , Female , Humans , Male , Neoplasms/pathology , Quality Assurance, Health Care/methods , Quality Assurance, Health Care/standards , Quality Assurance, Health Care/trends , Quality Control , Referral and Consultation/statistics & numerical dataABSTRACT
Myxofibrosarcoma is a soft tissue neoplasm that usually affects the extremities of the elderly. It usually presents as a slow-growing painless mass that can metastasize to the lung and bone. However, the reported incidence of primary osseous myxofibrosarcoma is very low. Moreover, the metastatic pattern of these bone tumors is largely unknown. We describe a unique case of a young Caucasian male with symptomatic low-grade myxofibrosarcoma arising in the left clavicle, who presented with multiple bone metastases.
ABSTRACT
Background: Many genomic alterations have been identified that are critical to the malignant phenotype. Some of these, termed "driver mutations," are critical for tumor proliferation and progression. The landscape of targeted therapy has expanded as well. Next-generation sequencing (NGS) of tumors reveals cancer-related genomic alterations and provides therapeutic recommendations for specific targeted therapy. We analyzed our experience with FoundationOne, a validated NGS genomic profiling test, in a community oncology network. Methods: NGS results from May 2014 to September 2016 from a community oncology network in Western Pennsylvania were analyzed. Medical records were reviewed for primary site, stage, biopsy site, time of testing, prior treatment, FDA-approved therapy in patient's and other tumor types and potential clinical trials based upon mutations detected. Two co-primary endpoints for this study were to determine the percentage of patients having mutations with a FDA-approved targeted agent and the percentage of patients in whom a treatment decision was made based on these NGS results. Results: One Fifty-Seven NGS results were available for analysis. 82% patients had a mutation with a FDA-approved targeted agent available while 18% patients had no FDA-approved targeted agent for the mutation detected. Clinical trials were available for 93% cases. The NGS results were utilized in treatment decisions in 18% patients (n = 28) with, 7% (n = 11) initiating a targeted agent, 6% (n = 9) were on an appropriate targeted agent prior to testing and 5% (n = 8) being unable to start a targeted agent because of insurance denial, clinical deterioration or patient preference. 38% cases were tested early in the disease course (at diagnosis, during or shortly after first-line treatment) and 62% at progression. Conclusions: NGS is a valuable tool to identify molecular targets for personalizing cancer care. From our experience, the actual number of patients starting a targeted agent based on NGS results is low but it provides substantial information in terms of providing additional treatment options, identifying resistance conferring mutations and facilitating clinical trial enrollment. Optimal time of testing, early or late in disease course, financial implications of testing and using targeted therapy and survival benefit of targeted therapy need further studies.
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INTRODUCTION: Focused and expanded mutation panels were assessed for the incremental utility of using an expanded panel in combination with microRNA risk classification. METHODS: Molecular results were reviewed for patients who underwent either a focused mutation panel (ThyGenX®) or an expanded mutation panel (ThyGeNEXT®) for strong and weak oncogenic driver mutations and fusions. microRNA results (ThyraMIR®) predictive of malignancy, including strong positive results highly specific for malignancy, were examined. RESULTS: Results of 12 993 consecutive patients were reviewed (focused panel = 8619, expanded panel = 4374). The expanded panel increased detection of strong drivers by 8% (P < .001), with BRAFV600E and TERT promoters being the most common. Strong drivers were highly correlated with positive microRNA results of which 90% were strongly positive. The expanded panel increased detection of coexisting drivers by 4% (P < .001), with TERT being the most common partner often paired with RAS. It increased the detection of weak drivers, with RAS and GNAS being the most common. 49% of nodules with weak drivers had positive microRNA results of which 33% were strongly positive. The expanded panel also decreased the number of nodules lacking mutations and fusions by 15% (P < .001), with 8% of nodules having positive microRNA results of which 22% were strongly positive. CONCLUSIONS: Using expanded mutation panels that include less common mutations and fusions can offer increased utility when used in combination with microRNA classification, which helps to identify high risk of malignancy in the cases where risk is otherwise uncertain due to the presence of only weak drivers or the absence of all drivers.
Subject(s)
MicroRNAs/genetics , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/genetics , Thyroid Nodule/genetics , Biopsy, Fine-Needle/methods , Female , Humans , Male , Middle Aged , Molecular Diagnostic Techniques , Proto-Oncogene Proteins B-raf/genetics , Telomerase/genetics , Thyroid Neoplasms/pathology , Thyroid Nodule/pathologyABSTRACT
The human epidermal growth factor receptor 2 (HER2) oncoprotein is overexpressed in about 20% of breast cancers, with HER2 gene amplification responsible for protein overexpression in the vast majority of patients. A subset of breast cancers have chromosome 17 aneusomy, due to either 17 monosomy (a single copy of chromosome 17) or polysomy (increased copy numbers of chromosome 17). Although HER2 overexpression is an established adverse prognostic factor in breast cancer, the role of unamplified chromosome 17 polysomy is uncertain and there is a paucity of literature on the correlation of chromosome 17 aneusomy with important prognostic and predictive pathologic factors in invasive breast carcinoma. Furthermore, while patients showing HER2 amplification with or without polysomy 17 are treated with trastuzumab with or without other chemotherapy, treatment of patients with unamplified chromosome 17 polysomy is not well defined. Currently most of these patients are treated similar to patients with neither amplification nor 17 polysomy. The aim of this study was to compare some prognostic and predictive factors in invasive breast carcinoma in patients with unamplified chromosome 17 polysomy with that seen in cases with HER2 gene amplification and those with neither amplification or polysomy. We found that invasive breast carcinomas with unamplified chromosome 17 polysomy are associated with several adverse prognostic indicators such as a higher nuclear grade, mitotic activity, Nottingham score, histologic grade, tumor stage, and greater estrogen receptor negativity with a trend towards the amplified group, in contrast to patients with neither amplification or polysomy. Although most patients with unamplified 17 polysomy have a 2+ equivocal score on immunohistochemistry, a minority has a 3+ positive score. An increased adverse role for unamplified polysomy along with 3+ protein expression in some patients supports the idea that these patients should be considered for therapy with trastuzumab and/or anthracyclines.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carcinoma/genetics , Carcinoma/pathology , Chromosomes, Human, Pair 17/genetics , Female , Gene Amplification , Gene Dosage , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Neoplasm Staging , Prognosis , Receptor, ErbB-2/genetics , Receptors, Estrogen/genetics , Receptors, Progesterone/geneticsABSTRACT
Neuroenteric cysts of the CNS are uncommon benign lesions usually involving the spinal cord or rarely the cerebellopontine angle (CPA). We report a rare example of multiple neuroenteric cysts arising from the CPA and foramen magnum in a 20-year-old Caucasian woman who presented with headaches and dizziness. An MRI showed three separate lesions, not communicating with each other. The first lesion, within the left posterior lateral aspect of the CPA, demonstrated isointensity to gray matter on the fluid-attenuated inversion recovery (FLAIR) sequence. The second lesion, within the left foramen of Luschka at the level of the CPA, demonstrated hyperintensity on the T(2)-weighted sequences, intermediate to slightly hyperintense on T(1)-weighted sequence and hyperintensity on FLAIR. The third lesion, within the anterior/inferior left cerebellum at the level of the foramen magnum, followed CSF signal intensity throughout. None of the lesions demonstrated significant enhancement or bone lesions. Due to compression effect, surgery was performed. Pathologic examination revealed cystic structures lined by a single layer of non-ciliated well-differentiated mucin-producing columnar epithelium with eosinophilic to amphophilic cytoplasm and round to oval nuclei with focal pseudostratification. Immunohistochemical studies showed focal positivity for cytokeratin 7, CK 5/6, synaptophysin, and carcinoembryonic antigen (CEA), diffuse positive staining for epithelial membrane antigen (EMA) and BerEP4; and negative staining for cytokeratin 20, TTF-1, and GFAP. The MIB-1 proliferation index was < 1%. One-year follow-up has shown no recurrence. The differential diagnosis and a brief review of the literature are also presented.
Subject(s)
Cerebellopontine Angle/pathology , Foramen Magnum/pathology , Neural Tube Defects/pathology , Cerebellopontine Angle/metabolism , Cerebellopontine Angle/surgery , Diagnosis, Differential , Female , Follow-Up Studies , Foramen Magnum/metabolism , Foramen Magnum/surgery , Humans , Immunohistochemistry , Magnetic Resonance Imaging , Neural Tube Defects/metabolism , Neural Tube Defects/surgery , Photomicrography , White People , Young AdultABSTRACT
OBJECTIVES: Real-world clinical results of (1) Bethesda categorization, (2) mutation analysis, and (3) a microRNA classifier were correlated to show the utility of molecular analysis in assessing malignancy risk of indeterminate thyroid nodules. METHODS: Cytology and molecular results of clinically tested thyroid nodules were compared. An additional microRNA threshold was determined based on nodules with known disease status, establishing a 3-tiered microRNA approach to clinical risk assessments. Expected rate of malignancy given mutation panel and 3-tiered microRNA approach was validated in an independent cohort of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm or suspicious for follicular neoplasm (FN/SFN) nodules with surgically derived outcomes. RESULTS: In 2685 patients clinically tested, PIK3CA, PAX8/PPARγ, and RET/PTC mutations occurred in less than 1%. Of note, 2% had BRAFV600E mutation and 82% lacked mutations. The maximum expected risk of malignancy in nodules lacking mutations was 9% and 17% for AUS/FLUS and FN/SFN nodules, respectively. Positive microRNA status further increased risk, with the most worrisome status (level-3) elevating risk to 36% and 54%, respectively. RAS mutations occurred in 15% of nodules tested clinically, including in 8% of those that were cytologically benign. The maximum expected risk of malignancy in nodules with RAS or PAX8/PPARγ mutations was 49% and 65% for AUS/FLUS and FN/SFN nodules, respectively. Positive microRNA status further increased risk, with the most worrisome microRNA status (level-3) elevating risk to 85% and 91%, respectively. CONCLUSIONS: Mutation panels alone do not sufficiently risk stratify thyroid nodular disease. microRNA classification complements cytology and mutation analysis with the capacity to better differentiate nodules at high risk of malignancy.
Subject(s)
Biomarkers, Tumor/standards , MicroRNAs/genetics , Mutation , Thyroid Nodule/genetics , Biomarkers, Tumor/genetics , Class I Phosphatidylinositol 3-Kinases/genetics , Humans , MicroRNAs/classification , PAX8 Transcription Factor/genetics , Predictive Value of Tests , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-ret/genetics , Thyroid Nodule/classification , Thyroid Nodule/pathologyABSTRACT
Many genomic mutations have been identified to be related to the metastasis of malignancies from various primary sites. In this study, we attempted to identify the loss of heterozygosity (LOH) that might be involved in metastasis of breast ductal carcinoma (BDC) and papillary thyroid carcinoma (PTC). We retrieved 14 BDC cases with metastasis and 19 BDC cases without metastasis as well as 12 PTC cases with metastasis and 14 PTC cases without metastasis. Analysis of 13 polymorphic microsatellite repeat markers targeting 1p34-36, 3p24-26, 9p21, 10q23, 17p13, 17q21, 21q22, and 22q13 was performed on DNA isolated from primary tumors. The results showed that LOH at 17p13 and 22q13 was shared by both BDC and PTC for metastasis. More detailed studies to identified genes in these shared loci of LOH may provide further insight into the molecular mechanisms underlying metastases in these 2 tumor types, and possibly other malignancies as well.
Subject(s)
Breast Neoplasms/genetics , Carcinoma, Ductal/genetics , Chromosomes, Human, Pair 17/genetics , Chromosomes, Human, Pair 22/genetics , Mammary Glands, Human/pathology , Thyroid Cancer, Papillary/genetics , Thyroid Neoplasms/genetics , Female , Humans , Loss of Heterozygosity , Microsatellite Repeats/genetics , Neoplasm Metastasis , Polymorphism, Genetic , PrognosisABSTRACT
Herpes simplex virus (HSV) hepatitis is an uncommon cause of fulminant hepatic failure, seen mostly in immunocompromised patients. Conventional treatment modalities for inflammatory bowel disease (IBD), such as steroids and azathioprine, have been known to cause HSV hepatitis. However, the reported incidence of HSV hepatitis in IBD patients undergoing tumor necrosis factor (TNF)-α inhibitor therapy is very rare. In this case report, we describe a rare case of fulminant HSV hepatitis that developed in a patient with Crohn's disease after treatment with the TNF-α inhibitor, adalimumab.
ABSTRACT
BACKGROUND: Endoscopic ultrasound (EUS) guided core needle biopsies (CNB) are increasingly being performed to diagnose solid pancreatic lesions. However, studies have been conflicting in terms of CNB improving diagnostic accuracy and procedural efficiency vs fine-needle aspiration (FNA), which this study aims to elucidate. METHODS: Data were prospectively collected on consecutive patients with solid pancreatic or peripancreatic lesions at a single tertiary care center from November 2015 to November 2016 that underwent either FNA or CNB. Patient demographics, characteristics of lesions, diagnostic accuracy, final and follow-up pathology, use of rapid on-site evaluation (ROSE), complications, and procedure variables were obtained. RESULTS: A total of 75 FNA and 48 CNB were performed; of these, 13 patients had both. Mean passes were lower with CNB compared to FNA (2.4 vs 2.9, P = .02). Use of ROSE was higher for FNA (97.3% vs 68.1%, P = .001). Mean procedure time was shorter with CNB (34.1 minutes vs 51.2 minutes, P = .02) and diagnostic accuracy was similar (89.2% vs 89.4%, P = .98). There was no difference in diagnostic accuracy when ROSE was performed for CNB vs not performed (93.5% vs 85.7%, P = .58). Additionally, diagnostic accuracy of combined FNA and CNB procedures was 92.3%, which was comparable to FNA (P = .73) or CNB (P = .52) alone. CONCLUSION: FNA and CNB had comparable safety and diagnostic accuracy. Use of CNB resulted in less number of passes and shorter procedure time as compared to FNA. Moreover, diagnostic accuracy for CNB with or without ROSE was similar.
Subject(s)
Pancreas , Pancreatic Neoplasms , Aged , Biopsy, Large-Core Needle , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Female , Humans , Male , Middle Aged , Pancreas/metabolism , Pancreas/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Prospective StudiesABSTRACT
Histologic criteria have a limited role in determining whether the synchronous bilateral breast carcinomas represent two primaries or a metastasis to the contralateral breast. We studied the molecular analysis of synchronous bilateral breast carcinoma and whether they are originating from a single or different clone. We examined 17 patients with breast carcinoma, including 12 patients with synchronous bilateral carcinomas and control group of 5 infiltrating ductal carcinomas with regional lymph node metastases. Mutations were quantitatively determined to detect loss of heterozygosity (LOH) and microsatellite size alterations for a broad panel of 15 markers, involving 10 chromosomes using polymerase chain reaction. The carcinomas were classified as de novo or metastasis based on three levels of concordance: (1) marker-affected tumors were considered concordant if 50% or more of the same markers were mutated, (2) same gene copy affected, and (3) temporal sequence of mutation acquisition. In synchronous bilateral breast carcinoma patients, molecular analysis showed discordant mutations in all cases, supporting the diagnosis of de novo bilateral primary breast carcinomas. In patients with lymph node metastases, the primary breast carcinoma and metastases shared the same mutations, revealing a metastatic lesion. In conclusion, the application of molecular technology may play an important role for the differential diagnosis of dual primary carcinomas vs a metastatic breast cancer to contralateral breast. In this study, synchronous bilateral breast cancers represent two independent primaries rather than metastatic events.