Day 1 :
Keynote Forum
Sin Hang Lee
Milford Molecular Diagnostics, USA
Keynote: Turn Cytopathology’s Crisis Into Opportunity
Time : 10.00 AM
Biography:
Sin Hang Lee, M.D. graduated from Wuhan Medical College in China. After a residency-fellowship at Cornell-New York Hospital and Memorial Hospital for Cancer, Dr. Lee was certified by the American Board of Pathology and obtained the F.R.C.P. (C) degree by examination in 1966. He was on the faculty of McGill University and Yale University from 1968-2004 while practicing hospital-based pathology. Dr. Lee is currently the director of Milford Molecular Diagnostics, Milford, Connecticut. In the past 10 years, Dr. Lee has developed Sanger sequencing-based testing methods for HPV, Neisseria gonorrhoeae, Chlamydia trachomatis, Lyme disease borreliae and Ebolavirus implementable in community hospitals.
Abstract:
Cytopathology is a profession created to implement Pap smear as a screening tool for cervical cancer prevention with great success. However, DNA test is much more sensitive in detecting HPV infection, a necessary factor in the pathologic process which may lead to cervical cancer development. The trend of detecting HPV infection as a surrogate indicator for cervical cancer risk assessment has been set. Pap smear cytopathology will continue to be used but probably as a gateway check to colposcopic biopsies rather than a primary screen test for its higher specificity in predicting CIN2/CIN3 lesions than HPV tests. The recent loss of test volumes has caused a feeling of uncertainty for the future among the cytopathology professionals. The author proposes that the practicing cytopathologists turn this crisis into an opportunity by getting actively involved in helping the community hospitals to create their own molecular diagnostic laboratories to perform Sanger sequencing-based molecular tests for various infectious diseases including the HPV, gonorrhoea, chlamydial and Lyme disease infections, the 4 major non-nosocomial infections. In the era of molecular personalized medicine, Sanger sequencing will be the routine “gold standard†tool as a Petri dish for the diagnosis of numerous infectious diseases and other common genetic abnormalities such as BRCA gene mutations which can be tested on the cell samples prepared for HPV assays. The cytopathologists are in the drivers’ seat in implementing Sanger sequencing in community hospital laboratories because they are directing the test flows of thousands of liquid-based cytology samples each year.
- Track 3: Molecular Cytopathology
Track 5: Veterinary Cytopathology
Track 7: Infection Control Cytopathology
Track 9: Drug discovery in Cytopathology
Chair
Sin Hang Lee
Milford Molecular Diagnostics, USA
Co-Chair
Qing Kay Li
The Johns Hopkins University School of Medicine, USA
Session Introduction
Amr H. El Bolok
Minia University, Egypt
Title: Histological and immunohistochemical evaluation of the effect of orlistat on parotid salivary gland of adult male albino rats
Biography:
Amr H. El Bolok has completed his Ph.D at the age of 33 years from Faculty of Oral and Dental Medicine Cairo University. He is the head of Oral Pathology Department Faculty of Dentistry. Minia University, He has published many papers in reputed journals in the prognosis and management of different oral diseases.
Abstract:
Orlistat 120 mg was approved as a prescription product by the FDA in 1999 for obesity management, Orlistat was purchased as a capsule with a trade name (Xenical) manufactured by Hoffmann-La Roche, Germany. This study will be conducted to evaluate the effect of oral administration of orlistat on parotid salivary gland of rats. The study was carried out on 45 healthy adult male albino rats of average weight (150 – 180) grams. The rats were divided into two groups, control group (15 rats) fed only on ordinary rat diet, and experimental group (30 rats) divided in to 2 groups (A) and (B) fed on diet supplemented with orlistat at a dose of 200 and 400 mg/kg. On termination of each month, 5 animals from each group will be humanely sacrificed and the parotid tissues were dissected out, cleaned and fixed in 10%buffered formalin solution. Then, paraffin wax sections were obtained and stained with: Haematoxylin and Eosin stain to verify histological details and histological changes happened in the parotid gland structure and immunohistochemical stain for visualization of TNF-alpha antibody utilizing Dako LSAB Kits.. Histological results in experimental group were time and dose dependent, experimental group (A) showed moderate destructive changes include the acini, ducts and also connective tissue capsules, while in experimental group (B) these changes were markedly severe and destruction was obvious, Immunohistochemical results showed that cytoplasm demonstrated immunopositive reaction, which is time and dose dependent and that indicted destruction and apoptosis of glandular tissues.
Filomena Aste Silveira
Federal University of Rio de Janeiro,Brazil
Title: Cytologic study of behavior, cytology of low grade squamous lesions associated with p16INK4a gene methylation and genotyping of human papillomavirus
Biography:
Filomena Aste Silveira graduated in Medicine, Ph.D. from the Federal University of Rio de Janeiro (UFRJ), and member of the Society of cervical pathology, with title of qualification. Member of the commission of sexually transmitted diseases (STDs), the Brazilian Federation of Gynecology and Obstetrics (FEBRASGO), Prof. Silveira responsible for Gynecology discipline of Valença Medical School (RJ-Brazil). Appraisal professor of gynecology specialist title of proof (TEGO). Medical Institute of Ginecologia- UFRJ - Brazil. Develops research in diseases precursor of cervical cancer and biomarkers, has published some articles in scientific journals.
Abstract:
The low grade cervical intraepithelial squamous lesion (LSIL) is a high prevalence and its behavior is variable. This lesion can minimize, persist or progress. The performance of viral proteins and the epigenetic abnormalities are factors involved in the carcinogenesis of uterine cervix. We studied about the identify the type of HPV-DNA in this lesion and detected the p16INK4a gene methylation too. We analyze the results found about type of HPV-DNA, and methylation then observed with development of LSIL. The time of observation was two years. There was association of oncogenic HPV 16 and 18 with persistence / progression of these lesions. The presence of p16INK4a gene methylation in LSIL was infrequent event and regardless of presence of HPV DNA. We observed that all patients who presented p16INK4a gene methylation showed persistence/progression of this lesion.
Je-Chiuan Ye
Taipei College of Maritime Technology, Taiwan
Title: Analyzing the Caffeic acid in Eugenia caryophyllata by HPLC with extracting method and treated with cervical cancer cell line
Biography:
Je-Chiuan Ye has completed his PhD from Chung Shan Medical University. He is the Director of Academic Development Center at Taipei College of Maritime Technology. He has published more than 10 papers in reputed journals
Abstract:
Eugenia caryophyllata Thunb. is an herbal medicine and caffeic acid is one of its main components. Caffeic acid (3, 4-dihydroxycinnamic acid ) has been known to control cholesterol and triglycerides level, reducing the activity of cancer cell and enhancing immunity in the human body. Caffeic acid can also be found in the vegetable oil, such as potato plants, curly kale oil and so on. This paper presents the method by using high performance liquid chromatography (HPLC) with extracting method in the E. caryophyllata Thunb., and we found that caffeic acid can suppress the growth of cervical cancer cell line (He-La). Its DNA fragmentation was noted in 83.94% of cells after exposure to 10 mM caffeic acid for 48 hr. We examined the effect of caffeic acid on expression of the P53 protein by western blotting. Exposure of HeLa cells to caffeic acid led to the disappearance of the anti-apoptotic Bcl-2 protein on the mitochondria and the release of cytochrome c into the cytosol. So our findings suggest that caffeic acid has a strong anti-tumor effect and, therefore, might be a promising chemopreventive or chemotherapeutic agent.
Biography:
James Joseph Navin is a MD Graduate from Creighton University, went back in the army in the senior year. He was Internship US Army Tripler Army Med Center, Honolulu in 1962-63. He was on the post of Pathology Residency TAMC between 1963-1967. He was the Chair of Anatomical Pathology TAMC 1969-1972 and Chair of Pathology Straub Clinic and Hospital & also at Kapiolani Women's and Childrens Hosptial and SmithKline Lab. Dr. James was the first Cytopathologist in Hawaii. He received multiple awards as teacher of the year from American Society of Cytopathology for outstanding advocacy efforts. President of American Pathology foundation and having recognition from ACOG for career long dedication to Women's Health .
Abstract:
Commercial labs set a pattern of low payment for Pap smears. They allowed clinicians to bill for the Paps as long as they sent the other work to the lab. This led to a marked reduction in payment to other labs which did Paps and resulted in Pap smears becoming a money losing test for the other labs. Insurance companies and Medicare lowered their payment as well. This produced financial problems for many labs. Some lived with the problem others began to reduce costs by screening faster, not using cytotechs and other ventures that greatly reduced quality. Upon recognizing the problem we began to fix it. We first went after local payors and when that was fixed we went after the Federal Govt. the following is the story of what transpired. It encompasses about 4 years of work which included going to DC every month sometime 3-4 times to meet with the players. Honolulu, by the way is not very close to DC
Suhail Al-Salam
United Arab Emirates University, UAE
Title: Fine needle aspiration cytology from screening to definite diagnosis: Role of Molecular diagnosis
Biography:
Suhail Al-Salam has completed his MD in 1981 from Baghdad University, then MSc pathology in 1988 from Glasgow University, UK, then Board degree in Pathology 1998 from Baghdad Iraq, then European board of pathology in 2005 Paris France, Member of International Academy of Cytology 2005 Germany, and Fellow of Royal College of Pathologists United Kingdom 2010. He is Associate Professor in Pathology in the department of Pathology, College of Medicine & Health Sciences, and Consultant Pathologist at Tawam Hospital in Affiliation with John Hopkins Medicine, ALAIN UAE. He has published more than 77 papers in reputed journals and has been serving as an Editorial Board Member of repute.
Abstract:
Fine needle aspiration cytology (FNA) is a simple inexpensive and non-traumatic technique used to assess tumors all over the body; usually prior to surgical removal. The brisk advances in imaging techniques and interventional radiology add a lot to the feasibility and accuracy of FNA. FNA samples can be processed either through conventional or liquid based techniques. Our experience through reviewing sections processed by both techniques favors conventional method over liquid based cytology in many aspects. To what does FNA helpin reaching accurate diagnosis? FNA will be of great help in giving guidance for appropriate approach to handle tumors. In the current practice FNA will be of help in selecting cases of surgical removal of tumors and monitoring tumor spread as definite diagnosis can only be achieved by surgical biopsy. Cytological samples are appropriate for many molecular techniques such as Real-time polymerase chain reaction, Fluorescent in situ hybridization, flow cytometry and others. Actually, FNA samples are better in handling and easier in processing for molecular techniques than tissue samples from biopsies. Molecular techniques can add a lot to accuracy of the diagnosis of FNA samples through identification of molecular changes that are specific for particular cancer. Specific molecular alteration are now documented for hemopoietic, lymphoid, breast, lung, colon, thyroid, renal and prostate malignancies which their identification in FNA samples together with morphologic changes in cytological smears will aid in confirming the diagnosis and facilitates abrupt treatment which will affect significantly the disease outcome. In conclusion, Molecular techniques will make FNA cytology more decisive and conclusive as well as will direct molecular treatment more accurately which will be translated into better prognosis.
Biography:
Amr Amin has completed his PhD at University of Illinois at Chicago, and received a post-doctoral training in the field of molecular genetics at the University Of Pennsylvania School Of Medicine. He started his academic career at UAE University where he serves now as a Full Professor of Cell and Molecular Biology. Amr’s research focuses on ways to control cancer, particularly liver cancer. He published many research and review articles and serves as reviewer and as an editorial member of many specialized peer-reviewed journals. He is also a member of many specialized societies and the sole recipient of many scientific awards.
Abstract:
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. The prognosis of patients with HCC is usually poor; hence, a novel approach against HCC is essential for a better therapeutic outcome. Saffron and its active constituents were reported to have antioxidant, anti-inflammatory, and anti-tumor properties. The aim of this study was to investigate chemopreventive action of crocin, one of the promising active constituents of saffron, against diethylnitrosamine (DEN)-induced liver cancer in rats, and the possible mechanisms by which crocin exerts its anti-tumor effects. Findings reported herein demonstrated the anti-proliferative and pro-apoptotic properties of crocin when administrated in DEN-treated rats. Additionally, crocin exhibited anti-inflammatory properties that inhibited NF-kB, among other inflammatory markers. According to our network analysis, NF-kB was identified as a regulatory hub, and therefore, a candidate therapeutic drug target. Taken together, our findings introduces crocin as a potent chemopreventive and therapeutic agent against HCC.
Alvaro Ibarra V
Anatomopatólogo Jefe, Servicio de AnatomÃa Patológica ClÃnica las Condes, USA
Title: Cytological intraoperative study of surgical margins and sentinel nodes in breast pathology
Biography:
Abstract:
The study of surgical margins in breast pathology is very important, because a diagnosis of negativity or positivity permits to make the best surgical procedure, obtaining in the majority of cases an excellent correlation with the results of definitive histopathological report. The intraoperative study of sentinel axillary nodes, in most of the cases, allows resolving in one surgical time, the regional treatment in breast cancer. We will show our experience with cytological study in more than eight hundreds of cases of breast tumors and sentinel axillary nodes, with simple and efficient technics.
Biography:
Abstract:
Accumulation of beta-amyloid (Aß) is an important molecular event in Alzheimer’s disease (AD). It is now well known that vaccination against fibrillar Aß prevents amyloid accumulation and preserves cognitive function in transgenic mouse models. To study the effect of vaccination against generic oligomer epitopes, Aß oligomers, islet amyloid polypeptide (IAPP) oligomers, random peptide oligomer (3A) & Aß fibrils were used to vaccinate Tg2576 and 3xtg mice, which develop a progressive accumulation of plaques, tangles and cognitive impairment. We vaccinated Tg2576 and 3xTg mice monthly with the above mentioned vaccines and studied various cognitive parameters at 6 months, 10 months and 14 months of age. We tested escape latency, number of platform crosses in the Morris water maze test (MWM) (which are related to hippocampus), novel object recognition (which is related to cortex) and inhibitory avoidance (which is related to amygdala). It was found that all vaccinated mice have a significant improvement in cognitive function compared to controls. In addition to cognitive improvement subcutaneous administration of these antigens markedly reduced total plaque load (Aβ burden) and hyper phosphorylated tau (tau pathology). We conclude that amyloid Aß sequence is not necessary to produce a protective immune response as the random peptide (3A) gives rise to an oligomer specific immune response. The critical epitope is a pathology-specific conformation of the peptide backbone that is independent of the specific amino acid sequence. It is therefore suggested that vaccination against a non-human amyloid oligomer epitope may be an effective strategy for developing a vaccine that does not have the potential for auto-inflammatory immune complications.
Sofoudis Chrisostomos
Breast Unit Metaxa Memorial Hospital, Greece
Title: Juvenile breast cancer. presentation of a rare case
Biography:
Abstract:
Introduction Younger women generally do not consider themselves to be at risk for breast cancer, and in fact, just under 7% of all breast cancer cases occur in women under 40 years old. The incidence is strongly associated with the apprearence of the prognostic factors. Juvenile breast cancer seems to be more aggressive in comparison with other age-related breast cancer types. We present a case of a 23 year old female patient with appearance of multifocal breast cancer successfully diagnosed and treated. Case A 23 year old female patient was admitted to our Department complaining of pain and presence of a palpable mass located at her right breast. The physical examination confirmed this atypical appearance. The breast ultrasound and mammography revealed the presence of multifocality (hypodencic lesions at 10th , 11th hour and near the nipple). Due to the multifocality of the lesion a FNA of these areas was performed. The FNA examination confirmed the malignancy of the lesion. The preoperative staging of the lesion( bone scanning , CT thorax and abdominal CT) did not reveal any signs of metastatic infiltration. The patient underwent total right mastectomy. The sentinel node biopsy was positive for malignancy. After carrying out the mastectomy , a total axillary dissection was followed. (9/45 lymph nodes were infiltrated) The patient was discharged from the hospital in a good clinical condition on the 5pod. Depending on the multidisciplinary decision, the patient is undergoing cycles of chemotherapy, hormonal therapy(ER+ PR+ receptors) and radiotherapy. Discussion Breast cancer is very rare in adolescents and very young women. Invasive breast cancer occurring in women before the age of 35 years has a more aggressive biological behaviour and is associated with a worse prognosis than in older premenopausal women. Breast cancers in these young women are more frequently poorly differentiated, oestrogen-receptor (ER)-negative, have lymphovascular invasion and high proliferating fractions. Breast conserving methods are accompanied with high reccurence rate and should be offered adjuvant therapy. Conclusion Juvenile breast cancer represents a rare entity in comparison with all other age-related types. It is characterized by the aggressive infiltration and the high recurrence rate. Multidisciplinary approach is mandatory in order to establish the ultimate confrontation.
Ivo JURANEK
Slovak Academy of Sciences Institute of Experimental Pharmacology and Toxicology, Slovakia
Title: On good radicals and bad antioxidants: A radical shift in understanding the role of free radicals in cellular damage?
Biography:
Ivo Juranek graduated Russian State Medical University in Moscow, completed his PhD in 1996 from Comenius University in Bratislava, and performed his postdoctoral studies in Tokushima University School of Medicine, Japan, University of Florida School of Medicine – Shands Hospital, Gainesville and Case Western Reserve University School of Medicine, Cleveland, OH, USA. He is the head of the Slovak Academy of Sciences Institute of Experimental Pharmacology and Toxicology Laboratory of Molecular Pharmacology and Biophysics. He has published more than 69 papers in reputed journals with more than 550 citations. In 2014, he was appointed a research professor in pharmacology.
Abstract:
Free (oxygen) radicals, produced in increased concentration during cellular damage, are generally considered as a cause of such damage. This substantiated theory of free-radical diseases when uncontrolled overproduction of reactive oxygen species (ROS), termed oxidative stress, leads to oxidative alteration of integral cellular components and important macromolecules, like lipids, proteins and nucleic acids, which readily results in cellular damage. Subsequently, cells may undergo death, which if occurring in a massive scale is manifested as tissue damage, which in turn often leads to organ dysfunction. That is why, substances with antioxidative properties were supposed to act as efficient agents towards free-radical diseases. However, a number of large-scale clinical trials have demonstrated that administration of exogenous antioxidants failed to be effective, and often led to serious complications. E.g., CARET study, involving 18,000 smokers and beta-carotene, reported significantly higher lung cancer incidence (by ~30%) as well as mortality rate due to lung cancer (by ~20%) in comparison to placebo group. The present paper covers negative findings from several unsuccessful clinical trials and provides a possible explanation of the phenomenon. Undesirable effects of antioxidants are likely due to their unfavorable action onto the fundamental ROS-mediated physiologic processes, such as oxidative phosphorylation, removal of defective and cancer cells, intra- and inter-cellular signaling. Concluding, use of exogenous antioxidants aiming to treat pathologies involving oxidative damage either in therapeutic or preventive/prophylactic mode has to be thoroughly weighed up. Acknowledgement: The paper was partly supported by the Slovak Agency VEGA (2/0149/12)
Biography:
Sahar Samaha, M.D. is board certified in AP/CP and Cytopathology. Has completed her residency and 2 fellowships in surgical pathology and cytopathology at University of Kansas Medical Center. She is in practice for over 15 years. She got her medical degree from Ain Shams University, Cairo, Egypt. Before moving to the united states, she finished her residency and obtained her master’s degree in Ophthalmology. She is the director of Aloha lab at Miraca life sciences.
Abstract:
At Miraca Life Sciences, we receive anorectal pap smears and biopsies from a colorectal clinic dealing primarily with “high risk†populations, mainly HIV positive patients. Our large database includes anorectal pap smears for screening and follw up as well as biopsies collected from the keratinized, non-keratinized portions and transformation zone. Dacron fiber swabs and liquid-based sampling are used. Questions to be answered, What is the natural history of the anorectal dysplasia? What is the difference between the cervical and anorectal pap? Follow up and treatment, is it different from cervical dysplasia? Correlation between anal pap smears and biopsies? Should anal-rectal cytology be a standared of patient care in high risk population and female patients with genital HPV infection?
Miral Patel
University of Pennsylvania, USA
Title: Protein extraction from methanol fixed paraffin embedded tissue blocks: A new possibility using cell blocks
Biography:
Miral was 23 years old when he completed his degree. He has Msc in Biotechnology from University of Pennsylvania. Currently, he is program manager for Biorepository at Children Hospital of Philadelphia. He is involved in many clinical and transitional researches. He said publish several articles mainly on the subject of Biobanking and quality of samples in Biobanks.
Abstract:
The traditional cellblock is an essential cytology preparation, which offers benefits over cytological smears by preservation of cell architecture and the performance of immunohistochemical studies. In the current era of minimally invasive techniques for obtaining tissue samples for diagnostic and prognostic markers, cellblocks containing “limited material†specimens are routinely used to provide the valuable information about pre-disease and disease processes. The methanol fixed and paraffin embedded cellblocks are prepared manually with minimal automation with their quality highly dependent upon the experience of the cytopreparation personnel. Currently, Cellient® automated cell block system is widely used for MFPE cellblock preparation to ensure consistent quality preparation by minimizing the operator dependency. Despite advances in technology, the relatively small size of the cytology scrapings MFPE cell blocks in comparison to the formalin fixed and paraffin embedded counterparts have caused them to be often overlooked in biomarker discovery. Recently, in the field of proteomics, there is an emphasis on utilizing limited tissue samples such as core biopsies and cellblocks for the evaluation of molecular biomarkers. These have the potential of being eventually converted into novel diagnostic marker assays that will aid in improving the efficacy of clinical intervention, as well as the validation of leads and targets. Proteomic platforms have developed over the past few years due to advances in scientific knowledge and technology with the next technologic leap being the application of proteomic technologies to the bedside. At present, there is a lack of established methods or resources for extracting proteins from MFPE cell blocks.
Marino E. Leon
University of South Florida, USA
Title: Molecular assays in cytopathology for thyroid cancer
Biography:
Dr. Leon is certified by the American Board of Pathology in Anatomic and Clinical Pathology and in the subspecialty of Cytopathology. At the H. Lee Moffitt Cancer Center and Research Institute, Dr. Leon works in the Head and Neck Pathology, and Cytopathology Clinical Services. He has an extensive experience in Fine needle aspiration, especially in Head and Neck and Thoracic tumors. His research interests include translational collaborative research on the development of novel biomarkers for cancer diagnosis and personalized cancer treatment. He is also actively involved in medical education and in pathology residents, oncologic surgical pathology fellows, cytopathology fellows training.
Abstract:
The rapid translation into the clinical field of new discoveries in the molecular basis of thyroid cancer has led to the development of several molecular tests that address the deficiencies of thyroid cytopathology. Despite lack of adequate, validated, independently performed clinical studies, several molecular tests are commercially available on the market and are being used on indeterminate thyroid nodules to guide patient-care decisions. This presentation will discuss and summarize the current evidence on the role and limitations of molecular tests used in combination with thyroid cytopathology to refine the pre-surgical diagnosis of thyroid nodules. The presentation will address the fact that the clinical performance of molecular tests depends on the pretest risk of malignancy within the specific cytological group being assessed. This risk is variable and should be assessed at each institution to optimize the selection of the molecular test and the interpretation of its results. The use of Next-generation sequencing (NGS) will be discussed; NGS has increased the sensitivity of oncogene panels while maintaining high specificity. Tests assessing the gene expression pattern have shown promising results, with high sensitivity but low specificity. The impact of the molecular markers on clinical practice remains in flux and their effect on health care costs remains poorly understood. Further large, independent, confirmatory, clinical validation studies and real-world, cost-effec¬tiveness studies are necessary before the widespread adoption of these tests can be endorsed as standard of care.
K Sujathan
Regional Cancer Centre (RCC-T), India
Title: Computer Aided Screening of Cervical Cancer using Methodologies of Quantitative Cytology
Biography:
Dr.K.Sujathan has completed his PhD at the age of 41 years from Annamalai University and postdoctoral studies from Regional Cancer Centre, Thiruvananthapuram, India. He is currently Associate Professor, Regional Cancer Centre, a premier Cancer treatment and research Institute. He has published 34 papers in reputed journals of Pathology and Cancer Research, some which has been cited in leading text books like Diagnostic Cytology and its histopathologic basis by LG Koss, Obstetrics and Gynecology for post graduates by Arul Kumaresan etc. His outstanding research works have received five national awards and he has been serving as reviewer and editorial board member of repute and PhD guide.
Abstract:
Cervical cancer is the fourth most common cancer among women with an estimated 528,000 new cases every year. Among the different screening methods, cytology based screening using PAP smear remains as the best method for the pre-selection of women with cervical intraepithelial lesions. However, this method pose a challenge in practical implementation as it is resource intensive requiring trained professionals skilled enough to identify a handful of abnormal cells among few hundred thousand cells. This motivates the need for automating the screening methodology. Since the 1960-ies several groups have attempted such automated screening systems leading also to a couple of commercial products. Still these have had limited impact on the screening situation in most of the world. C-DAC(T) together with RCC-T and Uppsala University has developed a semi-automated system which analyses digitized PAP slides prepared using LBC techniques and employs quantitative analysis using image processing and machine learning algorithms to screen out clearly normal smears and direct abnormal smears for human review. A low cost alternative to commercial LBC technique was also identified. The system filters out normal smears without human intervention while referring the suspicious cases for expert’s review. It was evaluated on 1006 smears with a sensitivity of 96% and specificity of 72% for high grade lesions, which is comparable to that of human experts. Since in screening programs, a big majority of cases are within normal limits, the system is able to drastically reduce the workload of Cytologists, thus able to screen a larger population even in low resource settings.
Sunita Arvind Bamanikar
Dr. D. Y. Patil Vidyapeeth, India
Title: Significance of marginal vacuoles in fine needle aspiration cytology of diffuse thyroid swelling
Biography:
Sunita Arvind Bamanikar is a Professor of Pathology at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India. She has obtained her Medical Graduation from Seth G.S. Medical College and KEM Hospital, Mumbai University in 1981. After getting her Doctorate (MD) in Pathology in 1987 from B.J. Medical College & Sassoon General Hospitals, Pune University, she held Faculty Assignments in Medical Colleges in India and abroad with over 12 years at the Sultan Qaboos University, Oman and Universiti Brunei Darussalam. She has published over 30 papers in reputed journals and is currently an Associate Editor for the Journal of Medical Research.
Abstract:
Evaluation of thyroid swelling by Fine Needle Aspiration Cytology (FNAC) is an established first-line diagnostic test. Marginal Vacuoles (MVs) or fire-flare appearance in Fine Needle Aspiration (FNA) smears stained by Leishman’s stain have been described as a distinctive feature of thyrotoxic goiter but was also found in various nontoxic thyroid lesions. Although these MVs have been characterized as dilated endoplasmic reticulum and manifestation of active pinocytosis/vacuoles containing colloid, their exact nature is not so far resolved. The aim of the study was to assess the presence of MVs in diffuse thyroid swelling and evaluate the strength of association between MVs, thyroid hormonal and biochemical tests and cytological diagnosis. Seventy six cases of diffuse thyroid swelling (goiter) were studied. Cytomorphological features were examined with special reference to MVs. Grading for MVs was adopted as grade I (scant), grade II (moderate) and grade III (abundant). The strength of association was studied by applying the Chi-square test and test of proportion; a P≤0.05 was considered significant. Abundant MVs were not associated with hypothyroidism in this study; 71% of these cases were hyperthyroid. Further, abundant MVs in thyroid FNACs were seen in cases of primary hyperplasia and Hashimoto's thyroiditis and Grave’s disease. There was a significant correlation between the presence of abundant/moderate MVs and primary hyperplasia and their absence in colloid goiter. Scant MVs in diffuse goiters were not found to correlate with thyroid function. Thus, all diffuse goiters with prominent MVs warrant hormonal evaluation to rule out hyper functioning goiter.
Natália Coelho Couto de Azevedo Fernandes
Adolfo Lutz Institute, Brazil
Title: Performance of liquid based cytology for the diagnosis of canine lymphoma
Biography:
Natália Fernandes is a scientific researcher at Adolfo Lutz Institute, one of the main Institutions for Public Health Surveillance in Brazil. She is Doctor of Veterinary Medicine, graduated at School of Veterinary Medicine and Animal Sciences of the University of São Paulo (USP) in 2008, where also concluded specialization in pathology. She is interested in new methods for cytopathology diagnostic, mainly liquid based cytology for comparative pathology. She is finishing her Master of Science degree at the Faculty of Medicine – USP with a project on standardization of liquid based cytology for lymphoma diagnosis and other applications in Veterinary Medicine.
Abstract:
Liquid-based Cytology (LBC) consists of immediate ï¬xation of cells in suspension with automated slide preparation. In this study, LBC with cell block (CB) immunocytochemistry was used to evaluate lymph node aspirates and results were compared with conventional cytology. The inter-rater reliability, unsatisfactory rate and accuracy between conventional cytology and LBC were assessed. Samples of enlarged lymph nodes were collected from 54 dogs through fine needle aspiration and ï¬xed in preservative for LBC, CB and immunophenotyping. Two CB techniques were tested: ï¬xed sediment method (FSM) with Bouin’s solution and agar method (AM). The morphology of the cells was blindly evaluated by 2 pathologists. Immunocytochemistry was performed with: Anti-CD79a, anti-Pax5, anti-CD3 and anti-Ki67. For inter-rater reliability, two veterinary pathologists classified the samples as POSITIVE, NEGATIVE or unsatisfactory for canine lymphoma, in a double-blind experiment. Results: of the 30 dogs, 80% had B cell lymphoma and 20%, T cell lymphoma. Considering conventional cytology, LBC smears showed better nuclear and nucleolar deï¬nition, but smaller cell size and worse cytoplasmic deï¬nition. FSM showed consistent cellular groups and were employed for immunocytochemistry, whereas AM presented sparse groups of lymphocytes that had been difficult to analyze. Anti-Pax-5 allowed identification of B cells. LBC inter-rater reliability was good (k=0.762). LBC with CB immunocytochemistry presented an accuracy of 89.47% compared to 68.42% from conventional cytology. Moreover, the unsatisfactory rate was reduced from 11.76% (conventional) to 3.71% (LBC + CB Immunocytochemistry). LBC and FSM, together, may be promising tools to improve canine lymphoma diagnosis through ï¬ne-needle aspiration.
- Track 1: Cancer Cytopathology
Chair
Sin Hang Lee
Milford Molecular Diagnostics, USA
Co-Chair
Sahar Samaha
Miraca Life Sciences, USA
Session Introduction
Merce Jorda
University of Miami Miller School of Medicine,USA
Title: Cytologic sub-classification of lung cancer; use of immunocytochemical and molecular techniques
Biography:
Merce Jorda, M.D. is board certified in American Board of Pathology-Cytopathology. Has completed her fellowship from Jackson Memorial Hospital in Affiliation with the University Of Miami School Of Medicine. Prof. Jorda is the Medical Director, Clinical Laboratory Services -UMHC/SCCC and UM Hospital. Dr. Jorda’s research interests include molecular pathology of cancer and immunocytochemistry of tumors. She is interested in all markers, immunohistochemical and molecular, which may give the diagnostic, prognostic, predictive and treatment information. Dr. Jorda’s research interests have been basically at the level of anatomic pathology and cytopathology, specifically in the areas of breast and genitourinary tract malignancies as well as cytopathology.
Abstract:
Lung carcinoma sub-classification into small-cell and non-small-cell carcinomas has important implications for clinical management and prognosis of the disease. With the introduction of target therapy and its associated significant therapeutic implications for patients with advanced stage lung cancer, the subclassification of non-small cell carcinomas into adenocarcinomas and squamous cell carcinomas has also become an important task for practicing pathologists. Moreover in recent years, cytologic samples including fine needle aspiration, bronchoscopic brushings and washings, and bronchoalveolar lavages have been increasingly used to establish the diagnosis of lung cancer and subclassification of these tumors. Based on cytomorphology alone, distinction between nonkeratinizing squamous cell carcinomas and poorly differentiated adenocarcinomas can be difficult . Moreover, in some clinical settings the differential diagnosis may include primary versus metastatic carcinomas or adenocarcinoma vs. malignant mesothelioma. Cytologic features of these tumors can overlap, and a variety of factors can distort the cytomorphology of the tumor cells. In addition, the cytologic material may be limited in quantity and present only in direct smears or cytospin slides. Therefore, the availability of a reliable ancillary technique such as immunocytochemistry applicable to such cytologic preparations is desirable. Molecular techniques used as prognostic and predictor markers will be discussed with emphasis to their application in cytologic material. Following the session, participants will be able to 1- Formulate a differential diagnosis based on routinely prepared cytologic slides, based on clinical, imaging and cytologic findings; 2- Learn how to identify and mark diagnostic cells properly for further application of immunocytochemistry, select a limited panel of antibodies based on available clinical and cytomorphologic imformation and to interpret immunostain results, being aware of diagnostic pitfall; 3- To apply molecular testing in primary lung carcinomas using cytologic material; 4- differentiate lung primary carcinomas from those of metastatic origin, accurately diagnose small cell carcinomas of lung and sub-classify non-small cell carcinomas into those with squamous differentiation and distinguish between malignant mesothelioma and lung adenocarcinoma.
Wilfrido D. Mojica
State University of New York at Buffalo, USA
Title: Core washing of needle biopsy specimens with microfluidics: a novel approach to meet the increasing demands of ancillary testing on small specimens
Biography:
Wilfrido Mojica MD is a Surgical Pathologist and Assistant Clinical Professor with the Department of Pathology at the University of Buffalo. He completed his MD degree from the St. Louis University School of Medicine and is trained and board certified in both Anatomic and Clinical Pathology. He is the Director of the Immunohistochemistry Laboratory within the Kaleida Health Laboratory. He has published over 25 peer reviewed manuscripts related to translational research and pathologic biospecimens.
Abstract:
An emerging problem pathologists are encountering is the receipt of vanishingly small core biopsy specimens and the increasing demands for molecular testing on them. Current tissue management requires traditional processing approaches to arrive at a point where a diagnosis can be made on morphologic grounds. However, even with judicious planning, examination of hematoxylin with eosin and immunohistochemically stained sections can lead to the depletion of these very small pieces of tissue, leaving nothing left over for molecular analysis. We have recently discovered that exfoliated cells can be recovered from core needle biopsies prior to their routine processing to create formalin fixed, paraffin embedded specimens. A wash step recovers cells which we believe are dislodged by the trauma associated with the mechanical procedure of performing this type of biopsy. Management of these cells using a microfluidic platform presents a novel paradigm capable of extending the diagnostic utility of the core needle biopsy, allowing for recovery of high molecular weight DNA, proteins and the possibility of other cellular constituents. Cytopathologic evaluation of these cells is integral to the success of this platform. A prototype working model is introduced with a discussion of the attributes this approach delivers relative to conventional pathologic specimen processing.
Qing Kay Li
The Johns Hopkins University School of Medicine, USA
Title: Improvement of cellular yield in the cell block preparation by using so-called ‘Blood Clot’ technique in Trans bronchial Needle Aspiration (TBNA) biopsy of lung cancers
Biography:
Li is an internationally recognized expert in the field of cytopathology and co-PI in Johns Hopkins Biomarker Discovery Center. She provides diagnostic service at Johns Hopkins, and conducts research in the field of novel biomarkers in lung and prostate cancers. Her research has been presented at many national/international meetings. Dr. Li also serves as editorial board members for several journals, committee member of the American Society of Cytopathology, and study sections of government agents and private organizations. She has more than 70 publications and book chapters. Dr. Li is also the editor of “Diagnostic Cytopathology Board Review and Self-Assessmentâ€.
Abstract:
Currently, the targeted therapy of cancers has changed the diagnostic and therapeutic paradigm of lung cancers from primarily morphological assessment of tumors to molecular analysis of genetic alterations in tumor cells. The molecular analysis requests certain quantity of tumor cells However, the cellularity of the conventional cell block (CB) preparation, particularly in TBNA specimens, is often low and inadequate for molecular study. We routinely apply a novel ‘blood clot’ technique (CB-BC) to improve the cellular yield in the CB preparation during TBNA procedures. By this technique, the cellular material within the aspirate needle is allowed to form a blood clot (CB-BC), and then, the cellular material is fixed in the formalin and processed in the histological laboratory. This technique enable us to improve the cellularity in the CB. We have compared this novel technique with conventional method (CB-NR) in the CB preparation. We have found that 84.6% of lung and 88.8% of lymph node samples have yielded sufficient material for diagnosis, immunohistochemistry studies and molecular analyses. In contrast, the conventional CB-NR method has yielded approximately 50% to 70% of the diagnostic rate. This novel technique improves the cellular yield, and provides material for molecular study without compromising the cytomorphological features of tumor cells.
Biography:
Ahmed El-Habashi has completed his MD, PhD at the age of 40 years from Cairo University and Tulane University in a channel system scholarship program. He got post-doctoral fellowship at Groningen University Hospital, The Netherlands at 1998. He is the past- director of pathology department, National Cancer Institute, Cairo University and now he is working in the capacity of Professor of Pathology. He got the International Board of Cytopathology from International Academy of Cytopathology at 2007. He is an international cytology speaker and he conducted many Cytopathology workshops in Egypt and Arab countries aiming to improve the cytology practice and profession. He has published more than 35 papers in reputed journals and has been serving as a reviewer for more than three reputed Journals.
Abstract:
Cytology is the diagnostic branch of medicine which, based on the microscopic cell examination, to recognise physiological conditions, and to diagnose benign, pre-malignant and malignant processes. It is easy, inexpensive, fast, reliable, and gives material for ancillary testing. Almost all surgeries for lung, pancreas, liver, thyroid, etc. are based on cytology diagnoses. Almost all biopsies of Cervix, bladder, etc. are done based on cytology diagnoses. However, cytology is different and difficult, due to potential subjectivity, heterogeneity and nonuniformity of material. Cytopathology studies diseases on the cellular level while in histopathology; cells are assessed in the spatial context. So cytology has different knowhow and diagnostic approach compared to histopathology. This presentation demonstrate diagnostic approach and general cytomorphology features (patterns, background, cell type, shape, cytoplasmic features,…..ect) in cytology material and potential diagnostic pitfalls and errors. High diagnostic accuracy and avoidance of cytologic pitfalls in cytopathology can be achieved by acquiring a detailed clinico-radiologic data, obtaining adequate specimens, having prior knowledge of the variety of diagnostic entities, strict application of established cytological criteria, and nothing can replace years of experience.
Biography:
Sahar Samaha, M.D. is board certified in AP/CP and Cytopathology. Has completed her residency and 2 fellowships in surgical pathology and cytopathology at University of Kansas Medical Center. She is in practice for over 15 years. She got her medical degree from Ain Shams University, Cairo, Egypt. Before moving to the united states, she finished her residency and obtained her master’s degree in Ophthalmology. She is the director of Aloha lab at Miraca life sciences.
Abstract:
At Miraca Life Sciences, we receive anorectal pap smears and biopsies from a colorectal clinic dealing primarily with “high risk†populations, mainly HIV positive patients. Our large database includes anorectal pap smears for screening and follw up as well as biopsies collected from the keratinized, non-keratinized portions and transformation zone. Dacron fiber swabs and liquid-based sampling are used. Questions to be answered, What is the natural history of the anorectal dysplasia? What is the difference between the cervical and anorectal pap? Follow up and treatment, is it different from cervical dysplasia? Correlation between anal pap smears and biopsies? Should anal-rectal cytology be a standared of patient care in high risk population and female patients with genital HPV infection?
Sin Hang Lee
Milford Molecular Diagnostics, USA
Title: Workshop on Combine Pap smear and HPV genotyping by DNA sequencing in cytopathology practice for optimum patient care
Biography:
Sin Hang Lee has graduated from Wuhan Medical College in China. After a Residency-Fellowship at Cornell-New York Hospital and Memorial Hospital for Cancer, he was certified by the American Board of Pathology and obtained the FRCP (C) degree by examination in 1966. He was on the Faculty of McGill University and Yale University from 1968-2004 while practicing hospital-based pathology. He is currently the Director of Milford Molecular Diagnostics, Milford, Connecticut. In the past 10 years, he has developed Sanger sequencing-based testing methods for HPV, Neisseria gonorrhoeae, Chlamydia trachomatis, Lyme disease borreliae and Ebola virus implementable in community hospitals.
Abstract:
Persistent infection by a high-risk human papillomavirus (HPV) is a necessary factor in the pathologic process which may lead to cervical cancer development. Absence of HPV in the cervico-vaginal cell suspension indicates no risk for cervical cancer and is invariably associated with a normal Pap smear. Since HPV infection precedes any morphologically recognizable “squamous intraepithelial lesionsâ€, commercial HPV assays have been introduced to replace Pap smears as the more sensitive screening test for cancer prevention. However, triage of HPV-16/-18 positive patients to colposcopy without concomitant cytologic evaluation is known to cause excessive unnecessary cervical biopsies because the HPV genotyping may be inaccurate or the HPV infection is transient. On the other hand, some of the commercial test kits may not be sensitive enough for detecting HPV with low copy numbers such as in the small cancer cells with little cytoplasm. This workshop summarizes the author’s experience in developing and using nested PCR detection of HPV followed by Sanger sequencing for accurate genotyping to maximize the sensitivity and specificity of HPV assays and implementation of this technology in a small community hospital. Extended applications of this technology in molecular diagnosis of Neisseria gonorrhoeae, Chlamydia trachomatis, Lyme disease borreliae, Ebola virus and BRCA1 185delAG mutation have been successful. The overall aim of this workshop is to show how easy it is for cytopathology professionals to play a pivotal role in a DNA sequencing-based diagnostic laboratory to help improve patient care through molecular personalized medicine.
Mousumi Majumder
Schulich School of Medicine and Dentistry, Canada.
Title: Cox-2 elevates oncogenic mir-526b in breast cancer by ep4 activation and this mirna is a promising biomarker for monitoring and personalizing breast cancer therapy
Biography:
Dr. Majumder has completed her PhD in 2009 from Human Genetics Unit of Indian Statistical Institute, Kolkata, India. Soon after she joined as a postdoctoral fellow in the Anatomy and Cell biology Department at the University of Western Ontario, Canada. She published 16 peer-reviewed publications and received several national and international awards as a graduate and postdoctoral fellow. Her expertise is in the field of cancer genetics and epidemiology, cancer stem cell biology and microRNA genetics.
Abstract:
MicroRNAs (miRs) are small regulatory molecules emerging as potential biomarkers in cancer. Previously, it was shown that COX-2 expression promotes breast cancer progression via multiple mechanisms including induction of stem-like cells (SLC), owing to activation of the prostaglandin E2 receptor EP4 (PTGER4). COX-2 over-expression also up-regulated microRNA-526b (miR-526b), in association with aggressive phenotype. We tested functional roles of miR-526b in breast cancer and the mechanistic role of EP4 signaling in miR-526b up-regulation were examined. A positive correlation was noted between miR-526b and COX-2 mRNA expression in breast cancer cell lines. Stable over-expression of miR-526b in poorly metastatic MCF7 and SKBR3 cell lines resulted in increased cellular migration, invasion, EMT phenotype and enhanced tumorsphere formation in vitro and lung colony formation in vivo in immunodeficient mice. Conversely, knockdown of miR-526b in aggressive MCF7-COX-2 and SKBR3-COX-2 cells reduced oncogenic functions and reversed the EMT phenotype, in vitro. Furthermore, it was determined that miR-526b expression is dependent on EP4 receptor activity and downstream PI3K/AKT and cyclic AMP (cAMP) signaling pathways. Additionally inhibition of COX-2, EP4, PI3K/PKA in COX-2 overexpressing cells down-regulated miR-526b and its functions in vitro. Finally, miR-526b expression was significantly higher in breast cancer tissues and associated with reduced patient survival. This study presents novel findings that miRNA 526b is a COX-2 up-regulated, oncogenic miRNA promoting stem-like cells, the expression of which follows EP4 receptor-mediated signaling. miR526b expression correlates with breast cancer patient survival and is a promising biomarker for monitoring and personalizing breast cancer therapy.
Gayane Badalian-Very
Gaia Medical Diagnostics and Intervention (GMDI), USA
Title: Personalized medicine: Diagnostics, companion diagnostics and complications in implementing them into clinical practice
Biography:
Dr Gayane Badalian-Very (MD, PhD) is a leading physician of the world and a Top Doctor. Dr. Badalian-Very has obtained her Medical degree from Semmelweis University and attended Harvard Medical School for a fellowship. During her fellowship training Dr. Badalian-Very and her collaborators at Dana Farber Cancer Institute and Harvard Medical School had a breakthrough when they demonstrated that Langerhans cell histiocytosis -an orphan childhood disease which had an unknown etiology for the past two centuries since the disease was defined by Langerhans- is a neoplasia. Currently the primary research focuses of Dr. Badalian-Very are secondary hepatic tumors, where lack of effective treatment gets manifested in 6-12 months of overall survival of affected individuals. Dr. Badalian-Very is a prominent speaker in international meetings and conferences and she serves as board member in several scientific societies. Dr. Badalian-Very has received several awards and recognitions from International societies such as Histiocytosis Association, Leading Physician of the World, National Association of Distinguished Professionals, Executive of the Year and Who’s Who in America. Gaia Medical Diagnostics and Intervention (GMDI) was Founded by Dr. Badalian-Very where she serves as Chief Executive Officer. GMDI focuses on personalized medicine and companion diagnostics to promote the medicine of future.
Abstract:
Personalized medicine attempts to identify tailored treatment based on the susceptibility profile of each individual. Although this approach has generated much excitement, few personalized-medicine therapies have achieved high levels of clinical adoption. To personalized medicine, one needs robust diagnostics and a clear understanding of disease pathomechanism. We have observed four main obstacles to the advancement of personalized medicine: scientific challenges (a poor understanding of molecular mechanisms or a lack of molecular markers associated with some diseases, for instance), economic challenges (poorly aligned incentives and high cost of new medications), lack of outcome based data (a comprehensive study of cost effectiveness/health benefit of personalized medicine) and operational issues. Although economic challenges remain, the scientific shortcomings and operational issues now seem to be the biggest hurdle. Diagnostics/companion diagnostics is the key to personalized medicine, yet it is hard to identify which tests truly save costs and select effective responders. On the other hand experimental testing leads to fears that although individual tests may not be very expensive, the overall eventual costs could be unjustifiably high. A third concern is the difficulty of enforcing standard protocols to ensure that physicians follow through with appropriate patient care based on test results. Fourth, test information could be misused—particularly in the early stages of investigation and development—which could harm patients and payers. Finally, there is no longitudinal accounting, which would enable payers to capture long-term cost savings from near-term testing. Even if operational issues get resolved within a particular stakeholder group, overcoming the scientific burden and correcting the incentive structure and modifying the relationships between stakeholders could be more complex.
Jacinto da Costa Silva Neto
Federal University of Pernambuco, Brazil
Title: Matrix metalloproteinase and their participation and usefulness as a predictor of progression of cervical lesions
Biography:
Jacinto was 23 years old when he completed his degree. He has an MSc in biophysics, a specialist in cytopathology at the Federal University of Pernambuco and a PhD from the University of São Paulo-USP. Currently: visiting professor at McGill University, Department of Oncology - Faculty of Medicine - Division of Cancer Epidemiology. Activities Federal University of Pernambuco-UFPE/Brazil: professor, coordinator of the cytopathology sector, coordinator of postgraduate cytopathology, professor/Supervisor of the Postgraduate Program in Pathology-POSPAT/UFPE, and professor/Supervisor of the Postgraduate Program in MorphoTechnology/UFPE. Lines of research: cancer (biomarkers and carcinogenesis), and Human Papillomavirus (HPV).
Abstract:
Cervical cancer is the third most common type of cancer among women worldwide. The infection and persistence of human papillomavirus (HPV) is the essential condition for this type of disease. However, only HPV infection is not enough for cervical pathogenesis are necessary cofactors and activation of intracellular and extracellular mechanisms to start and continue the process of progression of cervical lesions, such as the action of matrix metalloproteinase (MMP), one family endopeptidases capable of digesting the extracellular matrix components, basement membrane and induce tumor growth factors, leading to invasion and metastasis. Although much studied little is known about the specific mechanisms of MMPs in cervical lesions and its association with high-risk HPV oncoproteins. MMPs are important both for their role in carcinogenesis, as it constitutes potential markers for detection and analysis of prognostic and predictive of cervical lesions. This is because the initial intraepithelial lesions overexpressing certain MMPs tend to progress to invasion. Obtaining material for analysis of MMPs can be made by cytological brushed at the time of collection of the Pap smear or colposcopy as well as biopsies. Further study of the incidence of the polymorphisms of the MMP genes is also an additional form of predictive analysis in patients with cervical intraepithelial lesions.
Gramatiuk Svitlana
Grigoriev Istitute for Medical Radiology Hospital, Ukraine
Title: Mitochondrial complex as an essential driver of tumor growth and metastasis, potentially common to all breast cancer types
Biography:
Gramatik Svetlana she completed his Phd at the age of 33 years from Grigoriev Institute from the National Academy of Sciences of Ukraine. She has a master\'s degree in infectious diseases. She is the assistant director of Grigoriev Institute for Medical Radiology Hospital, Kharkov, Ukraine. Is the Head Department of Laboratory Diagnostic and Heads of research Projects summary. She has published more than 30 papers in reputed journals and serving as an editorial board member of repute. She has published more than 10 training manuals for students and bachelors.
Abstract:
Despite advances in clinical therapy, metastasis is still the leading cause of death in breast cancer patients. Tumor cells also generate high levels of reduced forms of NAD+, NADH, and NADPH as important cofactors and redox components. Aim our present study the markers of potentially common to all breast cancer types metabolism as an essential driver of tumor growth and metastasis. Materials and Methods. 210 patients breast cancer patients we examined. Among them 147 patients were with metastatic breast cancer (MBC), 63 patients were with non-metastatic breast cancer (NMBC). Serum proteins phosphorescence and the oxidation protein modification were studied by the intensity of serum phosphorescence in 159 patients with breast cancer. Diagnosis was confirmed by clinical and histo-morphological methods. Native fluorescence emission of tissue tryptophan (340 nm), collagen (380 nm), NAD+/NADH (460 nm) and flavins (525 nm). Results and Discussion. Thus, total protein was increased in 14.8% and 9.3%, in patients NMBC and MBC. Research has found disorders of protein and fat metabolism in patients with breast cancer at which it should be considered that catabolic processes predominate over anabolic. Serum phosphorescence intensity in patients at activation with monochromatic light of 290 nm wavelength raised up by 1.2 and 1.93 times accordingly in NMBC and metastatic breast cancer in comparison with a group of conditionally healthy people. At activation with wavelength of 400 nm serum phosphorescence in patients increased by 3.5 times, at 380 nm by 3.1 times in comparison with a group of conditionally healthy people.
Noeme Sousa Rocha
Universidade Estadual Paulista Júlio de Mesquita Filho, Brazil
Title: Sensibility cell block (FNA) for detection of CK5, ER and PR in spontaneous mammary carcinoma in female dogs
Biography:
Abstract:
Breast carcinomas in a dog is a malignant disease relatively frequent in bitches of 10 years old displays important morbidity and evolve to death. The cell block for the diagnosis of injury in women is the method of choice in the investigation, because it provides subsidies to provide for response to therapy. However, for the dog is unknown the application of this technique, therefore, this study aimed to correlate the morphological patterns of canine mammary tumors between cell block technique and surgical specimen and compare the immunohistochemical marking of ER, PR and CK5 between the two methods in 23 animals. After the diagnosis of breast carcinoma made by cytological exam the animal was submitted to mastectomy, FNA for cell block was made in the surgical specimen. The cell block and surgical specimens were submitted to histological processing, preparation of slides for HE and subsequent immunohistochemistry (IQ) for estrogen receptor α (ER) and cytokeratin 5 (CK5). Were considered positive for ER and CK5 the cases where there was marking on more than 10% of neoplastic cells. The level of agreement between the cell block and the surgical specimen was 86.9% for CK5 and 82.6% for the RE. Finally, the procedure that has been established for the woman when applied in dog kept the same benefits, such as affordable method, time and limited financial resources, sensitivity and specificity expressive. Therefore it validates the technique for the diagnosis of breast cancer in dogs.
Tamar A Giorgadze
Weill Cornell Medical College, Cornell University, USA
Title: Papillary thyroid carcinoma and its variants: The cytolomorphologic features and histologic correlates
Biography:
Dr. Giorgadze, Associate Professor of Pathology, received her MD and PhD degrees from Tbilisi State Medical University (Georgia). She completed her Anatomic and Clinical Pathology residency at East Tennessee State University, subsequently followed by Surgical Pathology and Cytopathology fellowships at the University of Pennsylvania. Dr. Giorgadze practices Surgical Pathology and Cytopathology and is an expert in Head and Neck Pathology. She has published more than 50 peer-reviewed papers in the major pathology journals. She is an editorial board member of Cytojournal and the journal of Applied Immunohistochemistry and Molecular Morphology, and is a committee member of Papanicolaou Society of Cytopathology.
Abstract:
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Fine needle aspiration (FNA) remains the cost-effective first line diagnostic modality in the evaluation of thyroid lesions. This practical presentation will focus on FNA cytomorphological of PTC variants, with the emphasis on its aggressive subtypes. The subtle cytomorphological differences between the common and aggressive variants of PTC seen in the conventional and liquid-based preparations (LBP) will be analyzed. A case-based approach will be used to discuss the pre-operative diagnosis of more aggressive PTC variants (tall cell, columnar cell, diffuse sclerosing, clear cell, and hobnail). Corresponding ultrasound images, gross and microscopic characteristics of follow-up surgical pathology specimens will be reviewed and correlated. The utility of ancillary studies (immunostains and molecular markers) which facilitate the diagnosis and help to differentiate variants of PTC from other primary thyroid tumors or metastatic malignancies will be addressed. Importance of recognition of aggressive variants of PTC in FNA specimens for the completeness of preoperative planning (total thyroidectomy, possible cervical lymph node dissection, and search for distance metastases) will be demonstrated. By the end of this presentation the participants will be able to recognize the differential cytomorphological criteria of PTC and its variants in the conventional and LBP preparations and effectively integrate clinical data, sonographic features and ancillary tests in the preoperative workup of these lesions.
Grace C. H. Yang
Weill Medical College of Cornell University, USA
Title: Ultrasound-Pathology Correlation of Thyroid Tumors
Biography:
Grace C. H. Yang, MD is Clinical Professor of Pathology and Laboratory Medicine at Weill Medical College of Cornell University. She has published more than 100 papers in reputed journals and serving as an editorial board member of Acta Cytologica and Journal of American Society of Cytopatholgy, and was editorial board member of Cancer Cytopathology until 2013. She published “Thyroid Fine Needle Aspiration†in 2013.
Abstract:
Ultrasound-guided fine needle aspiration (US-FNA) has become a first diagnostic modality and a gold standard for evaluation of thyroid nodules and thyroid has become the most popular site for FNA. Recently, cytopathologists started to show interest in performing US-FNA themselves. In addition to special training in performing FNA under the US-guidance, familiarity with US features of various thyroid lesions is essential. In addition, up to 15% of thyroid FNAs were reported indeterminate. One way to reduce the "indeterminate" rate is to use team approach and to gain the knowledge of thyroid ultrasound by correlating ultrasound with the final cytologic findings with follow-up surgical pathology, including gross pathology and histologic findings of aspirated lesion. Knowing the gross and histopathologic basis of thyroid ultrasound will be tremendously helpful in cytologic interpretation and in minimizing the indeterminate and non-diagnostic rates in thyroid cytology. The presenter has been doing on-site assessment of >100,000 US-FNA of thyroid, and would like to share her collection of ultrasound, Doppler, FNA cytology, gross image of resected tumors, and histology ranging from scanning to high magnifications. Cases selected for this presentation are adenomatoid nodule, follicular adenoma, follicular adenoma with cystic degeneration, angioinvasive follicular carcinoma, follicular variant of papillary carcinoma, encapsulated follicular variant of papillary carcinoma, HÈ•rthle cell adenoma with post-FNA infarction, HÈ•rthle cell carcinoma, classic papillary carcinoma with psammoma bodies, cystic papillary carcinoma, hobnail variant of papillary carcinoma, tall cell variant of papillary carcinoma, and poorly differentiated thyroid carcinoma.
MA El-Barrawy
Alexandria University, Egypt
Title: Comparative immunohistochemical analysis of beclin-1 & mdm-2 in benign & malignant ameloblastomas
Biography:
MA El-Barrawy post doctoral fellow of M.D. Anderson Cancer & Tumor Institute, Texas University (Houston, USA): October 1988-April 1989 and currently teaching and supervising postgraduate Physicians, Pharmacists, Chemists, and Veterinarians enrolled at HIPH, Alex. University, to get their postgraduate degree. Having experience in various investigations of: Microbiology (Bacteriology, Virology and Mycology), Immunology, Clinical Pathology, Histocompatibility, and field surveys .
Abstract:
Ameloblastoma is the most frequently encountered neoplasm arising from the odontogenic epithelium. Beclin 1 protein plays a critical role in autophagy as a tumor suppressor gene. Whereas, the Murine Double Minute 2 (MDM 2) is a cellular proto-oncogene capable, if amplified, of causing tumor-genesis. The expression & prognostic significance of both genes are largely unexplored, yet, in this neoplasia. Therefore, the present investigation aimed to assess their possible biological role in ameloblastomas. Methods: This study was done among 35 studied cases: 29 cases of benign ameloblastomas, and 6 cases of ameloblastic carcinomas. Labeled Streptavidin Biotin (LSAB + Dako) immunohistochemical method, utilizing monoclonal antibodies for Beclin 1 & MDM 2 genes, was used. Results: Most of the benign ameloblastomas showed intense total cell positivity for the Beclin 1, while, the ameloblastic carcinomas revealed mild to negative expression. Inversely, the MDM 2 oncoprotein demonstrated intense brown total cell reactivity in amelobastic carcinoma & loss of the reaction to mild brown stain in benign ameloblastoma. Conclusion: Based from these findings, one could conclude that, MDM 2 could be a specific marker to identify the proliferative activity, tumor aggressiveness & directly proportional with the degree of malignancy. In contrast, the high Beclin 1 expression could be a good indicator of prognosis in ameloblastomas. Hence, an overall comparison, both studied genes may be very promising molecular prognostic biomarkers.
Ahmed El-Habashi
National Cancer Institute, Cairo University, Egypt
Title: Diagnostic Role of Fine-Needle Aspiration Cytology in Management Breast Lesions: Diagnostic Criteria and Pitfalls
Biography:
Prof. DR. Ahmed El-Habashi has completed his MD, PhD at the age of 40 years from Cairo University and Tulane University in a channel system scholarship program. He got post-doctoral fellowship at Groningen University Hospital, The Netherlands at 1998. He is the past- director of pathology department, National Cancer Institute, Cairo University and now he is working in the capacity of Professor of Pathology. He got the International Board of Cytopathology from International Academy of Cytopathology at 2007. He is an international cytology speaker and he conducted many Cytopathology workshops in Egypt and Arab countries aiming to improve the cytology practice and profession. He has published more than 35 papers in reputed journals and has been serving as a reviewer for more than three reputed Journals.
Abstract:
Background: Fine-needle aspiration cytology (FNAC) has proven to be valuable tool in the primary diagnosis and management triage of patients with breast lesions. Objectives: This study aimed at evaluation of diagnostic utility of FNAC in breast lesions with an emphasis on potential cytological pitfalls that might lead to erroneous diagnoses. Methods: The study was carried out on 640 patients presented to breast clinic complaining of breast lumps. FNAC was performed after physical and radiological evaluation. The FNAC results were correlated with the available subsequent histological diagnoses and follow-up as a gold standard. The accuracy was calculated. The author discussed the cytologic pitfalls that may lead to “erroneous†false positive or false negative diagnoses. Results: The cytological diagnoses included unsatisfactory in 45 cases (7%), benign in 495 (78%), suspicious in 40 cases (6%) and malignant in 60 cases (9%). The potential causes of false positive diagnoses were fibroadenoma, Swiss cheese disease, lactating adenoma, Lactational mastitis, pregnancy changes, sclerosing adenosis, fat necrosis, ductectasia and others. The potential causes of false positive diagnoses were lobular carcinoma, mucinous carcinoma, adenoid cystic carcinoma, tubular carcinoma and proliferative changes with carcinoma transformation. The FNAC has achieved 94%, 100%, 100%, 98%, sensitivity, specificity, positive predictive value and negative predictive value, respectively, with an accuracy of 99%. Conclusions: This study confirmed the valuable diagnostic role of FNAC in management triage of patients with breast lumps. The diagnostic accuracy of this procedure can be significantly improved by acquiring a detailed clinico-radiologic data, obtaining an adequate specimen, having prior knowledge of the variety of diagnostic entities and strict application of established cytological criteria.
Sofoudis Chrisostomos
Breast Unit Metaxa Memorial Hospital, Greece
Title: Juvenile breast cancer. presentation of a rare case
Biography:
Abstract:
Introduction Younger women generally do not consider themselves to be at risk for breast cancer, and in fact, just under 7% of all breast cancer cases occur in women under 40 years old. The incidence is strongly associated with the apprearence of the prognostic factors. Juvenile breast cancer seems to be more aggressive in comparison with other age-related breast cancer types. We present a case of a 23 year old female patient with appearance of multifocal breast cancer successfully diagnosed and treated. Case A 23 year old female patient was admitted to our Department complaining of pain and presence of a palpable mass located at her right breast. The physical examination confirmed this atypical appearance. The breast ultrasound and mammography revealed the presence of multifocality (hypodencic lesions at 10th , 11th hour and near the nipple). Due to the multifocality of the lesion a FNA of these areas was performed. The FNA examination confirmed the malignancy of the lesion. The preoperative staging of the lesion( bone scanning , CT thorax and abdominal CT) did not reveal any signs of metastatic infiltration. The patient underwent total right mastectomy. The sentinel node biopsy was positive for malignancy. After carrying out the mastectomy , a total axillary dissection was followed. (9/45 lymph nodes were infiltrated) The patient was discharged from the hospital in a good clinical condition on the 5pod. Depending on the multidisciplinary decision, the patient is undergoing cycles of chemotherapy, hormonal therapy(ER+ PR+ receptors) and radiotherapy. Discussion Breast cancer is very rare in adolescents and very young women. Invasive breast cancer occurring in women before the age of 35 years has a more aggressive biological behaviour and is associated with a worse prognosis than in older premenopausal women. Breast cancers in these young women are more frequently poorly differentiated, oestrogen-receptor (ER)-negative, have lymphovascular invasion and high proliferating fractions. Breast conserving methods are accompanied with high reccurence rate and should be offered adjuvant therapy. Conclusion Juvenile breast cancer represents a rare entity in comparison with all other age-related types. It is characterized by the aggressive infiltration and the high recurrence rate. Multidisciplinary approach is mandatory in order to establish the ultimate confrontation.
- Track 2: General cytopathology
Track 4: Surgical Cytopathology
Track 6: Cytopathology In Laboratory Medicine Technology
Track 8: Advanced Cytopathology
Chair
Yao-Shan Fan
University of Miami Miller School of Medicine,USA
Co-Chair
Qing Kay Li
The Johns Hopkins University School of Medicine, USA
Session Introduction
Qing Kay Li
Johns Hopkins Medical Institutions, USA
Title: Value of Cytopathology in the diagnosis of respiratory diseases
Biography:
Dr. Li is an internationally recognized expert in the field of cytopathology and co-PI in Johns Hopkins Biomarker Discovery Center. She provides diagnostic service at Johns Hopkins, and conducts research in the field of novel biomarkers in lung and prostate cancers. Her research has been presented at many national/international meetings. Dr. Li also serves as editorial board members for several journals, committee member of the American Society of Cytopathology, and study sections of government agents and private organizations. She has more than 70 publications and book chapters. Dr. Li is also the editor of “Diagnostic Cytopathology Board Review and Self-Assessmentâ€.
Abstract:
Although the cytology (cytopathology) was first used as a diagnostic tool in the lung disease in early 1900s, it is not until the 1960s that pulmonary cytology becomes a diagnostic discipline. Since then, tremendous improvements have been made due to the innovation of sample collection and preparation techniques. The commonly used respiratory specimens in clinical diagnosis include: sputum, bronchial brushing and washing, bronchoalveolar lavage (BAL), transbronchial fine needle aspiration (TBNA), endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA), and transthoracic CT- or ultrasound-guided fine needle aspiration (FNA). The familiarity of cytomorphological features of respiratory cells, and current techniques of obtaining samples are crucial to make an accurate diagnosis. Similar to other type of non-gynecologic cytological specimens, the diagnoses of respiratory diseases are typically made based on the cytomorphological evaluation of respiratory cells. In addition, an explanation note of the diagnosis is often used in the report at our institution to report immunohistochemical and molecular results, and also provide suggestions to our clinical colleagues if necessary. In this presentation, we will discuss the cytomorphological findings of both benign and malignant respiratory diseases, and the differential diagnosis of lung cancers.
Noeme Sousa Rocha
Sao Paulo State University. Brazil
Title: Sensibility cell block (FNA) for detection of CK5, ER and PR in spontaneous mammary carcinoma in female dogs
Biography:
Noeme Sousa Rocha is graduated in Veterinary Medicine from the State University of Maranhão (1989), Masters in Pathology from the Sao Paulo State University (1994) and PhD in Pathology from the Sao Paulo State University (1998). It is currently - Journal of Animal Science Faculty, Veterinary Medicine and Agronomy (Uruguaiana) and associate professor of Sao Paulo State University. Has experience in the area of veterinary medicine, with emphasis on Animal Pathology Anatomy, acting on the following topics: veterinary, cytopathology, pathology, cancer and istopathology. Associate member of the International Academy of Pathology.
Abstract:
Breast carcinomas in a dog is a malignant disease relatively frequent in bitches of 10 years old displays important morbidity and evolve to death. The cell block for the diagnosis of injury in women is the method of choice in the investigation, because it provides subsidies to provide for response to therapy. However, for the dog is unknown the application of this technique, therefore, this study aimed to correlate the morphological patterns of canine mammary tumors between cell block technique and surgical specimen and compare the immunohistochemical marking of ER, PR and CK5 between the two methods in 23 animals. After the diagnosis of breast carcinoma made by cytological exam the animal was submitted to mastectomy, FNA for cell block was made in the surgical specimen. The cell block and surgical specimens were submitted to histological processing, preparation of slides for HE and subsequent immunohistochemistry (IQ) for estrogen receptor α (ER) and cytokeratin 5 (CK5). Were considered positive for ER and CK5 the cases where there was marking on more than 10% of neoplastic cells. The level of agreement between the cell block and the surgical specimen was 86.9% for CK5 and 82.6% for the RE. Finally, the procedure that has been established for the woman when applied in dog kept the same benefits, such as affordable method, time and limited financial resources, sensitivity and specificity expressive. Therefore it validates the technique for the diagnosis of breast cancer in dogs.
K Sujathan
Regional Cancer Centre (RCC-T), India
Title: Computer aided screening of cervical cancer using methodologies of quantitative Cytology
Biography:
Dr.K.Sujathan has completed his PhD at the age of 41 years from Annamalai University and postdoctoral studies from Regional Cancer Centre, Thiruvananthapuram, India. He is currently Associate Professor, Regional Cancer Centre, a premier Cancer treatment and research Institute. He has published 34 papers in reputed journals of Pathology and Cancer Research, some which has been cited in leading text books like Diagnostic Cytology and its histopathologic basis by LG Koss, Obstetrics and Gynecology for post graduates by Arul Kumaresan etc. His outstanding research works have received five national awards and he has been serving as reviewer and editorial board member of repute and PhD guide.
Abstract:
Cervical cancer is the fourth most common cancer among women with an estimated 528,000 new cases every year. Among the different screening methods, cytology based screening using PAP smear remains as the best method for the pre-selection of women with cervical intraepithelial lesions. However, this method pose a challenge in practical implementation as it is resource intensive requiring trained professionals skilled enough to identify a handful of abnormal cells among few hundred thousand cells. This motivates the need for automating the screening methodology. Since the 1960-ies several groups have attempted such automated screening systems leading also to a couple of commercial products. Still these have had limited impact on the screening situation in most of the world. C-DAC(T) together with RCC-T and Uppsala University has developed a semi-automated system which analyses digitized PAP slides prepared using LBC techniques and employs quantitative analysis using image processing and machine learning algorithms to screen out clearly normal smears and direct abnormal smears for human review. A low cost alternative to commercial LBC technique was also identified. The system filters out normal smears without human intervention while referring the suspicious cases for expert’s review. It was evaluated on 1006 smears with a sensitivity of 96% and specificity of 72% for high grade lesions, which is comparable to that of human experts. Since in screening programs, a big majority of cases are within normal limits, the system is able to drastically reduce the workload of Cytologists, thus able to screen a larger population even in low resource settings.
Ahmed El-Habashi
NCI, Cairo University, Egypt
Title: Thyroid lesions fine needle aspiration Cytology: Comprehensive cytomorphology and update reporting
Biography:
Prof. DR. Ahmed El-Habashi has completed his MD, PhD at the age of 40 years from Cairo University and Tulane University in a channel system scholarship program. He got post-doctoral fellowship at Groningen University Hospital, The Netherlands at 1998. He is the past- director of pathology department, National Cancer Institute, Cairo University and now he is working in the capacity of Professor of Pathology. He got the International Board of Cytopathology from International Academy of Cytopathology at 2007. He is an international cytology speaker and he conducted many Cytopathology workshops in Egypt and Arab countries aiming to improve the cytology practice and profession. He has published more than 35 papers in reputed journals and has been serving as a reviewer for more than three reputed Journals.
Abstract:
FNAC is recommended as a routine prime investigation in the work-up of the solitary cold thyroid nodule. Requirements for accurate diagnosis are adequate material, optimal smearing, proper staining and experience. The accuracy of FNAC in thyroid lesions is over 90%, with sensitivity of malignancy diagnosis almost 100%, false negative is about 10% and false positive is 1-3%. The author in this workshop will demonstrate cytomorphologic features of majority of diagnostic entities in thyroid lesions FNA together with an emphasis on potential diagnostic pitfalls. The updated Bethesda System (TBS) for thyroid lesions FNA cytology will be discussed with its clinical significance and management guidelines. The end of the talk will include case presentations to ensure that the audience will achieve the basic ILOs objectives of the workshop.
Biography:
Dr. Lazar obtained his MD (1989) with high honors at The University of Timisoara (Romania). He became a Specialist in Medical Clinical Biology and obtained his PhD in Molecular Biology (1997) with highest honors and the Prize of the University at The University René Descartes in Paris. Dr. Lazar is specialized in clinical biology, molecular biology, and molecular pathology, and has postgraduate degrees in biotechnology and project management. He is the author of six patents, and has authored / co-authored over 100 publications. Dr. Lazar initiated the WIN Consortium and serves as its Chief Operating Officer
Abstract:
Background: Combining three targeted therapies significantly improved outcomes in AIDS. A similar strategy could theoretically benefit patients with metastatic NSCLC, but a scientific method for rational selection of drug combinations is needed. Methods: We assessed genomics and the transcriptome (including miRNA), utilizing defined subsets of relevant genes/gene products, and scored information about the relationships between targeted drugs and genes, based in part on the biological hallmarks of cancer. Interventional points (genes/group of genes) that, when activated, could be blocked by a customized therapy combination, were identified. The underlying algorithm integrates and weighs the genomic (DNA sequencing) and transcriptomic data (mRNA and miRNA differential expression between tumor and normal -bronchial mucosa - tissues). Results: Key genes (N = 183) grouped in 24 interventional points forming the Simplified Interventional Mapping System (SIMS) were elucidated. Frequency and trends of coactivation derived from 121 NSCLC patients defined a list of candidate triple therapy combinations. The focus, in order to limit toxicity, was on the application of two small molecules (TKI) and an immune-modulator (anti-PD1L). Twenty-eight percent of NSCLC patients displayed the simultaneous activation of PD1L, Ras/Raf and mTor/PI3K interventional points. Overall, fifty two percent of NSCLC patients could be targeted by a triple combination that includes an anti-PD1L agent. Most individuals could benefit from two or even more triple combinations to overcome resistance. Conclusions: The SIMS’s strategy enables conversion of thousands of genomic and transcriptomic measurements into a simple and actionable result (a 1 to 10 score) that may be usable by physicians to select triple drug therapy. Comparing tumor and normal tissue biopsies has proven feasible in the ongoing WINTHER trial (NCT01856296). This novel strategy may allow deployment of personalized tri-targeted therapies that will be prospectively tested in a clinical trial with the objective to significantly impact survival in advanced NSCLC and other malignancies.
Sunita Arvind Bamanikar
Dr. D. Y. Patil Vidyapeeth, India
Title: Significance of marginal vacuoles in fine needle aspiration cytology of diffuse thyroid swelling
Biography:
Sunita Arvind Bamanikar is a Professor of Pathology at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India. She has obtained her Medical Graduation from Seth G.S. Medical College and KEM Hospital, Mumbai University in 1981. After getting her Doctorate (MD) in Pathology in 1987 from B.J. Medical College & Sassoon General Hospitals, Pune University, she held Faculty Assignments in Medical Colleges in India and abroad with over 12 years at the Sultan Qaboos University, Oman and Universiti Brunei Darussalam. She has published over 30 papers in reputed journals and is currently an Associate Editor for the Journal of Medical Research.
Abstract:
Evaluation of thyroid swelling by Fine Needle Aspiration Cytology (FNAC) is an established first-line diagnostic test. Marginal Vacuoles (MVs) or fire-flare appearance in Fine Needle Aspiration (FNA) smears stained by Leishman’s stain have been described as a distinctive feature of thyrotoxic goiter but was also found in various nontoxic thyroid lesions. Although these MVs have been characterized as dilated endoplasmic reticulum and manifestation of active pinocytosis/vacuoles containing colloid, their exact nature is not so far resolved. The aim of the study was to assess the presence of MVs in diffuse thyroid swelling and evaluate the strength of association between MVs, thyroid hormonal and biochemical tests and cytological diagnosis. Seventy six cases of diffuse thyroid swelling (goiter) were studied. Cytomorphological features were examined with special reference to MVs. Grading for MVs was adopted as grade I (scant), grade II (moderate) and grade III (abundant). The strength of association was studied by applying the Chi-square test and test of proportion; a P≤0.05 was considered significant. Abundant MVs were not associated with hypothyroidism in this study; 71% of these cases were hyperthyroid. Further, abundant MVs in thyroid FNACs were seen in cases of primary hyperplasia and Hashimoto\\\'s thyroiditis and Grave’s disease. There was a significant correlation between the presence of abundant/moderate MVs and primary hyperplasia and their absence in colloid goiter. Scant MVs in diffuse goiters were not found to correlate with thyroid function. Thus, all diffuse goiters with prominent MVs warrant hormonal evaluation to rule out hyper functioning goiter.
Resende, L.S.A
HRAN – Regional Hospital, Brazil
Title: Brazilian national screening program of cervical cancer: Critical analysis
Biography:
Leandro Resende has completed his Masters’s degree at the age of 32 years from State University of Campinas – UNICAMP, Campinas, SP, Brazil. He is currently responsible for colposcopy service HRAN (Regional Hospital) in Brasilia DF. Participates in the Unicamp research group, with Prof. PhD. Sophie Derchain
Abstract:
Introduction: Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide in Brazil, 17,540 women were diagnosed in 2012. Screening of precursor lesions of cervical cancer is done through the annual collection of cytology (Pap smear test) in women aged 25-64 and sexually active. Objective: Demonstrate poor adherence of the target population for screening for precursor lesions of cervical cancer in Brazil due to the current program adopted by the national health agency. Exhibit the prevalence of precursor lesions of cervical cancer in Brazil. Methods: All information was obtained by consulting the INCA (National Institute of Cancer) database and Federal District Health Department. Non-parametric tests were performed.Chi-squares (and Fisher’s Exact test where appropriate) were used to compare the prevalence of cytological abnormalities. Results: 27% of eligible women participated in the screening program in 2013-2014 and less than 1% were referred for colposcopy. The frequencies of cytological abnormalities were ASC-H (0.41%); AGC-HSIL (0.09%); HSIL (0.56%); invasive carcinoma (0.04%); adenocarcinoma in situ (0.03%) and invasive adenocarcinoma (0.01%). Discussion: The current screeningof precursor lesions of cervical cancer adopted in Brazil is not organized and has low catch-up program adherence. Women aged 25-64 are first attended for a primary screening and referred to a trained colposcopist if abnormal cytological result detected. Women's target population in Brasilia as the capital of Brazil is nearly 900,000 individuals. However, in the current program, few women have cytology collected annually and has a minority colposcopic assessment if necessary.
MA El-Barrawy
Alexandria University, Egypt
Title: Comparative immunohistochemical analysis of beclin-1 & mdm-2 in benign & malignant ameloblastomas
Biography:
MA El-Barrawy post doctoral fellow of M.D. Anderson Cancer & Tumor Institute, Texas University (Houston, USA): October 1988-April 1989 and currently teaching and supervising postgraduate Physicians, Pharmacists, Chemists, and Veterinarians enrolled at HIPH, Alex. University, to get their postgraduate degree. Having experience in various investigations of: Microbiology (Bacteriology, Virology and Mycology), Immunology, Clinical Pathology, Histocompatibility, and field surveys .
Abstract:
Ameloblastoma is the most frequently encountered neoplasm arising from the odontogenic epithelium. Beclin 1 protein plays a critical role in autophagy as a tumor suppressor gene. Whereas, the Murine Double Minute 2 (MDM 2) is a cellular proto-oncogene capable, if amplified, of causing tumor-genesis. The expression & prognostic significance of both genes are largely unexplored, yet, in this neoplasia. Therefore, the present investigation aimed to assess their possible biological role in ameloblastomas. Methods: This study was done among 35 studied cases: 29 cases of benign ameloblastomas, and 6 cases of ameloblastic carcinomas. Labeled Streptavidin Biotin (LSAB + Dako) immunohistochemical method, utilizing monoclonal antibodies for Beclin 1 & MDM 2 genes, was used. Results: Most of the benign ameloblastomas showed intense total cell positivity for the Beclin 1, while, the ameloblastic carcinomas revealed mild to negative expression. Inversely, the MDM 2 oncoprotein demonstrated intense brown total cell reactivity in amelobastic carcinoma & loss of the reaction to mild brown stain in benign ameloblastoma. Conclusion: Based from these findings, one could conclude that, MDM 2 could be a specific marker to identify the proliferative activity, tumor aggressiveness & directly proportional with the degree of malignancy. In contrast, the high Beclin 1 expression could be a good indicator of prognosis in ameloblastomas. Hence, an overall comparison, both studied genes may be very promising molecular prognostic biomarkers.
Marino E. Leon
University of South Florida, USA
Title: Molecular assays in cytopathology for thyroid cancer
Biography:
Dr. Leon is certified by the American Board of Pathology in Anatomic and Clinical Pathology and in the subspecialty of Cytopathology. At the H. Lee Moffitt Cancer Center and Research Institute, Dr. Leon works in the Head and Neck Pathology, and Cytopathology Clinical Services. He has an extensive experience in Fine needle aspiration, especially in Head and Neck and Thoracic tumors. His research interests include translational collaborative research on the development of novel biomarkers for cancer diagnosis and personalized cancer treatment. He is also actively involved in medical education and in pathology residents, oncologic surgical pathology fellows, cytopathology fellows training.
Abstract:
The rapid translation into the clinical field of new discoveries in the molecular basis of thyroid cancer has led to the development of several molecular tests that address the deficiencies of thyroid cytopathology. Despite lack of adequate, validated, independently performed clinical studies, several molecular tests are commercially available on the market and are being used on indeterminate thyroid nodules to guide patient-care decisions. This presentation will discuss and summarize the current evidence on the role and limitations of molecular tests used in combination with thyroid cytopathology to refine the pre-surgical diagnosis of thyroid nodules. The presentation will address the fact that the clinical performance of molecular tests depends on the pretest risk of malignancy within the specific cytological group being assessed. This risk is variable and should be assessed at each institution to optimize the selection of the molecular test and the interpretation of its results. The use of Next-generation sequencing (NGS) will be discussed; NGS has increased the sensitivity of oncogene panels while maintaining high specificity. Tests assessing the gene expression pattern have shown promising results, with high sensitivity but low specificity. The impact of the molecular markers on clinical practice remains in flux and their effect on health care costs remains poorly understood. Further large, independent, confirmatory, clinical validation studies and real-world, cost-effec¬tiveness studies are necessary before the widespread adoption of these tests can be endorsed as standard of care.
Matthew T. Olson
The Johns Hopkins University School of Medicine, USA
Title: The Paris system for reporting urinary cytology: Diagnostic paradigm shift, current topics, and the potential for molecular testing
Biography:
Matthew T. Olson, M.D. completed his medical education at The George Washington University, his Anatomic and Clinical Residency and his cytopathology fellowship at Johns Hopkins University where he is now faculty. He has published more than 40 peer reviewed original research papers mainly on the subject of diagnostic cytopathology and currently serves as a member of the steering committee TPS, chair of the adequacy subcommittee, and member of the ancillary studies subcommittee in addition other committees and ad hoc reviewer roles in a number of prominent journals.
Abstract:
Urinary cytology has long been used as a first-step in the evaluation of a patient with a clinical suspicion for urothelial carcinoma (UC) as well as for surveillance of patients who have a known history of UC. Urinary cytology is most sensitive and specific in the diagnosis of high-grade carcinoma, which is also the tumor that is most likely to invade, metastasize, and cause mortality and morbidity for the patient. As such, the Paris System (TPS) for Reporting Cytopathology, which is an international consensus system developed with the backing of the International Academy of Cytology (IAC) and the American Society of Cytopathology (ASC), focuses on standardizing the reporting template worldwide and optimizing it for the detection of high grade UC. As such, TPS represents a major paradigm shift both because it is the first time urinary cytological reports are poised to have international uniformity and because it clearly outlines the appropriate place for how urinary cytology should be used and interpreted. This level of standardization should enable the deployment of molecular and other ancillary testing to targeted clinical problems in a manner that is most conducive to guiding patient care in a clinically relevant and cost-effective manner. Several strategies, including the existing technologies as well as a new gene expression classifier that is in development, will be discussed specifically in the context of TPS.
Biography:
Sahar Samaha, M.D. is board certified in AP/CP and Cytopathology. Has completed her residency and 2 fellowships in surgical pathology and cytopathology at University of Kansas Medical Center. She is in practice for over 15 years. She got her medical degree from Ain Shams University, Cairo, Egypt. Before moving to the united states, she finished her residency and obtained her master’s degree in Ophthalmology. She is the director of Aloha lab at Miraca life sciences.
Abstract:
At Miraca Life Sciences, we receive anorectal pap smears and biopsies from a colorectal clinic dealing primarily with “high risk†populations, mainly HIV positive patients. Our large database includes anorectal pap smears for screening and follw up as well as biopsies collected from the keratinized, non-keratinized portions and transformation zone. Dacron fiber swabs and liquid-based sampling are used. Questions to be answered, What is the natural history of the anorectal dysplasia? What is the difference between the cervical and anorectal pap? Follow up and treatment, is it different from cervical dysplasia? Correlation between anal pap smears and biopsies? Should anal-rectal cytology be a standared of patient care in high risk population and female patients with genital HPV infection?
Miral Patel
University of Pennsylvania, USA
Title: Protein extraction from methanol fixed paraffin embedded tissue blocks: A new possibility using cell blocks
Biography:
Miral was 23 years old when he completed his degree. He has Msc in Biotechnology from University of Pennsylvania. Currently, he is program manager for Biorepository at Children Hospital of Philadelphia. He is involved in many clinical and transitional researches. He said publish several articles mainly on the subject of Biobanking and quality of samples in Biobanks.
Abstract:
The traditional cellblock is an essential cytology preparation, which offers benefits over cytological smears by preservation of cell architecture and the performance of immunohistochemical studies. In the current era of minimally invasive techniques for obtaining tissue samples for diagnostic and prognostic markers, cellblocks containing “limited material†specimens are routinely used to provide the valuable information about pre-disease and disease processes. The methanol fixed and paraffin embedded cellblocks are prepared manually with minimal automation with their quality highly dependent upon the experience of the cytopreparation personnel. Currently, Cellient® automated cell block system is widely used for MFPE cellblock preparation to ensure consistent quality preparation by minimizing the operator dependency. Despite advances in technology, the relatively small size of the cytology scrapings MFPE cell blocks in comparison to the formalin fixed and paraffin embedded counterparts have caused them to be often overlooked in biomarker discovery. Recently, in the field of proteomics, there is an emphasis on utilizing limited tissue samples such as core biopsies and cellblocks for the evaluation of molecular biomarkers. These have the potential of being eventually converted into novel diagnostic marker assays that will aid in improving the efficacy of clinical intervention, as well as the validation of leads and targets. Proteomic platforms have developed over the past few years due to advances in scientific knowledge and technology with the next technologic leap being the application of proteomic technologies to the bedside. At present, there is a lack of established methods or resources for extracting proteins from MFPE cell blocks.
Filomena Aste Silveira
Federal University of Rio de Janeiro,Brazil
Title: Cytologic study of behavior, cytology of low grade squamous lesions associated with p16INK4a gene methylation and genotyping of human papillomavirus
Biography:
Filomena Aste Silveira graduated in Medicine, Ph.D. from the Federal University of Rio de Janeiro (UFRJ), and member of the Society of cervical pathology, with title of qualification. Member of the commission of sexually transmitted diseases (STDs), the Brazilian Federation of Gynecology and Obstetrics (FEBRASGO), Prof. Silveira responsible for Gynecology discipline of Valença Medical School (RJ-Brazil). Appraisal professor of gynecology specialist title of proof (TEGO). Medical Institute of Ginecologia- UFRJ - Brazil. Develops research in diseases precursor of cervical cancer and biomarkers, has published some articles in scientific journals.
Abstract:
The low grade cervical intraepithelial squamous lesion (LSIL) is a high prevalence and its behavior is variable. This lesion can minimize, persist or progress. The performance of viral proteins and the epigenetic abnormalities are factors involved in the carcinogenesis of uterine cervix. We studied about the identify the type of HPV-DNA in this lesion and detected the p16INK4a gene methylation too. We analyze the results found about type of HPV-DNA, and methylation then observed with development of LSIL. The time of observation was two years. There was association of oncogenic HPV 16 and 18 with persistence / progression of these lesions. The presence of p16INK4a gene methylation in LSIL was infrequent event and regardless of presence of HPV DNA. We observed that all patients who presented p16INK4a gene methylation showed persistence/progression of this lesion.
Biography:
James Joseph Navin is a MD Graduate from Creighton University, went back in the army in the senior year. He was Internship US Army Tripler Army Med Center, Honolulu in 1962-63. He was on the post of Pathology Residency TAMC between 1963-1967. He was the Chair of Anatomical Pathology TAMC 1969-1972 and Chair of Pathology Straub Clinic and Hospital & also at Kapiolani Women's and Childrens Hosptial and SmithKline Lab. Dr. James was the first Cytopathologist in Hawaii. He received multiple awards as teacher of the year from American Society of Cytopathology for outstanding advocacy efforts. President of American Pathology foundation and having recognition from ACOG for career long dedication to Women's Health .
Abstract:
Commercial labs set a pattern of low payment for Pap smears. They allowed clinicians to bill for the Paps as long as they sent the other work to the lab. This led to a marked reduction in payment to other labs which did Paps and resulted in Pap smears becoming a money losing test for the other labs. Insurance companies and Medicare lowered their payment as well. This produced financial problems for many labs. Some lived with the problem others began to reduce costs by screening faster, not using cytotechs and other ventures that greatly reduced quality. Upon recognizing the problem we began to fix it. We first went after local payors and when that was fixed we went after the Federal Govt. the following is the story of what transpired. It encompasses about 4 years of work which included going to DC every month sometime 3-4 times to meet with the players. Honolulu, by the way is not very close to DC
Hyeyoung Lee
College of Health Sciences, South Korea
Title: Use of HPV E6/E7 and hTERT mRNA RT-qPCR assays in combination for diagnosing high grade cervical lesions
Biography:
Hyeoyung Lee has completed her PhD at the age of 30 years from University of Minnesota, Dept. of Microbiology. She is the professor at the Yonsei Univesity Wonju Campus of the Department of Biomedical Laboratory Science, College of Health Sciences, South Korea. She has published more than 82 papers in reputed journals and has over 30 patents registered
Abstract:
Human papillomavirus (HPV) is a major cause of cervical cancer, which is the third most common cancer in women. HPV E6 oncoprotein initiates degradation of cellular tumor suppressor protein p53, and induces human telomerase reverse transcriptase (hTERT) activity. Activation of hTERT then leads to progressive cervical carcinogenesis. In this study, multiplex RT-qPCR assay which detects 16 HPV high-risk subtypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68 and 69), and the RT-qPCR assay which detects hTERT mRNA were evaluated using 545 ThinPrepⓇ Pap (Hologic Inc., Bedford, MA, USA) samples of Korea. The rates of positivity for the HPV E6/E7 mRNA RT-qPCR assay were 94.4%, 95.2%, 82.4%, 46.5%, 25.0%, and 1.1% in SCC, HSIL, ASC-H, LSIL, ASC-US and normal cytology samples, respectively. Five CIN2+ samples were not detected by the HPV E6/E7 mRNA assay; however they exhibited positive signals in the hTERT mRNA assay. Notably, the hTERT mRNA expression level was increased in high grade cervical lesions, but was very low in all 288 normal samples. These data suggest that the combination of HPV E6/E7 and hTERT mRNA expression levels could be used in a complementary manner in diagnosing high grade cervical lesions, and might be useful as a predictive marker in monitoring low grade cervical lesions
Biography:
Zhongren (David) Zhou has completed his MD and PhD in 1993. Dr. Zhou finished his posdoctoral training in MIT in 1998 and had Instructor in Havard Medical School. He finished his resident training at Bonston University. He had his Cytopathology Fellow in Baylor Medical College and his surgical pathology fellow in MD Anderson Cancer Center. Now he is an interim Director of Cytopathology in University of Rochester. He is invovled in many clinical and translation research. He is also a committee member of Research and Current Concepts Committee in ASC and TCGA GI committee in National Cancer Institute.
Abstract:
Recent advances in imaging technology have resulted in an increase in incidental discoveries of pancreatic cystic lesions. Pancreatic cysts comprise a wide variety of lesions and include non-neoplastic cysts and neoplastic cysts. Because some pancreatic cysts have more of a malignant potential than others, it is absolutely essential that an accurate diagnosis is rendered so that effective care can be given to each patient. In many centers, EUS-guided FNA has emerged as the modality of choice that enables one to distinguish between mucinous and non-mucinous lesion. Multiple methods including pancreatic enzyme levels, genetic analysis, and other tumor biomarkers are used to study cyst fluid for further diagnostic studies.
Biography:
Amr Amin has completed his PhD at University of Illinois at Chicago, and received a post-doctoral training in the field of molecular genetics at the University Of Pennsylvania School Of Medicine. He started his academic career at UAE University where he serves now as a Full Professor of Cell and Molecular Biology. Amr’s research focuses on ways to control cancer, particularly liver cancer. He published many research and review articles and serves as reviewer and as an editorial member of many specialized peer-reviewed journals. He is also a member of many specialized societies and the sole recipient of many scientific awards.
Abstract:
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. The prognosis of patients with HCC is usually poor; hence, a novel approach against HCC is essential for a better therapeutic outcome. Saffron and its active constituents were reported to have antioxidant, anti-inflammatory, and anti-tumor properties. The aim of this study was to investigate chemopreventive action of crocin, one of the promising active constituents of saffron, against diethylnitrosamine (DEN)-induced liver cancer in rats, and the possible mechanisms by which crocin exerts its anti-tumor effects. Findings reported herein demonstrated the anti-proliferative and pro-apoptotic properties of crocin when administrated in DEN-treated rats. Additionally, crocin exhibited anti-inflammatory properties that inhibited NF-kB, among other inflammatory markers. According to our network analysis, NF-kB was identified as a regulatory hub, and therefore, a candidate therapeutic drug target. Taken together, our findings introduces crocin as a potent chemopreventive and therapeutic agent against HCC.
Alvaro Ibarra V
Anatomopatólogo Jefe, Servicio de AnatomÃa Patológica ClÃnica las Condes, USA
Title: Cytological intraoperative study of surgical margins and sentinel nodes in breast pathology
Biography:
Abstract:
The study of surgical margins in breast pathology is very important, because a diagnosis of negativity or positivity permits to make the best surgical procedure, obtaining in the majority of cases an excellent correlation with the results of definitive histopathological report. The intraoperative study of sentinel axillary nodes, in most of the cases, allows resolving in one surgical time, the regional treatment in breast cancer. We will show our experience with cytological study in more than eight hundreds of cases of breast tumors and sentinel axillary nodes, with simple and efficient technics.