Rotation Summaries - Clinical Pathology
Molecular Diagnostics, Cytogenetics and Biochemical Genetics - Multi-institutional Rotation
The mission of the resident rotation in the Genetics Laboratories is to prepare physicians with a working knowledge of the basic science, technologies, and organization involved in testing patients for inherited and acquired genetic disease. This training experience will integrate the modern methods of genetic testing into a comprehensive experience that enables a trainee to use this knowledge in their daily practice of medicine as a pathologist.
Genetic testing is clearly increasing in its application for the diagnosis, prognosis and monitoring of acquired diseases (mostly premalignant and malignant conditions), in addition to its traditional role in the work up of constitutional disease. The field is extremely dynamic, with significant advances in technology and rapidly increasing disease information, due in part to advances associated with the Human Genome Project. The overall goal of the genetics rotation is to train residents to be able to fluidly move between the subspecialties of genetics, including cytogenetics, molecular genetics and biochemical genetics. After completion of the rotation, a resident should are able to:
- Integrate the various genetic test results with morphologic, clinical, and other relevant laboratory data to arrive at a single interpretation for diagnostic and prognostic purposes.
- Recognize the advantages and limitations of the different testing modalities such that they are able to help physicians to prioritize test requests and eliminate redundant testing.
- Acquire knowledge of how to access and utilize published literature and databases to be able to continue to integrate new findings in the genetics field into daily clinical practice.
In order to meet these overall goals, the genetics rotation includes a combination of:
- Didactic lectures to provide basic theoretical and empirical knowledge about the various disease entities and genetic technologies.
- Dedicated time within the individual genetic laboratories to become more intimately familiar with the individual specialty tests, their applications and interpretations.
- Experience in collecting, coordinating and integrating testing of a given patient's specimen, interpretation and sign out of results.
- Experience in verbally communicating genetic testing results to referring physicians.
- Opportunity for performing a research project utilizing at least two of the different genetic testing methodologies.
- Attendance at patient related conferences to see how genetic test results are integrated into clinical care.
Organization of the Genetics Laboratories
The organization of the genetics laboratories is based on the perspective that all types of genetic testing, involving the principles of cellular and molecular genetics, are part of the oversight of these laboratories. This perspective involves the implementation of strategies for making diagnoses for constitutional and acquired genetic diseases through a combination of tests that may include karyotyping, nucleic acid methods, or advanced procedures in the biochemical analysis of clinical materials.
The Genetics Laboratories consist of the clinical laboratory sections for Cytogenetics, Molecular Diagnostics and Biochemical Genetics
Coordinating Teaching Faculty Members
Michelle Dolan, MD
Dr. Dolan is the Director of the Molecular Diagnostics Laboratory.
Betsy Hirsch, Ph.D.
Dr. Hirsch is the Director of the Cytogenetics Laboratory.
Mike Tsai, Ph.D.
Dr. Tsai is the Director and founder of the Biochemical Genetics laboratory.
Molecular Diagnostics
The rotation in the Molecular Diagnostics Laboratory (MDL) is designed to provide the resident with an introduction to molecular diagnostics, including basic concepts in molecular genetics and molecular pathology , methods and techniques, laboratory logistics (i.e., specimen procurement, processing, and a general knowledge of laboratory work-flow), and indications for /appropriate utilization of molecular testing.
Coordinating Teaching Faculty Member
Michelle Dolan, MDTraining Site:
Molecular Diagnostics Laboratory, D210, Mayo.Duration of Rotation:
Two monthsPost Graduate Level of Residents Involved
PGY 2-5
Guidelines for Patient Care and Specimen Handling
Specimen handling in the Molecular Diagnostics Laboratory is the direct responsibility of the laboratory technologists.
Resident decision making in the laboratory is under the direct supervision of the MDL fellow and staff.
Overview of Daily Duties and Responsibilities
- For those patients referred to the laboratory for gene rearrangements, BCR-ABL testing and BMT engratment studies, the resident is exected to obtain clinical histories and relevant results from other laboratories (Special Hematology, Flow Cytometry/Immunophenotyping, Surgical Pathology, Cytogenetics). This information should be obtained PRIOR to reviewing cases with staff person on service.
- Review test results as they become available with the Molecular Diagnostics Fellow PRIOR to case sign out with the staff person on service. The resident should be prepared to answer any questions regarding any particular case.
- Attend case sign out with staff person on service.
- Answer clinician inquires with regard to test offerings and patient results.
- Enter Morphologic Interpretation into Gene Rearrangement and BCR-ABL reports on the computer.
- Perform literature searches regarding unusual/difficult cases.
Goals and Objectives
- Know specimen requirements for molecular diagnostic testing.
- Obtain an understanding of DNA and RNA extraction
- Understand what is involved in setting up a Southern transfer
- Understand the polymerase chain reaction and RT-PCR.
- Understand the basic principles of DNA sequencing.
- Understand the basic principles of assays used in the MDL.
- Understand basic principles of molecular biology.
- Understand the basic principles of human genetics.
- Understand the basic molecular pathology of those diseases commonly tested for in the clinical molecular diagnostic laboratory.
- Understand the use of molecular testing in the diagnosis and management of disease and the relationship/overlap between molecular testing and other laboratory tests (e.g., flow cytometry, cytogenetics).
- Understand laboratory practice issues including proficiency testing, certification, QA/QC, and medicare compliance.
Resident Opportunities to Function as a Consultant to Other Physicians
The residents on rotation in the molecular diagnostics laboratory are expected to obtain relevant patient information from the referring physician. The resident is also expected to answer quiries with regard to appropriate testing and patient results. These interactions may include physicians from Medical Genetics, Pediatrics, Family Practice, OB/GYN, Oncology, and BMT Clinic. The resident is also expected to be able to discuss molecular diagnostic results with residents, fellows and staff from other Special Diagnostics Laboratories including Special Hematology, Cytogenetics, and Flow Cytometry.
Description of On-call Duties
At the present time, the resident is "on-call" in Molecular Diagnostics during regular working hours. In an urgent situation, the resident should contact either the supervisor or an MDL faculty member.
Structured Formal Education in Management of the Molecular Diagnostics Laboratory
- The resident is invited to attend the monthly "Special Diagnostics" Administrative Meeting
- The resident is required to attend the weekly Molecular Diagnsotics Staff Meeting.
- The resident participates in the sign-out of any CAP or other proficiency testing specimens which are analyzed in the laboratory during the resident's rotation.
- While on rotation in the MDL, residents may elect to be involved in the development of a clinical assay. This project is dependent upon needs of the MDL, and is chosen at the discretion ot the laboratory staff. The rationale for the development of a particular assay is discussed with the resident.
Required Conferences/Seminars
- Molecular Diagnostics Staff Meeting, Discussion of issues in laboratory management, and interesting cases in the MDL.
- Hematologic Malignancy Conference, This meeting involves the discussion of difficult and/or unusual hematologic-malignancy cases. The meeting involves FUMC clinicians and staff from the Special Diagnsotics Laboratories.
- Special Diagnostics Administrative Meeting, Discussion of administrative issues in the "Specialty Diagnostics" laboratories.
Other Conferences
- GI Pathology Conference
- Laboratory Medicine and Pathology Grand Rounds
- Clinical Pathology Case Conference
- Dermatopathology Conference
- Cytology Conference
- Institute of Human Genetics Seminar
- Resident's Conference
Scholarly Activities/Research Activities During and After Rotation
During the rotation, residents are expected to perform literature searches with regard to difficult/unusual cases. The findings of the literature search are discussed with the MDL staff and fellows. The resident is also expected to present the case and the results of the literature search at the weekly MDL staff meeting. The MDL directors emphasize that staying current with the literature is essential in a rapidly changing field such as molecular diagnostics. Residents are also expected to participate in a laboratory project. The project may be bench oriented (e.g. participation in the development of a new laboratory protocol or technology), or library-oriented (e.g. creation or supplementation of the Laboratory Disease Reference Book). The scope/topic of the project will be agreed upon by the resident and the staff. Residents who are interested in continuing work in the MDL after the rotation period may participate in more involved development projects or in research projects associated with molecular diagnostics. Residents who pursue a fellowship in the MDL are expected to devote 50% of their time to development or research activities.
Basis, Method and Criteria for Resident Evaluation
- Residents will be evaluated on performance of daily activities (described previously).
- Residents will be evaluated on participation in required meetings and conferences.
- Residents will be evaluated on presentations to the MDL staff meeting.
- Residents will be evaluated on participation in a laboratory project (either bench-related or library-related).
Educational Resources
References and Reading Material
- Strachman T., and Read A. Human Molecular Genetics
- Thompson and Thompson. Genetics in Medicine
- Heim and Mittelman. Cancer Cytogenetics
- Wells and Warren. Genetic Instabilities and Hereditary Neurological Diseases.
- Current Protocols in Molecular Genetics.
- Maniatis. Molecular Cloning.
The MDL also has a teaching file of gels and autoradiograms illustrating interesting/unusual cases. The MDL also has a Disease Reference Book including background information, testing protocols, and result interpretation for each of the diseases tested for in the MDL.
Cytogenetics
The Cytogenetics rotation is aimed at providing residents with basic knowledge in the techniques and applications of classic cytogenetics and molecular cytogenetics, clinical indicators for evaluation of potential constitutional or acquired chromosomal abnormalities, correct use and interpretation of standard cytogenetic nomenclature, and interpretation of cytogenetic findings. Emphasis will be placed on correlation of cytogenetic findings with clinical, morphologic and other laboratory data for purposes of differential diagnosis and prognostication.
Because of the high degree of complexity of cytogenetic testing, and the length of time required to become proficient at identifying subtle abnormalities in chromosome banding patterns, it is not expected that, upon completion of the rotation, the residents will be able to independently review and critique patients' studies. The residents will, however, have sufficient training to identify numerical and major structural abnormalities, to recognize the major recurring abnormalities in hematologic malignancies, solid tumors and specific (delete word) constitutional genetic syndromes. Additionally, the rotation requires searching of published literature so that residents become familiar with appropriate search strategies, genetic databases, and current data which impact the cytogenetic interpretation.
Coordinating Teaching Faculty Member
Betsy Hirsch, Ph.D.Duration of Rotation:
One monthsPost Graduate Level of Residents Involved
PGY 2-5
Goals and Objectives:
- Obtain clinical information and other ancillary testing on patient referrals (Core competency: Patient care)
- Learn the primary reasons for referral for cytogenetic testing (Core competency: Medical knowledge)
- Be able to determine the appropriate testing methodology for given patient referrals (new diagnoses, follow-up studies) (e.g., G-banding vs. fluorescence in-situ hybridization vs. molecular diagnostics) (Core competencies: Patient care, medical knowledge, practice-based learning and improvement)
- Learn the major recurring abnormalities associated with the hematopoietic malignancies and with subsets of solid tumors and the current utilization of these abnormalities for subclassification of disease, prognostication and planning of therapy (Core competencies: Medical knowledge, practice-based learning and improvement)
- Learn the basics of the International System of Cytogenetic Nomenclature, 2005 (Core competency: Medical knowledge)
- Learn to search peer-reviewed literature for updates regarding the clinical significance of cytogenetic abnormalities and for newly developed technologies (Core competencies: Medical knowledge, practice-based learning and improvement)
- Learn to triage cases according to clinical care needs (Core competencies: Patient care, systems-based practice)
- Learn to utilize lab resources effectively for patient care; identify studies that represent redundant testing or those which will likely not yield an informative result for patient care (Core competencies: Patient care, systems-based practice
- Learn to communicate with Referring Physicians regarding requested testing and results of these tests (Core competencies: Patient care, interpersonal and communication skills, professionalism)
- Learn how to read a Cytogenetics report (Core competencies: Patient care, medical knowledge)
- Learn the basics of tissue processing for Cytogenetics, including G-banding and fluorescence in-situ hybridization (Core competencies: Medical knowledge)
- Prepare a brief (30-minute) talk for the laboratory staff on their choice of topic (Core competencies: Interpersonal and communication skills, professionalism)
To achieve these goals, the Cytogenetics rotation will involve the following:
- Each morning, the Residents will review all of the new referrals to the laboratory. They will collect relevant clinician and ancillary lab data, and determine the reason for referral, the best testing methodology to apply, and triage the case. Each referral will be discussed with the Medical Director.
- Each day, a single current case will be identified for more extensive research and review by the Residents. These cases will be selected based on their representation of a major group of cytogenetic referrals: e.g., leukemias, lymphomas, solid tumors, etc. A few key published papers will be provided to the Residents and they will be asked to supplement these with one or more current papers from the literature. The Residents will prepare a brief write-up of the major findings in the literature to include the major cytogenetic abnormalities associated with the particular disease entity and their prognostic significance. Every one to two days during the rotation, the Medical Director will meet to discuss the case and disease entity with the Residents, including with this discussion some finalized cytogenetic reports and karyotypes.
- Each day during their rotation, one Resident will be assigned to review cases that may be appropriate for cancellation. He/she will review the reasons why a cancellation approval is being sought, and will make the appropriate request to the Referring Physician (after approval by the Medical Director).
- Each day during their rotation, one Resident will be assigned as the “go-to” person for the Cytogenetic technologists, to obtain further clinical or laboratory data that will be used to determine appropriate processing of specimens.
- Each day, the Residents will review cases as the Medical Director interprets and signs them out.
- Before the end of the rotation, each Resident will provide a brief (30-minute) talk for the laboratory staff. This talk will integrate clinical, pathologic and cytogenetic findings and will be based on a current case and review of the literature.
In order to achieve these goals, the Residents will be expected to have regular attendance in the laboratory. If the Resident is absent for more than one day due to illness or other excused reason, he or she will provide written summaries of cases in lieu of oral discussion. The Residents are expected to demonstrate and maintain a professional demeanor at all times in the clinical laboratory.
Biochemical Genetics
The rotation in the Biochemical Genetics Laboratory is intended to provide the resident with an introduction to inborn errors of metabolism, their diagnoses, basic concepts in chromatography methods and techniques, general knowledge of laboratory work-flow, and typical ordering practices.
Coordinating Teaching Faculty Member
Mike Tsai, Ph.D.Duration of Rotation:
Two weeksPost Graduate Level of Residents Involved
PGY 2-5
Goals and Objectives
- Learn amino acid analysis and organic acid screening performed in the Biochemical Genetics Laboratory.
- Learn specimen requirements for biochemical genetics testing.
- Obtain an understanding of HPLC, GC and GC/MS technology.
- Understand basic principles of biochemical genetics.
- Understand the basic principles of human genetics.
- Understand laboratory practice issues including proficiency testing, certification, QA/QC, and Medicare compliance.
Overview of Daily Duties and Responsibilities
- Review test results with Dr. Tsai during the interpretation process.
- Attend case sign out with staff person on service.
- Investigate unusual/difficult cases and give feedback to laboratory about possible diagnosis and further testing to recommend.
- Answer clinician inquires with regard to test offerings and interpretation of patient results.