Molecular Pathology

Goals and Objectives

Patient Care

• Knowledge of proper methodologies for the analysis of the genetic disorders
• Understand test validation in regards to accuracy, precision, analytic sensitivity, and specificity
• Competent in laboratory safety and laboratory regulatory requirements
• Understand the basics of laboratory developed test (LDT) and FDA approved tests.
• Understand pre-analytic concepts before the specimen arrives in the laboratory so education can be provided to the collecting laboratories or ordering physicians.
• To be able to provide advice to clinicians about appropriate specimens and handling requirements for different types of nucleic acid based diagnostic tests
• Describe the clinical settings in which various molecular tests are ordered for hematopathology, infectious disease, and solid tumors.
• Correlate molecular diagnostic data with morphology and clinical information in diagnosing hematopathology, infectious disease, and solid tumors. 

Medical Knowledge

• Understand the physical and chemical methods used for the purification, analysis and detection of nucleic acids.
• Know the molecular structures, biological functions and physicochemical properties of nucleic acids that are relevant to modern methods of nucleic acid analysis of clinical specimens
• Know the catalytic activities of enzymes used for the analysis of nucleic acid specimens including amplification of specific nucleic acid sequences.
• Understand the rationale for specimen requirements used in molecular testing
• Be able to estimate adequacy of tissue for FFPE nucleic acid extraction for a given assay
• Be able to outline manual preparative methods for DNA/RNA from various sample types and explain rationale of each step and know safety issues for relevant solvents
• Describe the method and interpret results of the molecular test for immunoglobulin heavy chain and T-cell receptor gene rearrangements and immunoglobulin heavy chain V-region mutational analysis.
• Understand molecular classifications of leukemia and lymphoma and appropriate method for testing
• Understand biology and significance of solid tumor markers
• Understand the classification of solid tumor and hematopathology biomarkers by indications: diagnostic, prognostic, and/or predictive.
• Understand the algorithm for Lynch syndrome testing and the methylation marker MLH1 
• Understand Next-Generation Sequencing (NGS): principles and techniques associated with sequencing of gene panels, whole exomes, or whole genomes
• Understand the technical details of next-generation sequencing – limitations and advantages of different methods of library preparation and sequencing.
• Understand the assay design process, including selecting capture baits for hybridization and primers for microdroplet PCR.
• Understand the refinement steps of assay design to optimize data generation at difficult genomic regions, e.g., at repetitive sequences or GC-rich sequences.
• Understand limitations of sequence depth coverage and implications for diagnostic testing.
• Observe NGS read alignment, variant calling and confirmation
• Understand the analysis of NGS data with respect to the bioinformatics and statistical components

Practice Based Learning and Improvement

• Understand the use of quality assurance and control in the molecular laboratory.
• Explain 'unidirectional flow' with regards to contamination prevention and effective strategies for contamination prevention, with respect to the appropriate design and workflow in molecular laboratories to ensure quality and reduce the risk of carry-over contamination
• Able to interpret quality parameters to determine the quality of extracted nucleic acids.
• Analyze and interpret sequencing data for solid tumor, hematopathology, infectious disease, and inherited diseases specimens, including appropriate reporting and medical significance of positive and negative test results.
• Perform a literature search on an assigned clinical test and give a presentation to the UHTL faculty and staff.

Professionalism

• Convey information to laboratory staff in a timely manner
• Reading independently on topics related to patient case material and search primary sources
• Demonstrate self-motivation and organization in pursuit of rotation requirements (reading and clinical service time)
• Demonstrate a commitment to ethical principles pertaining to (1) patient privacy and autonomy, (2) the provision or withholding of test results, (3) confidentiality of patient information, (4) informed consent, (5) conflict of interest, and (6) business practices that are in conflict with stated principles of professionalism.
• Demonstrate courteous and collegial behavior with laboratory staff (laboratory supervisor will evaluate resident based on input from laboratory personnel)

Interpersonal and Communication Skills

• To effectively communicate with clinicians about test ordering and test results with appropriate interpretation.
• To effectively communicate with lab staff about appropriate sample identification and selection, issues regarding test result interpretation and trouble-shooting

Systems-Based Practice

• Understand concepts of laboratory design and procedure that are specific to nucleic acid testing.
• Understand primary issues of QA/QC in molecular amplification, including common sources of false positive and negative results, and basic trouble-shooting
• Explain the regulatory requirements governing all molecular tests, including laboratory developed tests, and compare the differences and similarities among them.
• Define the test designations RUO, IUO, ASR, IVD, and LDT
• Describe the validation process for a lab developed test and requirements for lot validation for all test types.
• Contrast verification of an IVD with validation of an LDT
• Explain the important legal, ethical, and social implications with regards to larger scale/genomic testing and the ability to 'blind' analytes to prevent unintended data analysis (i.e. NGS for tumor discovering AD condition)
• Integrate molecular diagnostic results into hematopathology, inherited disease, infectious disease, and solid tumors pathology reports
• Act as a consultant to clinicians and other pathologists for the use and selection of molecular testing.  Provide appropriate consultations regarding test results.
• Perform an evaluation of lab quality control and quality assurance program.

Duration

The rotation in molecular pathology is four weeks and typically occurs during years 3 or 4 at the UHTL.

Duties and Responsibilities of Residents

• Because the core curriculum is taught at one point in the Resident's training, responsibilities do not change on a yearly basis.
• Review incoming cases for order accuracy and follow up on questions to ordering providers
• Review and sign out all results with the Attending Pathologist
• Review laboratory procedures
• Participate in division case conference, QA meetings, and other meetings as applicable
• Present briefly (15 min) on a relevant topic to the UHTL faculty and staff

Teaching Staff

• Jennifer Yoest, MD - Rotation Director
• Navid Sadri, MD, PhD - Division Director

Supervision and Evaluation

Residents meet on a regular basis with the Attending Pathologist and with the lead technologists for supervision. Residents are evaluated on a monthly basis with regard to acquisition of the Core Competencies listed in this Program Statement. Evaluations are forwarded to the Residency Program Director, where they are available for review. Direct observation and feedback. In addition, residents may take pre- and/or post-rotation examination.