Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

A Fully Integrated Histo-Molecular Pathology Report

Margaret L. Gulley, MD, Professor of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill

Q: The CAP, ASCO, ASCP and AMP have developed guidelines for interpretation and reporting of NGS variants in cancers. These analyses are performed in a wide range of types of labs and involve professionals from many disciplines. The reports should take into consideration the bioinformatics, molecular data, source of specimen, age, gender, and location of patient, treatment background, morphologic diagnosis, immunohistochemical tumor profile, and special stains. Who is the best qualified and positioned person to consolidate all of this information and produce a final integrated pathology report and how should this be accomplished?

A: Pathologists are the best professionals to synthesize data from all the tests done on a given tumor specimen via an integrated report that is actionable for downstream medical decision-making.
Hematopathologists enthusiastically embrace new technologies and they are the role models for data integration and analysis of microscopy, flow cytometry, histochemistry (IHC, ISH, FISH), karyotype, PCR, or sequencing.
College of American Pathologists guidance for reporting molecular test results suggests that all results on a given tissue be synthesized by one pathologist, typically the histopathologist although increasingly the molecular pathologist who performs ancillary genomic testing. Since molecular results are best interpreted in the context of histomorphology of input tissue (e.g. percent malignant cells), and in the context of the clinical dilemma to be solved by the test, good communication is essential to assuring that professionals selecting the tissue block, doing the test, and interpreting results provide answers to pertinent medical questions. Access to patient medical records promotes high quality interpretation of histo-molecular findings.
Pathologists are in the best position to allocate precious (often small) specimens and to prioritize which ancillary tests are most critical in a given clinical scenario. Certain tests are feasible only on selected specimen preparations (e.g. karyotype requires fresh tissue), and the pathologist is vital to assuring that tissue is processed in a manner that maximizes success.
In many cases, ancillary tests are ordered by the surgical pathologist who feels comfortable synthesizing results of the test with histomorphology, even if different professionals (e.g. cytogeneticists, molecular pathologists) performed and interpreted raw data. What about ancillary tests ordered by clinicians, sometimes months or years after the microscopist issued their histopathologic interpretation? Specimen requirements must be considered (e.g. fixative type, size, % malignant cells) along with whether to test primary vs metastasis, recent biopsy vs an older or larger resection, in situ vs invasive components, etc. There needs to be better compensation for the expert work of the surgical pathologist to understand the clinician request in order to retrieve and select the best archival tissue portion for the test. Compensation is also needed for the resources required to incorporate test findings into a revised integrated report.
Ancillary tests have benefits and limitations that are best understood by the testing laboratory, so it may be realistic for the testing laboratory to synthesize data from the surgical pathology report, rather than expecting the surgical pathologist to integrate lab data. When a histopathologist feels uncomfortable performing an integrative interpretation of lab data, the histopathologist should at least make it clear in their (addendum) pathology report what test(s) were ordered on which block in order to facilitate work by another professional in synthesizing findings and minimizing accidental repeat testing.
The criteria pathologists use for tumor diagnosis and classification are evidence-based and are updated periodically by various professional groups. Increasingly, ancillary tests are value-added components of standard-of-care surgical pathology workups. Since every patient is different and every tumor is different, pathologists should be valued for their expert judgment and for taking responsibility for translating histo-chemical findings into expert consultations.
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