diseases that have a documented, notoriously high degree of interobserver variation in diagnostic interpretation, it can be an important issue for both patient management and research. In such cases, it is considered standard of care to seek a second, specialty pathologic opinion, such as the consultative opinions produced for specimens submitted to the JPC repository and its predecessors. Verification of diagnosis by obtaining a new pathologic analysis in every case used for research is recommended.

However, it may also be problematic for research if the diagnosis that accompanies the case is outdated and no longer appropriately classifies the disease. Outdated diagnostic terminology (correct diagnosis but arcane language) or outdated diagnostic criteria for identification (classification according to a schema that is no longer in use) may cause considerable difficulty in mapping a historical case to a current diagnostic category accurately. Over the span of decades that the JPC repository has existed, pathologic classification of disease has evolved substantially. In some disease categories, such a hematopathologic malignancies, entire disease classifications have changed repeatedly because knowledge of pathogenesis has grown. Modern diagnosis of lymphoma and leukemia may require delineation of specific molecular features that were never tested for in older cases. Depending on the specific preanalytic variation associated with a historical case, it may not even be possible to test accurately for the molecular features required for diagnostic classification.

The more common problem in all disease categories is the lack of standardization in diagnostic terminology that was widespread in pathology for many years. That has been exemplified both by the use of a given diagnostic term for different disease entities and by the use of multiple diagnostic terms for a given disease entity (Cooper, 2006). A researcher using a historical case may not have the requisite expertise to interpret the existing diagnostic terminology accurately and map it to the current diagnostic terminology standard correctly. Failure to reclassify cases correctly according to current diagnostic standards and current diagnostic terminology for any of the above reasons may skew research data.

Preanalytic variations related to preoperative or intraoperative factors may create molecular artifacts.

Many drugs used in preoerative and intraoperative periods and such surgical events as devascularization or arterial ligation with cessation of blood supply during resection (called warm ischemia time) may cause changes in the molecular profiles of resected tumor and normal tissues and preclude use of specimens for research. Shifts in molecular profiles due to iatrogenic interventions may not be recognized as artifacts and may be mistakenly interpreted as disease signatures. Some drugs used in perioperative and interoperative periods have powerful molecular effects and are, in fact,



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