The Pathology Core (Dr. Cook) will provide thorough central pathology review of all patient samples studied in Projects 1-4 of this grant, utilizing web-based e-pathology resources and providing additional ancillary testing analyses when required to arrive at a consensus diagnosis. Tissue microarrays will also be constructed from paraffin blocks for Projects 2 and 3, facilitating cost-efficient downstream analysis.
Aim 1) To provide a system for central pathology review utilizing digital slide imaging. Central review by a panel of internationally recognized lymphoma experts has been one of the cornerstones of prior LLMPP studies. Each case is reviewed by four lymphoma pathology experts, and agreement by at least three pathologists defines a consensus diagnosis. For cases where an initial consensus is not reached, the cases are reviewed by the entire pathology committee together and a consensus diagnosis established by majority opinion. Web based e-pathology resources based in the Cleveland Clinic e-pathology center will be utilized by the Pathology Core to facilitate central review in a cost efficient manner. Routine sections and immunohistochemical stains will be scanned using an Aperio whole slide imaging system, and reviewing pathologists will be provided access to review their assigned cases through a web based interface.
Aim 2) To complete ancillary studies as required to reach a final pathologic diagnosis. Additional ancillary testing may include immunohistochemical stains, fluorescence in situ hybridization (FISH) studies and/or lymphoid clonality testing, may be necessary in some cases to arrive at a definitive consensus diagnosis. Such testing, when requested by the pathologists performing central review, will be performed in the Cleveland Clinic research core laboratories which include 1 Ventana Discovery, 3 Ventana Benchmark XT, 2 Ventana Benchmark Ultra, and 1 Dako immunohistochemistry platforms. An extensive FISH menu and PCR clonality assays employing gold standard Euroclonality primer sets are also available.
Aim 3) To facilitate individual research projects through construction of tissue microarrays. Tissue microarrays will be constructed from samples submitted for Projects 2 and 3. Dr. James Cook will serve as PI for the Pathology Core. Dr. Cook has extensive experience in central pathology review for multi-institutional studies, having been a member of the LLMPP lymphoma pathology committee and the SWOG lymphoma pathology committee since 2005. Dr. Cook is supported by a strong Research core group within the Cleveland Clinic Pathology and Laboratory Medicine Institute, including research technologists, project managers, accounting experts, and other administrative support. This Core will impact each of the Projects 1-4 in this grant by ensuring each case studied has been thoroughly vetted and providing a gold standard, consensus pathologic diagnosis
The Pathology Core will support the NCI public health goals by creating the system for central pathology review amongst the participating sites in this proposal, facilitating sharing of information and ensuring diagnostic accuracy of all tested primary patient samples. The resulting gold standard pathologic diagnosis will provide an essential baseline for studying disease with new technologies that may impact diagnosis, prognosis, and/or treatment resistance of malignant lymphomas.
