1. Characterizing the Histologic Morphology of Liver Cancer: Creating a Formalin Fixed Paraffin Embedded Tissue Repository
Tamar Taddei, MD

2. Background
Hepatocellular carcinoma is rising in incidence globally, and tripled in the US in over the last three decades
It is the 3rd most common cause of cancer-related death worldwide (700,000 deaths/year)
HCC is the leading cause of death in cirrhosis
WHO – Liver Cancer 2008; El –Serag NEJM 2011, Ryerson et al. Cancer 2016

3. Incidence/Mortality: HCC vs Others
SEER Cancer Statistics Review, (Vintage 2009 Populations), National Cancer Institute.

4. HCC Deaths in the “Birth Cohort”
Ryerson et al. Cancer 2016

5. Opportunities and Challenges
HCC is the only solid organ tumor that can be diagnosed by radiographic imaging alone
Because of this, there is a paucity of tissue for analysis, hampering efforts at developing large repositories
Most repositories are representative of early stage cancer and consist entirely of liver resection or explant specimens
85% of HCC in the US is unresectable at diagnosis; 50% present at advanced stages

6. Opportunities and Challenges
Few repositories are morphologically annotated; most clinical annotation cannot match the depth we can offer
HCC is a heterogeneous disease and tumor morphology/tumor milieu may give us unique insights into this disease
Large genetic studies of HCC have shown no clear, targetable oncogenic addiction loop, so the field is moving to examining the tumor microenvironment

7. Tumor Heterogeneity Tumor Milieu H HCC F Clear cell HCC Scirrhous HCC
Here are three distinct tumor morphologies. In the first slide, the intersection of hepatocytes (H), a band of collagen fibrosis (F), and the tumor (HCC) all intersect.
Clear cell HCC
Scirrhous HCC
Steatotic HCC
Mitchell J Clin Gastro 2013

8. Logistics of Sample Acquisition
Identifying tumors and their location (station)
Identifying a willing participant (pathologist)
Applying for approval (amendment to VACS, IRB protocol, IRB waivers, waiver of non-engagement)
Developing a curated list from review of pathology reports
Negotiating tissue blocks and/or slides
Making shipping as easy as possible

9. Logistics of Sample Tracking
A system to label specimens uniquely
Block and slide review for routine and immunohistochemical staining
Monitoring the movement of the specimen from pathologist, to research lab for staining, to two pathologists for independent review, then follow-up of additional stains if required
Return of block/slides to originating institution, or archive if return is not required
Significant station variability!

10. Logistics of Pathology Review
Two pathologists (K. Mitchell-Richards, X. Zhang)
Careful histologic and morphologic annotation
Several meetings to determine key features to capture in tumor and background, essential stains (e.g. CD4, CD8), and definitions to allow concordant reporting

11. Pathology Database

12. Goals and Progress 6 VACS sites participating
10 other stations engaged in discussion, of which 2 have a waiver of non-engagement
Tracking and pathology database complete
Shipping, receiving, and flow of specimen from arrival to return or archive has been mapped and tested
11 specimens obtained and in the process of review
Goal: 250 specimens