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Background Colorectal carcinoma (CRC) during the peri-partum period is challenging to diagnose due to the overlapping symptoms of CRC and pregnancy. This is the first case series to investigate clinicopathologic, hormonal and molecular features of CRC diagnosed during the peri-partum period. We hypothesized that advanced presentations of CRC could possibly be mitigated by pregnancy-related hormonal factors. Methods We conducted a retrospective review of five women diagnosed with CRC during the peri-partum period and studied the clinical and molecular features of their cancer. Results All patients presented with stage IV CRC at diagnosis; three had primary tumors in the rectum and two had primary tumors in the sigmoid colon. The liver was the most common metastatic site (three of five women). Immunohistochemistry stains were negative for estrogen receptors alpha (ERα) and beta (ERβ), and one tumor demonstrated low-level positivity for PR (1%). Formalin-fixed and paraffin-embedded (FFPE) biopsies from each case were tested with next-generation sequencing and found that all tumors were mismatch repair (MMR) proficient, and three harbored a KRAS mutation. Germline testing showed no predisposition to CRC; however, several somatic variants of undetermined significance (VUS) were identified. Discussion CRC in the peri-partum period poses significant risk factors for presentations with advanced disease due to diagnostic challenges. While our study provides no evidence that pathogenesis of CRC during pregnancy is driven by elevated estrogen and/or progesterone levels during pregnancy, additional putative etiologic factors, including placental growth factors, the immunosuppressive state of pregnancy and other physiologic processes during pregnancy, warrant future study.

Organ donors are systematically screened for infection, whereas screening for malignancy is less rigorous. The true incidence of donor-transmitted malignancies is unknown due to a lack of universal tumor testing in the posttransplant setting. Donor-transmitted malignancy may occur even when not suspected based on donor or recipient factors, including age and time to cancer diagnosis. We describe the detection of a gastrointestinal adenocarcinoma transmitted from a young donor to 4 transplant recipients. Multidimensional histopathologic and genomic profiling showed aCDH1mutation andMETamplification, consistent with gastric origin. At the time of writing, one patient in this series remains alive and without evidence of cancer after prompt organ explant after cancer was reported in other recipients. Because identification of a donor-derived malignancy changes management, our recommendation is to routinely perform short tandem repeat testing (or a comparable assay) immediately upon diagnosis of cancer in any organ transplant recipient. Routine testing for a donor-origin cancer and centralized reporting of outcomes are necessary to establish a robust evidence base for the future development of clinical practice guidelines.

e16169 Background: Rare cancers including FLC make up 25% of adult tumors, but are difficult to study due to low incidence and incomplete case identification. FLC occurs in adolescents and young adults without liver dysfunction. Hyperammonemia has been frequently reported in FLC patients, but is poorly understood. Methods: Data from three clinical trials allowed us to establish the incidence of hyperammonemia (serum ammonia value > 75 µmol/L) in FLC. In these studies, FLC patients received everolimus, estrogen deprivation therapy (EDT) with leuprolide + letrozole or everolimus + EDT (Oncologist. 2020 25(11):925-e1603), ENMD-2076 (Oncologist. 2020 25(12):e1837-e1845), or neratinib (J Clin Oncol 39, 2021 (suppl 3; abstr 310); ammonia was tested prospectively in the latter two studies. To assess impacts of cancer therapy or liver dysfunction, we studied hyperammonemia in FLC and non-FLC patients at UCSF in parallel. Using Natural Language Processing (NLP) of pathology reports and oncology notes from > 2300 liver cancer patients from the last 12 years of UCSF records, we identified a cohort of patients with FLC, contrasting their laboratory data to all UCSF patients with ammonia testing for the last 10 years. We used leiden clustering and umap dimensionality reduction to contrast FLC and other patients to assess the clinical context of hyperammonemia. Results: Data from the 3 trials showed hyperammonemia in 10 of 32 (31.3%) FLC patients during study participation, independent of the therapy received. These patients exhibited hyperammonemia with varying levels, and at different points in their treatment. NLP identified 37 patients with FLC ( < 0.1% of liver cancer patients), with 33% showing hyperammonemia. Across all UCSF patients, we found 24,000 independent visits where ammonia was tested, with > 2400 demonstrating hyperammonemia. Using leidan clustering on all encounters with ammonia > 75 µmol/L, we found distinct subsets of hyperammonemia corresponding to known metabolic and physiologic processes (e.g., fulminant liver failure, tumor lysis syndrome, etc). FLC patients clustered separately from hepatocellular carcinoma patients with hyperammonemic encephalopathy due to cirrhosis. Conclusions: NLP of large EMRs is a valuable tool to study FLC, a rare cancer. Herein, we have defined hyperammonemia as a frequent event in FLC, not directly linked to hepatic dysfunction or individual therapies. Further investigation may determine whether hyperammonemia is related to FLC tumor biology.

414 Background: Donor-derived malignancy may occur even when not suspected based on donor or recipient factors, including age and time to cancer diagnosis. Early recognition of donor-derived malignancy has treatment implications. We describe the molecular characterization of a gastric cancer transmitted from an organ donor to heart, liver (LR), left kidney (LKR), and right kidney-pancreas (KPR) recipients. Methods: IRB approval for chart review was obtained; LR, LKR, and KPR also provided research consent for molecular profiling. Short Tandem Repeat (STR) genotyping was performed by polymerase chain reaction and gel electrophoresis. Tumor and germline DNA from patients and the organ donor were subjected to next generation sequencing (NGS) of 479 genes. Fluorescence in situ hybridization (FISH) was used to confirm MET amplification. Results: Donor origin was established by STR analysis, with the tumors showing high levels of donor alleles. Pathology revealed a poorly differentiated adenocarcinoma with signet ring features. Immunohistochemical staining and CA-19-9 elevation were most consistent with gastric or pancreas origin. Tumor sequencing was notable for somatic mutation of CDH1, MET amplification and wild-type KRAS genes. Tumors from LR and KPR were nearly identical based on pathogenic variants, allele frequency, and copy number variation. Insufficient tumor cellularity in all LKR specimens precluded NGS profiling, but clinical testing found that the cancer was mismatch repair proficient; ERBB2 equivocal; and PDL-1 positive. A circulating tumor DNA test did not uncover any genomic alterations; however, MET amplification was confirmed in this tumor using FISH probes. Conclusions: STR analysis and reporting should be standard immediately following diagnosis of cancer in an organ transplant recipient to ascertain donor derivation. Further molecular characterization, including NGS, may aid in defining primary tumor origin. Here, diagnosis with PDL1-positive gastric cancer enabled use of pembrolizumab. One patient remains alive and without evidence of cancer following prompt organ explant after cancer was reported in other recipients.