title: Primary Hepatic Small Cell Carcinoma: Two Case Reports, Molecular Characterization and Pooled Analysis of Known Clinical Data.
abstract: Primary hepatic small cell carcinoma (HSCC) is a rare malignancy that has previously been described in only few case reports. The clinicopathological course, natural history, molecular markers and ideal treatment strategy for this tumor have not been fully elucidated. Herein, we report on two cases of spontaneously arising, metastatic primary HSCC that were treated at our Institution. Both patients succumbed to their disease within two months of initial presentation. Both cases underwent postmortem examination and no evidence of a pulmonary or other non-hepatic small cell primary was found. Unlike pulmonary small cell tumors, these two hepatic primaries showed only locoregional spread and very few distant metastases. Formalin-fixed samples were obtained at autopsy and sequenced using single-nucleotide polymorphism arrays and whole-genome sequencing. Four mutations in the epidermal growth factor receptor (EGFR) gene known to be associated with response to tyrosine kinase inhibitors (TKIs) were detected in one of the two HSCC samples. A systematic review and pooled analysis of all previously reported cases of primary HSCCs was conducted. The median overall survival was estimated at 4 months. Surgical resection was significantly associated with longer overall survival (hazard ratio =0.13, 95% confidence interval=0.03-0.69). Although several case reports of primary HSCC have been reported prior to this publication, to our knowledge this is the first time that molecular and systematic analysis has been conducted in order to more fully characterize this rare disease. Our results indicate that surgical resection, when feasible, may be a valid option in primary HSCC, and that some tumors may respond to TKIs against EGFR.
authors.affiliation: Department of Oncology, Montefiore Medical Center & Albert Einstein College of Medicine, Bronx, NY, U.S.A. ashastri@montefiore.org.
authors.forename: Aditi
authors.initials: A
authors.lastname: Shastri
authors.affiliation: Department of Internal Medicine, Jacobi Medical Center, Bronx, NY, U.S.A.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Msaouel
authors.affiliation: Department of Genetics and Pathology, Albert Einstein College of Medicine, Bronx, NY, U.S.A.
authors.forename: Cristina
authors.initials: C
authors.lastname: Montagna
authors.affiliation: Department of Pathology, Jacobi Medical Center, Bronx, NY, U.S.A.
authors.forename: Sherry
authors.initials: S
authors.lastname: White
authors.affiliation: Department of Genetics and Pathology, Albert Einstein College of Medicine, Bronx, NY, U.S.A.
authors.forename: Maria
authors.initials: M
authors.lastname: Delio
authors.affiliation: Department of Genetics and Pathology, Albert Einstein College of Medicine, Bronx, NY, U.S.A.
authors.forename: Kunjan
authors.initials: K
authors.lastname: Patel
authors.affiliation: Department of Oncology, Jacobi Medical Center, Bronx, NY, U.S.A.
authors.forename: Karenza
authors.initials: K
authors.lastname: Alexis
authors.affiliation: Department of Oncology, Jacobi Medical Center, Bronx, NY, U.S.A.
authors.forename: Marianna
authors.initials: M
authors.lastname: Strakhan
authors.affiliation: Department of Oncology, Jacobi Medical Center, Bronx, NY, U.S.A.
authors.forename: Tarek N
authors.initials: TN
authors.lastname: Elrafei
authors.affiliation: Department of Oncology, Jacobi Medical Center, Bronx, NY, U.S.A.
authors.forename: Louis Juden
authors.initials: LJ
authors.lastname: Reed
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
keywords: Primary hepatic carcinoma; neuroendocrine tumor; small cell cancer