title: Hepatic small vessel neoplasm, a rare infiltrative vascular neoplasm of uncertain malignant potential.
abstract: Characteristic but rare vascular neoplasms in the adult liver composed of small vessels with an infiltrative border were collected from an international group of collaborators over a 5-year period (N=17). These tumors were termed hepatic small vessel neoplasm (HSVN), and the histologic differential diagnosis was angiosarcoma (AS). The average age of patients was 54years (range, 24-83years). HSVN was more common in men. The average size was 2.1cm (range, 0.2-5.5cm). Diagnosis was aided by immunohistochemical stains for vascular lineage (CD31, CD34, FLI-1), which were uniformly positive in HSVN. Immunohistochemical stains (p53, c-Myc, GLUT-1, and Ki-67) for possible malignant potential are suggestive of a benign/low-grade tumor. Capture-based next-generation sequencing (using an assay that targets the coding regions of more than 500 cancer genes) identified an activating hotspot GNAQ mutation in 2 of 3 (67%) tested samples, and one of these cases also had a hotspot mutation in PIK3CA. When compared with hepatic AS (n=10) and cavernous hemangioma (n=6), the Ki-67 proliferative index is the most helpful tool in excluding AS, which demonstrated a tumor cell proliferative index greater than 10% in all cases. Strong p53 and diffuse c-Myc staining was also significantly associated with AS but not with HSVN or cavernous hemangioma. There have been no cases with rupture/hemorrhage, disseminated intravascular coagulation, or Kasabach-Merritt syndrome. Thus far, there has been no metastasis or recurrence of HSVN, but complete resection and close clinical follow-up are recommended because the outcome remains unknown.
authors.affiliation: University of California, San Francisco, Department of Pathology, San Francisco, California, United States, 94143. Electronic address: ryan.gill@ucsf.edu.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Gill
authors.affiliation: University of California, San Francisco, Department of Pathology, San Francisco, California, United States, 94143.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Buelow
authors.affiliation: University of California, San Francisco, Department of Pathology, San Francisco, California, United States, 94143.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Mather
authors.affiliation: University of California, San Francisco, Department of Pathology, San Francisco, California, United States, 94143.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Joseph
authors.affiliation: Universidade de Sao Paulo, Department of Pathology, Sao Paulo, Brazil, 05508-090.
authors.forename: Venancio
authors.initials: V
authors.lastname: Alves
authors.affiliation: Washington University, Department of Pathology and Immunology, St Louis, MO, United States, 63110.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Brunt
authors.affiliation: Washington University, Department of Pathology and Immunology, St Louis, MO, United States, 63110.
authors.forename: Ta-Chiang
authors.initials: TC
authors.lastname: Liu
authors.affiliation: NCI, NIH, Rockville, MD, United States, 20850.
authors.forename: Hala
authors.initials: H
authors.lastname: Makhlouf
authors.affiliation: Ottawa Hospital, Department of Pathology, Ottawa, Ontario, Canada, K1H 8L6.
authors.forename: Celia
authors.initials: C
authors.lastname: Marginean
authors.affiliation: Washington University, Department of Pathology and Immunology, St Louis, MO, United States, 63110.
authors.forename: ILKe
authors.initials: I
authors.lastname: Nalbantoglu
authors.affiliation: Institut Universitaire de Pathologie, CHUV, Lausanne, Switzerland, CH-1011.
authors.forename: Christine
authors.initials: C
authors.lastname: Sempoux
authors.affiliation: Fairview Southdale Hospital, Edina, MN, 55435; Department of Laboratory Medicine and Pathology, The University of Minnesota Medical School, Minneapolis, MN, 55435.
authors.forename: Dale C
authors.initials: DC
authors.lastname: Snover
authors.affiliation: Mount Sinai Health System, Department of Pathology, NY, New York, United States, 10029.
authors.forename: Swan N
authors.initials: SN
authors.lastname: Thung
authors.affiliation: University. of Washington, Department of Pathology, Seattle, Washington, United States, 98195.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.affiliation: University of California, San Francisco, Department of Pathology, San Francisco, California, United States, 94143.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Ferrell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D049109:Cell Proliferation; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics; D006392:Hemangioma, Cavernous / Q000473:pathology; D006394:Hemangiosarcoma / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008113:Liver Neoplasms / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011237:Predictive Value of Tests; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D009626:Terminology as Topic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D019043:Vascular Neoplasms / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000473:pathology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C554061:GNAQ protein, human; D019394:Ki-67 Antigen; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: Angiosarcoma; GNAQ; Hemangioma; Hepatic small vessel neoplasm; Liver