title: Case study of the morphologic variation of circulating tumor cells.
abstract: We report a detailed cytomorphologic evaluation of the circulating component of widely metastatic breast carcinoma. A previously healthy 38-year-old woman was diagnosed with breast cancer. Wide local excision revealed a 1.7-cm infiltrating ductal adenocarcinoma, BSR score 7/9 with angiolymphatic invasion, and 4/20 lymph nodes positive for carcinoma. Five years later, a bone marrow biopsy revealed involvement of bone marrow by metastatic breast carcinoma, and shortly thereafter, metastases were identified in the liver and lung hilum. She enrolled in a clinical investigation for the detection of circulating tumor cells (CTCs) in breast carcinoma. A total of 659 CTCs were identified in a 10-mL blood sample using an immunofluorescent protocol targeting cytokeratins and detected using fiber-optic array scanning technology. The detected CTCs were subsequently stained with a Wright-Giemsa stain, and representative cells were evaluated in detail by light microscopy for morphologic evaluation. We find that the patient's CTCs exhibit a high degree of pleomorphism including CTCs with high and low nuclear-to-cytoplasmic ratios along with CTCs exhibiting early and late apoptotic changes. In addition, in comparison with her tumor cells in other sites, the full morphologic spectrum of cancer cells present in primary and metastatic tumor is also present in peripheral blood circulation.
authors.affiliation: The Scripps-PARC Institute for Advanced Biomedical Science, Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Dena
authors.initials: D
authors.lastname: Marrinucci
authors.forename: Kelly
authors.initials: K
authors.lastname: Bethel
authors.forename: Richard H
authors.initials: RH
authors.lastname: Bruce
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Curry
authors.forename: Ben
authors.initials: B
authors.lastname: Hsieh
authors.forename: Mark
authors.initials: M
authors.lastname: Humphrey
authors.forename: Robert T
authors.initials: RT
authors.lastname: Krivacic
authors.forename: Joan
authors.initials: J
authors.lastname: Kroener
authors.forename: Lindsay
authors.initials: L
authors.lastname: Kroener
authors.forename: Andras
authors.initials: A
authors.lastname: Ladanyi
authors.forename: Nicole H
authors.initials: NH
authors.lastname: Lazarus
authors.forename: Jorge
authors.initials: J
authors.lastname: Nieva
authors.forename: Peter
authors.initials: P
authors.lastname: Kuhn
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology*; D003592:Cytophotometry; D017809:Fatal Outcome; D005260:Female; D005336:Fiber Optic Technology; D006801:Humans; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D055100:Optical Fibers