title: Colorectal Choriocarcinoma in a Patient with Probable Lynch Syndrome.
abstract: BACKGROUND
  Personalized therapy of colorectal cancer is influenced by morphological, molecular, and host-related factors. Here, we report the comprehensive clinicopathological and molecular analysis of an extra-gestational colorectal choriocarcinoma in a patient with probable Lynch syndrome.
  
  
  METHODS
  A 61-year-old female with history of gastric cancer at age 36 presented with a transmurally invasive tumor of the right hemicolon and liver metastasis. A right hemicolectomy was performed. Histopathological analysis showed a mixed trophoblastic and syncytiotrophoblastic differentiation, consistent with choriocarcinoma. Disease progression was rapid under oxaliplatin, capecitabine, irinotecan, and bevacizumab. Molecular phenotyping identified loss of mismatch-repair protein immunostaining for PMS2, microsatellite instability, a lack of MLH1 promoter methylation, and lack of BRAF mutation suggestive of Lynch syndrome. Targeted next-generation sequencing revealed an ataxia telangiectasia mutated (p.P604S) missense mutation. A bleomycin, etoposide, and cisplatin treatment protocol targeting germ cell neoplasia lead to disease remission and prolonged survival of 34 months.
  
  
  CONCLUSIONS
  Comprehensive immunohistochemical and genetic testing is essential to identify uncommon cancers possibly related to Lynch syndrome. For rare tumors, personalized therapeutic approaches should take both molecular and morphological information into account.
authors.affiliation: Cantonal Hospital Baselland, Institute of Pathology, Liestal, Switzerland; Translational Research Unit (TRU), Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Viktor H
authors.initials: VH
authors.lastname: Koelzer
authors.affiliation: Radio Onkologie Allschwil , Allschwil , Switzerland.
authors.forename: Karl
authors.initials: K
authors.lastname: Steuer
authors.affiliation: Division of Diagnostic Molecular Pathology, University Hospital Zürich , Zürich , Switzerland.
authors.forename: Ulrike Camenisch
authors.initials: UC
authors.lastname: Gross
authors.affiliation: Division of Diagnostic Molecular Pathology, University Hospital Zürich , Zürich , Switzerland.
authors.forename: Dieter
authors.initials: D
authors.lastname: Zimmermann
authors.affiliation: Cantonal Hospital Baselland, Institute of Pathology , Liestal , Switzerland.
authors.forename: Aino
authors.initials: A
authors.lastname: Paasinen-Sohns
authors.affiliation: Cantonal Hospital Baselland, Institute of Pathology , Liestal , Switzerland.
authors.forename: Kirsten D
authors.initials: KD
authors.lastname: Mertz
authors.affiliation: Cantonal Hospital Baselland, Institute of Pathology , Liestal , Switzerland.
authors.forename: Gieri
authors.initials: G
authors.lastname: Cathomas
keywords: Lynch syndrome; ataxia telangiectasia mutated; choriocarcinoma; colorectal cancer; microsatellite instability; molecular pathology; next-generation sequencing; personalized medicine