Pseudomyxoma peritonei of a mature ovarian teratoma caused by mismatch repair deficiency in a patient with Lynch syndrome: a case report

BMC Med Genet. 2016 Dec 9;17(1):94. doi: 10.1186/s12881-016-0356-5.

Abstract

Background: Pseudomyxoma peritonei (PMP) is a rare disease with an estimated incidence of 1-2 cases per million individuals per year. PMP is characterized by the accumulation of abundant mucinous or gelatinous fluid derived from disseminated tumorous cells. Most of the tumorous cells are originated from rupture of appendiceal neoplasms, but some are from the metastasis of cancer of the colon, ovary, fallopian tube, urachus, colorectum, gallbladder, stomach, pancreas, lung and breast. Although frequent mutations in KRAS and/or GNAS genes have been reported, precise molecular mechanism underlying PMP remains to be elucidated. It is of note that mucinous tumour is one of the frequent histological features of colorectal cancer (CRC) in Lynch syndrome (LS), an autosomal dominantly inherited disease caused by a germline mutation of the DNA mismatch repair (MMR) genes including human mutL homolog 1 (MLH1), human mutS homolog 2 (MSH2), human mutS homolog 6 (MSH6), and postmeiotic segregation increased 2 (PMS2). Therefore, typical LS-associated tumours show mismatch repair instability. Although LS patients are most strongly predisposed to CRC, PMPs from mucinous CRC have not been reported in LS patients.

Case presentation: In this report, we report a case of PMP originating from an ovarian teratoma in a LS patient. The patient had surgical treatment of PMP arising from an ovarian teratoma at the age of 38 years, and later developed a transverse colon cancer at the age of 40. The patient's family history fulfilled the Amsterdam criteria, and genetic analysis of the peripheral leukocytes identified a germ line mutation in the MLH1 gene (MLH1 c.1546dupC p.Q516PfsX3). Interestingly, immunohistochemical staining showed that the expression of MLH1 was lost in the colon cancer as well as the ovarian teratoma. Consistent with the loss of MLH1 expression, both tumours showed high microsatellite instability (MSI-H).

Conclusion: This case suggested that LS patients may develop various types of tumours including ovarian PMP, and that mismatch repair deficiency may play a role in the development of PMP derived from, at least, a part of ovarian teratomas.

Keywords: Lynch syndrome; Microsatellite instability; Mismatch repair; Ovarian teratoma; Pseudomyxoma peritonei.

Publication types

  • Case Reports

MeSH terms

  • Abdomen / diagnostic imaging
  • Adult
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / secondary
  • Colorectal Neoplasms, Hereditary Nonpolyposis / complications*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • DNA / chemistry
  • DNA / isolation & purification
  • DNA / metabolism
  • DNA Mismatch Repair
  • Female
  • Germ-Line Mutation
  • Humans
  • Magnetic Resonance Imaging
  • Microsatellite Instability
  • MutL Protein Homolog 1 / genetics
  • Ovarian Neoplasms / complications*
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics*
  • Pedigree
  • Pseudomyxoma Peritonei / complications*
  • Pseudomyxoma Peritonei / genetics*
  • Pseudomyxoma Peritonei / surgery
  • Recurrence
  • Teratoma / complications*
  • Teratoma / diagnosis
  • Teratoma / genetics*
  • Tomography, X-Ray Computed

Substances

  • MLH1 protein, human
  • DNA
  • MutL Protein Homolog 1

Supplementary concepts

  • Teratoma, Ovarian