Malignant fibrous histiocytoma is a rare Lynch syndrome-associated tumor in two German families

Fam Cancer. 2011 Sep;10(3):591-5. doi: 10.1007/s10689-011-9455-9.

Abstract

Lynch syndrome is characterized by germline mutations of the DNA mismatch repair genes MLH1 and MSH2. The tumor spectrum includes early onset colorectal, urogenital and other cancers. Soft tissue sarcomas have been anecdotally reported in patients with Lynch syndrome, but coincidental manifestation could not be excluded. In this report, we screened a cohort of Lynch syndrome families for tumors outside the established tumor spectrum. We identified two patients with Lynch syndrome and a malignant fibrous histiocytoma (MFH). In both families a causative MSH2 germline mutation (MSH2 c.2038C ≥ T or MSH2 c.942 ± 3A ≥ T) could be detected. Archival tumor material from both resected MFH was analyzed for microsatellite instability expression of MLH1 and MSH2. A mutator phenotype was detected in both MFH with loss of MSH2 protein expression. Subsequently, the causative MSH2 germline mutation was confirmed in both patients. Of note, both tumors were diagnosed at a local advanced stage but could be curatively resected 21 and 11 year ago, respectively. Both patients are alive without local or distant recurrence. In conclusion, our data further support that patients with Lynch syndrome are at increased risk for rare tumors such as MFH. However, the prognosis compared to sporadic MFH seems to be favorable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Colorectal Neoplasms, Hereditary Nonpolyposis / complications*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • DNA Mismatch Repair / genetics
  • Family
  • Female
  • Germ-Line Mutation / genetics*
  • Germany
  • Histiocytoma, Malignant Fibrous / etiology*
  • Histiocytoma, Malignant Fibrous / pathology
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Microsatellite Instability
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics*
  • MutS Homolog 2 Protein / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • MLH1 protein, human
  • Nuclear Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein