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.
Similar content being viewed by others
Abbreviations
- MMR:
-
DNA mismatch repair
- MFH:
-
Malignant fibrous histiocytoma
- MSI:
-
Microsatellite instability
References
Lynch HT, de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348(10):919–932
Hampel H, Frankel WL, Martin E et al (2005) Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 352(18):1851–1860
Vasen HF, Moslein G, Alonso A et al (2007) Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet 44(6):353–362
Umar A, Boland CR, Terdiman JP et al (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96(4):261–268
Meyer C, Brieger A, Plotz G et al (2009) An interstitial deletion at 3p21.3 results in the genetic fusion of MLH1 and ITGA9 in a Lynch syndrome family. Clin Cancer Res 15(3):762–769
Walsh MD, Buchanan DD, Cummings MC et al (2010) Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry. Clin Cancer Res 16(7):2214–2224.
Bauer CM, Ray AM, Halstead-Nussloch BA et al (2011) Hereditary prostate cancer as a feature of Lynch syndrome. Fam Cancer 10(1):37–42
Arana VM, del Pino YB, Garcia-Castro C, Gonzalez-Aguilera JJ, Fernandez-Peralta A, Hermoso FG (2002) Highly aggressive leiomyosarcoma associated with Lynch II syndrome: increasing the range of extracolonic cancers related with hereditary non-polyposis colonic cancer. Annals Oncol 13(5):807–808
den Bakker MA, Seynaeve C, Kliffen M, Dinjens WN (2003) Microsatellite instability in a pleomorphic rhabdomyosarcoma in a patient with hereditary non-polyposis colorectal cancer. Histopathology 43(3):297–299
Sijmons R, Hofstra R, Hollema H et al (2000) Inclusion of malignant fibrous histiocytoma in the tumour spectrum associated with hereditary non-polyposis colorectal cancer. Genes Chromosom Cancer 29(4):353–355
Kratz CP, Holter S, Etzler J et al (2009) Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome. J Med Genet 46(6):418–420
Hirata K, Kanemitsu S, Nakayama Y et al (2006) A novel germline mutation of MSH2 in a hereditary nonpolyposis colorectal cancer patient with liposarcoma. J Gastroenterol 101(1):193–196
Nilbert M, Therkildsen C, Nissen A, Akerman M, Bernstein I (2009) Sarcomas associated with hereditary nonpolyposis colorectal cancer: broad anatomical, morphological spectrum. Familial Cancer 8(3):209–213
Pineda M, Gonzalez S, Lazaro C, Blanco I, Capella G (2010) Detection of genetic alterations in hereditary colorectal cancer screening. Mutat Res 693(1–2):19–31
Liu B, Parsons RE, Hamilton SR et al (1994) hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds. Cancer Res 54(17):4590–4594
Kolodner RD, Hall NR, Lipford J et al (1995) Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlh1 mutations. Cancer Res 55(2):242–248
Hampel H, Frankel W, Panescu J et al (2006) Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res 66(15):7810–7817
Martin SS, Hurt WG, Hedges LK, Butler MG, Schwartz HS (1998) Microsatellite instability in sarcomas. Ann Surg Oncol 5(4):356–360
Vasen HF, Stormorken A, Menko FH et al (2001) MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J Clin Oncol 19(20):4074–4080
Shinjo K (1994) Analysis of prognostic factors, chemotherapy of malignant fibrous histiocytoma of soft tissue: a preliminary report. Jpn J Clin Oncol 24(3):154–159
Weiss SW, Enzinger FM (1978) Malignant fibrous histiocytoma: an analysis of 200 cases. Cancer 41(6):2250–2266
Matushansky I, Charytonowicz E, Mills J, Siddiqi S, Hricik T, Cordon-Cardo C (2009) MFH classification: differentiating undifferentiated pleomorphic sarcoma in the 21st Century. Expert Rev Anticancer Ther 9(8):1135–1144
Acknowledgments
This work was supported by a grant from the Wilhelm Sander Foundation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Brieger, A., Engels, K., Schaefer, D. et al. Malignant fibrous histiocytoma is a rare Lynch syndrome-associated tumor in two German families. Familial Cancer 10, 591–595 (2011). https://doi.org/10.1007/s10689-011-9455-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-011-9455-9