Skip to main content

Advertisement

SpringerLink
Log in

Ovarian metastasis from uveal melanoma with MLH1/PMS2 protein loss in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence?

  • Brief Report
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Currently, uveal melanoma is not considered within the Lynch syndrome tumor spectrum. However, there are studies suggesting a contribution of microsatellite instability in sporadic uveal melanoma tumorigenesis. We report a 45-year-old woman who was referred for genetic counseling due to a family history of Lynch syndrome caused by a MLH1 mutation. She originally underwent enucleation of the right eye secondary to a uveal spindle cell melanoma diagnosed at age 25. The tumor recurred 22 years later presenting as an ovarian metastasis and concurrently a microscopic endometrial endometrioid carcinoma, grade 1/3 was diagnosed. Subsequent studies highlighted that the uveal melanoma showed high microsatellite instability and loss of MLH1 and PMS2 protein expression, with no MLH1 promoter methylation or BRAF mutation. Additionally, a GNAQ mutation was found. We conclude that our patient’s uveal melanoma is most likely related to MLH1 germline mutation and thus Lynch syndrome related. To the best of our knowledge, this is the first report of uveal melanoma showing MLH1/PMS2 protein loss in the context of Lynch syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Richman S (2015) Deficient mismatch repair: read all about it (review). Int J Oncol 47:1189–1202

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Watson P, Riley B (2005) The tumor spectrum in the Lynch syndrome. Familial Cancer 4:245–248

    Article  PubMed  Google Scholar 

  3. Karamurzin Y, Zeng Z, Stadler ZK et al (2012) Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature. Hum Pathol 43:1677–1687

    Article  CAS  PubMed  Google Scholar 

  4. Ponti G, Losi L, Pellacani G et al (2008) Malignant melanoma in patients with hereditary nonpolyposis colorectal cancer. The British journal of dermatology 159:162–168

    Article  CAS  PubMed  Google Scholar 

  5. Hussein MR, Haemel AK, Albert DM et al (2005) Microsatellite instability and alterations of mismatch repair protein expression in choroidal melanomas. Arch Ophthalmol 123:1705–1711

    Article  CAS  PubMed  Google Scholar 

  6. Boland CR, Thibodeau SN, Hamilton SR et al (1998) A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257

    CAS  PubMed  Google Scholar 

  7. Mancini I, Santucci C, Sestini R et al (2010) The use of COLD-PCR and high-resolution melting analysis improves the limit of detection of KRAS and BRAF mutations in colorectal cancer. The Journal of molecular diagnostics: JMD 12:705–711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Van Raamsdonk CD, Griewank KG, Crosby MB et al (2010) Mutations in GNA11 in uveal melanoma. N Engl J Med 363:2191–2199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jovanovic P, Mihajlovic M, Djordjevic-Jocic J et al (2013) Ocular melanoma: an overview of the current status. International journal of clinical and experimental pathology 6:1230–1244

    PubMed  PubMed Central  Google Scholar 

  10. Schoenfield L (2014) Uveal melanoma: a pathologist’s perspective and review of translational developments. Adv Anat Pathol 21:138–143

    Article  CAS  PubMed  Google Scholar 

  11. McCluggage WG, Bissonnette JP, Young RH (2006) Primary malignant melanoma of the ovary: a report of 9 definite or probable cases with emphasis on their morphologic diversity and mimicry of other primary and secondary ovarian neoplasms. International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 25:321–329

    Article  Google Scholar 

  12. Gupta D, Deavers MT, Silva EG et al (2004) Malignant melanoma involving the ovary: a clinicopathologic and immunohistochemical study of 23 cases. Am J Surg Pathol 28:771–780

    Article  PubMed  Google Scholar 

  13. Young RH, Scully RE (1991) Malignant melanoma metastatic to the ovary: a clinicopathologic analysis of 20 cases. Am J Surg Pathol 15:849–860

    Article  CAS  PubMed  Google Scholar 

  14. Mandato VD, Kobal B, Di Stefano A et al (2010) Choroidal melanoma metastasized to the ovary: case report and review of the literature. Eur J Gynaecol Oncol 31:109–113

    CAS  PubMed  Google Scholar 

  15. Yu VP, Novelli M, Payne SJ et al (2009) Unusual presentation of Lynch syndrome. Hereditary cancer in clinical practice 7:12

    Article  PubMed  PubMed Central  Google Scholar 

  16. Barrow E, Hill J, Evans DG (2013) Cancer risk in Lynch syndrome. Familial Cancer 12:229–240

    Article  CAS  PubMed  Google Scholar 

  17. Westin SN, Lacour RA, Urbauer DL et al (2008) Carcinoma of the lower uterine segment: a newly described association with Lynch syndrome. J Clin Oncol Off J Am Soc Clin Oncol 26:5965–5971

    Article  Google Scholar 

  18. Yu X, Ambrosini G, Roszik J et al (2015) Genetic analysis of the ‘uveal melanoma’ C918 cell line reveals atypical BRAF and common KRAS mutations and single tandem repeat profile identical to the cutaneous melanoma C8161 cell line. Pigment cell & melanoma research 28:357–359

    Article  CAS  Google Scholar 

  19. Alvino E, Marra G, Pagani E et al (2002) High-frequency microsatellite instability is associated with defective DNA mismatch repair in human melanoma. The Journal of investigative dermatology 118:79–86

    Article  CAS  PubMed  Google Scholar 

  20. Kim SJ, Kim HR, Kim SH et al (2014) hMLH1 promoter methylation and BRAF mutations in high-frequency microsatellite instability colorectal cancers not fulfilling the revised Bethesda guidelines. Annals of surgical treatment and research 87:123–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal

    João Lobo & Carla Bartosch

  2. Cancer Biology and Epigenetics Group, Research Center (CI-IPOP), Portuguese Oncology Institute of Porto, Porto, Portugal

    João Lobo, Micaela Freitas, Carmen Jerónimo & Carla Bartosch

  3. Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal

    João Lobo, Manuel R. Teixeira & Carmen Jerónimo

  4. Department of Genetics, Portuguese Oncology Institute of Porto, Porto, Portugal

    Carla Pinto, Manuela Pinheiro & Manuel R. Teixeira

  5. Department of Pathology, Centro Hospitalar do Porto, Porto, Portugal

    Rámon Vizcaino

  6. James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, MA, USA

    Esther Oliva

  7. Department of Pathology, Harvard Medical School, Boston, MA, USA

    Esther Oliva

  8. Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal

    Carla Bartosch

Authors
  1. João Lobo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carla Pinto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Micaela Freitas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manuela Pinheiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rámon Vizcaino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Esther Oliva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Manuel R. Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Carmen Jerónimo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carla Bartosch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carla Bartosch.

Ethics declarations

Funding

This study was supported by the IPO Porto Research Center (CI-IPOP) (Financiamento Base_GOG-n° 26 and Financiamento Base_GEBC-n° 27). MP is a research fellow with a grant from the Fundação para a Ciência e Tecnologia (FCT) (SFRH/BPD/113014/2015).

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lobo, J., Pinto, C., Freitas, M. et al. Ovarian metastasis from uveal melanoma with MLH1/PMS2 protein loss in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence?. Virchows Arch 470, 347–352 (2017). https://doi.org/10.1007/s00428-016-2052-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-016-2052-4

Keywords

Search

Navigation