Skip to main content

Advertisement

SpringerLink
Log in

Expanding morphological and clinical aspects of hereditary leiomyomatosis and renal cell carcinoma (HLRCC): a case report in a patient with unusual morphology and clinical presentation

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

Abstract

Renal cell carcinoma (RCC) accounts for 2–3% of all malignant disease in adults. Hereditary RCC represents 5 to 8% of kidney tumors. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) represents an autosomal dominant syndrome that results from a germline mutation in fumarate hydratase gene (FH). HLRCC patients typically present with skin or uterine leiomyomas and renal neoplasms. HLRCC was recently recognized as a distinct renal tumor subtype by the WHO 2016 classification. Many morphological patterns such as papillary, solid, tubular, and cystic had been described as part of morphological aspects of HLRCC. In this study, we describe a case of a patient that had a history of persistence of ductus arteriosus (PDA) and cryptorchidism. In addition, the renal tumor showed a very unusual hystiocytoid morphological aspect. We confirmed the presence of a FH germline mutation both in the patient and his mother.

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. King SC, Pollack LA, Li J et al (2014 Jun) Continued increase in incidence of renal cell carcinoma, especially in young patients and high grade disease: United States 2001 to 2010. J Urol 191(6):1665–1670

    Article  Google Scholar 

  2. Shuch B, Vourganti S, Ricketts CJ, Middleton L, Peterson J, Merino MJ, Metwalli AR, Srinivasan R, Linehan WM (2014 Feb 10) Defining early-onset kidney cancer: implications for germline and somatic mutation testing and clinical management. J Clin Oncol 32(5):431–437

    Article  Google Scholar 

  3. Linehan WM, Bratslavsky G, Pinto PA, Schmidt LS, Neckers L, Bottaro DP et al (2010) Molecular diagnosis and therapy of kidney cancer. Annu Rev Med 61:329–343

    Article  CAS  Google Scholar 

  4. Sanz-Ortega J, Vocke C, Stratton P, Linehan WM, Merino MJ (2013 Jan) Morphologic and molecular characteristics of uterine leiomyomas in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome. Am J Surg Pathol 37(1):74–80

    Article  Google Scholar 

  5. Moch H, Cubilla AL, Humphrey PA et al (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs—part a: renal, penile, and testicular tumours. Eur Urol 70:93–105

    Article  Google Scholar 

  6. Merino MJ, Torres-Cabala C, Pinto P et al (2007) The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Am J Surg Pathol 31:1578–1585

    Article  Google Scholar 

  7. Wei MH, Toure O, Glenn GM et al (2006) Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer. J Med Genet 43:18–27

    Article  CAS  Google Scholar 

  8. Smith SC, Trpkov K, Chen YB, Epstein JI et al (2016) Tubulocystic carcinoma of the kidney with poorly differentiated foci: a frequent morphologic pattern of fumarate hydratase-deficient renal cell carcinoma. Am J Surg Pathol 40(11):1457–1472

    Article  Google Scholar 

  9. Reed WB, Walker R, Horowitz R (1973) Cutaneous leiomyomata with uterine leiomyomata. Acta Derm Venereol 53:409–416

    CAS  PubMed  Google Scholar 

  10. Launonen V, Vierimaa O, Kiuru M, Isola J, Roth S, Pukkala E, Sistonen P, Herva R, Aaltonen LA (2001) Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci U S A 98:3387–3392

    Article  CAS  Google Scholar 

  11. Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, Leigh I et al (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 30:406–410

    Article  CAS  Google Scholar 

  12. Toro JR, Nickerson ML, Wei MH et al (2003) Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. Am J Hum Genet 73:95–106

    Article  CAS  Google Scholar 

  13. Trpkov K, Hes O, Agaimy A et al (2016) Fumarate hydratase-deficient renal cell carcinoma is strongly correlated with fumarate hydratase mutation and hereditary leiomyomatosis and renal cell carcinoma syndrome. Am J Surg Pathol 40:865–875

    Article  Google Scholar 

  14. Bardella C, El-Bahrawy M, Frizzell N et al (2011) Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status. J Pathol 225:4–11

    Article  CAS  Google Scholar 

  15. Tolvanen J, Uimari O, Ryynänen M et al (2012) Strong family history of uterine leiomyomatosis warrants fumarate hydratase mutation screening. Hum Reprod 27(6):1865–1869

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, AC Camargo Cancer Center, Rua Professor Antônio Prudente 211, São Paulo, 01509-900, Brazil

    Isabela Werneck da Cunha, Mariana A. Morini, Stephania Martins Bezerra, Dirce Maria Carraro, Giovana Tardin Torrezan & Fernando Augusto Soares

  2. National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation, São Paulo, Brazil

    Isabela Werneck da Cunha, Dirce Maria Carraro, Giovana Tardin Torrezan & Fernando Augusto Soares

  3. Department of Pathology, Rede D’OR-São Luiz, São Paulo, Brazil

    Isabela Werneck da Cunha, Mariana A. Morini & Fernando Augusto Soares

  4. Department of Urology, AC Camargo Cancer Center, São Paulo, Brazil

    Walter Henriques da Costa, Gustavo Cardoso Guimaraes & Stenio Cassio Zequi

  5. Department of Oncogenetics, AC Camargo Cancer Center, São Paulo, Brazil

    Maria Nirvana Cruz Formiga

Authors
  1. Isabela Werneck da Cunha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Walter Henriques da Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mariana A. Morini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stephania Martins Bezerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dirce Maria Carraro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giovana Tardin Torrezan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maria Nirvana Cruz Formiga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gustavo Cardoso Guimaraes
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stenio Cassio Zequi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fernando Augusto Soares
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isabela Werneck da Cunha.

Ethics declarations

This work was funded by the Department of Pathology of AC Camargo Cancer Center. The authors declare that they have no conflict of interest. This work was approved by the local ethics committee, number EC47/17.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

da Cunha, I.W., da Costa, W.H., Morini, M.A. et al. Expanding morphological and clinical aspects of hereditary leiomyomatosis and renal cell carcinoma (HLRCC): a case report in a patient with unusual morphology and clinical presentation. Virchows Arch 473, 775–779 (2018). https://doi.org/10.1007/s00428-018-2420-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-018-2420-3

Keywords

Search

Navigation