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Open Access 01-03-2012 | Original Article

Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age: implications for surveillance

Authors: Karin Y. van Spaendonck-Zwarts, Sadhanna Badeloe, Sjoukje F. Oosting, Sjoerd Hovenga, Harry J. F. Semmelink, R. Jeroen A. van Moorselaar, Jan Hein van Waesberghe, Arjen R. Mensenkamp, Fred H. Menko

Published in: Familial Cancer | Issue 1/2012

Abstract

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation carriers starting at the age of 20 years. However, recently an 18-year-old woman from a Dutch family with HLRCC presented with metastatic renal cancer. We describe the patient and family data, evaluate current evidence on renal cancer risk and surveillance in HLRCC and consider the advantages and disadvantages of starting surveillance for renal cancer in childhood. We also discuss the targeted therapies administered to our patient.

Linehan WM, Srinivasan R, Schmidt LS (2010) The genetic basis of kidney cancer: a metabolic disease. Nat Rev Urol 7:277–285PubMedCrossRef

Maher ER (2011) Genetics of familial renal cancers. Nephron Exp Nephrol 118:e21–e26PubMedCrossRef

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 31:1578–1585PubMedCrossRef

Grubb RL III, Franks ME, Toro J et al (2007) Hereditary leiomyomatosis and renal cell cancer: a syndrome associated with an aggressive form of inherited renal cancer. J Urol 177:2074–2080PubMedCrossRef

Lehtonen HJ (2011) Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics. Fam Cancer 10:397–411PubMedCrossRef

Tomlinson IPM, Alam NA, Rowan AJ et al (2002) The multiple leiomyoma consortium. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cancer. Nat Genet 30:406–410PubMedCrossRef

Alam NA, Barclay E, Rowan AJ et al (2005) Clinical features of multiple cutaneous and uterine leiomyomatosis: an underdiagnosed tumor syndrome. Arch Dermatol 141:199–206PubMedCrossRef

Wei M-H, 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 43:18–27PubMedCrossRef

Bayley JP, Launonen V, Tomlinson IP (2008) The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency. BMC Med Genet 9:20PubMedCrossRef

10.

Vahteristo P, Koski TA, Naatsaari L et al (2010) No evidence for a genetic modifier for renal cancer risk in HLRCC syndrome. Fam Cancer 9:245–251PubMedCrossRef

11.

Alrashdi I, Levine S, Paterson J et al (2010) Hereditary leiomyomatosis and renal cell carcinoma: very early diagnosis of renal cancer in a paediatric patient. Fam Cancer 9:239–243PubMedCrossRef

12.

Smit DL, Mensenkamp AR, Badeloe S et al (2011) Hereditary leiomyomatosis and renal cell cancer in families referred for fumarate hydratase germline mutation analysis. Clin Genet 79:49–59PubMedCrossRef

13.

Badeloe S, van Spaendonck-Zwarts KY, van Steensel MA et al (2009) Wilms tumour as a possible early manifestation of hereditary leiomyomatosis and renal cell cancer? Br J Dermatol 160:707–709PubMedCrossRef

14.

Badeloe S, Bladergroen RS, Jonkman MF et al (2008) Hereditary multiple cutaneous leiomyoma resulting from novel mutations in the fumarate hydratase gene. J Dermatol Sci 51:139–143PubMedCrossRef

15.

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

16.

Chan I, Wong T, Martinez-Mir A et al (2005) Familial multiple cutaneous and uterine leiomyomas associated with papillary renal cancer. Clin Exp Dermatol 30:75–78PubMedCrossRef

17.

Lehtonen HJ, Kiuru M, Ylisaukko-oja SK et al (2006) Increased risk of cancer in patients with fumarate hydratase germline mutation. J Med Genet 43:523–526PubMedCrossRef

18.

Lehtonen HJ, Blanco I, Piulats JM et al (2007) Conventional renal cancer in a patient with fumarate hydratase mutation. Hum Pathol 38:793–796PubMedCrossRef

19.

Al Refae M, Wong N, Patenaude F et al (2007) Hereditary leiomyomatosis and renal cancer: an unusual and aggressive form of hereditary renal carcinoma. Nat Clin Pract Oncol 4:256–261CrossRef

20.

Ghaninejad H, Moeineddin F, Rajaee A et al (2008) Hereditary leiomyomatosis and renal cell carcinoma syndrome: a case report. Dermatol Online J 14:16

21.

Ahvenainen T, Lehtonen HJ, Lehtonen R et al (2008) Mutation screening of fumarate hydratase by multiplex ligation-dependent probe amplification: detection of exonic deletion in a patient with leiomyomatosis and renal cell cancer. Cancer Genet Cytogenet 183:83–88PubMedCrossRef

22.

Rongioletti F, Fausti V, Ferrando B et al (2010) A novel missense mutation in fumarate hydratase in an Italian patient with a diffuse variant of cutaneous leiomyomatosis (Reed’s syndrome). Dermatology 221:378–380PubMedCrossRef

23.

Gardie B, Remenieras A, Kattygnarath D et al (2011) Novel FH mutations in families with hereditary leiomyomatosis and renal cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma. J Med Genet 48:226–234PubMedCrossRef

24.

Yamasaki T, Tran TAT, Oz OK et al (2011) Exploring a glycolytic inhibitor for the treatment of an FH-deficient type-2 papillary RCC. Nat Rev Urol 8:165–171PubMedCrossRef

25.

Meister M, Choyke P, Anderson C et al (2009) Radiological evaluation, management, and surveillance of renal masses in Von-Hippel-Lindau disease. Clin Radiol 64:589–600PubMedCrossRef

26.

Isaacs JS, Jung YJ, Mole DR et al (2005) HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell 8:143–153PubMedCrossRef

27.

Selak MA, Armour SM, MacKenzie ED et al (2005) Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 7:77–85PubMedCrossRef

28.

Choueiri TK, Atkins MB (2009) Targeted therapies: sunitinib in RCC-expanded access equals expanded benefit? Nat Rev Clin Oncol 6:679–680PubMedCrossRef

29.

Plimack ER, Tannir N, Lin E, Bekele BN, Jonasch E (2009) Patterns of disease progression in metastatic renal cell carcinoma patients treated with antivascular agents and interferon: impact of therapy on recurrence patterns and outcome measures. Cancer 115:1859–1866PubMedCrossRef

30.

Ravaud A, Bello CL (2011) Exposure-response relationships in patients with metastatic renal cell carcinoma receiving sunitinib: maintaining optimum efficacy in clinical practice. Anticancer Drugs 22:377–383PubMedCrossRef

31.

Dutcher JP, de Souza P, McDermott D et al (2009) Effect of temsirolimus versus interferon-alpha on outcome of patients with advanced renal cell carcinoma of different tumor histologies. Med Oncol 26:202–209PubMedCrossRef

32.

Chuang GS, Martinez-Mir A, Engler DE et al (2006) Multiple cutaneous and uterine leiomyomata resulting from missense mutations in the fumarate hydratase gene. Clin Exp Dermatol 31:118–121PubMedCrossRef

Title: Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age: implications for surveillance
Authors: Karin Y. van Spaendonck-Zwarts
Sadhanna Badeloe
Sjoukje F. Oosting
Sjoerd Hovenga
Harry J. F. Semmelink
R. Jeroen A. van Moorselaar
Jan Hein van Waesberghe
Arjen R. Mensenkamp
Fred H. Menko
Publication date: 01-03-2012
Publisher: Springer Netherlands
Published in: Familial Cancer / Issue 1/2012
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI: https://doi.org/10.1007/s10689-011-9491-5

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