REVIEW ARTICLE
Review of hereditary leiomyomatosis renal cell carcinoma with focus on clinical and pathobiological aspects of renal tumors
Submission date: 2016-03-26
Acceptance date: 2017-10-05
Publication date: 2018-03-06
Pol J Pathol 2017;68(4):284-290
KEYWORDS
TOPICS
ABSTRACT
The entity of hereditary leiomyomatosis renal cell carcinoma (HLRCC)-associated RCC has been proposed and integrated into the recent International Society of Urologic Pathology (ISUP) of renal tumors. This tumor is characterized by presence of cutaneous and/or uterine leiomyomas and RCC and autosomal dominant hereditary form. Grossly, HLRCC arising in the kidney show the solid tumor with frequent partial cystic area. Microscopically, the tumor typically shows papillary RCC, type 2, with eosinophilic large nucleoli reminiscent of cytomegaloviral inclusion and perinuclear clearing/haloes. Immunohistochemically, tumor cells show the overexpression for 2SC and reduced expression of FH. Germline mutation of fumarate hydratase (FH) gene, the HLRCC responsible gene mapped to chromosome 1q43, has been identified in patients with HLRCC. As the renal cancer in patients with HLRCC generally behave aggressively even in a small size, complete surgical resection and retroperitoneal lymph node resection should be performed promptly when the tumor is discovered. The surveillance of renal tumor in FH gene germline mutation-positive patients should be started from the early age using ultrasound sonography or magnetic resonance imaging.
REFERENCES (84)
1.
Kloepfer HW, Krafchuk J, Derbres V, et al. Hereditary multiple leiomyoma of the skin. Am J Hum Genet 1958; 10: 48-52.
2.
Reed WB, Walker R, Horowitz R. Cutaneous leiomyomata with uterine leiomyomata. Acta Derm Venereol 1973; 53: 409-416.
3.
Launonen V, Vierimaa O, Kiuru M, et al. Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci USA 2001; 98: 3387-3392.
4.
Kiuru M, Launonen V, Hietala M, et al. Familial cutaneous leiomyomatosis is a two-hit condition associated with renal cell cancer of characteristic histopathology. Am J Pathol 2001; 159: 825-829.
5.
Tomlinson IP, Alam NA, Rowan AJ, et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 2002; 30: 406-410.
6.
Srigley JR, Delahunt B, Eble JN, et al. International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. Am J Surg Pathol 2013; 37: 1469-1489.
7.
Smit DL, Mensenkamp AR, Badeloe S, et al. Hereditary leiomyomatosis and renal cell cancer in families referred for fumarate hydratase germline mutation analysis. Clin Genet 2011; 79: 49-59.
8.
Schmidt LS, Linehan WM. Hereditary leiomyomatosis and renal cell carcinoma. Int J Nephrol Renovasc Dis 2014; 7: 253-260.
9.
Toro JR, Nickerson ML, Wei MH, et al. Mutation in the fumarate hydratase gene case hereditary leiomyomatosis and renal cell cancer in families in North America. Am J Hum Genet 2003; 73: 95-106.
10.
Pfaffenroth EC, Linehan WM. Genetic basis for kidney cancer. Expert Opin Biol Ther 2008; 8: 779-790.
11.
Rosner I, Bratslavsky G, Pinto PA, et al. The clinical implications of the genetics of renal cell carcinoma. Urol Oncol 2009; 27: 131-136.
12.
Folkins AK, Longacre TA. Hereditary gynaecological malignancies: advances in screening and treatment. Histopathology 2013; 62: 2-30.
13.
Surch B, Linehan WM, Srinivasan R. Aerobic glycolysis: A novel target in kidney cancer. Expert Rev Anticancer Ther 2013; 13: 711-719.
14.
Randall JM, Millard F, Kurzrock R. Molecular aberrations, targeted therapy, and renal cell carcinoma: current state-of-the art. Cancer Metastasis Rev 2014; 33: 1109-1124.
15.
Merino MJ, Torres-Cabala C, Pinto P, et al. The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Am J Surg Pathol 2007; 31: 1578-1585.
16.
Chen YB, Brannon AR, Toubaji A, et al. Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer Recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry. Am J Surg Pathol 2014; 38: 627-637.
17.
Wong MH, Tan CS, Lee SC, et al. Potential genetic anticipation in hereditary leiomyomatosis-renal cell cancer (HLRCC). Fam Cancer 2014; 13: 281-289.
18.
Refae MAI, Wong N, Patenaude F, et al. Hereditary leiomyomatosis and renal cell cancer: an unusual and aggressive form of hereditary renal carcinoma. Nat Clin Prac 2007; 4: 256-261.
19.
Alrashdi I, Levine S, Paterson J, et al. Hereditary leiomyomatosis renal cell carcinoma: very early diagnosis of renal cancer in a paediatric patient. Fam Cancer 2010; 9: 239-243.
20.
van Spaendonck-Zwarts KY, Badeloe S, Oosting SF, et al. Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age: implications for surveillance. Fam Cancer 2012; 11: 123-129.
21.
Lehtonen HJ, Kiuru M, Ylisaukko-oja SK, et al. Increased risk of cancer in patients with fumarate hydratase germline mutation. J Med Genet 2006; 43: 523-526.
22.
Linehan WM, Pinto PA, Bratslavsky G, et al. Hereditary kidney cancer. Unique opportunity for disease-based therapy. Cancer 2009; 115: 2252-2261.
23.
Lencastre A, Cabete J, Goncalves R, et al. Cutaneous leiomyomatosis in a mother and daughter. An Bras Dermatol 2013; 88: 124-127.
24.
Kakar R, Davis JC, Crowe DR. Multiple linear leiomyomas of the forehead as the presenting sign of Reed syndrome. Int.
26.
Udager AM, Alva A, Chen YB, et al. hereditary leiomyomatosis and renal cell carcinoma (HLRCC). A rapid of autopsy report of metastatic renal cell carcinoma. Am J Surg Pathol 2014; 38: 567-577.
27.
Hayedeh G, Fatemeh M, Ahmadreza R, et al. Hereditary leiomyomatosis and renal cell carcinoma syndrome: A case report. Dermatol Online J 2008; 14: 16.
28.
Kamai T, Tomosugi N, Abe H, et al. Protein profiling of blood samples from patients with hereditary leiomyomatosis and renal cell cancer by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Int J Med Sci 2012; 13 14518-14532.
29.
Venables ZC, Ramaiya A, Holden S, et al. Hereditary leiomyomatosis associated with renal cell carcinoma. Clin Exp Dermatol 2014; 40: 99-100.
30.
Marque M, Gardie B, Bressac B, et al. Novel FH mutation in a patient with cutaneous leiomyomatosis associated with cutis verticis gyrate, eruptive collagenoma and Charcot-Marie-Tooth disease. Br J Dermatol 2010; 163: 1337-1339.
31.
McKelvey KD, Siraj S, Kelsay J, et al. Male infertility associated with hereditary leiomyomatosis and renal cell carcinoma. Fertil Steril 2010; 93: 2075e1-e2.
32.
Huller C, Grunow N, Nadler T, et al. Cutaneous and uterine leiomyomatosis and ovarian cystadenoma associated with deficiency of fumarate hydratase. Dermatol Pract Concept 2011; 1: 7.
33.
Shuch B, Ricketts CJ, Vocke CD, et al. Adrenal nodular hyperplasia in hereditary leiomyomatosis and renal cell cancer. J Urol 2013; 189: 430-435.
34.
Lee JJ, Nambudiri VE, Henneberry J, et al. Post-transplant diagnosis of hereditary leiomyomatosis and renal cell carcinoma syndrome in a kidney donar. Clin Kindey J 2014; 7: 615-616.
35.
Mustafa S, Jadidi N, Faraj SF, et al. Case of hereditary papillary renal cell carcinoma. J Comm Hosp Int Med Perspect 2011; 1: 9468.
36.
Benes CL, Schlegel C, Shoukier M, et al. Hereditary papillary renal cell carcinoma primarily diagnosed in a cervical lymph nodes: a case report of a 30-year-old woman with multiple metastasis. BMC Urol 2013; 13: 3.
37.
Kuwada M, Chihara Y, Lou Y, et al. Novel missense mutation in the FH gene in familial renal cell cancer patients lacking cutaneous leiomyomas. BMC Res Notes 2014; 7: 203.
38.
Lehtonen HJ, Blanco I, Piulats JM, et al. Conventional renal cancer in a patient with fumarate hydratase mutation. Hum Pathol 2007; 38: 793-796.
39.
Soni SS, Gowrishankar S, Adlkey GK, et al. Hereditary leiomyomatosis with renal cell carcinoma. Indian J Dermatol Venereol Leprol 2008; 74: 63-64.
40.
Ristau BT, Kamat SN, Tarin TV. Abnormal cystic tumor in a patient with hereditary leiomyomatosis and renal cell cancer syndrome: evidence of a precursor lesion? Case Rep Urol 2015; 2015: 303872.
41.
Crumley S, Divatia M, Troung L, et al. Renal cell carcinoma: evolving and emerging subtypes. World J Clin Cases 2013; 16: 262-275.
42.
Eng C, Kiuru M, Fernandez MJ, et al. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev 2003; 3: 193-202.
43.
Linehan WM, Vasselli J, Srinivasan R, et al. Genetic basis of cancer of the kidney: disease-specific approaches to therapy. Clin Cancer Res 2004; 10: 6282s-6289s.
44.
Chan I, Wing T, Martinez-Mir A, et al. Familial multiple cutaneous and uterine leiomyomas associated with papillary renal cell cancer. Clin Exp Dermatol 2005; 30: 75-78.
45.
Gardie B, Remenieras A, Kattygnarath D, et al. Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma. J Med Genet 2011; 48: 226-234.
46.
Maher ER. Genetics of familial renal cancers. Nephron Exp Nephrol 2011; 118: e21-e26.
47.
Singer EA, Bratlavsky G, Middelton L, et al. Impact of genetics on the diagnosis and treatment of renal cancer. Curr Urol Rep 2011; 12: 47-55.
48.
Raymond VM, Herron CM, Giordano TJ, et al. Familial renal cancer as an indicator of hereditary leiomyomatosis and renal cell cancer syndrome. Fam Cancer 2012; 11: 115-121.
49.
de Velasco G, Munoz C, Sepulveda JM, et al. Sequential treatments in hereditary leiomyomatosis and renal cell carcinoma (HLRCC): Case report and review of the literature. Can Urol Assoc 2015; 9: E243-6.
50.
Kiuru M, Kujala M, Aittomäki K. Inherited forms of renal cell carcinoma. Scand J Surg 2004; 93: 103-111.
51.
Haas NB, Nathanson KL. Hereditary renal cancer syndromes. Adv Chronic Kidney Dis 2014; 21: 81-90.
52.
Badeloe S, van Spaendonck-Zwarts KY, van Steensel MAM, et al. Wilms tumour as a possible early manifestation of hereditary leiomyomatosis and renal cell cancer? Br J Dermatol 2009; 160: 707-709.
53.
Harris M, Wallace J, Winship I, et al. Hereditary renal cell carcinoma: the clue can be in the skin. Int Med J 2009; e12-e13.
54.
Rongioletti F, Fausti V, Ferrando B, et al. A novel missense mutation in fumarate hydratase in a Italian patient with a diffuse variant of cutaneous leiomyomatosis (Reed’s syndrome). Dermatology 2010; 221: 378-380.
55.
Linehan WM, Pinto PA, Srinivasan R, et al. Identification of the genes for kidney cancer: opportunity for disease-specific targeted therapeutics. Clin Cancer Res 2007; 13: 671s-679s.
56.
Stewart L, Glenn GM, Stratton P, et al. Association of germline mutations in the fumarate hydratase gene and uterine fibroids in women with hereditary leiomyomatosis and renal cell cancer. Arch Dermatol 2008; 144: 1584-1592.
57.
Garg K, Tickoo SK, Soslow RA, et al. Morphologic features of uterine leiomyomas associated with hereditary leiomyomatosis and renal cell carcinoma syndrome: A case report. Am J Surg Pathol 2011; 35: 1235-1237.
58.
Sanz-Ortega J, Vocke C, Stratton P, et al. Morphologic and molecular characteristics of uterine leiomyomas in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome. Am.
60.
Mann ML, Ezzati M, Tarnawa ED, et al. Fumarate hydratase mutation in a young woman with uterine leiomyoma and a family history of renal cell cancer. Obstet Gynecol 2015; 126: 90-92.
61.
Martinek P, Grossmann P, Hes O, et al. genetic testing of leiomyoma tissue in women younger than 30 years old might provide an effective screening approach for the hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC). Virchows Arch 2015; 467: 185-191.
62.
Ulamec M, Skenderi F, Zhou M, et al. Molecular genetic alterations in renal cell carcinoma with tubulocystic pattern: tubulocystic renal cell carcinoma, tubulocystic renal cell carcinoma with heterogeneous component and familial leiomyomatosis-associated renal cell carcinoma. Clinicopathological and molecular genetic analysis of 15 cases. App Immunohistochem Mol Morphol 2016; 24: 521-530.
63.
Orseth ML, Redick D, Pinczewski J, et al. Something to Reed about Fibroids, cutaneous leiomyomas, and renal cell carcinoma. Am J Obstet Gynecol 2014; 210: 584e1-2.
64.
Stewart L, Glenn G, Toro JR. Cutaneous leiomyomas: a clinical marker of risk for hereditary leiomyomatosis and renal cell cancer. Dematol Nurs 2006; 18: 335-341.
65.
Varol A, Stapleton K, Rscioli T. The syndrome of hereditary leiomyomatosis and renal cell cancer (HLRCC): The clinical features of an individual with fumarate hydratase gene mutation. Austral J Dermatol 2006; 47: 274-276.
66.
Henley ND, Tokarz VA. Multiple cutaneous and uterine leiomyomatosis in a 36-year-old female, and discussion of hereditary leiomyomatosis and renal cell carcinoma. Int J Dermatol 2012; 51: 1213-1216.
67.
Choudhary S, McLeod M, Torchia D, et al. Multiple cutaneous and uterine leiomyomatosis syndrome: A review. J Clin Aesthet Dermatol 2013; 6: 16-21.
68.
Frey MK, Worley MJ, Heyman KP, et al. A case report of hereditary leiomyomatosis and renal cell cancer. Am J Obstet Gynecol 2010; 68: e8-e9.
69.
Joseph NM, Solomon DA, Frizzell N, et al. Morphology and immunohistochemistry for 2SC and FH aid in detection for fumarate hydratase gene aberrations in uterine leiomyomas from young patients. Am J Surg Pathol 2015; 39: 1529-1539.
70.
Reyes C, Karamurzin Y, Frizzell N, et al. Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(s-scuccino)-cysteine immunohistochemistry. Mod Pathol 2014; 27: 1020-1027.
71.
Alam NA, Rowan AJ, Wortham NC, et al. Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. Hum Mol Genet 2003; 12: 1241-1252.
72.
Ahvenainen T, Lehtonen HJ, Lehtonen R, et al. 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 2008; 183: 83-88.
73.
Bayley JP, Launonen V, Tomlinson IPM. The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency. BMC Med Gent 2008; 9: 20.
74.
Coughlin EM, Christensen E, Krisnamoorthy KS, et al. Molecular analysis and prenatal diagnosis of human fumarase deficiency. Mol Genet Metab 1998; 63: 254-262.
75.
Lehtonen R, Kiuru M, Vanharanta S, et al. Biallelic inactivation of fumarate hydratase (FH) occurs in nonsyndromic uterine leiomyomas but is rare in other tumors. Am J Pathol 2004; 164: 17-22.
76.
Kiuru M, Lehtonen R, Arola J, et al. Few FH mutations in sporadic counterparts of tumor types observed in hereditary leiomyomatosis and renal cell cancer families. Cancer Res 2002; 62: 4554-4557.
77.
Barrisford GW, Singer EA, Rosner IL, et al. Familial renal cancer: Molecular genetics and surgical treatment. Int J Surg Oncol 2011; 2011: 658767.
78.
Koski TA, Lehtonen HJ, Jee KJ, et al. Array comparative genomic hybridization identifies as a distinct DNA copy number profile in renal cell cancer associated with hereditary leiomyomatosis and renal cell cancer. Genes Chromsom Cancer 2009; 48: 544-551.
79.
Vahteristo P, Koski TA, Näätsaari L, et al. No evidence for a genetic modifier for renal cell cancer risk in HLRCC syndrome. Fam Cancer 2010; 9: 245-251.
80.
Alam NA, Olpin S, Rowan A, et al. Missense mutations in fumarate hydratase in multiple cutaneous and uterine leiomyomatosis and renal cell cancer. J Mol Diagn 2005; 7: 437-443.
81.
Menko FH, Maher E, Schmidt LS, et al. Hereditary leiomyomatosis and renal cell cancer (HLRCC). Renal cancer risk, surveillance and treatment. Fam Cancer 2014; 13: 637-644.
82.
Linehan WM, Bratslavsky G, Pinto PA, et al. Molecular diagnosis and therapy of kidney cancer. Annu Rev Med 2010; 61: 329-343.
83.
Metwalli AR, Linehan WM. Nephron-sparing surgery for multifocal and hereditary renal tumors. Curr Opin Urol 2014; 24: 466-473.
84.
Kiuru M, Lehtonen R, Eerola H, et al. No germline FH mutations in familial breast cancer patients. Eur J Hum Genet 2005; 13: 506-509.
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