Top

Published in:

01-12-2018 | Brief Report

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

Authors: Isabela Werneck da Cunha, Walter Henriques da Costa, Mariana A. Morini, Stephania Martins Bezerra, Dirce Maria Carraro, Giovana Tardin Torrezan, Maria Nirvana Cruz Formiga, Gustavo Cardoso Guimaraes, Stenio Cassio Zequi, Fernando Augusto Soares

Published in: Virchows Archiv | Issue 6/2018

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.

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):1665–1670CrossRef

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):431–437CrossRef

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 61:329–343CrossRef

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):74–80CrossRef

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 70:93–105CrossRef

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 31:1578–1585CrossRef

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 43:18–27CrossRef

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):1457–1472CrossRef

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

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 98:3387–3392CrossRef

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 30:406–410CrossRef

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 73:95–106CrossRef

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 40:865–875CrossRef

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 225:4–11CrossRef

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):1865–1869CrossRef

Title: 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
Authors: Isabela Werneck da Cunha
Walter Henriques da Costa
Mariana A. Morini
Stephania Martins Bezerra
Dirce Maria Carraro
Giovana Tardin Torrezan
Maria Nirvana Cruz Formiga
Gustavo Cardoso Guimaraes
Stenio Cassio Zequi
Fernando Augusto Soares
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: Virchows Archiv / Issue 6/2018
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-018-2420-3

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2018

A novel Sudan Black B-based analogue revives lipofuscin as a biomarker for in vivo senescence

Book review—Diagnostic pathology: intraoperative consultation, 2nd edition

Mutational and copy number asset of primary sporadic neuroendocrine tumors of the small intestine

RUSSCO-RSP comparative study of immunohistochemistry diagnostic assays for PD-L1 expression in urothelial bladder cancer

Increased PKR level in human CADASIL brains

Granulysin, a novel marker for extranodal NK/T cell lymphoma, nasal type