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Tumorprädispositionssyndrome und Nephroblastom

Frühe Diagnose mit Bildgebung

Tumor predisposition syndromes and nephroblastoma

Early diagnosis with imaging

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Zusammenfassung

Klinisches/methodisches Problem

Das Beckwith-Wiedemann-Spektrum (BWSp) und die WT1-vermittelten Syndrome, Denys-Drash-Syndrom (DDS) und WAGR-Spektrum (Wilms-Tumor, Aniridie, urogenitale Anomalien und eine Reihe an Entwicklungsverzögerungen) zählen zu den Tumorprädispositionssyndromen (TPS) des Wilms-Tumors (WT). Patienten mit TPS haben ein höheres Risiko für eine chronische Nierenerkrankung und weisen eine erhöhte Rate an bilateralen und metachronen Tumoren sowie nephrogenen Resten (NR) auf.

Radiologische Standardverfahren

Zur bildgebenden Standarddiagnostik des WT zählen die Sonographie und die Magnetresonanztomographie (MRT). In den aktuellen Nierentumorstudien Umbrella SIOP-RTSG 2016 und Randomet 2017 wird zudem standardmäßig eine Thorax-Computertomographie (CT) empfohlen. Positronen-Emissions-Tomographie (PET)/CT und Ganzkörper-MRT sind hingegen nicht Teil der Routinediagnostik.

Methodische Innovationen

In aktuellen Publikationen wird bei klinischem Verdacht bzw. molekulargenetisch nachgewiesenem TPS eine renale Sonographie in 3‑monatlichen Abständen bis zum Alter von 7 Jahren routinemäßig empfohlen.

Leistungsfähigkeit

Patienten mit TPS und regelmäßiger sonographischer Vorsorgeuntersuchung haben bei WT-Diagnose kleinere Tumorvolumina und niedrigere Tumorstadien als Patienten ohne Vorsorgeuntersuchung. Dies ermöglicht eine Reduktion der Therapieintensität sowie die erleichterte Durchführung einer nierenerhaltenden Teilresektion, welche insbesondere bei bilateralen WT prognostisch relevant ist.

Bewertung

Die frühzeitige Diagnostik eines WT im Kontext eines TPS gewährleistet den größtmöglichen Erhalt von gesundem Nierengewebe. Einheitliche sonographische Vorsorgeuntersuchungen sollten daher in der klinischen Praxis fest etabliert werden.

Empfehlung für die Praxis

Die initiale Diagnostik eines TPS erfolgt klinisch und erfordert bei zum Teil subtiler klinischer Manifestation, insbesondere im Fall eines BWSp, einen geübten und achtsamen Untersucher. An die klinische Diagnostik sollte sich eine genetische Untersuchung anschließen, gefolgt von einer sonographischen Vorsorge.

Abstract

Clinical/methodical issue

The Beckwith–Wiedemann spectrum (BWSp) as well as the WT1-related syndromes, Denys–Drash syndrome (DDS) and WAGR spectrum (Wilms tumor, Aniridia, genitourinary anomalies and a range of developmental delays) are tumor predisposition syndromes (TPS) of Wilms tumor (WT). Patients with associated TPS are at higher risk of developing chronic kidney disease and bilateral and metachronous tumors as well as nephrogenic rests.

Standard radiological methods

Standard imaging diagnostics for WT include renal ultrasound and magnetic resonance imaging (MRI). In the current renal tumor studies Umbrella SIOP-RTSG 2016 and Randomet 2017, thoracic computed tomography (CT) is also recommended as standard. Positron emission tomography (PET)-CT and whole-body MRI, on the other hand, are not part of routine diagnostics.

Methodological innovations

In recent publications, renal ultrasound is recommended every 3 months until the age of 7 years in cases of clinical suspicion or molecularly proven TPS.

Performance

Patients with TPS and regular renal ultrasounds have smaller tumor volumes and lower tumor stages at WT diagnosis than patients without such a screening. This allows a reduction of therapy intensity and facilitates the performance of nephron sparing surgery, which is prognostically relevant especially in bilateral WT.

Achievements

Early diagnosis of WT in the context of TPS ensures the greatest possible preservation of healthy and functional renal tissue. Standardized screening by regular renal ultrasounds should therefore be firmly established in clinical practice.

Practical recommendations

The initial diagnosis of TPS is clinical and requires a skilled and attentive examiner in the presence of sometimes subtle clinical manifestations, especially in the case of BWSp. Clinical diagnosis should be followed by genetic testing, which should then be followed by sonographic screening.

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Literatur

  1. Reinhard H et al (2004) Results of the SIOP 93-01/GPOH trial and study for the treatment of patients with unilateral nonmetastatic Wilms tumor. Klin Padiatr 216:132–140

    Article  CAS  PubMed  Google Scholar 

  2. Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M (2005) WAGR syndrome: a clinical review of 54 cases. Pediatrics 116:984–988

    Article  PubMed  Google Scholar 

  3. Pelletier J et al (1991) Germline mutations in the Wilms’ tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 67:437–447

    Article  CAS  PubMed  Google Scholar 

  4. Lehnhardt A et al (2015) Clinical and molecular characterization of patients with heterozygous mutations in wilms tumor suppressor gene 1. Clin J Am Soc Nephrol 10:825–831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Brioude F et al (2018) Expert consensus document: clinical and molecular diagnosis, screening and management of Beckwith–Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol. https://doi.org/10.1038/nrendo.2017.166

    Article  PubMed  PubMed Central  Google Scholar 

  6. Narod SA, Hawkins MM, Robertson CM, Stiller CA (1997) Congenital anomalies and childhood cancer in Great Britain. Am J Hum Genet 60:474–485

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Merks JH, Caron HN, Hennekam RC (2005) High incidence of malformation syndromes in a series of 1,073 children with cancer. Am J Med Genet A 134A(2):132–143. https://doi.org/10.1002/ajmg.a.30603

    Article  PubMed  Google Scholar 

  8. Dumoucel S et al (2014) Malformations, genetic abnormalities, and wilms tumor. Pediatr Blood Cancer 61:140–144

    Article  CAS  PubMed  Google Scholar 

  9. Segers H et al (2012) Frequency of WT1 and 11p15 constitutional aberrations and phenotypic correlation in childhood Wilms tumour patients. Eur J Cancer 48:3249–3256

    Article  CAS  PubMed  Google Scholar 

  10. Welter N et al (2021) Characteristics of nephroblastoma/nephroblastomatosis in children with a clinically reported underlying malformation or cancer predisposition syndrome. Cancers 13:5016

    Article  PubMed  PubMed Central  Google Scholar 

  11. Brioude F et al (2018) Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol 14:229–249

    Article  PubMed  PubMed Central  Google Scholar 

  12. Scalabre A et al (2016) Is nephron sparing surgery justified in Wilms tumor with Beckwith-Wiedemann syndrome or isolated hemihypertrophy? Pediatr Blood Cancer 63:1571–1577

    Article  CAS  PubMed  Google Scholar 

  13. Hol JA et al (2021) Wilms tumour surveillance in at-risk children: literature review and recommendations from the SIOP-Europe Host Genome Working Group and SIOP Renal Tumour Study Group. Eur J Cancer 153:51–63

    Article  CAS  PubMed  Google Scholar 

  14. van den Heuvel-Eibrink MM et al (2017) Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP–RTSG 2016 protocol. Nat Rev Urol 14:743–752

    Article  PubMed  Google Scholar 

  15. Brisse HJ, de la Monneraye Y, Cardoen L, Schleiermacher G (2020) From Wilms to kidney tumors: Which ones require a biopsy? Pediatr Radiol 50:1049–1051

    Article  PubMed  Google Scholar 

  16. Watson T, Oostveen M, Rogers H, Pritchard-Jones K, Olsen Ø (2020) The role of imaging in the initial investigation of paediatric renal tumours. Lancet Child Adolesc Health 4:232–241

    Article  PubMed  Google Scholar 

  17. Jackson TJ et al (2022) How we approach paediatric renal tumour core needle biopsy in the setting of preoperative chemotherapy: a review from the SIOP Renal Tumour Study Group. Pediatr Blood Cancer. https://doi.org/10.1002/pbc.29702

    Article  PubMed  Google Scholar 

  18. Schenk J‑P et al (2021) Bildgebung renaler Tumoren im Kindesalter. Radiologe 61:619–628

    Article  PubMed  Google Scholar 

  19. Beek JN et al (2022) MRI characteristics of pediatric renal tumors: a SIOP-RTSG radiology panel Delphi study. J Magn Reson Imaging 55:543–552

    Article  PubMed  Google Scholar 

  20. Hales PW, Olsen ØE, Sebire NJ, Pritchard-Jones K, Clark CA (2015) A multi-Gaussian model for apparent diffusion coefficient histogram analysis of Wilms’ tumour subtype and response to chemotherapy. NMR Biomed 28:948–957

    Article  PubMed  Google Scholar 

  21. Beckwith JB, Kiviat NB, Bonadio JF (1990) Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms’ tumor. Pediatr Pathol 10:1–36

    Article  CAS  PubMed  Google Scholar 

  22. Scott RH et al (2006) Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice. Arch Dis Child 91:995–999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Stock K, Kübler H, Maurer T, Slotta-Huspenina J, Holzapfel K (2018) CEUS – Diagnostik solider Nierentumoren. Radiologe 58:553–562

    Article  CAS  PubMed  Google Scholar 

  24. Dietrich CF et al (2021) European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB): an update on the pediatric CEUS registry on behalf of the “EFSUMB Pediatric CEUS Registry Working Group”. Ultraschall Med 42:270–277

    Article  PubMed  Google Scholar 

  25. Gessler M, Bruns GAP (1989) A physical map around the WAGR complex on the short arm of chromosome 11. Genomics 5:43–55

    Article  CAS  PubMed  Google Scholar 

  26. Scott RH, Stiller CA, Walker L, Rahman N (2006) Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. J Med Genet 43:705–715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Van Heyningen V, Hoovers JMN, De Kraker J, Crolla JA (2007) Raised risk of Wilms tumour in patients with aniridia and submicroscopic WT1 deletion. J Med Genet 44:787–790

    Article  PubMed  PubMed Central  Google Scholar 

  28. Royer-Pokora B (2013) Genetics of pediatric renal tumors. Pediatr Nephrol 28:13–23

    Article  PubMed  Google Scholar 

  29. Drash A, Sherman F, Hartmann WH, Blizzard RM (1970) A syndrome of pseudohermaphroditism, Wilms’ tumor, hypertension, and degenerative renal disease. J Pediatr 76:585–593

    Article  CAS  PubMed  Google Scholar 

  30. Shannon RS (1982) Wilms’s tumour and aniridia: clinical and cytogenetic features. Arch Dis Child 57:685–690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Schumacher V et al (1998) Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations. Kidney Int 53:1594–1600

    Article  CAS  PubMed  Google Scholar 

  32. Hol JA et al (2021) Clinical characteristics and outcomes of children with WAGR syndrome and Wilms tumor and/or nephroblastomatosis: the 30-year SIOP-RTSG experience. Cancer 127:628–638

    Article  PubMed  Google Scholar 

  33. Breslow NE et al (2005) End stage renal disease IN patients WITH Wilms tumor: results from the national Wilms tumor study group and the United States renal data system. J Urol 174:1972–1975

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ritchey ML et al (1996) Renal failure in Wilms’ tumor patients: a report from the National Wilms’ Tumor Study Group. Med Pediatr Oncol 26:75–80

    Article  CAS  PubMed  Google Scholar 

  35. MacFarland SP et al (2018) Diagnosis of Beckwith-Wiedemann syndrome in children presenting with Wilms tumor. Pediatr Blood Cancer 65:e27296

    Article  PubMed  PubMed Central  Google Scholar 

  36. Reik W et al (1995) Imprinting mutations in the Beckwith–Wiedemann syndrome suggested by an altered imprinting pattern in the IGF2–H19 domain. Hum Mol Genet 4:2379–2385

    Article  CAS  PubMed  Google Scholar 

  37. Choufani S, Shuman C, Weksberg R (2010) Beckwith-Wiedemann syndrome. Am J Med Genet C Semin Med Genet 154:343–354

    Article  Google Scholar 

  38. Mussa A et al (2016) (Epi)genotype-phenotype correlations in Beckwith-Wiedemann syndrome. Eur J Hum Genet 24:183–190

    Article  CAS  PubMed  Google Scholar 

  39. Brzezinski J et al (2017) Wilms tumour in Beckwith–Wiedemann Syndrome and loss of methylation at imprinting centre 2: revisiting tumour surveillance guidelines. Eur J Hum Genet 25:1031–1039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bergeron C et al (2001) Does nephroblastomatosis influence the natural history and relapse rate in Wilms’ tumour? A single centre experience over 11 years. Eur J Cancer 37:385–391

    Article  CAS  PubMed  Google Scholar 

  41. Rohrschneider WK et al (1998) US, CT and MR imaging characteristics of nephroblastomatosis. Pediatr Radiol 28:435–443

    Article  CAS  PubMed  Google Scholar 

  42. Sandberg JK et al (2020) Imaging characteristics of nephrogenic rests versus small Wilms tumors: a report from the children’s oncology group study AREN03B2. AJR Am J Roentgenol 214:987–994

    Article  PubMed  PubMed Central  Google Scholar 

  43. Tan TY, Amor DJ (2006) Tumour surveillance in Beckwith-Wiedemann syndrome and hemihyperplasia: a critical review of the evidence and suggested guidelines for local practice. J Paediatr Child Health 42:486–490

    Article  PubMed  Google Scholar 

  44. Zarate YA et al (2009) Experience with hemihyperplasia and Beckwith-Wiedemann syndrome surveillance protocol. Am J Med Genet A 149:1691–1697

    Article  Google Scholar 

  45. Furtwängler R et al (2022) The variable clinical spectrum of nephroblastomatosis—results from the German Society of Pediatric Oncology and Hematology (GPOH) childhood kidney tumor group. Res Sq. https://doi.org/10.21203/rs.3.rs-1459521/v2

    Article  Google Scholar 

  46. Graf N et al (2012) Characteristics and outcome of stage II and III non-anaplastic Wilms’ tumour treated according to the SIOP trial and study 93-01. Eur J Cancer 48:3240–3248

    Article  PubMed  Google Scholar 

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Danksagung

MRT Bilder aus der Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum des Saarlandes, Homburg; Sonographie Bilder aus der Klinik für pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes, Homburg.

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Authors and Affiliations

  1. Klinik für pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes, 66421, Homburg/Saar, Deutschland

    N. Welter, R. Furtwängler & N. Graf

  2. Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum des Saarlandes, Homburg, Deutschland

    G. Schneider

  3. Sektion Pädiatrische Radiologie, Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Heidelberg, Heidelberg, Deutschland

    J.-P. Schenk

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  1. N. Welter
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Correspondence to N. Welter.

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Interessenkonflikt

N. Welter, R. Furtwängler, G. Schneider, N. Graf und J.-P. Schenk geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Welter, N., Furtwängler, R., Schneider, G. et al. Tumorprädispositionssyndrome und Nephroblastom. Radiologie 62, 1033–1042 (2022). https://doi.org/10.1007/s00117-022-01056-w

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