Onkologische Erkrankungen des Neugeborenen

In Deutschland erkranken jährlich zwischen 1500 und 1800 Kinder unter 16 Jahren an Krebs. Etwa 2 % dieser Tumoren werden pränatal oder innerhalb der ersten 28 Lebenstage diagnostiziert. Die Einzigartigkeit neonataler Tumoren eröffnet neue Einblicke in die Onkogenese und ist deswegen auch für ältere Kinder und Erwachsene bedeutsam. Der Beitrag stellt die häufigsten onkologischen Erkrankungen beim Neugeborenen vor und gibt Tipps für Therapie und Diagnostik.

Kernaussagen

• Neonatale Tumoren sind alle gut- und bösartigen Neubildungen, die pränatal oder innerhalb der ersten 28 Lebenstage diagnostiziert werden.

• Tumoren des Neugeborenen unterscheiden sich hinsichtlich der Verteilung, der Häufigkeit, des Verlaufs und der Anforderungen an eine effektive Therapie von in späteren Lebensaltern auftretenden Krebserkrankungen.

• Im Gegensatz zu den Tumoren des älteren Kindes handelt es sich in der Mehrheit der neonatalen Krebserkrankungen um gutartige solide Tumoren.

• Selbst maligne Krebserkrankungen können beim Neonaten klinisch gutartig verlaufen und sich sogar vollständig zurückbilden.

• Seltenheit und einzigartiges biologisches Verhalten neonataler Tumoren erfordern in Verbindung mit den physiologischen und anatomischen Besonderheiten des Neugeborenen eine interdisziplinäre Zusammenarbeit für die Diagnostik und Therapie.

• Die wichtigste Methode der pränatalen Diagnostik ist die von einem erfahrenen Untersucher durchgeführte Ultraschalluntersuchung.

• Beim Neugeborenen ist jede Krebstherapie eine Herausforderung: Aufgrund der Vulnerabilität des wachsenden Organismus müssen in die Therapieplanung sowohl die Nebenwirkungen als auch die Auswirkungen auf das Wachstum und die weitere somatische und geistige Entwicklung mit einbezogen werden.

• Diagnostik und Therapie müssen hinsichtlich der Relevanz für den Patienten und möglicher Auswirkungen auf die spätere Lebensqualität kritisch geprüft werden.

• Literatur

• 1 Halperin EC. Neonatal neoplasms. Int J Radiat Oncol Biol Phys 2000; 47: 171-178
• 2 Davis CF, Carachi R, Young DG. Neonatal tumours: Glasgow 1955–86. Arch Dis Child 1988; 63: 1075-1078
• 3 Lakhoo K, Sowerbutts H. Neonatal tumours. Pediatr Surg Int 2010; 26: 1159-1168
• 4 Parkes SE, Muir KR, Southern L. et al. Neonatal tumours: a thirty-year population-based study. Med Pediatr Oncol 1994; 22: 309-317
• 5 Birch JM, Blair V. The epidemiology of infant cancers. Br J Cancer Suppl 1992; 18: 2-4
• 6 Moore SW, Satge D, Sasco AJ. et al. The epidemiology of neonatal tumours. Report of an international working group. Pediatr Surg Int 2003; 19: 509-519
• 7 Orbach D, Sarnacki S, Brisse HJ. et al. Neonatal cancer. Lancet Oncol 2013; 14: e609-e620
• 8 Lakhoo K. Neonatal teratomas. Early Hum Dev 2010; 86: 643-647
• 9 Wilson RD, Hedrick H, Flake AW. et al. Sacrococcygeal teratomas: prenatal surveillance, growth and pregnancy outcome. Fetal Diagn Ther 2009; 25: 15-20
• 10 Sankila R, Olsen JH, Anderson H. et al. Risk of cancer among offspring of childhood-cancer survivors. Association of the Nordic Cancer Registries and the Nordic Society of Paediatric Haematology and Oncology. N Engl J Med 1998; 338: 1339-1344
• 11 Batcup G. Cancer in the very young child – pitfalls and problems for the pathologist. Br J Cancer Suppl 1992; 18: 5-7
• 12 Waibel P. Neonatale Tumore. Kind & Radiologie 2005; 2005: 6
• 13 Doll R, Wakeford R. Risk of childhood cancer from fetal irradiation. Br J Radiol 1997; 70: 130-139
• 14 Cecen E, Gunes D, Uysal KM. et al. Atypical teratoid/rhabdoid tumor in an infant conceived by in vitro fertilization. Childs Nerv Syst 2010; 26: 263-266
• 15 Gholipour A, Estroff JA, Barnewolt CE. et al. Fetal MRI: A Technical Update with Educational Aspirations. Concepts Magn Reson Part A Bridg Educ Res 2014; 43: 237-266
• 16 Braun T, Brauer M, Fuchs I. et al. Mirror syndrome: a systematic review of fetal associated conditions, maternal presentation and perinatal outcome. Fetal Diagn Ther 2010; 27: 191-203
• 17 Fisher JP, Tweddle DA. Neonatal neuroblastoma. Semin Fetal Neonatal Med 2012; 17: 207-215
• 18 Proust S, Philippe HJ, Paumier A. et al. Mirror pre-eclampsia: Ballantyne's syndrome. Two cases. J Gynecol Obstet Biol Reprod (Paris) 2006; 35: 270-274
• 19 Takahashi H, Matsubara S, Kuwata T. et al. Maternal manifestation of Ballantyne's syndrome occurring concomitantly with the development of fetal congenital mesoblastic nephroma. J Obstet Gynaecol Res 2014; 40: 1114-1117
• 20 Roybal JL, Moldenhauer JS, Khalek N. et al. Early delivery as an alternative management strategy for selected high-risk fetal sacrococcygeal teratomas. J Pediatr Surg 2011; 46: 1325-1332
• 21 van Mieghem T, Al-Ibrahim A, Deprest J. et al. Minimally invasive therapy for fetal sacrococcygeal teratoma: case series and systematic review of the literature. Ultrasound Obstet Gynecol 2014; 43: 611-619
• 22 Ozgunen FT, Gulec UK, Evruke IC. et al. Fetal Oropharyngeal and Neck Tumors: Determination of the Need for Ex–Utero Intrapartum Treatment Procedure. Balkan Med J 2015; 32: 221-225
• 23 Littman P, D'Angio GJ. Radiation therapy in the neonate. Am J Pediatr Hematol Oncol 1981; 3: 279-285
• 24 Siegel SE, Moran RG. Problems in the chemotherapy of cancer in the neonate. Am J Pediatr Hematol Oncol 1981; 3: 287-296
• 25 Veal GJ, Errington J, Sastry J. et al. Adaptive dosing of anticancer drugs in neonates: facilitating evidence-based dosing regimens. Cancer Chemother Pharmacol 2016; 77: 685-692
• 26 Swamy R, Embleton N, Hale J. Sacrococcygeal teratoma over two decades: birth prevalence, prenatal diagnosis and clinical outcomes. Prenat Diagn 2008; 28: 1048-1051
• 27 Chisholm CA, Heider AL, Kuller JA. et al. Prenatal diagnosis and perinatal management of fetal sacrococcygeal teratoma. Am J Perinatol 1999; 16: 47-50
• 28 Adzick NS. Open fetal surgery for life-threatening fetal anomalies. Semin Fetal Neonatal Med 2010; 15: 1-8
• 29 Kochling J, Pistor G, Marzhauser Brands S. et al. The Currarino syndrome – hereditary transmitted syndrome of anorectal, sacral and presacral anomalies. Case report and review of the literature. Eur J Pediatr Surg 1996; 6: 114-119
• 30 Volkl TM, Langer T, Aigner T. et al. Klinefelter syndrome and mediastinal germ cell tumors. Am J Med Genet A 2006; 140: 471-481
• 31 Yong D, Lim JG, Choi JR. et al. A case of Klinefelter syndrome with retroperitoneal teratoma. Yonsei Med J 2000; 41: 136-139
• 32 Yao W, Li K, Zheng S. et al. Analysis of recurrence risks for sacrococcygeal teratoma in children. J Pediatr Surg 2014; 49: 1839-1842
• 33 Derikx JP, De Backer A, van de Schoot L. et al. Factors associated with recurrence and metastasis in sacrococcygeal teratoma. Br J Surg 2006; 93: 1543-1548
• 34 Bader JL, Miller RW. US cancer incidence and mortality in the first year of life. Am J Dis Child 1979; 133: 157-159
• 35 Isaacs Jr H. Fetal and neonatal leukemia. J Pediatr Hematol Oncol 2003; 25: 348-361
• 36 van der Linden MH, Creemers S, Pieters R. Diagnosis and management of neonatal leukaemia. Semin Fetal Neonatal Med 2012; 17: 192-195
• 37 Handler MZ, Schwartz RA. Neonatal leukaemia cutis. J Eur Acad Dermatol Venereol 2015; 29: 1884-1889
• 38 Mondi V, Piersigilli F, Salvatori G. et al. The Skin as an Early Expression of Malignancies in the Neonatal Age: A Review of the Literature and a Case Series. Biomed Res Int 2015; 2015: 809406
• 39 Hain RD, Rayner L, Weitzman S. et al. Acute tumour lysis syndrome complicating treatment of stage IVS neuroblastoma in infants under six months old. Med Pediatr Oncol 1994; 23: 136-139
• 40 Jona JZ. Progressive tumor necrosis and lethal hyperkalemia in a neonate with sacrococcygeal teratoma (SCT). J Perinatol 1999; 19: 538-540
• 41 Brethon B, Cave H, Fahd M. et al. Infant acute leukemia. Bull Cancer 2016; 103: 299-311
• 42 McNutt DM, Holdsworth MT, Wong C. et al. Rasburicase for the management of tumor lysis syndrome in neonates. Ann Pharmacother 2006; 40: 1445-1450
• 43 van der Linden MH, Valsecchi MG, De Lorenzo P. et al. Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol. Blood 2009; 114: 3764-3768
• 44 Lanz S, Schwinger W, Sovinz P. et al. Successful Unrelated Stem Cell Transplantation in an Infant With Congenital Acute Myelogenous Leukemia FAB M5 Showing Massive Cutaneous Infiltrations – A Challenging Multidisciplinary Approach. Pediatr Blood Cancer 2016; 63: 160-163
• 45 Tsujimoto H, Kounami S, Mitani Y. et al. Neonatal Acute Megakaryoblastic Leukemia Presenting with Leukemia Cutis and Multiple Intracranial Lesions Successfully Treated with Unrelated Cord Blood Transplantation. Case Rep Hematol 2015; 2015: 610581
• 46 Roy A, Roberts I, Vyas P. Biology and management of transient abnormal myelopoiesis (TAM) in children with Down syndrome. Semin Fetal Neonatal Med 2012; 17: 196-201
• 47 Zipursky A. Transient leukaemia – a benign form of leukaemia in newborn infants with trisomy 21. Br J Haematol 2003; 120: 930-938
• 48 Gamis AS, Alonzo TA, Gerbing RB. et al. Natural history of transient myeloproliferative disorder clinically diagnosed in Down syndrome neonates: a report from the Children's Oncology Group Study A2971. Blood 2011; 118: 6752-6759 ; quiz 6996
• 49 Klusmann JH, Creutzig U, Zimmermann M. et al. Treatment and prognostic impact of transient leukemia in neonates with Down syndrome. Blood 2008; 111: 2991-2998
• 50 Minkov M, Prosch H, Steiner M. et al. Langerhans cell histiocytosis in neonates. Pediatr Blood Cancer 2005; 45: 802-807
• 51 Kushner BH, Helson L, Lane JM. et al. Metastatic neuroblastoma after 52 years of apparent dormancy. N Engl J Med 1986; 315: 196-197
• 52 Dhir S, Wheeler K. Neonatal neuroblastoma. Early Hum Dev 2010; 86: 601-605
• 53 Moppett J, Haddadin I, Foot AB. Neonatal neuroblastoma. Arch Dis Child Fetal Neonatal Ed 1999; 81: 134-137
• 54 Maris JM, Matthay KK. Molecular biology of neuroblastoma. J Clin Oncol 1999; 17: 2264-2279
• 55 Maris JM, Kyemba SM, Rebbeck TR. et al. Molecular genetic analysis of familial neuroblastoma. Eur J Cancer 1997; 33: 1923-1928
• 56 Cohn SL, Tweddle DA. MYCN amplification remains prognostically strong 20 years after its “clinical debut”. Eur J Cancer 2004; 40: 2639-2642
• 57 Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 2003; 3: 203-216
• 58 Weiss WA, Aldape K, Mohapatra G. et al. Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J 1997; 16: 2985-2995
• 59 Yiallouros M. Neuroblastom (Kurzinfo). Im Internet: http://www.kinderkrebsinfo.de/erkrankungen/weitere_solide_tumoren/pohneuroblpatinfo120120611/pohneuroblpatinfokurz120120611/index_ger.html ; Zugriff am 22.03.2017
• 60 Curtis MR, Mooney DP, Vaccaro TJ. et al. Prenatal ultrasound characterization of the suprarenal mass: distinction between neuroblastoma and subdiaphragmatic extralobar pulmonary sequestration. J Ultrasound Med 1997; 16: 75-83
• 61 Flanagan SM, Rubesova E, Jaramillo D. et al. Fetal suprarenal masses – assessing the complementary role of magnetic resonance and ultrasound for diagnosis. Pediatr Radiol 2016; 46: 246-254
• 62 Maki E, Oh K, Rogers S. et al. Imaging and differential diagnosis of suprarenal masses in the fetus. J Ultrasound Med 2014; 33: 895-904
• 63 De Bernardi B, Pianca C, Pistamiglio P. et al. Neuroblastoma with symptomatic spinal cord compression at diagnosis: treatment and results with 76 cases. J Clin Oncol 2001; 19: 183-190
• 64 Gigliotti AR, De Ioris MA, De Grandis E. et al. Congenital neuroblastoma with symptoms of epidural compression at birth. Pediatr Hematol Oncol 2016; 1-8
• 65 De Bernardi B, Gerrard M, Boni L. et al. Excellent outcome with reduced treatment for infants with disseminated neuroblastoma without MYCN gene amplification. J Clin Oncol 2009; 27: 1034-1040
• 66 Gigliotti AR, Di Cataldo A, Sorrentino S. et al. Neuroblastoma in the newborn. A study of the Italian Neuroblastoma Registry. Eur J Cancer 2009; 45: 3220-3227
• 67 Canete A, Gerrard M, Rubie H. et al. Poor survival for infants with MYCN–amplified metastatic neuroblastoma despite intensified treatment: the International Society of Paediatric Oncology European Neuroblastoma Experience. J Clin Oncol 2009; 27: 1014-1019
• 68 Schilling FH, Spix C, Berthold F. et al. Children may not benefit from neuroblastoma screening at 1 year of age. Updated results of the population based controlled trial in Germany. Cancer Lett 2003; 197: 19-28
• 69 Honjo S, Doran HE, Stiller CA. et al. Neuroblastoma trends in Osaka, Japan, and Great Britain 1970–1994, in relation to screening. Int J Cancer 2003; 103: 538-543
• 70 Ioka A, Inoue M, Yoneda A. et al. Effects of the Cessation of Mass Screening for Neuroblastoma at 6 Months of Age: A Population-Based Study in Osaka, Japan. J Epidemiol 2015; 26: 179-84
• 71 Sawada T, Todo S, Fujita K. et al. Mass screening of neuroblastoma in infancy. Am J Dis Child 1982; 136: 710-712
• 72 Spix C, Michaelis J, Berthold F. et al. Lead-time and overdiagnosis estimation in neuroblastoma screening. Stat Med 2003; 22: 2877-2892
• 73 Powis M. Neonatal renal tumours. Early Hum Dev 2010; 86: 607-612
• 74 Isaacs Jr H. Fetal and neonatal renal tumors. J Pediatr Surg 2008; 43: 1587-1595
• 75 Thompson PA, Chintagumpala M. Renal and hepatic tumors in the neonatal period. Semin Fetal Neonatal Med 2012; 17: 216-221
• 76 Do AY, Kim JS, Choi SJ. et al. Prenatal diagnosis of congenital mesoblastic nephroma. Obstet Gynecol Sci 2015; 58: 405-408
• 77 Panda SS, Mandelia A, Gupta DK. et al. Antenatally detected solid tumour of kidney. BMJ Case Rep 2014; 2014
• 78 Schild RL, Plath H, Hofstaetter C. et al. Diagnosis of a fetal mesoblastic nephroma by 3D-ultrasound. Ultrasound Obstet Gynecol 2000; 15: 533-536
• 79 Takahashi H, Ohkuchi A, Kuwata T. et al. Congenital mesoblastic nephroma: Its diverse clinical features – A literature review with a case report. J Obstet Gynaecol 2015; 1-5
• 80 Fung TY, Fung YM, Ng PC. et al. Polyhydramnios and hypercalcemia associated with congenital mesoblastic nephroma: case report and a new appraisal. Obstet Gynecol 1995; 85: 815-817
• 81 Malone PS, Duffy PG, Ransley PG. et al. Congenital mesoblastic nephroma, renin production, and hypertension. J Pediatr Surg 1989; 24: 599-600
• 82 Tsuchida Y, Shimizu K, Hata J. et al. Renin production in congenital mesoblastic nephroma in comparison with that in Wilms' tumor. Pediatr Pathol 1993; 13: 155-164
• 83 Furtwaengler R, Reinhard H, Leuschner I. et al. Mesoblastic nephroma – a report from the Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH). Cancer 2006; 106: 2275-2283
• 84 Isaacs Jr H. Fetal and neonatal rhabdoid tumor. J Pediatr Surg 2010; 45: 619-626
• 85 Isaacs Jr H. Fetal and neonatal hepatic tumors. J Pediatr Surg 2007; 42: 1797-1803
• 86 Marsciani A, Pericoli R, Alaggio R. et al. Massive response of severe infantile hepatic hemangioma to propanolol. Pediatr Blood Cancer 2010; 54: 176
• 87 Menezes MD, McCarter R, Greene EA. et al. Status of propranolol for treatment of infantile hemangioma and description of a randomized clinical trial. Ann Otol Rhinol Laryngol 2011; 120: 686-695
• 88 Regier TS, Ramji FG. Pediatric hepatic hemangioma. Radiographics 2004; 24: 1719-1724
• 89 Howard D, La Rosa FG, Huang S. et al. Consumptive hypothyroidism resulting from hepatic vascular tumors in an athyreotic adult. J Clin Endocrinol Metab 2011; 96: 1966-1970
• 90 Fernandez-Pineda I, Cabello-Laureano R. Differential diagnosis and management of liver tumors in infants. World J Hepatol 2014; 6: 486-495
• 91 Haberle B, Bode U, von Schweinitz D. Differentiated treatment protocols for high– and standard–risk hepatoblastoma––an interim report of the German Liver Tumor Study HB99. Klin Padiatr 2003; 215: 159-165
• 92 Ismail H, Broniszczak D, Kalicinski P. et al. Changing treatment and outcome of children with hepatoblastoma: analysis of a single center experience over the last 20 years. J Pediatr Surg 2012; 47: 1331-1339
• 93 Tannuri AC, Cristofani LM, Teixeira RA. et al. New concepts and outcomes for children with hepatoblastoma based on the experience of a tertiary center over the last 21 years. Clinics (São Paulo) 2015; 70: 387-392
• 94 Ferrari A, Orbach D, Sultan I. et al. Neonatal soft tissue sarcomas. Semin Fetal Neonatal Med 2012; 17: 231-238
• 95 Minard-Colin V, Orbach D, Martelli H. et al. Soft tissue tumors in neonates. Arch Pediatr 2009; 16: 1039-1048
• 96 Mendez R, Arnaiz S, Montero M. et al. Clinical patterns of soft-tissue sarcoma in children. Cir Pediatr 2001; 14: 14-20
• 97 Lasky JL, Choi EJ, Johnston S. et al. Congenital brain tumors: case series and review of the literature. J Pediatr Hematol Oncol 2008; 30: 326-331
• 98 Buetow PC, Smirniotopoulos JG, Done S. Congenital brain tumors: a review of 45 cases. AJNR Am J Neuroradiol 1990; 11: 793-799
• 99 Hwang SW, Su JM, Jea A. Diagnosis and management of brain and spinal cord tumors in the neonate. Semin Fetal Neonatal Med 2012; 17: 202-206
• 100 Vasilatou-Kosmidis H. Cancer in neonates and infants. Med Pediatr Oncol 2003; 41: 7-9
• 101 Cavalheiro S, Moron AF, Hisaba W. et al. Fetal brain tumors. Childs Nerv Syst 2003; 19: 529-536
• 102 Shamji MF, Vassilyadi M, Lam CH. et al. Congenital tumors of the central nervous system: the MCH experience. Pediatr Neurosurg 2009; 45: 368-374
• 103 Rickert CH. Neuropathology and prognosis of foetal brain tumours. Acta Neuropathol 1999; 98: 567-576
• 104 Wakai S, Arai T, Nagai M. Congenital brain tumors. Surg Neurol 1984; 21: 597-609
• 105 Raisanen JM, Davis RL. Congenital brain tumors. Pathology (Phila) 1993; 2: 103-116
• 106 Isaacs Jr H. I. Perinatal brain tumors: a review of 250 cases. Pediatr Neurol 2002; 27: 249-261
• 107 Isaacs Jr H. II. Perinatal brain tumors: a review of 250 cases. Pediatr Neurol 2002; 27: 333-342