Download PDF
Klin Padiatr 2017; 229(06): 322-328
DOI: 10.1055/s-0043-118662
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Clinical characteristics and outcome of 60 pediatric patients with malignant melanoma registered with the German Pediatric Rare Tumor Registry (STEP)

Klinische Charakteristika von 60 Patienten mit malignem Melanom des Registers für Seltene Tumorerkrankungen in der Pädiatrie (STEP)
Sonja Offenmueller
1   Kinder- und Jugendklinik, Universitatsklinikum Erlangen, Erlangen, Germany
,
Ulrike Leiter
2   Department of Dermatology, University Hospital Tübingen, Tübingen, Germany
,
Benedikt Bernbeck
3   Klinikum Dortmund, Westfälisches Kinderzentrum, Dortmund, Germany
,
Claus Garbe
2   Department of Dermatology, University Hospital Tübingen, Tübingen, Germany
,
Thomas Eigentler
2   Department of Dermatology, University Hospital Tübingen, Tübingen, Germany
,
Arndt Borkhardt
4   Klinik für Kinder-Hämatologie, -Onkologie und -Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
,
Carl Friedrich Classen
5   Pediatric Oncology and Hematology, University Children’s Hospital Rostock, Rostock, Germany
,
Selim Corbacioglu
6   Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany
,
Uta Dirksen
7   Pediatrics III, Hematology/Oncology, University Hospital Essen, Essen, Germany
,
Georg Ebetsberger-Dachs
8   Department of Pediatrics, Kepler Universitatsklinikum GmbH, Linz, Austria
,
Lucie Heinzerling
9   Department of Dermatology, Universitatsklinikum Erlangen, Erlangen, Germany
,
Norbert Jorch
10   Department of Pediatrics, Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany
,
Michaela Kuhlen
11   Paediatric Haematology and Oncology, University Hospital of Duesseldorf, Duesseldorf, Germany
,
Jennifer Lawlor
12   Universitatsklinikum Erlangen, Pediatric Hematology and Oncology, Erlangen, Germany
,
Felix Niggli
13   Universitäts-Kinderklinik, Zürich, Switzerland
,
Monika Streiter
14   Department of Pediatric Hematology and Oncology, Children’s Hospital Heilbronn, Heilbronn, Germany
,
Dominik T Schneider   *
15   Klinikum Dortmund gGmbH, Klinik für Kinder- und Jugendmedizin, Dortmund, Germany
,
Ines Brecht   *
16   Department of Hematology/Oncology, Children's University Hospital, Tuebingen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
10 October 2017 (online)

Also available at
    Permissions and Reprints

Abstract

Background Malignant melanoma (MM) is a common malignancy in adults while it is rare in children. Thus, information on clinical behavior of pediatric MM is incomplete.

Patients The German Pediatric Rare Tumor Registry (STEP) presents a prospective analysis of 60 childhood MM cases diagnosed between June 2006 and December 2014.

Method Patients’ ages ranged between 0 and 17 years at initial diagnosis (median age 9.6 years). Information on patient’s and tumor characteristics was obtained by standardized documentation. Three-year overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier test.

Results Follow-up ranged from 0 to 116 months with a median of 36.5 months, however, univariate analysis was performed for 46 cases with a follow-up > 3 months, only. Cases with spitzoid histotype (40%) did not show a significantly different outcome compared to cases with non-spitzoid MM. Breslow thickness ≤ 2.00 mm was identified in 30% of the cases and 18% were Clark level I to III. Adjuvant therapy was used in 45% of cases. OS at 3 years was 100%, EFS 95.2%.

Conclusion We present a series of cases with a high number of spitzoid malignant melanoma and advanced pediatric melanoma, but surprisingly good overall survival rates. Spitzoid and non-spitzoid MM do not differ in clinical behavior and survival.

Zusammenfassung

Hintergrund Maligne Melanome (MM) zählen zu den häufigsten Malignomen im Erwachsenenalter. Im Gegensatz dazu sind sie eine seltene Diagnose im Kindes- und Jugendalter. Die Datenlage über das klinische Verhalten von pädiatrischen MM ist somit unvollständig.

Patienten Das deutsche Register für „Seltene Tumorerkrankungen in der Pädiatrie“ (STEP) stellt hier eine prospektive Analyse von 60 kindlichen Fällen maligner Melanome vor, die zwischen Juni 2006 und Dezember 2014 erstdiagnostiziert wurden.

Methoden Daten über Tumor- und Patientencharakteristika wurden durch standardisierte Dokumentation erhoben. Das Gesamtüberleben (OS) und ereignisfreie Überleben (EFS) zum Zeitpunkt von 3 Jahren wurden durch den Kaplan-Meier-Test ermittelt.

Ergebnisse Das Alter der Patienten lag bei Erstdiagnose zwischen 0 und 17 Jahren (mittleres Alter 9,6 Jahre). Verlaufskontrollen wurden bis zu 116 Monate nach Diagnose mit einem Median von 36,5 Monaten durchgeführt. Eine univariate Analyse wurde nur in 46 Fälle mit einer Nachbeobachtung von > 3 Monaten durchgeführt. Fälle mit spitzoider Histologie (40%) zeigten kein signifikant unterschiedliches Überleben im Vergleich zu Fällen mit nicht-spitzoider Histologie (60%). Eine Breslow Dicke ≤ 2,00 mm wurde in 30% der Fälle identifiziert und 18% wurden im Clark Level I bis III klassifiziert. Eine adjuvante Therapie wurde in 45% der Fälle verabreicht. Das OS zum Zeitpunkt von 3 Jahren betrug 100%, das EFS 95,2%.

Diskussion Wir zeigen eine Serie pädiatrischer MM mit einer hohen Anzahl von spitzoidem Subtyp und fortgeschrittenen Stadien, aber einem auffällig guten Gesamtüberleben. Spitzoide MM unterscheiden sich im klinischen Verhalten und Überleben nicht von den nicht-spitzoiden MM.

Key words

malignant melanoma - rare pediatric tumors - pediatric oncology - German Rare Pediatric Tumor Registry - orphan disease - STEP Registry

Schlüsselwörter

pädiatrische Onkologie - maligne Melanome - seltene kindliche Tumore - Register fur Seltene Tumorerkrankungen in der Pädiatrie - STEP Register

* the authors contributed equally to this work


 

  • References

  • 1 Balch CM, Gershenwald JE, Soong SJ. et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009; 27: 6199-6206
    CrossrefPubMedGoogle Scholar
  • 2 Berk DR, LaBuz E, Dadras SS. et al. Melanoma and melanocytic tumors of uncertain malignant potential in children, adolescents and young adults – the Stanford experience 1995–2008. Pediatric dermatology 2010; 27: 244-254
    CrossrefPubMedGoogle Scholar
  • 3 Brecht IB, Bremensdorfer C, Schneider DT. et al. Rare malignant pediatric tumors registered in the German Childhood Cancer Registry 2001–2010. Pediatric blood & cancer 2014; 61: 1202-1209
    CrossrefPubMedGoogle Scholar
  • 4 Brecht IB, Garbe C, Gefeller O. et al. 443 paediatric cases of malignant melanoma registered with the German Central Malignant Melanoma Registry between 1983 and 2011. European journal of cancer (Oxford, England: 1990) 2015; 51: 861-868
    CrossrefPubMedGoogle Scholar
  • 5 Brecht IB, Graf N, Schweinitz D. et al. Networking for children and adolescents with very rare tumors: foundation of the GPOH Pediatric Rare Tumor Group. Klinische Padiatrie 2009; 221: 181-185
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Annals of surgery 1970; 172: 902-908
    CrossrefPubMedGoogle Scholar
  • 7 Chao MM, Schwartz JL, Wechsler DS. et al. High-risk surgically resected pediatric melanoma and adjuvant interferon therapy. Pediatric blood & cancer 2005; 44: 441-448
    CrossrefPubMedGoogle Scholar
  • 8 Clark WHJ. A classification of malignant melanoma in man correlated with histogenesis and biologic behaviour. New York: Pergamon Press; 1967
    Google Scholar
  • 9 Da Forno PD, Fletcher A, Pringle JH. et al. Understanding spitzoid tumours: new insights from molecular pathology. The British journal of dermatology 2008; 158: 4-14
    PubMedGoogle Scholar
  • 10 Dall'Igna P, De Corti F, Alaggio R. et al. Sentinel node biopsy in pediatric patients: the experience in a single institution. European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery [et al]=Zeitschrift fur Kinderchirurgie 2014; 24: 482-487
    PubMedGoogle Scholar
  • 11 de Vries E, Steliarova-Foucher E, Spatz A. et al. Skin cancer incidence and survival in European children and adolescents (1978-1997). Report from the Automated Childhood Cancer Information System project. European journal of cancer (Oxford, England: 1990) 2006; 42: 2170-2182
    PubMedGoogle Scholar
  • 12 Dika E, Fanti PA, Fiorentino M. et al. Spitzoid tumors in children and adults: a comparative clinical, pathological, and cytogenetic analysis. Melanoma research 2015; 25: 295-301
    CrossrefPubMedGoogle Scholar
  • 13 Ferrari A, Bisogno G, Cecchetto G. et al. Cutaneous melanoma in children and adolescents: the Italian rare tumors in pediatric age project experience. The Journal of pediatrics 2014; 164: 376-382 e371–372
    CrossrefPubMedGoogle Scholar
  • 14 Ferrari A, Bono A, Baldi M. et al. Does melanoma behave differently in younger children than in adults? A retrospective study of 33 cases of childhood melanoma from a single institution. Pediatrics 2005; 115: 649-654
    CrossrefPubMedGoogle Scholar
  • 15 Ferrari A, Schneider DT, Bisogno G. The founding of the European Cooperative Study Group on Pediatric Rare Tumors – EXPeRT. Expert review of anticancer therapy 2013; 13: 1-3
    PubMedGoogle Scholar
  • 16 Gill M, Cohen J, Renwick N. et al. Genetic similarities between Spitz nevus and Spitzoid melanoma in children. Cancer 2004; 101: 2636-2640
    CrossrefPubMedGoogle Scholar
  • 17 Hodi FS, Chesney J, Pavlick AC. et al. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. The Lancet Oncology 2016; 17: 1558-1568
    CrossrefPubMedGoogle Scholar
  • 18 Howman-Giles R, Shaw HM, Scolyer RA. et al. Sentinel lymph node biopsy in pediatric and adolescent cutaneous melanoma patients. Annals of surgical oncology 2010; 17: 138-143
    CrossrefPubMedGoogle Scholar
  • 19 Huynh PM, Grant-Kels JM, Grin CM. Childhood melanoma: update and treatment. International journal of dermatology 2005; 44: 715-723
    CrossrefPubMedGoogle Scholar
  • 20 Lange JR, Palis BE, Chang DC. et al. Melanoma in children and teenagers: an analysis of patients from the National Cancer Data Base. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2007; 25: 1363-1368
    CrossrefPubMedGoogle Scholar
  • 21 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft DK, AWMF): Diagnostik TuNdML, 2016, AW, MF Registernummer: 032/024OL hl-odMh, (Zugriff am: 08.04.2017).
    PubMed
  • 22 Livestro DP, Kaine EM, Michaelson JS. et al. Melanoma in the young: differences and similarities with adult melanoma: a case-matched controlled analysis. Cancer 2007; 110: 614-624
    CrossrefPubMedGoogle Scholar
  • 23 Long GV, Flaherty KT, Stroyakovskiy D. et al. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. Annals of oncology: official journal of the European Society for Medical Oncology 2017; DOI: 10.1093/annonc/mdx176.
    PubMedGoogle Scholar
  • 24 Mu E, Lange JR, Strouse JJ. Comparison of the use and results of sentinel lymph node biopsy in children and young adults with melanoma. Cancer 2012; 118: 2700-2707
    CrossrefPubMedGoogle Scholar
  • 25 Neier M, Pappo A, Navid F. Management of melanomas in children and young adults. Journal of pediatric hematology/oncology 2012; 34 (Suppl. 02) S51-S54
    CrossrefPubMedGoogle Scholar
  • 26 Paradela S, Fonseca E, Pita-Fernandez S. et al. Prognostic factors for melanoma in children and adolescents: a clinicopathologic, single-center study of 137 Patients. Cancer 2010; 116: 4334-4344
    CrossrefPubMedGoogle Scholar
  • 27 Paradela S, Fonseca E, Pita-Fernandez S. et al. Spitzoid and non-spitzoid melanoma in children. A prognostic comparative study. J Eur Acad Dermatol Venereol 2012; DOI: 10.1111/j.1468-3083.2012.04686.x.
    PubMedGoogle Scholar
  • 28 Pol-Rodriquez M, Lee S, Silvers DN. et al Influence of age on survival in childhood spitzoid melanomas. Cancer 2007; 109: 1579-1583
    CrossrefPubMedGoogle Scholar
  • 29 Ries LAG, KCea EM. SEER Cancer Statistics Review, 1975–2001. National Cancer Institute; Bethesda, MD: http://seer.cancer.gov/csr/1975_2001/ 2004
    Google Scholar
  • 30 van Dijk MC, Bernsen MR, Ruiter DJ. Analysis of mutations in B-RAF, N-RAS, and H-RAS genes in the differential diagnosis of Spitz nevus and spitzoid melanoma. The American journal of surgical pathology 2005; 29: 1145-1151
    CrossrefPubMedGoogle Scholar