Aggiornamento monografico
Oncologia pediatrica: le tappe della diagnosi
PAEDIATRIC ONCOLOGY: EVOLUTION OF THE DIAGNOSTIC APPROACH
Paolo Paolucci1, Ilaria Mariotti2, Elena Bigi3, Simone Schiavo3, Carmen Cano1,
1UO di Ematologia e Oncologia Pediatrica; 2Scuola di Specializzazione di Pediatria; 3Medico Frequentatore
Università di Modena e Reggio Emilia
Febbraio 2009 - pagg. 85 -93
Abstract
The objective of cure for more than 70% of children with cancer outlines the successful routes built up
by paediatric oncologists over the latest 40 years. This successful story stands for the development and
evolution of the diagnostic routes where the clinical diagnosis of a paediatric tumour still represents
a fundamental step. Indeed, as opposed to adult tumours, primary and secondary prevention do not
work in paediatric oncology. Childhood tumours derive mainly from embryonic cells, i.e. undifferentiated
resting stem cells, as opposed to adult tumours deriving generally from differentiated proliferating
cells mainly of epithelial origin (carcinomas). As a consequence, the former cells lack of
markers useful for their indirect identification, the latter cells need to enter processes of “de-differentiation”,
which favour the production of more and more easily identifiable tumour markers (precocious
diagnosis). Nevertheless, clinical diagnosis developed in strict conjunction with a number of research
progresses in the fields of cytomorphology, immunophenotyping, cytogenetics and molecular genetics
stands as a fundamental step. A precise identification of tumour cells by differential diagnosis
is the first element of a successful treatment, since tumours show wide variation in response to specific
therapies and their misdiagnosis can lead to suboptimal therapy. In recent years, knowledge of the
molecular genetics of childhood cancers has been increasing at an exponential rate. The study of the
molecular mechanisms of oncogenesis has led to an understanding of the role that tumour suppressors,
oncogenes, and deoxyribonucleic acid (DNA) repair genes play in the development of the disease.
Chromosomal translocations can lead to the disruption of growth regulatory genes and/or the
formation of growth stimulatory fusion genes in leukaemias and some solid tumours. These alterations
can occur sporadically or can be inherited, which often leads to cancer in children or young adults.
Therefore, the development of more specific diagnostic tools, allowing a continuous reassessment of
the bio-molecular features of paediatric tumours, has prompted important improvements of patients’
risk group definition in order to develop more and more targeted clinical trials. Finally, it is conceivable
that the progress of our understanding of the molecular bases of the neoplastic transformation
will open more opportunities to interfere directly with genes and their products altered inside the tumour cell.
Parole chiave
Suggerite dall'AI
Classificazione MeSH
Bibliografia
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4. Desandes E. Survival from adolescent cancer. Cancer Treat Rev 2007;33:609-15.
5. Castelberry RP. Neuroblastoma. Eur J Cancer 1997;33:1430-7.
6. Tsubono Y, Hisamichi S. A halt to neuroblastoma screening in Japan. N Engl J Med 2004; 350:2010-1.
7. Conter V, Jankovic M, Rizzari C, Palazzi G, Sala A, Paolucci P. La leucemia linfoblastica acuta: un modello di percorso terapeutico della pediatria moderna. Prospettive in Pediatria 2004;136:261-70.
8. Pui CH, Evans WE. Acute lymphoblastic leukemia. N Engl JMed 1998;339:605-15.
9. Faderl S, Kantarjian HM, Talpaz M, Estrov Z. Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic leukemia. Blood 1998;91:3995-4019.
10. Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet 2008;371: 1030-43.
11. Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 2002;1:133- 43.
12. Croce CM. Oncogenes and Cancer. N Engl J Med 2008;358:502-11.
13. Gajjar A, Herman R, Kocak M, et al. Clinical, histopatologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma. J Clin Oncol 2004;22:984-93.
14. Ellison, Onilude OE, Lindsey JC, et al. β catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children’s Cancer Study Group Brain Tumor Committee. J Clin Oncol 2005;23: 7951-7.
15. Polkinghorn WR, Tarbell NJ. Medulloblastoma: tumorigenesis, current clinical paradigm, and efforts to improve risk stratification. Nat Clin Pract Oncol 2007;4:295-304.
16. Rutkowski S, von Bueren A, von Hoff K, et al. Prognostic relevance of clinical and biological risk factors in childhood medulloblastoma: results of patients treated in the prospective multicenter trial HIT ’91. Clin Cancer Res 2007;13:2651-7.
17. Giangaspero F, Wellek S, Masuoka J, et al. Stratification of medulloblastoma on the histopathological grading. Acta Neuropathol 2006;112:5-12.
18. Conte M, Parodi S, De Bernardi B, et al. Neuroblastoma in adolescents: the Italian experience. Cancer 2006;106:1409-17.
19. Cecchetto G, Mosseri V, De Bernardi B, et al. Surgical risk factors in primary surgery for localized neuroblastoma: the LNESG1 study of the European International Society of Pediatric Oncology Neuroblastoma Group. J Clin Oncol 2005;23:8483-9.
20. Fletcher CD. The evolving classification of soft tissue tumours: an update based on the new WHO classification. Histopathology 2006; 48:3-12.
21. Romualdi C, De Pitta C, Tombolan L, et al. Defining the gene expression signature of rhabdomyosarcoma by meta-analysis. BMC Genomics 2006;7:287.
22. Pizzo PL, Poplack DG. Principles and Practice of Pediatric Oncology. Lippincott Williams & Wilkins Eds, IV edizione, 2002.
23. Bisogno G, Garaventa A, De Fazio V, et al. Attualità e prospettive nella diagnosi e terapia dei tumori solidi pediatrici. Prospettive in Pediatria 2007;148:243-59.
2. Gatta G, Capocaccia R, Coleman MP, Ries LA, Berrino F. Childhood cancer survival in Europe and the United States. Cancer 2002; 95:1767-72.
3. Dama E, Pastore G, Mosso ML, et al. Time trends and prognostic factors for survival from children cancer: a report from the Childhood Cancer Registry of Piedmont (Italy). Eur J Pediatr 2006;165:240-9.
4. Desandes E. Survival from adolescent cancer. Cancer Treat Rev 2007;33:609-15.
5. Castelberry RP. Neuroblastoma. Eur J Cancer 1997;33:1430-7.
6. Tsubono Y, Hisamichi S. A halt to neuroblastoma screening in Japan. N Engl J Med 2004; 350:2010-1.
7. Conter V, Jankovic M, Rizzari C, Palazzi G, Sala A, Paolucci P. La leucemia linfoblastica acuta: un modello di percorso terapeutico della pediatria moderna. Prospettive in Pediatria 2004;136:261-70.
8. Pui CH, Evans WE. Acute lymphoblastic leukemia. N Engl JMed 1998;339:605-15.
9. Faderl S, Kantarjian HM, Talpaz M, Estrov Z. Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic leukemia. Blood 1998;91:3995-4019.
10. Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet 2008;371: 1030-43.
11. Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 2002;1:133- 43.
12. Croce CM. Oncogenes and Cancer. N Engl J Med 2008;358:502-11.
13. Gajjar A, Herman R, Kocak M, et al. Clinical, histopatologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma. J Clin Oncol 2004;22:984-93.
14. Ellison, Onilude OE, Lindsey JC, et al. β catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children’s Cancer Study Group Brain Tumor Committee. J Clin Oncol 2005;23: 7951-7.
15. Polkinghorn WR, Tarbell NJ. Medulloblastoma: tumorigenesis, current clinical paradigm, and efforts to improve risk stratification. Nat Clin Pract Oncol 2007;4:295-304.
16. Rutkowski S, von Bueren A, von Hoff K, et al. Prognostic relevance of clinical and biological risk factors in childhood medulloblastoma: results of patients treated in the prospective multicenter trial HIT ’91. Clin Cancer Res 2007;13:2651-7.
17. Giangaspero F, Wellek S, Masuoka J, et al. Stratification of medulloblastoma on the histopathological grading. Acta Neuropathol 2006;112:5-12.
18. Conte M, Parodi S, De Bernardi B, et al. Neuroblastoma in adolescents: the Italian experience. Cancer 2006;106:1409-17.
19. Cecchetto G, Mosseri V, De Bernardi B, et al. Surgical risk factors in primary surgery for localized neuroblastoma: the LNESG1 study of the European International Society of Pediatric Oncology Neuroblastoma Group. J Clin Oncol 2005;23:8483-9.
20. Fletcher CD. The evolving classification of soft tissue tumours: an update based on the new WHO classification. Histopathology 2006; 48:3-12.
21. Romualdi C, De Pitta C, Tombolan L, et al. Defining the gene expression signature of rhabdomyosarcoma by meta-analysis. BMC Genomics 2006;7:287.
22. Pizzo PL, Poplack DG. Principles and Practice of Pediatric Oncology. Lippincott Williams & Wilkins Eds, IV edizione, 2002.
23. Bisogno G, Garaventa A, De Fazio V, et al. Attualità e prospettive nella diagnosi e terapia dei tumori solidi pediatrici. Prospettive in Pediatria 2007;148:243-59.
Corrispondenza: paolo.paolucci@unimore.it