Pediatric Tumors

Diagnosis and therapy of pediatric tumors have a very long and productive history, and we feel indebted toward those pioneers who first opened the way to the understanding of the pathways that underlie the basic mechanisms of these special tumor types. The diagnosis of pediatric malignant tumors is often challenging.[1] [2] [3] Accordingly, over the last two decades, there has been an increasing interest worldwide about the identification of tumor markers useful for both diagnostic and therapeutic purposes in pediatric oncology.[4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Apart from neuroblastoma, hepatoblastoma, and germ cell tumors, the majority of solid pediatric tumors have no tumor-specific markers detectable in the serum of patients.

In the present special issue, our aim is to provide original and review articles dealing with some pediatric tumors, emphasizing clinical, biochemical, and pathological features, which can be exploited by pediatricians, regardless of their subspecialties, in their daily practice. The need for a multidisciplinary approach, particularly with the joint effort of clinical and laboratory counterparts, is evident throughout the articles presented herein.

This special issue begins with an overview on adrenocortical tumors in childhood. These neoplasms are relatively rare in pediatric age and their diagnosis (benign vs. malignant) is still challenging.[15] In this regard, the article by Salvatorelli et al discusses the clinical, laboratory, and pathologic features useful in daily practice for achieving an accurate diagnosis. The article by Tumino et al summarizes the current understanding on bone marrow transplantation for both malignant and nonmalignant hemopathies. They report some new interesting acquisitions about the allogeneic transplant with a haploidentical, semi-compatible, donor.[16] The article by Ruggeri et al focuses on the pathophysiology of merlin structure and function, on its posttranslational and upstream/downstream regulation in the different forms of NF2 in the pediatric age.[17] Neuroblastoma is one of the most frequent solid tumors in children. About half of the cases are metastatic, and its prognosis today still remains unfavorable despite many new therapeutical approaches. The articles by Marino et al and Balaguer et al deal with typical biomarkers of neuroblastoma: the former focuses mainly on vanillylmandelic and homovanillic acids,[18] whereas the latter on metaiodobenzylguanidine (MIBG), a molecule that can be marked with radioactive 123- or 131-iodine; due to the ability of neuroblastoma to uptake MIBG, this marker turns out to be extremely useful for diagnosis, follow-up, and treatment.[19] Acute lymphoblastic leukemia is the most frequent childhood neoplasm, and its prognosis in the last two decades has become very good for most patients. Bonaccorso and colleagues discuss about the pathways involved in the leukemogenic process, and the prospective of a tailored treatment according to single specific profile, to further increase the efficacy with less toxicity.[20] Extracranial malignant germ cell tumors have a favorable prognosis in children, with more than 80% survival rate. Yolk sac tumor is the histotype producing alfa-fetoprotein. Moscheo et al, in their article, discuss the role of this marker at diagnosis and in the follow-up, as well as a prognostic factor.[21] La Spina et al review the state of art of tumoral lysis syndrome by providing a comprehensive overview of a complication that can occur in all pediatric neoplasms. The early recognition and, preferably, the prevention of tumoral lysis syndrome may have a huge impact on clinical practice.[22] Bone sarcomas in childhood, if treated with a multidisciplinary approach including orthopedics and oncologists, present good results in terms of outcome for localized cases, while patients with metastatic disease are even today very difficult to cure. The article by D'Angelo et al deals with the two most frequent malignant bone tumors, namely, osteosarcoma and Ewing sarcoma, describing also the more recent therapeutic approaches.[23] Finally, we would like to thank all the authors of this special issue for providing an overview on the state of the art regarding some pediatric tumors, prompting pediatricians and pathologists to plan further clinical, pathological, and molecular studies in the fascinating and intriguing field of pediatric oncology.

• References

• 1 Folpe AL, Hill CE, Parham DM, O'Shea PA, Weiss SW. Immunohistochemical detection of FLI-1 protein expression: a study of 132 round cell tumors with emphasis on CD99-positive mimics of Ewing's sarcoma/primitive neuroectodermal tumor. Am J Surg Pathol 2000; 24 (12) 1657-1662
• 2 Magro G, Greco P, Alaggio R, Gangemi P, Ninfo V. Polypoid angiomyofibroblastoma-like tumor of the oral cavity: a hitherto unreported soft tissue tumor mimicking embryonal rhabdomyosarcoma. Pathol Res Pract 2008; 204 (11) 837-843
• 3 Alaggio R, Boldrini R, Di Venosa B, Rosolen A, Bisogno G, Magro G. Pediatric extra-renal rhabdoid tumors with unusual morphology: a diagnostic pitfall for small biopsies. Pathol Res Pract 2009; 205 (7) 451-457
• 4 Arnold MA, Schoenfield L, Limketkai BN, Arnold CA. Diagnostic pitfalls of differentiating desmoplastic small round cell tumor (DSRCT) from Wilms tumor (WT): overlapping morphologic and immunohistochemical features. Am J Surg Pathol 2014; 38 (9) 1220-1226
• 5 Magro G, Musumeci G, Parenti R. Immunomarkers in human developing and pediatric neoplastic tissues. Acta Histochem 2015; 117 (4–5) 311-312
• 6 Fagone P, Nicoletti F, Vecchio GM, Parenti R, Magro G. Cyclin D1 in pediatric neuroblastic tumors: a microarray analysis. Acta Histochem 2015; 117 (8) 820-823
• 7 Salvatorelli L, Parenti R, Leone G, Musumeci G, Vasquez E, Magro G. Wilms tumor 1 (WT1) protein: Diagnostic utility in pediatric tumors. Acta Histochem 2015; 117 (4–5) 367-378
• 8 Magro G, Salvatorelli L, Puzzo L, Musumeci G, Bisceglia M, Parenti R. Oncofetal expression of Wilms' tumor 1 (WT1) protein in human fetal, adult and neoplastic skeletal muscle tissues. Acta Histochem 2015; 117 (4–5) 492-504
• 9 Magro G, Brancato F, Musumeci G, Alaggio R, Parenti R, Salvatorelli L. Cyclin D1 is a useful marker for soft tissue Ewing's sarcoma/peripheral Primitive Neuroectodermal Tumor in children and adolescents: a comparative immunohistochemical study with rhabdomyosarcoma. Acta Histochem 2015; 117 (4–5) 460-467
• 10 Dome JS, Graf N, Geller JI , et al. Advances in Wilms tumor treatment and biology: progress through international collaboration. J Clin Oncol 2015; 33 (27) 2999-3007
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• 15 Magro G, Esposito G, Cecchetto G , et al. Pediatric adrenocortical tumors: morphological diagnostic criteria and immunohistochemical expression of matrix metalloproteinase type 2 and human leucocyte-associated antigen (HLA) class II antigens. Results from the Italian Pediatric Rare Tumor (TREP) Study project. Hum Pathol 2012; 43 (1) 31-39
• 16 Bertaina A, Merli P, Rutella S , et al. HLA-haploidentical stem cell transplantation after removal of αβ+ T and B cells in children with nonmalignant disorders. Blood 2014; 124 (5) 822-826
• 17 Ruggieri M, Praticò AD, Evans DG. Diagnosis, management, and new therapeutic options in childhood neurofibromatosis type 2 and related forms. Semin Pediatr Neurol 2015; 22 (4) 240-258
• 18 Cangemi G, Barco S, Reggiardo G , et al. Interchangeability between 24-hour collection and single spot urines for vanillylmandelic and homovanillic acid levels in the diagnosis of neuroblastoma. Pediatr Blood Cancer 2013; 60 (12) E170-E172
• 19 Cistaro A, Quartuccio N, Caobelli F , et al. 124I-MIBG: a new promising positron-emitting radiopharmaceutical for the evaluation of neuroblastoma. Nucl Med Rev Cent East Eur 2015; 18 (2) 102-106
• 20 Dandekar S, Romanos-Sirakis E, Pais F , et al. Wnt inhibition leads to improved chemosensitivity in paediatric acute lymphoblastic leukaemia. Br J Haematol 2014; 167 (1) 87-99
• 21 Schneider DT, Calaminus G, Göbel U. Diagnostic value of alpha 1-fetoprotein and beta-human chorionic gonadotropin in infancy and childhood. Pediatr Hematol Oncol 2001; 18 (1) 11-26
• 22 Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J Med 2011; 364 (19) 1844-1854
• 23 Tancredi R, Zambelli A, DaPrada GA , et al. Targeting the EWS-FLI1 transcription factor in Ewing sarcoma. Cancer Chemother Pharmacol 2015; 75 (6) 1317-1320