Klinefelter Syndrome and Neuroblastoma

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  • Pediatr Blood Cancer 2011;57:696

    LETTER TO THE EDITORKlinefelter Syndrome and Neuroblastoma

    To the Editor: Klinefelter syndrome (KS) has been associated to

    increased risk of cancer in adulthood [1]. However, the absence of

    epidemiological studies including children, limit the statistical data

    needed to assess the risk of pediatric tumors in these patients.

    Noteworthy is that, due to the lack of reported cases in the literature,

    KS has been speculated as protective against neuroblastoma [2]. A

    constitutional supernumerary X chromosome may protect against

    neuroblastomameanwhile Xmonosomy, Turner syndrome, tends to

    be prone to neurogenic tumors and gonadal tumors [3].

    We report a tenmonth old child with intrauterine diagnose of KS

    (47,XXYvisible onmetaphase preparations), left polycystic kidney

    and arthrogryposis. A routine surveillance ultrasonography dis-

    closed a right heterogeneous adrenalmasswhich contained calcium.

    Ferritin, lactate dehydrogenase, and urine catecholamines and

    metabolites, including vanillylmandelic acid, homovanillic acid and

    dopamine, were within normal ranges. A magnetic resonance

    imaging (MRI) conrmed an enlarged right adrenal gland measur-

    ing 6 cm 5 cm 3.5 cm. A 123I metaiodobenzylguanidine(MIBG) scintigraphy revealed right adrenal uptake. Bone scan99Tc and bone marrow aspirates were negative. The patient was

    treated with radical excision alone according to the protocol for

    localized resectable neuroblastoma (LNESG2) of the International

    Society of Pediatric Oncology (SIOP). He also underwent left

    nephrourectomy due to non-functional left polycystic kidney. The

    histological study concluded poorly differentiated neuroblastoma,

    stage 2B. Cytogenetic studies showed tetraploidy by ow cytometry

    and noMYCNamplication or 1p deletion by uorescence-based in

    situ hybridization (FISH). Five years after initial diagnosis the

    patient remains alive without remarkable events.

    Reports of constitutional chromosome anomalies in children

    presenting with particular embryonal tumors precludes identica-

    tion of genes involved in the development of cancer. Less aggressive

    tumors have been seen with viable genetic conditions, whereas

    severe genetic conditions were associated with large and dissemi-

    nated tumors that occurred earlier as reported by Satge et al. [4] The

    numerous chromosomes and chromosome regions involved in

    karyotype anomalies reported in neuroblastomas suggest that

    several pathways lead to this tumor and to different tumoral

    aggressivity [4]. Neuroblastoma has the highest rate of spontaneous

    regression among malignant tumors, especially at younger age.

    When screening programs have been undertaken, there has been a

    higher incidence of neuroblastoma reported [5]. This overdiagnosis

    may be due to spontaneous regression in stages 4S and in other non-

    stage 4S especially if primarily located in the adrenal gland. It may

    be adduced that genetic diagnosis of KS is usually made in

    adolescences and early adulthood explaining the lack of reported

    neuroblastomas in this age group. It is possible that lower stage

    neuroblastoma is more often associated to KS in early childhood

    that involutes and is not diagnosed, or that by itself excess X

    chromosome prompts involution of neuroblastoma.

    The casewe are reporting could have probably gone unnoticed if

    the neuroblastoma had not been found by periodic abdominal

    ultrasonography exams performed due to the patients renal

    pathology; furthermore, it might have spontaneously regressed

    without treatment.

    Mara Elena Mateos, MD, PhD*

    Pediatric Oncology Unit

    Department of Pediatrics

    University Hospital Reina Sofa

    Cordoba, Spain

    Eduardo Lopez-Laso, MD, PhD

    Pediatric Neurology Unit

    Department of Pediatrics

    University Hospital Reina Sofa

    Cordoba, Spain

    Juan Luis Perez-Navero, MD, PhD

    Pediatric Intensive Care Unit

    Department of Pediatrics

    University Hospital Reina Sofa

    Cordoba, Spain


    1. Swerdlow AJ, Schoemaker MJ, Higgins CD, et al. Cancer incidence and

    mortality inmenwithKlinefelter syndrome:A cohort study. JNatl Cancer Inst


    2. Satge D, Sasco AJ, Plantaz D, et al. Abnormal number of X chromosomes and

    neuroblastic tumors. J Pediatr Hematol Oncol 2001;23:331332.

    3. Satge D, Moore SW, Stiller CA, et al. Abnormal constitutional karyotypes in

    patients with neuroblastoma: A report of four new cases and review of 47

    others in the literature. Cancer Genet Cytogenet 2003;147:8998.

    4. Sasaki Y, Nakayama H, Ikeda M. Turner syndrome and ganglioneuroma.

    J Pediatr Hematol Oncol 2000;22:8990.

    5. Hero B, Simon T, Spitz R, et al. Localized infant neuroblastomas often show

    spontaneous regression: Results of the prospective trials NB95-S and NB97.

    J Clin Oncol 2008;26:15041510.

    2011 Wiley-Liss, Inc.DOI 10.1002/pbc.23089Published online 30 June 2011 in Wiley Online Library(wileyonlinelibrary.com).

    Abbreviations: KS, Klinefelter syndrome; SIOP, International Society

    of Pediatric Oncology; MRI, magnetic resonance imaging; MIBG,

    123I metaiodobenzylguanidine; FISH, uorescence-based in situ


    *Correspondence to: Mara Elena Mateos, MD, PhD, Pediatric

    Oncology Unit, Department of Pediatrics, University Hospital Reina

    Sofa, Cordoba, Av. Menendez Pidal, s/n, 14004 Cordoba, Spain.

    E-mail: marielmateos@gmail.com

    Received 17 November 2010; Accepted 25 January 2011


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