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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) confirmed 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 flow cytometry
and noMYCNamplification or 1p deletion by fluorescence-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 identifica-
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 patient’s renal
pathology; furthermore, it might have spontaneously regressed
without treatment.
Marıa Elena Mateos, MD, PhD*
Pediatric Oncology Unit
Department of Pediatrics
University Hospital Reina Sofıa
Cordoba, Spain
Eduardo Lopez-Laso, MD, PhD
Pediatric Neurology Unit
Department of Pediatrics
University Hospital Reina Sofıa
Cordoba, Spain
Juan Luis Perez-Navero, MD, PhD
Pediatric Intensive Care Unit
Department of Pediatrics
University Hospital Reina Sofıa
Cordoba, Spain
REFERENCES
1. Swerdlow AJ, Schoemaker MJ, Higgins CD, et al. Cancer incidence and
mortality inmenwithKlinefelter syndrome:A cohort study. JNatl Cancer Inst
2005;97:1204–1210.
2. Satge D, Sasco AJ, Plantaz D, et al. Abnormal number of X chromosomes and
neuroblastic tumors. J Pediatr Hematol Oncol 2001;23:331–332.
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;147:89–98.
4. Sasaki Y, Nakayama H, Ikeda M. Turner syndrome and ganglioneuroma.
J Pediatr Hematol Oncol 2000;22:89–90.
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;26:1504–1510.
� 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, fluorescence-based in situ
hybridization.
*Correspondence to: Marıa Elena Mateos, MD, PhD, Pediatric
Oncology Unit, Department of Pediatrics, University Hospital Reina
Sofıa, Cordoba, Av. Menendez Pidal, s/n, 14004 Cordoba, Spain.
E-mail: [email protected]
Received 17 November 2010; Accepted 25 January 2011