PEDIATRICS INTERNATIONAL
Official Journal of the Japan Pediatric Society
JAPAN PEDIATRIC SOCIETY
Adrenocortical tumor with precocious puberty in a 2-month-old girl
Jean-Baptiste Marret,1 Lara Raffoul,5 Virginie Ribault,2,3,4 Philippe Ravasse1,3,4 and Julien Rod1,3,4
1 Department of Pediatric Surgery, University of Caen Hospital, Caen, France, 2Department of Pediatric Endocrinology, University of Caen Hospital, Caen, France, 3University of Caen Hospital, Caen, France, 4University of Caen Normandy, UFR Medicine, Caen, France and5Department of Pediatric Surgery, University of Necker Hospital, Paris, France
Abstract
Adrenocortical tumor is a rare childhood tumor with a median age at onset of 3.2 years. Virilization is the most common sign. Laparotomy is the reference treatment and has a favorable course. The diagnosis of adrenal tumor can be difficult. The main parameters of malignant tumors are size and metastasis. Analysis of TP53 mutation can facilitate final diagnosis. We report a case of virilizing adrenal tumor that developed in a 2-month-old girl, and which was treated with laparoscopic adrenalectomy.
Key words adrenocortical tumor, pediatric, virilization, young.
Adrenocortical tumors are rare in childhood and account for <0.2% of all pediatric tumors.1,2 Peak incidence occurs before 4 years of age and around the fourth decade.3,4 Clinical presentation includes, most commonly, signs of virilization. Congenital malformations could be associated to this type of tumor, particu- larly Li-Fraumeni and Beckwith-Wiedemann syndrome.3,4 We report the first case of precocious puberty in a 2-month-old girl.
Case report
A 2-month-old girl was brought to the pediatric emergency department with pubic hair development. Clinical examination indicated precocious puberty (Tanner stage P3S1; Fig. 1), with an accelerated growth curve (2SD; birthweight, 3800 g; weight at 2 months, 6400 g). No associated malformations were found. Abdominal ultrasonography showed a right round adrenal mass. Evaluation was completed with abdominal computed tomogra- phy and magnetic resonance imaging. Both confirmed the presence of a right adrenal mass 17 × 9.2 × 11 mm in size, with calcifications (Fig. 2). Ovaries were identified and were of normal aspect. Increases in testosterone and delta-4- androstenedione were noted: 0.480 µg/L and 0.920 µg/L, respectively (normal range at this age: testosterone, <0.05 µg/L; delta-4-androstenedione, 0.1-0.6 µg/L).
Search for TP53 mutation was negative. Surgical treatment consisted of laparoscopic adrenalectomy. Four ports were inserted: an umbilic port of 5 mm (for the optic of 30°), and three ports of 3 mm (one in the right iliac fossa, another in the right hypochondrium, and the last in the left hypochondrium). The tumor was dissected and freed from adhesions.
Resection limits were free of disease but histology was not able to indicate whether it was an adrenocortical carcinoma or
a cortical adenoma. The tumor was 14 × 12 mm in size and weighed 2.6 g. It was surrounded by a beige capsule along with small orange nodules 1 mm each. Tumor cells were mostly eosinophilic with a very pronounced anisokaryosis and areas of necrosis.
The postoperative course was uneventful. Hospital stay was 2 days. Two months postoperatively, the growth curve normalized and signs of puberty disappeared. One year after surgery the patient was well, and no recurrences were noted.
Discussion
Adrenocortical tumor is a very rare tumor in the pediatric popula- tion (<0.2% of childhood tumors.1,2
In the English-language literature, 31 pediatric cases have been reported to date, with the youngest patient being a 20-month-old child.5 Michalkiewicz et al., in a report on the International Pediat- ric Adrenocortical Tumor Registry of 2004, noted a median age of occurrence of 3.2 years.6 The overall female to male ratio is 1.6:1 but it varies widely according to age group. Female children pre- dominate in the age groups 0-3 years (ratio, 1.7:1) and >13 years (ratio, 6.2:1). In the pediatric literature on adrenocortical tumor, female to male ratio is 2:1, with three children presenting with Cushing’s syndrome2,4 and one with an associated Beckwith- Wiedemann syndrome.7 The most common clinical presentation (84.2%) includes signs of virilization, but excessive linear growth is often noted.8
Chen etal. reviewed 34 patients aged <15 years with an ad- renocortical carcinoma or cortical adenoma.9 Fourteen had signs of precocious puberty, 10 had precocious puberty along with Cushing’s syndrome, five had isolated Cushing’s syndrome, and five others did not have any symptoms. On laboratory tests, anomalies of circadian rhythm of cortisol (93.8%) were seen most frequently, followed by increased serum testosterone (89.7%).
When age is <4 years, outcome appears to be better.6 In the McAteer et al.1º study, the most significant predictors of cancer- related death were age 5-19 years (HR, 8.6; P=0.001) and distant disease occurrence (HR, 3.3; P=0.01).1º Complete resection is
Correspondence: Jean-Baptiste Marret, MD, Avenue Côte de Nacre, CHU de Caen -Service de Chirurgie Pédiatrique, 14033 Caen, Cedex 9, France. Email: marret-jb@chu-caen.fr
Received 7 October 2014; revised 14 March 2015; accepted 26 March 2015.
COR OBI15 32
SCANNER THURAL
02040359
TAP
9,2 mm
17 mm
required for cure.11 Surgery is the standard treatment and enables normalization of growth and disappearance of virilization.8 Ciftci etal. reported four cases of recurrence after complete surgical resection.12 Laparoscopic adrenalectomy en- ables complete resection of both benign and malignant adrenal masses,1,13,14 and provides good results. Lopes et al. treated nine children with adrenocortical tumor via laparoscopic adrenalec- tomy, with no perioperative complications.14 Different surgical procedures can be performed depending on associated malformations, patient overall health status, bilateralism of the disease, and surgeon expertise.1
Final diagnosis can be difficult, and determining the benign or malignant nature of the tumor can be complicated.1 Features asso- ciated with possible malignant behavior include tumor weight (>400 g), tumor size (>10.5 cm), vena cava invasion, capsular and/or vascular invasion, extension to periadrenal soft tissue, confluent necrosis, severe nuclear atypia (>15 mitotic figures/20 HPF, and the presence of atypical mitotic figures) and metastasis.11
Moreover, constitutional mutations of p53 are frequently reported in young children with a diagnosis of adrenocortical tumor. Familial genetic predisposition to cancer (p53 mutations) and selected genetic syndromes (Beckwith-Wiedemann syn- drome7) have been associated with childhood adrenocortical cancer in general.3
In case of positive TP53 mutation, mainly in Li-Fraumeni syn- drome (a genetic disorder that greatly increases the incidence of several types of cancer, especially in the bones, soft tissue, brain, blood, and adrenal glands), the recurrence rate is significant. There- fore, follow up of several years is recommended.15
Conclusion
Adrenal tumors can be found at any age, even in very young chil- dren. Treatment consists of surgical resection, which can be done via laparoscopy when the tumor is small. Resection should be com- plete without shredding of the tumor. Diagnosis can be very com- plicated and histology does not always aid in defining the nature of the tumor. Finally, analysis of TP53 mutation must always be done in order to help define the nature of the tumor, especially in young patients.
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