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UROLOGY - ORIGINAL PAPER
Clinical characteristics of adrenal tumors in children: a retrospective review of a 15-year single-center experience
Xiaokun Lin1 . Dazhou Wu2 . Congde Chen1 . Na Zheng2
Received: 10 November 2016 / Accepted: 6 December 2016 @ Springer Science+Business Media Dordrecht 2016
Abstract
Objective Adrenal tumors are rare in children. The aim of this study is to review and analyze clinical data on the diag- nosis and management of adrenal tumors in children.
Methods Between 2001 and 2015, 48 pediatric patients (<14 years old) admitted to our institute with adrenal tumors were reviewed. Clinical features, imaging studies, surgical approaches, as well as pathological diagnoses were recorded.
Results The series comprised 28 males and 20 females. Adrenomedullary tumors were 37, including 24 cases of neuroblastoma, 10 cases of ganglioneuroma, 2 cases of ganglioneuroblastoma, and 1 case of pheochromocy- toma. Adrenocortical tumors were 10: 9 cases of cortical adenoma and 1 case of cortical cancer. The other one was hematoma. Fever, pain, and abdominal distention were the main clinical manifestations of adrenomedullary tumors, while Cushing syndrome was the most frequent presenting symptom of adrenocortical tumors. Both computed tomog- raphy and magnetic resonance imaging showed a high diagnostic yield. Some patients had an elevated hormone level. Open adrenalectomy was performed in 40 patients (83.3%), while a laparoscopic approach was employed in eight patients (16.7%).
Results Adrenal tumors in children have various types,as well as clinical manifestations. Imaging and laboratory
☒ Xiaokun Lin linxk2000@163.com
1 Department of Pediatric Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
2 Department of Pediatric Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
data could be useful for differentiation of malignant from benign tumor. Final diagnosis depends on pathology. Surgi- cal excision of the adrenal tumors is the standard of care.
Keywords Adrenal tumor · Neuroblastoma . Children . Diagnoses · Surgery
Introduction
The incidence of adrenal tumors is much lower than that of other tumors in children. Because of the rarity of pedi- atric adrenal tumors, no single pediatric oncology center has acquired extensive experience with these tumors [1]. More experience comes from adult oncology center [2-4]. Furthermore, most reported series describe only a few pedi- atric patients with a certain tumor which was observed over a period of several years [5-7]. Correctly diagnosed and properly treated, most adrenal tumors in children are curable; misdiagnosed or improperly managed, they can be fatal, particularly adrenocortical cancer. Pediatric adre- nal tumors seem to have a consistent clinical and biologic course. In this study, we reviewed a series of 48 pediatric adrenal tumors treated at our institute over the last 15 years, analyzing the clinical data and suggesting a strategy of diagnosis and treatment.
Methods
From January 2001 to December 2015, a total of 48 patients (<14 years old) with adrenal tumor were treated operatively at the department of pediatric surgery in the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (Wenzhou, China). All the
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clinical details, radiologic, laboratory, and pathologic find- ings were collected from the department’s database.
Results
From 2001 to 2015, 48 pediatric patients were diagnosed with adrenal tumors. Patients’ ages ranged from 1 day to 14 years (Fig. 1). Those <1 year old were more likely to have adrenal tumors than those of other ages. Table 1 shows the characteristics of the 48 pediatric patients with adrenal tumors. Adrenal tumors were diagnosed in 28 male (58.3%) and 20 female patients (41.7%). There was no sig- nificant sex difference in overall incidence, but the male- to-female ratio for cortex tumors was significantly lower, which was about 1:3. Twenty-five patients (52.1%) har- bored right-sided adrenal lesions, while 23 patients (47.9%) had left-sided adrenal lesions. The size of the tumors ranged from 1.5 x 2 cm up to 15 x 12 cm. The diame- ters of most tumors were less than 5 cm. In the 48 patients, 15 patients were benign tumors (31.25%) and 33 patients were malignant tumors (68.75%). Patients with malignant tumors were treated with conventional chemotherapy after operations in hematology department. The chemotherapy consisted of carboplatin, cyclophosphamide, doxorubicin, and etoposide.
As shown in Table 2, 38 patients had obvious symp- toms and signs. The remaining 10 patients had no clinical signs or presentation. They were discovered accidentally by ultrasonography (US) in routine examinations, most of whom were <1 year old. Radiologic studies such as US, enhanced abdominal computed tomography (CT) scan or abdominal magnetic resonance imaging (MRI) study showed adrenal mass in all patients. Hormonal determi- nations were performed in 48 patients, with an elevated hormone level in serum and/or urine found in 18 (37.5%).
| Medulla tumors | Cortex tumors | Other | Total | |
|---|---|---|---|---|
| Number | 38 | 9 | 1 | 48 |
| Age (years) | ||||
| <1 | 18 | 0 | 0 | 18 |
| >1 | 20 | 9 | 1 | 38 |
| Sex | ||||
| Male | 25 | 2 | 1 | 28 |
| Female | 13 | 7 | 0 | 20 |
| Location | ||||
| Left | 15 | 7 | 1 | 23 |
| Right | 23 | 2 | 0 | 25 |
| Diameter (cm) | ||||
| <5 | 24 | 6 | 1 | 31 |
| >5 | 14 | 3 | 0 | 17 |
| Characteristic | ||||
| Benign | 7 | 8 | 1 | 16 |
| Malignant | 31 | 1 | 0 | 32 |
| Medulla tumors | Cortex tumors | Other | Total | |
|---|---|---|---|---|
| Pain | 11 | 1 | 1 | 13 |
| Fever | 8 | 0 | 0 | 8 |
| Abdominal | 5 | 0 | 0 | 5 |
| distention | ||||
| Hypertension | 1 | 0 | 0 | 1 |
| Palpable mass | 3 | 0 | 0 | 3 |
| Incidentally | 10 | 0 | 0 | 10 |
| discovered | ||||
| Sexual precocity | 0 | 2 | 0 | 2 |
| Cushing syndrome | 0 | 6 | 0 | 6 |
Of 29 patients with neuroblastoma, 14 (48.3%) patients were positive, including an abnormal urinary vanillyl- mandelic acid (VMA) level of 24 h (range from 55.2 to 97.6 umol/24 h). Only 4 patients with cortex tumors had a high level of serum cortisol (range from 42.3 to 64.8 µg/ ml).
When adrenal mass was found and the nature of the mass was uncertain, we usually chose the treatment of operation positively. Unless the preoperative estimation of the tumor was difficult to resect completely, we would choose biopsy. Excision of the diagnosed masses was offered to all patients. Forty patients were subjected to open adrenalectomy through a lumbar and abdominal approach (30 and 10 patients, respectively), while a transperitoneal laparoscopic approach was offered to eight patients. All of the masses were successfully resected, except for one with
| Histopathology | n | % |
|---|---|---|
| Neuroblastoma | 29 | 60.4 |
| Ganglioneuroblastoma | 2 | 4.2 |
| Ganglioneuroma | 6 | 12.5 |
| Pheochromocytoma | 1 | 2.1 |
| Cortical adenoma | 8 | 16.6 |
| Adrenocortical carcinoma | 1 | 2.1 |
| Hematoma | 1 | 2.1 |
| Total | 48 | 100 |
adrenocortical carcinoma who had a giant tumor associ- ated with inferior vena cava thrombosis. Pathology of the excised tumors is shown in Table 3. There were no wound infections, intra-abdominal bleeding, and any other intra- operative complications. Twenty-four patients of neuro- blastomas recovered well with no relapse for 3-6 months of follow-up as well as other patients with adrenal tumors. But we had not got long-term follow-up results.
Discussion
Adrenal tumors were difficult to be found because of their particular location. The prevalence of adrenal tumors iden- tified at autopsy increased from <1% among individuals <30 years of age to about 7% in those >70 years of age [4]. The overall incidence of adrenal tumors in children was not yet clear, and the reports were only on some kind of those. Neuroblastoma was the most common extracranial solid neoplasm in children, accounting for 10% of all pediatric neoplasms, and 15% of all childhood mortality from neo- plasms [8]. Primary tumors of the adrenal cortex were rare in children, with a worldwide incidence of 1.5 per million per year before the age of 15 years [9]. Pheochromocytoma was a relatively uncommon tumor whose annual incidence ranged from two to eight cases per million populations [10].
The adrenal gland had two distinct parts: the cortex and the medulla. Each part had different types of tumors. Tumors arose from the adrenal medulla included neuro- blastoma, ganglioneuroblastoma, ganglioneuroma, and pheochromocytoma. Tumors that arose from the adrenal cortex included adrenocortical carcinoma and adenoma. The present study had 48 cases of the adrenal tumor. Thirty-nine were tumors of adrenal medulla and 8 were tumors of adrenal cortex with ratio of medullary to corti- cal tumors as 4:1. About 50% of adrenomedullary tumors occurred under 1 year. The male-to-female ratio of adre- nomedullary tumors was 2:1. Neuroblastoma was the most common tumor in adrenomedullary tumors, followed by
ganglioneuroma and ganglioneuroblastoma. Neuroblas- toma accounted for 60.4% of adrenal tumors. Cortical adenoma was the most common tumor in adrenocorti- cal tumors, followed by adrenocortical carcinoma. The male-to-female ratio of adrenocortical tumors was 1:3. In Enzo Lalli et al.’s study, adrenocortical tumors in children under 15 years of age also affected girls more frequently than boys [11]. In our study, most of medullary tumors were malignant, while cortical tumors were mostly benign. Meanwhile, the mean diameter of benign tumors was less than that of malignancies, most of those were generally larger than 5 cm in diameter. Cagle et al. [12] found that only size (expressed as weight) was a reliable predictor of malignancy, with a weight greater than 500 g indicative of a carcinoma.
Clinical manifestations of adrenal tumors were various, with no specificity. In general, abdominal pain, fever, and abdominal distention were the main symptoms of adre- nomedullary tumors. Some had no clinical signs or pres- entation. In our study, seven were discovered by US in prenatal examination and three in routine health examina- tions. One patient with pheochromocytoma manifested the main symptom of hypertension, without any other discom- forts. Sutton et al. [13] described about 54% of patients with clinically unsuspected pheochromocytomas who also had a history of hypertension. In contrast to adults, most children with adrenocortical tumor had clinical evidence of an endocrine syndrome including Cushing syndrome and peripheral precocious puberty. In our study, the most common clinical presentation of adrenocortical adenoma was Cushing syndrome, which was presented in six chil- dren, followed by peripheral precocious puberty, which was presented in two children. However, the children with adrenocortical carcinoma presented only with abdominal pain without endocrine abnormality. Mihai [14] described most adrenocortical carcinoma presented with endocrine dysfunction, of which with virilization being the most com- mon presentation, followed by Cushing syndrome.
In our series, all of the masses could be detected by US. Because of its being easy and cheap, US was employed as a routine imaging tool for the characterization of adrenal masses. However, its sensitivity and specificity were not as good as CT and MRI. CT and MRI were not only use- ful in detection and localization of adrenal masses but also helpful in evaluating tumor characteristics. CT was better than MRI in detecting and localizing adrenal tumor, and MRI was more helpful than CT in distinguishing benign and malignant tumors, by comparing signal intensities and by contrast enhancement with gadolinium DTPA [15]. We performed various hormonal determinations in blood and/ or urine according to the patient’s symptoms and signs. The VMA of 24 h in urine was valuable for the diagnosis of neuroblastoma, but it was not raised in all of the cases of
neuroblastoma. Meanwhile, the detected value of VMA in each patient was different. As the detection method and the normal value setting in our hospital maybe different from others, the value of VMA was in a low level. The labora- tory characteristics of adrenocortical tumors were the dis- cordantly elevated serum levels of sexual corticosteroids. Some had disturbance of the normal circadian rhythm of cortisol secretion [16]. In our series, four cortical adeno- mas had a high level of serum cortisol. All of the auxiliary examinations were to identify the type of tumors before operation, but the final diagnosis depended on postopera- tive pathology. However, to identify a tumor as a benign or malignant tumor sometimes was difficult even in pathology.
Surgical approaches to the adrenal tumors were the standard treatments. The open adrenalectomy was pre- ferred for adrenal lesions suspicious of malignancy, espe- cially those of large size with signs of local infiltration or venous involvement [17]. Biopsy was a safer choice for the patients with adrenal tumors that cannot be resected completely by one time. The open approach had been described previously, including a lumbar approach and an anterior transabdominal approach [18]. However, in expe- rienced hands, laparoscopic adrenalectomy was a safe and minimally invasive surgical technique with a short hospi- talization stay and minimal complication rate [19]. Lapa- roscopic adrenalectomy had been proved to be superior in pediatric patients [20, 21]. In our series, most patients were subjected to open adrenalectomy, while a transperitoneal laparoscopic approach was offered to eight patients. All of the masses were successfully resected, except for one with adrenocortical carcinoma who had a giant tumor associated with inferior vena cava thrombosis.
Conclusions
Adrenal tumors in children have various types, as well as clinical manifestations. Imaging and laboratory data could be useful for differentiation of malignant from benign tumors. Final diagnosis depends on pathology. Surgical excision of the adrenal tumors is the standard treatment. Adrenal tumors are curable under proper and prompt management.
Acknowledgement We would like to thank our colleagues from the Department of Pediatric Surgery, for their assistance with data collection.
Compliance with ethical standards
Conflict of interest Xiaokun Lin declares that he has no conflict of interest. Dazhou Wu declares that he has no conflict of interest. Con- gde Chen declares that he has no conflict of interest. Na Zheng declares that she has no conflict of interest.
Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethic committee of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University and with the 1964 Declaration of Helsinki and its later amendments or comparable ethi- cal standards.
Informed consent Informed consent was obtained from all individual participants included in the study.
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