Pubertas praecox and hypothalamic hamartoma

Summary Precocious puberty of cerebral origin is classified into pseudoprecocious puberty and true precocious puberty. Pseudoprecocious puberty is caused by HCG secreting tumours. True precocious puberty is caused by various hypothalamic diseases. Among them, hypothalamic hamartoma is the most common cause. Precocious puberty is caused by elevated blood pituitary gonadotropin concentration, secondary to the elevated hypothalamic LHRH secretion. The hypothalamic hamartoma is not infrequently associated with laughing (gelastic) seizures as well as convulsions. Diagnosis of a hypothalamic hamartoma is easily made by CT. Although the hypothalamic hamartoma is difficult to operate on, the value of surgery is stressed for treatment of precocious puberty. This is also confirmed by recent reports.     

Treatments of hamartoma with neuroendoscopic surgery and stereotactic radiosurgery: a case report.

Hypothalamic hamartoma is a non-neoplastic tumor manifesting as gelastic seizure, precocious puberty, and abnormal behavior. Treatment of it is very complicated due to its location. We report a case of hypothalamic hamartoma treated by neuroendoscopic surgery and stereotactic radiosurgery. A 5-year-old girl presented with violent behavior, precocious puberty, gelastic seizure and atonic seizure. She was diagnosed with hypothalamic hamartoma by CT and magnetic resonance imaging at 11 months of age. Tumor size did not change, but tumor intensity had changed on the MR image at 5 years of age. Magnetic resonance spectroscopy revealed decreased N-acetylaspartate and increased choline and creatine in the tumor. After neuroendoscopic biopsy, she underwent linear accelerator stereotactic radiosurgery. But her symptoms remained unchanged for 6 months. She then underwent partial resection and laser coagulation of the tumor by a neuroendoscopic approach. After the procedure, the frequency of her seizures was remarkably decreased, and her violent behavior improved. The transventricular neuroendoscopic approach to the hypothalamus is less invasive than the radical surgery. Neuroendoscopic surgery can be one of the treatments of choice for hypothalamic hamartoma.     

The relationship between magnetic resonance imaging findings and clinical manifestations of hypothalamic hamartoma.

OBJECT: Hypothalamic hamartoma is generally diagnosed based on its magnetic resonance (MR) imaging characteristics and the patient's clinical symptoms, but the relationship between the neuroradiological findings and clinical presentation has never been fully investigated. In this retrospective study the authors sought to determine this relationship. METHODS: The authors classified 11 cases of hypothalamic hamartoma into two categories based on the MR findings. Seven cases were the "parahypothalamic type," in which the hamartoma is only attached to the floor of the third ventricle or suspended from the floor by a peduncle. Four cases were the "intrahypothalamic type," in which the hamartoma involved or was enveloped by the hypothalamus and the tumor distorted the third ventricle. Six patients with the parahypothalamic type exhibited precocious puberty, which was controlled by a luteinizing hormone-releasing hormone analog, and one patient was asymptomatic. No seizures or mental retardation were observed in this group. All patients with the intrahypothalamic type had medically intractable seizures, and precocious puberty was seen in one. Severe mental retardation and behavioral disorders including aggressiveness were seen in two patients. The seizures were controlled in only one patient, in whom stereotactically targeted irradiation of the lesion was performed. This topology/symptom relationship was reconfirmed in a review of 61 reported cases of hamartoma, in which the MR findings were clearly described. The parahypothalamic type is generally associated with precocious puberty but is unaccompanied by seizures or developmental delay, whereas the intrahypothalamic type is generally associated with seizures. Two thirds of patients with the latter experience developmental delays, and half also exhibit precocious puberty. CONCLUSIONS: Classification of hypothalamic hamartomas into these two categories based on MR findings resulted in a clear correlation between symptoms and the subsequent clinical course.     

Study on cases of precocious puberty

Two boys and one girl with idiopathic precocious puberty were treated with medroxyprogesterone acetate (MPA) for 2 years and 2 months to 9 years and 5 months, and its efficiency was evaluated. Treatment with MPA suppressed the gonadotropin levels, the signs and symptoms of patients with precocious puberty, and also had a suppressive effect on bone-age advance, so these patients showed almost normal growth in height. There has been controversy about the age when treatment for idiopathic precocious puberty should be finished. Our data suggested that the treatment should be stopped at 11-13 years when patients reach the age of puberty.     

Controlling precocious puberty--surgical excision of hypothalamic hamartoma causing precocious puberty

Among the causes of precocious puberty, hypothalamic hamartoma comprises a small percentage. However, the frequency of precocious puberty in the presence of hypothalamic hamartoma is quite high. Recently, results of surgery in 14 cases of hypothalamic hamartoma were reported. Precocious puberty completely subsided in three cases and slight improvement was achieved in another three cases. We performed surgery in four patients with hypothalamic hamartomas, with the goal of decreasing the symptoms of precocious puberty. The patients were two females (aged 1 yr, 3 mo and 6 mo) and two males (aged 3 yr, 7 mo and 1 yr, 9 mo). The main symptoms were precocious puberty and mental retardation of varying degrees. The males had excessive growth of body and external genitalia, while the females had genital bleeding and premature breast development. In each case, computed tomographic scans disclosed a round, isodense mass in the interpeduncular cistern, attached to the base of the hypothalamus. Contrast enhancement was negative. Endocrinologically, in case 1, testosterone was 92.6 ng/ml, FSH was 16 mIU/ml, and LH was 2.2 mIU/ml. Although LH was within normal limits, it overresponded to LH-RH stimulation. In case 2, estrogen was 13.5 ng/day, LH was 5.2 mIU/ml, FSH was 5.3 mIU/ml, and LH showed an exaggerated response to LH-RH stimulation. In case 3, testosterone was 362 ng/ml, LH was 8.8 mIU/ml, FSH was 4.8 mIU/ml, and LH showed an abnormally high response to LH-RH stimulation. In case 4, LH was 18.4 mIU/ml, FSH was 12.0 mIU/ml, and both hormones were stimulated abnormally strongly by LH-RH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypothalamic hamartoma successfully treated by operation. Case report

An 18-month-old boy was diagnosed as having a hypothalamic hamartoma. When he was 1 year old, he developed precocious puberty, and at 18 months old, endocrinological tests revealed abnormally high follicle-stimulating hormone, luteinizing hormone, and testosterone levels. The center of the hamartoma was subtotally excised, as confirmed on the postoperative computerized tomography scan. Precocious puberty subsided after the operation.     

Disconnecting surgical treatment of hypothalamic hamartoma in children and adults with refractory epilepsy and proposal of a new classification

A series of 17 patients aged from 9 months to 32 years with refractory epilepsy due to hypothalamic hamartoma were treated by total removal (one case) and disconnection (16 cases) between 1997 and 2002. The mean age at seizure onset was 16 months. Sixteen patients had gelastic seizures, 14 had partial seizures and three had generalized tonic-clonic seizures. The mean seizure frequency was 21 per day. Four patients had borderline intelligence quotient and the others were mentally retarded. Five patients presented with precocious puberty, one with acromegaly, and four suffered from obesity. Brain magnetic resonance imaging, performed at least twice in each patient, showed the hamartoma as a stable homogeneous interpeduncular mass implanted either on the mammilary tubercle or on the wall of the third ventricle with variable extension to the bottom. Ictal single photon emission computed tomography, performed in four patients, showed hyperperfusion within the hamartoma in two patients. Twenty-five operations were performed in the 17 patients. The first patient underwent total removal of the hamartoma, whereas the following 16 patients underwent disconnection through open surgery (14 procedures) and/or endoscopy (9 procedures). Eight patients became seizure-free, one patient had only brief gelastic seizures, and eight patients were dramatically improved with a mean follow up of 18.6 months (8 days to 43 months). Surgery was safe in all but two patients: the first patient had transient hemiplegia and the third cranial nerve paresis, and the other developed hemiplegia due to ischemia of the middle cerebral artery territory. The quality of life, and behavior and school performance were greatly improved in most patients. Our series illustrates the feasibility and relative safety of disconnection surgery for hypothalamic hamartomas with seizure relief in 53% of patients and dramatic improvement in the others. Surgical observations led us to propose a new anatomical classification according to the anatomical relationship between the hamartoma and the adjacent hypothalamus and third ventricle. Endoscopic disconnection seems to be a very safe way to treat hamartomas in intraventricular locations.     

Identification of gonadotropin-releasing hormone in neurons of a hypothalamic hamartoma in a boy with precocious puberty

We have studied a 3 1/12-year-old boy who presented with a hypothalamic mass and precocious puberty. His history suggested a course of isosexual precocity progressing from birth. Gelastic seizures also began at an early age. Endocrine evaluation revealed normal thyroid-stimulating hormone and growth hormone secretion, elevated basal and stimulated prolactin concentrations, and luteinizing hormone responses to sequential intravenous injections of gonadotropin-releasing hormone (GnRH) that were pubertal in pattern and magnitude. A needle biopsy of the mass recovered tissue that contained neurons histologically similar to those found in the normal hypothalamus, and the mass was characterized as a hypothalamic hamartoma. Immunohistochemical staining of this tissue with anti-GnRH antiserum demonstrated positive staining for GnRH immunoreactivity in neurons. This suggests a neurosecretory pathogenesis for the precocious puberty found in patients with hamartomas in the hypothalamic region.     

Gamma knife radiosurgery for refractory epilepsy caused by hypothalamic hamartomas

BACKGROUND: Hypothalamic hamartomas are associated with precocious puberty and chronic epilepsy characterized by gelastic seizures. The seizure disorder is usually refractory to most antiepileptic drugs. Gamma knife surgery has emerged as an alternative to microsurgical removal or radiofrequency ablation to improve seizure control. We present our experience with radiosurgery in 4 patients afflicted by this disorder. METHODS: Using gamma knife radiosurgery, 4 patients with intractable gelastic seizures and complex epilepsy were managed. Patient age varied from 5 to 29 years. The duration of symptoms was 4-28 years. A conformal radiosurgery plan was designed with a mean of 4.25 isocenters to cover the hamartoma at the 50% isodose line. A mean margin dose of 17.5 Gy was used. The clinical outcome was evaluated with the Engel scale. RESULTS: No complication occurred. After a median follow-up of 22 months, 3 patients had shown some improvement, with 2 attaining Engel class II status. CONCLUSION: Gamma knife surgery is a promising alternative to microsurgical removal for patients with refractory epilepsy caused by hypothalamic hamartomas.     

A super long-acting LH-RH analogue induces regression of hypothalamic hamartoma associated with precocious puberty

Summary We treated a 1-year-old female with a hypothalamic hamartoma and precocious puberty with leuprolide acetate depot, a super long-acting hormone-releasing hormone analogue (Tap-144-SR; [D-Leu⁶-[des-Gly¹⁰-NH₂]-LH-RH ethylamide acetate). The infant's major symptoms were genital bleeding and gynaecomastia. The LH-RH analogue (30 g/kg) was injected subcutaneously once every 4 weeks. Clinical and laboratory manifestations of precocious puberty showed marked improvement. A follow-up after 16 months of treatment, the size of the tumour decreased significantly and remained unchanged for 2 years of further follow-up. To the best of our knowledge, this is the first hypothalamic hamartoma case in whom a decrease of tumour size under treatment with LH-RH analogue has been documented. But, because diagnosis of hamartoma is only based on neuroradiological and not on histological examinations, the possibility of a gangliocytoma cannot be excluded with certainty.     

Hypothalamic hamartoma with precocious puberty--a case report

A case of hypothalamic hamartoma with precocious puberty is presented and the literature of reported cases is reviewed. An 8-year-old boy was admitted to our hospital because of precocious puberty and mental retardation. His genital development was Tanner's stage 4 and pubic hair was Tanner's stage 3. Bone age was 11 years. Plain CT showed an isodense mass in the suprasellar cistern which was not enhanced following contrast administration. Metrizamide CT cisternography showed a filling defect in the suprasellar cistern. Endocrinological evaluation revealed high levels of serum luteinizing hormone (LH) and testosterone with a marked response of LH to LH-RH injection. A left frontotemporal craniotomy was performed and the tumor was partially removed. The tumor was gray, firm and well-circumscribed with poor vascularity. Postoperatively, a right oculomotor palsy and transient diabetes insipidus developed. He was discharged ambulatory one month later. Serum LH and testosterone returned to normal and the response of LH to LH-RH injection became normal. Hamartoma was diagnosed on histological examination. Electron micrographic study showed numerous dense granules with approximately 0.1 mu in diameter, in which Judge proved LH-RH by immunofluorescent study in 1977. Our case supports the hypothesis that hypothalamic hamartoma may cause precocious puberty by autonomous secretion of LH-RH and we consider that neurosurgical treatment is recommended.     

Hypothalamic hamartoma: the role of surgery

A hypothalamic hamartoma associated with true precocious puberty in a 7-month-old girl is hereby reported. Hormonal studies disclosed elevated serum levels of luteinizing hormone (LH) and follicle stimulating hormone, both of which responded well to LH-releasing hormone stimulation. Following a subtotal removal of the tumor, the clinical manifestations of precocious puberty as well as associated endocrinological abnormalities returned to normal. The role of surgery for this lesion, which appears to be safe when a planned microsurgical course is employed, is discussed.     

Skeletal age assessment from elbow radiographs. Review of the literature

Skeletal age is important to evaluate remaining growth. In 50% of normal children and adolescents, skeletal age does not differ from chronological age. During puberty, skeletal age is an important tool when performing a lower limb epiphysiodesis or when treating (conservatively or surgically) patients with spinal deformities. Skeletal age alone is not enough and should be assessed together with other clinical and radiological findings such as standing and sitting heights, Risser sign, Tanner stages and annual growth rate. Puberty starts at 11 years of skeletal age and ends at 13 years of skeletal age in girls; in boys, puberty starts two years later (13 years of skeletal age) and then ends at a skeletal age of 15. Most current clinical and radiographic markers do not help paediatric orthopaedic surgeons to clearly distinguish maturity levels prior to Risser I. Sauvegrain et al. developed a method to assess skeletal age by using elbow radiographs (AP and lateral projections). Between 11 and 13 years of skeletal age in girls and between 13 and 15 years of skeletal age in boys, the olecranon apophysis is characterised by a clear morphological development. This method is a reliable tool to assess skeletal age during puberty because significant morphological changes in the elbow happen every six months.     

Pubertal development in Danish children: comparison of recent European and US data

Two recent epidemiological studies (PROS and NHANES III) from the USA noted earlier sexual maturation in girls, leading to increased attention internationally to the age at onset of puberty. We studied the timing of puberty in a large cohort of healthy Danish children in order to evaluate differences between USA and Denmark, as well as to look for possible secular trends in pubertal development. Healthy Caucasian children from public schools in Denmark participated in the study which was carried out in 1991-1993. A total number of 826 boys and 1,100 girls (aged 6.0-19.9 years) were included, and pubertal stages were assessed by clinical examination according to methods of Tanner. In boys testicular volume was determined using an orchidometer. We found that age at breast development 2 (B2) was 10.88 years, and mean menarcheal age was 13.42 years. Girls with body mass index (BMI) above the median had significantly earlier puberty (age at B2 10.42 years) compared with girls with BMI below the median (age at B2 11.24 years, p < 0.0001). Similarly, menarcheal age was significantly lower in girls with BMI above the median compared with girls with BMI below the median (13.12 vs. 13.70 years, p = 0.0012). In Danish boys we found that age at genital stage 2 (G2) was 11.83 years. Both sexes were significantly taller compared with data from 1964, but timing of pubertal maturation seemed unaltered. Finally, puberty occurred much later in Denmark compared with recent data from USA. We could not detect any downwards secular trend in the timing of puberty in Denmark between 1964 and 1991-1993 as seen in the US. Obesity certainly plays a role in the timing of puberty, but the marked differences between Denmark and USA cannot be attributed exclusively to differences in BMI. A possible role of other factors like genetic polymorphisms, nutrition, physical activity or endocrine disrupting chemicals must therefore also be considered. Therefore, we believe it is crucial to monitor the pubertal development closely in Denmark in the coming decades.     

Skeletal age assessment from elbow radiographs. Review of the literature

Skeletal age is important to evaluate remaining growth. In 50% of normal children and adolescents, skeletal age does not differ from chronological age. During puberty, skeletal age is an important tool when performing a lower limb epiphysiodesis or when treating (conservatively or surgically) patients with spinal deformities. Skeletal age alone is not enough and should be assessed together with other clinical and radiological findings such as standing and sitting heights, Risser sign, Tanner stages and annual growth rate. Puberty starts at 11 years of skeletal age and ends at 13 years of skeletal age in girls; in boys, puberty starts two years later (13 years of skeletal age) and then ends at a skeletal age of 15. Most current clinical and radiographic markers do not help paediatric orthopaedic surgeons to clearly distinguish maturity levels prior to Risser I. Sauvegrain et al. developed a method to assess skeletal age by using elbow radiographs (AP and lateral projections). Between 11 and 13 years of skeletal age in girls and between 13 and 15 years of skeletal age in boys, the olecranon apophysis is characterised by a clear morphological development. This method is a reliable tool to assess skeletal age during puberty because significant morphological changes in the elbow happen every six months.     

Ureteric calculi in children: preliminary experience with holmium:YAG laser lithotripsy

OBJECTIVE: To determine the efficacy and safety of holmium:YAG laser lithotripsy in children with ureteric calculi. PATIENTS AND METHODS: Between 1999 and 2003, 28 ureteroscopic laser procedures were carried out on 26 children (14 boys and 12 girls, mean age 6.5 years) with ureteric calculi. The mean (range) stone size was 1.21 (0.4-2.2) cm. At ureteroscopy the calculi were in the upper ureter in six (23%), mid-ureter in five (19%) and lower ureter in 15 (58%) patients. A rigid 8 F ureteroscope was used and the Ho:YAG laser energy delivered at 0.6-1.4 J and 6-10 Hz. All patients were evaluated after 3 months with intravenous urography to confirm stone clearance and to exclude ureteric stricture formation. RESULTS: The overall stone-free rate was 92% (24 children) after 28 ureteroscopic procedures. Stones were completely cleared in 83%, 80% and 100% of the procedures in the upper, mid- and lower ureters, respectively. In two children the procedure failed; they were salvaged by ureterolithotomy in one and extracorporeal shockwave lithotripsy in the other. During the procedures, a ureteric perforation was caused by several factors, including a technically difficult procedure and higher laser energy. At the mean (range) follow-up of 18 (3-39) months, low grade vesico-ureteric reflux was detected in two children, and there were no ureteric strictures in any. CONCLUSION: Holmium:YAG laser lithotripsy is an efficient and safe treatment for ureteric calculi in children.     

Effect of renal transplantation in childhood on longitudinal growth and adult height

BACKGROUND: Severe growth failure is frequently observed in children suffering from end-stage renal disease (ESRD). METHODS: We analyzed the effect of renal transplantation (RTx) on longitudinal growth and final height in 37 children (19 girls) with ESRD with a mean follow-up of 8.5 years. The mean age at RTx was 11.3 years. RESULTS: In children transplanted before start of puberty, mean height velocity increased significantly from 4.9 to 8.0 cm/year (P < 0.01), resulting in an increase in standardized height of 0.6 SD within two years post RTx. Although peak height velocity during puberty was significantly increased compared with healthy children, total pubertal height gain was reduced by 20% because of its shortened duration. Mean standardized height significantly increased from the time of RTx until final height by 1.3 SD and 0.7 SD in children transplanted before and after start of puberty, respectively. Mean adult height (boys 170 cm; girls 151 cm) was normal (> -2 SD) in 68% of patients. Change in standardized height from RTx until adult height was associated with initial degree of stunting and glomerular filtration rate (GFR; cumulative r2 0.49). Total pubertal height gain was associated with the age at start of puberty, GFR, and age at RTx (cumulative r2 0.57). CONCLUSION: RTx in children with ESRD induces moderate catch-up growth during the prepubertal growth period. However, final height is reduced in about one third of patients due to the reduced pubertal height gain and preexisting height deficit at the time of RTx.     

Suprasellar arachnoid cyst associated with precocious puberty: report of an operated case and review of the literature]

The pathogenesis remains unknown in the majority of patients with precocious puberty, and yet infrequently such causative cerebral lesions as hypothalamic hamartomas are associated with sexual precocity. We reported a rare case of suprasellar arachnoid cyst in an infant presenting with precocious puberty, which eventually disappeared after a cyst-peritoneal shunt. It was believed that the mass effect of the arachnoid cyst upon the hypothalamus was, at least in part, responsible for development of precocious puberty. The role of surgical decompression of the cyst was also discussed. A one-year-old girl was admitted to the hospital for evaluation of genital bleeding which had persisted on and off for two months. The height, 80cm, and the weight, 12.4kg, exceeded by far the two standard deviations from the mean level of the normal population. In addition she had the development of breast tissue as classified Tanner's Stage II, and both pubic and axillary hair. The bone age by skeletal survey of the hand was rated as 3 years. Endocrinological examination showed that serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol had increased for her age, to levels equivalent to those for females at puberty. An LH-RH test revealed an excessive LH reaction. There were no definite neurological deficits. CT and MRI demonstrated the presence of a large arachnoid cyst involving the suprasellar region as well as the right middle and posterior fossa. After the patient underwent a cyst-peritoneal shunt, the cyst decreased in size and such symptoms as genital bleeding and breast growth disappeared. Serum levels of her LH and FSH also significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bone Mass and Strength in School‐Age Children Exhibit Sexual Dimorphism Related to Differences in Lean Mass: The Generation R Study

Bone strength, a key determinant of fracture risk, has been shown to display clear sexual dimorphism after puberty. We sought to determine whether sex differences in bone mass and hip bone geometry as an index of strength exist in school‐age prepubertal children and the degree to which the differences are independent of body size and lean mass. We studied 3514 children whose whole‐body and hip scans were measured using the same densitometer (GE‐Lunar iDXA) at a mean age of 6.2 years. Hip dual‐energy X‐ray absorptiometry (DXA) scans underwent hip structural analyses (HSA) with derivation of bone strength indices. Sex differences in these parameters were assessed by regression models adjusted for age, height, ethnicity, weight, and lean mass fraction (LMF). Whole‐body bone mineral density (BMD) and bone mineral content (BMC) levels were 1.3% and 4.3% higher in girls after adjustment by LMF. Independent of LMF, boys had 1.5% shorter femurs, 1.9% and 2.2% narrower shaft and femoral neck with 1.6% to 3.4% thicker cortices than girls. Consequent with this geometry configuration, girls observed 6.6% higher stresses in the medial femoral neck than boys. When considering LMF, the sexual differences on the derived bone strength indices were attenuated, suggesting that differences in muscle loads may reflect an innate disadvantage in bone strength in girls, as consequence of their lower muscular acquisition. In summary, we show that bone sexual dimorphism is already present at 6 years of age, with boys having stronger bones than girls, the relation of which is influenced by body composition and likely attributable to differential adaptation to mechanical loading. Our results support the view that early life interventions (ie, increased physical activity) targeted during the pre‐ and peripubertal stages may be of high importance, particularly in girls, because before puberty onset, muscle mass is strongly associated with bone density and geometry in children. © 2015 American Society for Bone and Mineral Research.     

Functioning adrenocortical neoplasms in children

OBJECTIVE: To describe the clinical features, treatment and outcome of functioning adrenocortical tumours in children, and to assess the value of tumour size as a marker for malignant potential. PATIENTS AND METHODS: Twenty-one children (mean age at presentation 4.9 years, range 0.6-11; 12 girls and nine boys) who presented with a functioning adrenal mass over a 29-year period (1972-2000) were assessed. Clinicopathological features and outcome information were obtained from a structured review of the case-notes. Before 1980 the diagnosis and staging was mainly obtained by intravenous pyelography and plain X-ray. Since 1980, ultrasonography, computed tomography and more recently magnetic resonance imaging were the methods of choice. RESULTS: The mean (range) duration of symptoms before diagnosis was 31 (2-108) months. The symptoms and signs at presentation comprised virilization (18 children), Cushingoid features (three), precocious puberty (three) and hypertension (four). Three children had malignant neoplasms, one presented with metastasis and of the other two, one died from the disease within 6 months, despite adjuvant chemotherapy and radiotherapy. The third girl is disease-free 11 years after complete excision of the neoplasm. Eighteen children had a benign neoplasm and all are alive and free of recurrence. In most of the children surgical extirpation was relatively simple, blood loss minimal, recovery uneventful and the hospital stay short (mean 5 days). The virilizing effects of all the neoplasms gradually resolved after surgery within a median (range) of 27 (6-108) months. CONCLUSIONS: Functioning adrenocortical neoplasms in children are rare, with a peak incidence in the first decade, are predominantly unilateral and more common in girls. Most are benign, but both benign and malignant lesions can present with virilizing and Cushingoid features. The malignant neoplasms have an extremely poor prognosis, especially if excision is incomplete, despite adjuvant chemotherapy and radiotherapy. Although there is an association between tumour size and malignancy, this cannot be used as a reliable individual discriminator.