Long-term Functional and Oncologic Outcomes of Partial Adrenalectomy for Pheochromocytoma.

OBJECTIVE: To evaluate the recurrence and functional outcomes in a primarily hereditary cohort of patients undergoing partial adrenalectomy for pheochromocytoma. METHODS: A retrospective review from a prospectively managed database of patients undergoing partial adrenalectomy from 1995 to 2018 at the National Cancer Institute was performed. Local recurrence was defined as imaging evidence of a recurrent or de novo lesion on the operative side. Steroid dependency was defined as requiring daily steroid replacement at time of last follow-up. RESULTS: One hundred and twenty-four partial adrenalectomies, removing 162 tumors, were performed in 107 patients. Most patients had a known hereditary predisposition to develop bilateral, multifocal, and recurrent pheochromocytoma. Median tumor size was 2 cm (interquartile range (IQR) 1.5-2.8). Median follow-up was 60 months (IQR 13-131). Local recurrence occurred in 17 patients (15.8%) and were managed with active surveillance or surgery. A single patient (1/106, 0.9%) developed metastatic spread of pheochromocytoma approximately 14 years after his first of 2 partial adrenalectomies and remains alive under active surveillance. Median time to recurrence was 71 months (IQR 26-127) with 10 patients (9.3%) requiring daily steroid replacement at time of last follow-up. CONCLUSION: Partial adrenalectomy offers excellent oncologic and functional outcomes, sparing most patients from lifelong steroid replacement therapy. Recurrences can be easily managed with repeat surgery or active surveillance via functional work-up and imaging. Partial adrenalectomy remains the recommended surgical management for patients pre-disposed to development of bilateral, multifocal and recurrent pheochromocytoma.

Imaging features of adrenal gland masses in the pediatric population.

The spectrum of adrenal masses in the pediatric population markedly differs from that in the adult population. Imaging plays a crucial role in detecting adrenal masses, differentiating malignant from benign lesions, recognizing extra-adrenal lesions in the suprarenal fossa, and directing further management. Ultrasound is the primary imaging modality of choice for the evaluation of adrenal masses in the neonatal period, whereas MRI or CT is used as a problem-solving tool. In older children, computed tomography or magnetic resonance imaging is often required after initial sonographic evaluation for further characterization of a lesion. Herein, we discuss the salient imaging features along with pathophysiology and clinical features of pediatric adrenal masses.

Congenital adrenal hyperplasia as a cause of adrenal incidentaloma.

Congenital adrenal hyperplasia (CAH) can present as a benign adrenal tumour, which should be treated medically. The diagnosis of CAH must be considered in a patient presenting with adrenal incidentaloma in order to avoid unnecessary adrenalectomy. Urinary steroid profiling is a useful diagnostic tool to identify the presence of CAH.

Congenital Adrenal Neuroblastoma With and Without Cystic Change: Differentiating Features With an Emphasis on the of Value of Ultrasound.

OBJECTIVE: The purpose of this study was to compare the features of congenital adrenal neuroblastomas with and without cystic changes and to emphasize the value of ultrasound in the diagnostic evaluation of cystic congenital adrenal neuroblastoma. MATERIALS AND METHODS: A total of 41 patients with surgically confirmed congenital adrenal neuroblastoma were enrolled. We divided the patients into two groups according to presence or absence of cystic change in the tumor, as determined from the initial ultrasound findings. Clinical and laboratory findings, disease stage, and patient outcome were investigated with a statistical comparison between the two groups. The imaging findings for cystic congenital adrenal neuroblastoma were reviewed to compare the additional diagnostic value of CT and MRI when paired with ultrasound. RESULTS: There were 22 patients (54%) in the group without cystic changes and 19 patients (46%) in the group with cystic changes. Prenatal detection and absence of metastasis were significantly more common in the cystic group than in the noncystic group (p < 0.05). Sensitivities of tumor marker levels were also significantly lower in the cystic group. Patient outcome was excellent, and there was no significant difference between the groups. With regard to imaging of cystic congenital adrenal neuroblastoma, in the 15 cases in which CT or MRI was paired with ultrasound, no additional diagnostic information was discerned with CT or MRI. CONCLUSION: Nearly one-half of congenital adrenal neuroblastomas are cystic, and these tumors have clinical and laboratory features that distinguish them from noncystic congenital adrenal neuroblastoma. Diagnostic tests, including CT, MRI, and assessment of tumor markers, have low diagnostic value in the evaluation of cystic congenital adrenal neuroblastoma.

Congenital neuroblastoma in a neonate with isotretinoin embryopathy.

We describe a neonate with isotretinoin embryopathy and an incidental finding of congenital neuroblastoma. Diffuse liver metastases led to the decision to provide oncologic therapy followed by tumor resection. Despite the possible need for chronic care related to the comorbidities of the isotretinoin embryopathy and oncologic management, the patient remains disease-free. Because of the uncertain etiology of neuroblastoma, it remains unclear whether exposure to isotretinoin during embryogenesis and fetal development had an oncogenic effect on this patient.

Congenital neuroblastoma with placental involvement.

We describe an extremely rare case of congenital neuroblastoma with placental involvement. A fetus with a left abdominal mass detected during ultrasonography at 23 weeks' gestation developed hydrops fetalis by 26 weeks' gestation. The mother developed hypertension at 26 5/7 weeks' gestation. Based on a clinical diagnosis of pregnancy-induced hypertension, labor was induced at 26 6/7 weeks. However, intrauterine fetal death was diagnosed during delivery. Postmortern examination revealed a solid tumor at the site of the left adrenal gland. Histological examination of the tumor revealed dense proliferation of small round tumor cells with sparse cytoplasm and hyperchromatic nuclei. Some tumor-cell complexes contained abundant neurofibrils and Hormer-Wright rosettes were observed. A diagnosis of neuroblastoma of the left adrenal gland was made. The liver was markedly enlarged and was extensively replaced by neuroblastoma cells. In addition, small nests of tumor cells were detected in the blood vessels of various organs including the heart, lung, spleen, kidneys, stomach, small and large intestine, thyroid gland, testis, spinal cord, and bone marrow. Histological examination of the enlarged placenta revealed numerous neuroblastoma cells in the villous fetal capillary spaces. The present case was unusual in that the tumor cells were found not only in the chorionic villi, but also in the intervillous space of the maternal vascular system. However, there was no clinical evidence of maternal metastasis.

Long-term follow-up of the "wait and see" approach to localized perinatal adrenal neuroblastoma.

BACKGROUND: Evidence-based guidelines for the management of localized perinatal adrenal neuroblastoma are not yet available. We describe our preliminary experience managing this tumor with a "wait and see" policy. METHODS: A single-center prospective study (February 2002 to December 2009) was conducted with 12 consecutive patients in whom an adrenal mass was detected antenatally or within the first 3 months of life. Diagnostic workup included the following investigations: measurement of urine catecholamine metabolites, imaging studies (ultrasonography, magnetic resonance imaging, or computed tomography), metaiodobenzylguanidine scintigraphy, and/or core needle biopsy. RESULTS: The male/female ratio was 1.4:1.0. Median tumor size at presentation was 29 mm (range 10-50 mm). Eight lesions were detected antenatally. Ten lesions were diagnosed as localized neuroblastoma. Of these ten lesions, four were excised because of parental preference (n = 2), tumor enlargement (n = 1) or tumor persistence (n = 1). The remaining six patients underwent watchful clinical observation, which showed progressive tumor shrinkage and complete regression within 10-39 months (median 12.5 months). The final two lesions were small predominantly cystic lesions without a clear-cut diagnosis. They were managed noninvasively. At an overall median follow-up of 109 months (range 30-122 months), all patients are alive and disease-free, although one patient progressed to stage 4 disease despite early excision of the primary tumor. CONCLUSIONS: Spontaneous regression of localized perinatal adrenal neuroblastoma occurs often, and a "wait and see" strategy seems justified in these small infants. Patients with enlarging or stable lesions that have persisted for several months may benefit from surgery, although prompt excision may not prevent tumor progression.

Causa infrecuente de hipertensión arterial en lactantes: neuroblastoma congénito quístico suprarrenal: caso clínico / A rare cause of hypertension in childhood: congenital cystic adrenal neuroblastoma: clinical case

The frequency of hypertension (HBP) in children has increased significantly over the past decade. The younger the patient the greater the likelihood of having secondary HBP. Thus, the main causes of hypertension in new-borns are of renovascular or parenchymatous origin. objective: To present the case of an infant with hypertension caused by a congenital cystic neuroblastoma (NB). Case History: Newborn with prenatal diagnosis of adrenal cyst, who evolved with significant hypertension unresponsive to medical therapy. Neuroblastoma was suspected on the basis of magnetic resonance imaging findings and resection of the lesion was able to resolve the hypertension and to confirm the diagnosis by anatomo-pathological study. Conclusion: Most cases of neonatal hypertension are of renal origin, with the 2 largest categories being renovascular and renal parenchymal diseases. NB is the most common neonatal malignancy. It usually presents as an abdominal mass of antenatal diagnosis, being the hypertension an unusual form of presentation.

La frecuencia de hipertensión arterial (HTA) en niños ha aumentado significativamente en la última década. A menor edad del paciente mayor es la probabilidad de que la HTA sea secundaria. Así, las principales causas de HTA en recién nacidos son de origen renovascular o parenquimatoso. objetivo: Presentar el caso de un lactante hipertenso por neuroblastoma (NB) congénito quístico. Caso Clínico: Recién nacido con diagnóstico prenatal de quiste suprarrenal, quien evolucionó con HTA por sobre el percentil 99 para edad, sexo y talla, sin respuesta a terapia farmacológica. La resonancia magnética permitió realizar el diagnóstico presuntivo de neuroblastoma congénito y la resección de la lesión permitió resolver la HTA y confirmar el diagnóstico. Conclusión: La HTA en recién nacidos generalmente se debe a causas secundarias. El NB es el tumor maligno neonatal más frecuente que se puede presentar como una masa abdominal de diagnóstico antenatal, siendo la HTA una forma infrecuente de presentación.

Screening of mutations in genes that predispose to hereditary paragangliomas and pheochromocytomas.

Thirty per cent of the paragangliomas and pheochromocytomas reported are hereditary. Mutations in SDHB, SDHC, SDHD, and more recently SDHAF2 and TMEM127 genes have been described in these hereditary tumors. We looked for mutations in these 5 genes in a series of 269 patients with paragangliomas and/or pheochromocytomas. The SDHB, SDHC, and SDHD genes were analyzed in a series of 269 unrelated index patients with paragangliomas and/or pheochromocytomas using dHPLC screening of point mutations followed by direct sequencing and Multiplex PCR Liquid Chromatography to detect large rearrangements confirmed by quantitative PCR. In a second phase, we adapted Multiplex PCR Liquid Chromatography to the SDHAF2 and TMEM127 genes. This method and direct sequencing were applied to 230 patients without the SDHB, C, D mutations. Of the 269 patients, 44 carried a mutation (16.3%). Thirty-seven different mutations were identified: 18 in SDHB (including 2 large deletions), 8 in SDHD, 6 in SDHC, 5 in TMEM127, and no mutations in SDHAF2. Thirteen mutations have not been published so far. An exhaustive study of the different genes is needed to make possible a familial genetic diagnosis in paraganglioma and pheochromocytoma hereditary syndromes. Although mutations in SDHC and TMEM127 are less frequent than mutations in SDHB and SDHD, they also have less evident clinical feature indicators. Analyzing SDHAF2 must be restricted to familial extra-adrenal paragangliomas. Multiplex PCR Liquid Chromatography is a sensitive, fast, and inexpensive method for screening large rearrangements, which are infrequent in these syndromes.

Congenital neuroblastoma: an autopsy report.

Neuroblastoma (NB) is the foremost malignant neoplasm of the fetus and neonate. It has a distinct biologic behavior and varied clinical manifestations. The perinatal tumors are most frequently associated with a favorable outcome. We describe an autopsy case of a 2-day-old baby with congenital NB of the left adrenal with extensive metastatic deposits in the liver. Despite the tumor having a favorable histology, it proved to be fatal with death occurring on the second day of life.

An update on the genetics of paraganglioma, pheochromocytoma, and associated hereditary syndromes.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are catecholamine-secreting tumors of neural crest origin. Once collectively known as the '10% tumor', based on the frequency of inherited forms of the disease, they are now referred to as the '10-gene tumor', based on the number of susceptibility genes identified to date. Most familial cases of pheochromocytoma and/or paraganglioma and 10-20% sporadic cases carry germline mutations in VHL, RET, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, or MAX. The finding of somatic mutations in VHL and RET in an additional 10-15% of tumors has brought the proportion of all patients with PCC and/or PGL due to a genetic disruption in these genes to approximately one half. These findings impact on the clinical management of patients. The diversity in the genetic etiology has transcription correlates, which are reflected in the 2 main transcription signatures underlying these mutations: a pseudohypoxic cluster (VHL and SDH gene mutation carriers) and a cluster rich in kinase receptor signaling and protein translation pathways (RET, NF1, TMEM127 and MAX mutation carriers). Recognition of these clusters offers clues to better understand tumor pathogenesis as well as a rationale for the development of targeted therapies. In this report we provide an overview of the transcription-based classification of PCCs and PGLs, an update on the more recently identified susceptibility genes and an outline of current gaps in this research field as well as challenges for the coming years.

Comparison of clinico-radiological features between congenital cystic neuroblastoma and neonatal adrenal hemorrhagic pseudocyst.

OBJECTIVE: To evaluate the radiological and clinical findings of congenital cystic neuroblastomas as compared with those of the cystic presentation of neonatal adrenal hemorrhage. MATERIALS AND METHODS: We analyzed the US (n = 52), CT (n = 24), and MR (n = 4) images as well as the medical records of 28 patients harboring congenital cystic neuroblastomas (n = 16) and neonatal adrenal hemorrhagic pseudocysts (n = 14). The history of prenatal detection, location, size, presence of outer wall enhancement, internal septations, solid portion, calcification, turbidity, vascular flow on a Doppler examination, and evolution patterns were compared in two groups of cystic lesions, by Fischer's exact test. RESULTS: All (100%) neuroblastomas and three (21%) of the 14 hemorrhagic pseudocysts were detected prenatally. Both groups of cystic lesions occurred more frequently on the right side; 11 of 16 (69%) for neuroblastomas and 11 of 14 (79%) for hemorrhagic pseudocysts. The size, presence of solid portion, septum, enhancement, and turbidity did not differ significantly (p > 0.05) between the two groups of cystic lesions. However, tiny calcifications (n = 3) and vascular flow on color Doppler US (n = 3) were noted in only neuroblastomas. The cystic neuroblastomas became complex solid and cystic masses, and did not disappear for up to 90 days in the three following cases, whereas 11 of the 14 (79%) hemorrhagic pseudocysts disappeared completely and the three remaining (27%) evolved to calcifications only. CONCLUSION: Although the imaging findings of two groups of cystic lesions were similar, prenatal detection, the presence of calcification on initial images, vascularity on color Doppler US, and evolution to a more complex mass may all favor neuroblastomas.

Comparison of Clinico-Radiological Features between Congenital Cystic Neuroblastoma and Neonatal Adrenal Hemorrhagic Pseudocyst

OBJECTIVE: To evaluate the radiological and clinical findings of congenital cystic neuroblastomas as compared with those of the cystic presentation of neonatal adrenal hemorrhage. MATERIALS AND METHODS: We analyzed the US (n = 52), CT (n = 24), and MR (n = 4) images as well as the medical records of 28 patients harboring congenital cystic neuroblastomas (n = 16) and neonatal adrenal hemorrhagic pseudocysts (n = 14). The history of prenatal detection, location, size, presence of outer wall enhancement, internal septations, solid portion, calcification, turbidity, vascular flow on a Doppler examination, and evolution patterns were compared in two groups of cystic lesions, by Fischer's exact test. RESULTS: All (100%) neuroblastomas and three (21%) of the 14 hemorrhagic pseudocysts were detected prenatally. Both groups of cystic lesions occurred more frequently on the right side; 11 of 16 (69%) for neuroblastomas and 11 of 14 (79%) for hemorrhagic pseudocysts. The size, presence of solid portion, septum, enhancement, and turbidity did not differ significantly (p > 0.05) between the two groups of cystic lesions. However, tiny calcifications (n = 3) and vascular flow on color Doppler US (n = 3) were noted in only neuroblastomas. The cystic neuroblastomas became complex solid and cystic masses, and did not disappear for up to 90 days in the three following cases, whereas 11 of the 14 (79%) hemorrhagic pseudocysts disappeared completely and the three remaining (27%) evolved to calcifications only. CONCLUSION: Although the imaging findings of two groups of cystic lesions were similar, prenatal detection, the presence of calcification on initial images, vascularity on color Doppler US, and evolution to a more complex mass may all favor neuroblastomas.

Clinical features and surgical outcome of a suprarenal mass detected before birth.

PURPOSE: With the widespread use of the obstetrical ultrasound, identification of a fetal suprarenal mass has become more common. Most of these masses prove to be congenital neuroblastomas (CNB), but the diagnosis is often confused with other benign lesions and the postnatal management remains to be controversial. METHODS: The medical records of 18 patients that underwent primary surgical excision for an antenatally detected suprarenal mass, between January 1995 and April 2009, were reviewed. The clinical, radiological, surgical, and pathological data were collected. Staging evaluation was performed after histological confirmation of the CNB. RESULTS: There were 13 cases of CNB, 1 adrenal cyst, 2 adrenal hemorrhages, and 2 pulmonary sequestrations. The differential diagnosis was impossible before surgery. Most of the CNBs were stage I (N = 11), with 1 stage IV and 1 stage IV-S. Four patients (3 stage I and 1 stage IV-S) had more than one copy of N-myc gene. The stage I patients were cured by surgery alone, and stage IV patients underwent nine cycles of adjuvant chemotherapy and currently have no evidence of disease. The five benign lesions were cured with excision alone. There were no postoperative complications. CONCLUSION: For early diagnosis and treatment, surgical excision should be considered as the primary therapy for an antenatally detected suprarenal mass. The surgery can be safely performed during the neonatal period and provides a cure in most cases.

Prenatal diagnosis of a mass in the adrenal region that proved to be a teratoma.

A prenatally detected suprarenal cystic mass measuring 2 cm was found to have enlarged upon postnatal ultrasonography at 6 weeks of age. Magnetic resonance imaging showed a 57 x 50 mm mass in the left adrenal region displacing the kidney inferiorly. The infant underwent an adrenalectomy with total resection of the tumor, which proved on histologic examination to be a mature teratoma. Prenatally detected suprarenal masses are likely to be neuroblastoma or adrenal hemorrhage, but may be rare benign lesions such as extralobar pulmonary sequestration, bronchogenic cyst, or renal dysplasia. Although teratoma in the adrenal region is extremely rare, it should be included in the clinical and radiologic differential diagnosis of prenatally detected suprarenal masses. Total excision of the mass for histologic diagnosis is indicated.

Congenital stage 1 neuroblastoma evolved into stage 4s.

A newborn with a prenatally detected adrenal mass underwent complete resection of a stage 1 favorable histology neuroblastoma (NB) without MYC-N amplification. Two months later, the infant presented with a local recurrence and multiple hepatic metastases. Close follow-up without therapy was adopted for stage 4s NB. Enlarging tumor lesions were seen until the child was 8 months old, followed by later decrease in size. At 36 months of follow-up, the child is alive and disease-free. We describe this case of NB and its abnormally short evolution from stage 1 to stage 4s, despite initial surgery. Its spontaneous regression may help us understand the natural history of congenital NB.

[Mosaic trisomy of chromosome 20 in a patient with congenital anomalies--10-years observation]. / Postac mozaikowa trisomii chromosomu 20 u pacjentki z zaburzeniami rozwojowymi--10-letnia obserwacja.

Trisomy 20 is one of the most often identified disorders in amniocytes, but in a postnatal analysis is detected rather rarely. We present a girl with dysmorphic features, congenital defects, tumor of a suprarenal gland, hypothyroidism and abnormal intelligence. The recognition of mosaic trisomy 20 was confirmed after cytogenetic examination of the skin fibroblast. The karyotype is described as mos 47,XX,+20/46,XX. The karyotype from peripheral blood lymphocytes, which was examined in the 1st year of life, was normal female (46,XX) and the Turner syndrome was excluded. During 10 years we observed that the dysmorphic features were increased and suggested genetic reasons of these features. In children with dysmorphic features and normal karyotype of blood lymphocytes a wide-ranged genetic counseling is necessary.

Favorable histology, MYCN-amplified 4S neonatal neuroblastoma.

We report a neonate with 4S neuroblastoma and MYCN amplification, but favorable Shimada histology, successfully treated with chemotherapy and 13-cis-retinoic acid without stem cell transplantation. MYCN amplification in neuroblastoma is usually associated with unfavorable Shimada histology; the presence of these features in infants with 4S disease confers a poor prognosis. A small number of infants with 4S neuroblastoma and MYCN amplification have favorable Shimada histology. In this subgroup of infants, histopathology may be equally important in predicting outcome.