Interesting pancreatic tumour in the background of Tuberous Sclerosis.

Tuberous Sclerosis Complex (TSC) is easily discernible by a myriad of manifestations, most notably dermatological. It is associated with well known and recognised intra-abdominal tumours like angiomyolipoma of the kidney. However, rarer tumours like pancreatic neuroendocrine tumours can occur in the setting of TSC. A high index of suspicion is necessary to identify and treat these lesions early in their natural course. Early identification augurs well with complete surgical excision and excellent survival.

Congenital pancreatoblastoma: report of an atypical case and review of the literature.

Pancreatoblastoma is a rare malignant tumor of the pancreas mostly diagnosed in childhood. The clinical presentation and outcome of infantile and congenital pancreatoblastoma have not been clearly elucidated. This report describes our recent institutional experience with an unusual case of congenital pancreatoblastoma. Review of the scientific literature identifies approximately 200 cases of pancreatoblastoma. We describe the 9 infantile (aged 3 mo and younger) and 4 congenital cases previously reported and summarize their clinical presentation and outcome. We also define the close association of infantile/congenital pancreatoblastoma and Beckwith-Wiedemann syndrome (50%) versus all affected age groups (4.5%).

Primary pancreatic neuroblastoma: an unusual tumor in infancy.

Fetal imaging has dramatically impacted neonatal care by providing an advanced warning of many different congenital anomalies. The advancements and widespread use of fetal imaging has, however, increased the identification of various incidental findings that is creating new challenges for neonatal diagnosis and treatment. We report such a case where a fetal pancreatic neuroblastoma (NB) was incidentally detected by computed tomographic scan of the maternal abdomen. Primary pancreatic NB is a very uncommon childhood neoplasm that, to our knowledge, has never been previously reported in the English language presenting in either the prenatal or neonatal periods. A 21-year-old woman complaining of acute abdominal pain and carrying a 35 weeks' gestation fetus was referred for computed tomographic scan because of the concern of maternal appendicitis. That scan was inconclusive for appendicitis but did incidentally detect a fetal mass in the general region of the pancreas. At 36 weeks' gestation, the fetus developed signs of distress, which prompted a cesarean delivery. Neonatal workup confirmed the presence of an abdominal mass in the region of the pancreas, but precise anatomic localization was not possible. Also noted on neonatal workup were elevated urinary catecholamines consistent with a hormonal active tumor. These findings prompted an abdominal exploration of this neonate, which revealed a solid tumor contained in the distal pancreas. The mass was managed by an uncomplicated distal pancreatectomy. The neonate fully recovered, and histologic diagnosis revealed NB, whereas the postoperative urine catecholamines normalized. This case underscores the unintended clinical challenges created by widespread fetal imaging, while presenting the first prenatally diagnosed case in the English language medical literature and earliest treated patient with pancreatic NB.

NUT midline carcinoma in a newborn with multiorgan disseminated tumor and a 2-year-old with a pancreatic/hepatic primary.

NUT midline carcinoma (NMC) is a rare and aggressive malignant epithelial tumor defined by rearrangement of the NUT gene on chromosome 15. In two thirds of cases, NUT is involved in a balanced translocation with BDR4 on chromosome 19, while in the remaining cases, NUT is rearranged with variant fusion partners such as BRD3. These undifferentiated tumors primarily affect midline structures, usually in the upper aerodigestive tract and mediastinum. Most reported cases have followed a rapidly lethal clinical course. We report the clinical and pathological findings of NMC in the youngest patients identified so far. The 1st case involves a newborn who presented with a supraorbital mass and extensive multiorgan involvement, including the spine, lungs, liver, pancreas, adrenal glands, and subcutaneous tissue. The 2nd patient was a 2-year-old male with an abdominal mass involving the liver and pancreas with pulmonary metastasis. Histopathological analysis of both tumors showed undifferentiated malignant neoplasms, and immunohistochemistry showed positivity for epithelial markers. Both tumors demonstrated t(15;19), and immunohistochemistry with NUT monoclonal antibodies and fluorescent in situ hybridization confirmed NUT rearrangement. The patients died from disease at 1 and 2 months postpresentation. Thus far, 25 cases have been reported, including our 2 current cases. Presentation ages range from 0 to 78 years (mean, 23 years). Herein, we report the 2 youngest reported cases of NMC, including the 1st congenital case and the 1st case arising within the liver/pancreas. Increased awareness and further molecular studies are required for a better understanding of NMC pathobiology and improved therapeutic outcomes.

Congenital hyperinsulinism in an infant caused by a macroscopic insulin-producing lesion.

Congenital hyperinsulinism is the most common cause of persistent neonatal hypoglycemia. Severe congenital hyperinsulinism is most often due to inactivating mutations in either the ABCC8 or KCNJ11 genes, which encode the SUR1 and Kir6.2 proteins, respectively--the two components of the ATP-sensitive K+ (KATP) channel; neonatal hypoglycemia due to macroscopic insulin-producing pancreatic lesions or adenomas are extremely rare. KATP channel hyperinsulinism is classified as diffuse or focal, the latter being associated with paternally-derived mutations of ABCC8 or KCNJ11 and somatic loss of heterozygosity of the maternal alleles. KATP channelopathies usually produce microscopic intra-pancreatic lesions and are typically unresponsive to drug therapy, requiring > 95% pancreatectomy for diffuse disease and occasionally more limited pancreatic resection for focal disease; macroscopic pancreatic lesions and adenomas are focally excised. We describe a 1 month-old infant with severe congenital hyperinsulinism who had a macroscopic insulin-producing pancreatic lesion successfully treated with focal lesion enucleation.

Unbalanced expression of 11p15 imprinted genes in focal forms of congenital hyperinsulinism: association with a reduction to homozygosity of a mutation in ABCC8 or KCNJ11.

Congenital hyperinsulinism (CHI), previously named persistent hyperinsulinemic hypoglycemia of infancy, is characterized by profound hypoglycemia because of excessive insulin secretion. CHI presents as two different morphological forms: a diffuse form with functional abnormality of islets throughout the pancreas and a focal form with focal islet cell adenomatous hyperplasia, which can be cured by partial pancreatectomy. Recently, we have shown that focal adenomatous hyperplasia involves the specific loss of the maternal 11p15 region and a constitutional mutation of a paternally inherited allele of the gene encoding the regulating subunit of the K(+)(ATP) channel, the sulfonylurea receptor (ABCC8 or SUR1). In the present study on a large series of 31 patients, describing both morphological features and molecular data, we report that 61% of cases (19 out of 31) carried a paternally inherited mutation not only in the ABCC8 gene as previously described but also in the second gene encoding the K(+)(ATP) channel, the inward rectifying potassium channel (KCNJ11 or KIR6.2), in 15 cases and 4 cases, respectively. Moreover our results are consistent with the presence of a duplicated paternal 11p15 allele probably because of mitotic recombination or reduplication of the paternal chromosome after somatic loss of the maternal chromosome. In agreement with the loss of the maternal chromosome, the level of expression of a maternally expressed tumor suppressor gene, H19, was greatly reduced compared to the level of expression of the paternally expressed growth promoter gene, IGF2. The expression of IGF2 was on average only moderately increased. Thus, focal forms of CHI can be considered to be a recessive somatic disease, associating an imbalance in the expression of imprinted genes in the 11p15.5 region to a somatic reduction to homozygosity of an ABCC8- or KCNJ11-recessive mutation. The former is responsible for the abnormal growth rate, as in embryonic tumors, whereas the latter leads to unregulated secretion of insulin.

Pancreatic tumors in children: report of three cases.

From 1981 to 1996, we experienced 3 cases of pancreatic tumors in children--two pancreatoblastomas (PB) and one solid and cystic tumor (SCT). The ages were 1 month, 4 years, and 13 years of age respectively. The two cases of pancreatoblastoma initially presented as chronic diarrhea with failure to thrive, the other case presented with abdominal mass. All of them were studied by laboratory examination, ultrasonography, computed tomography and pathology. Increasing alpha- fetoprotein (AFP) levels were found in the 2 pancreatoblastoma cases, however, the level in the SCT case was normal. Abdominal sonography showed pancreatic masses with or without calcification, and the echogenicity may be solid and/or cystic. All patients underwent total excision of the tumors. We have reviewed the literature and find no pancreatoblastoma with chronic diarrhea was reported in young children, especially in neonate. Therefore, we suggest that young children presenting with an abdominal mass and/or weight loss should undergo imaging studies for the possibility of pancreatic tumors.

[Pancreatoblastoma--a rare pancreatic malignancy in childhood]. / Das Pankreatoblastom--ein seltenes Pankreasmalignom des Kindesalters.

Between 1885 and 1991 only 71 cases of malignant pancreatic tumours in childhood and adolescence have been reported in literature; the majority of these were pancreatoblastomas. The symptoms, pathology and therapy of this rare tumour are demonstrated in the case of a 17-year-old girl. The tumour is believed to develop at an early stage of pancreatic cell differentiation. Usually it is composed of both exocrine and endocrine cell types. The treatment of choice is radical resection. In contrast to pancreatic neoplasms in adult patients the pancreatoblastoma has a favourable prognosis. The role of adjuvant chemotherapy or radiotherapy is still under discussion due to the small number of patients treated as yet.

Cystadenoma of the pancreas in a newborn.

Cystadenoma of the pancreas is a rare entity. In the pediatric population, three cases have been reported. We present a case of cystadenoma of the pancreas in a newborn. The tumor involved the head and body of the pancreas. Subtotal pancreatectomy with preservation of the duodenum, common bile duct, and pancreatic tail was performed.

Brief clinical report: a 46,XY phenotypic female with Smith-Lemli-Opitz syndrome.

A phenotypic female infant with Smith-Lemli-Opitz (SLO) syndrome was found to have a 46,XY karyotype. Autopsy showed normal tests for age and normal Wolffian duct structures. The serum testosterone level was unusually high, suggesting that the failure of virilization of the external genitalia in the child might be due to a defect in testosterone conversion to dihydrotestosterone or a lack of end-organ receptors for the same. An additional feature not previously described in association with SLO syndrome was present, which was clinical hypoglycemia with nesidioblastosis.

Ectopic pancreas and the islet cell dysmaturational syndrome.

Two cases of ectopic pancreas are described in the setting of the islet cell dysmaturational syndrome. Microscopic and immunostaining studies revealed both lesions to be composed of primarily (80 percent to 90 percent) islet tissue with nuclear hyperchromasia and probable depletion of immunoreactive insulin in one case. Persistent hyperinsulinemic hypoglycemia required a second laparotomy with resection of ectopic pancreas in one case. Awareness of the phenomenon led to successful identification and resection of ectopic islet tissue on first surgery in a subsequent case. Ectopic pancreas is a relatively common developmental pancreatic anomaly, and knowledge of its potential contribution to life-threatening hypoglycemia may obviate the need for multiple surgeries in some cases of islet cell dysmaturational syndrome.

The surgical management of hyperinsulinism in infancy due to nesidioblastosis.

Severe neonatal hypoglycemia due to nesidioblastosis demands prompt diagnosis and treatment to prevent mental retardation. Early central venous catheter placement is essential for a constant glucose infusion. At surgery, near-total (95%) pancreatectomy is done, starting at the tail and preserving the spleen. Bipolar electrocoagulation is very useful for the tiny vessels. The uncinate process is removed leaving a small amount of pancreas adjacent to the preserved common bile duct. Three patients, diagnosed shortly after birth, had surgery at 34 days, 2 years, and 17 days of life. Two patients developed staphylococcal infections, one of whom exhibited the "scalded baby" syndrome and required reoperation for evisceration. Insulin was required for one to seven days in two and for three months in one. Diazoxide was needed for 18 months in the initial patient, who did not have uncinate resection. All patients are healthy and off medication with a postoperative follow-up period of 11, 12, and 65 months.

Congenital pancreatoblastoma in Beckwith-Wiedemann syndrome: an emerging association.

We present a male newborn (weight 4000 g) who died at age 12 days with a clinical history of persistent hypoglycemia and polycythemia. Clinical examination disclosed somatic hemihypertrophy (left side), a large umbilical hernia, macroglossia, and an intraabdominal tumor, consistent with the diagnosis of Beckwith-Wiedemann syndrome (EMG syndrome) and hemihypertrophy. Necropsy findings included visceromegaly (left kidney and adrenal), cytomegaly of the fetal cortex and nodular arrangement of both adrenals, diffuse nesidioblastosis and islet cell hyperplasia of the pancreas, and persistent glomerulogenesis. The tumor was a cystic pancreatoblastoma attached to the anterior surface of the pancreas. Three other examples of this association, congenital pancreatoblastoma and Beckwith-Wiedemann syndrome, all in males, are on record in the literature, indicating a strong relationship between both conditions.

[Diffuse nephroblastomatosis and carcinoid tumor of the pancreas in a newborn infant]. / Diffuznyi nefroblastomatoz i kartsinoid podzheludochnoi zhelezy u novorozhdennogo.

An observation of primary multiple tumours in a newborn girl who died at the age of 3 1/2 days is described. Diffuse nephroblastomatosis of right kidney and carcinoid tumour of the pancreas (nesidioblastosis) were found at the necropsy. Mother has had a respiratory infection at the 18th and 25th weeks of the pregnancy, this being considered as a possible factor in the genesis of tumours. According to the author, diffuse nephroblastomatosis is observed in 0.2% of neonatal necropsies.

Surgical operations on the pancreas in malignant disease in children.

Because of the danger of irreversible brain damage in children, effective therapy for hypoglycaemia must be initiated as rapidly as possible. If drug therapy fails, only surgery remains after thorough metabolic, endocrinological and radiological investigations to completely cure B-cell adenoma. I conclude with a quotation from Sauerbruch (15), who had successfully removed an insulinoma from a 7-year-old girl: If in medicine we can speak about causally induced disorders, then it is justified here. A tangible, anatomically unequivocal finding causes a localized disease, which disappears without trace after the removal of a small tumour. Other endocrine disorders cannot be detected with such convincing clarity and interpreted in the same way, nor can they be as successfully treated as this.