White-Light Endoscopy Is Adequate for Lynch Syndrome Surveillance in a Randomized and Noninferiority Study.

BACKGROUND & AIMS: Dye-based pancolonic chromoendoscopy is recommended for colorectal cancer surveillance in patients with Lynch syndrome. However, there is scarce evidence to support its superiority to high-definition white-light endoscopy. We performed a prospective study assess whether in the hands of high detecting colonoscopists, high-definition, white-light endoscopy is noninferior to pancolonic chromoendoscopy for detection of adenomas in patients with Lynch syndrome. METHODS: We conducted a parallel controlled study, from July 2016 through January 2018 at 14 centers in Spain of adults with pathogenic germline variants in mismatch repair genes (60% women; mean age, 47 ± 14 years) under surveillance. Patients were randomly assigned to groups that underwent high-definition white-light endoscopy (n = 128) or pancolonic chromoendoscopy (n = 128) evaluations by 24 colonoscopists who specialized in detection of colorectal lesions in high-risk patients for colorectal cancer. Adenoma detection rates (defined as the proportion of patients with at least 1 adenoma) were compared between groups, with a noninferiority margin (relative difference) of 15%. RESULTS: We found an important overlap of confidence intervals (CIs) and no significant difference in adenoma detection rates by pancolonic chromoendoscopy (34.4%; 95% CI 26.4%-43.3%) vs white-light endoscopy (28.1%; 95% CI 21.1%-36.4%; P = .28). However, pancolonic chromoendoscopy detected serrated lesions in a significantly higher proportion of patients (37.5%; 95% CI 29.5-46.1) than white-light endoscopy (23.4%; 95% CI 16.9-31.4; P = .01). However, there were no significant differences between groups in proportions of patients found to have serrated lesions of 5 mm or larger (9.4% vs 7.0%; P = .49), of proximal location (11.7% vs 10.2%; P = .68), or sessile serrated lesions (3.9% vs 5.5%; P = .55), respectively. Total procedure and withdrawal times with pancolonic chromoendoscopy (30.7 ± 12.8 minutes and 18.3 ± 7.6 minutes, respectively) were significantly longer than with white-light endoscopy (22.4 ± 8.7 minutes and 13.5 ± 5.6 minutes; P < .001). CONCLUSIONS: In a randomized parallel trial, we found that for Lynch syndrome surveillance, high-definition white-light endoscopy is not inferior to pancolonic chromoendoscopy if performed by experienced and dedicated endoscopists. ClinicalTrials.gov no: NCT02951390.

Hybrid Lesion: Extralobar Sequestration with Cystic Adenomatoid Malformation - Misdiagnosed as Pulmonary Tuberculosis.

We report a rare case of bronchopulmonary extralobar sequestration in a 9-year girl mimicking pulmonary tuberculosis. Patient had recurrent chest infections and two episodes of massive hemoptysis. Preoperative x-ray chest showed an opacity in left lower lobe and computed tomography-aortogram showed that the lesion had systemic arterial supply from celiac trunk. Diagnosis of pulmonary sequestration was made and left lateral muscle sparing thoracotomy was planned. Intraoperatively, extralobar sequestration was found with dual systemic blood supply. Histopathology confirmed it to be a hybrid lesion.

Congenital renal tumor: metanephric adenoma, nephrogenic rest, or malignancy?

We report a renal tumor detected by prenatal ultrasound and resected at 2 months of age. This 9-cm, solid mass was composed of tubular and papillary structures lined by small, uniform epithelial cells. There was local invasion into renal parenchyma and a tumor deposit in a hilar lymph node. The tumor was immunopositive for WT1, pankeratin, and CD10; focally positive for CK7; and negative for EMA and TFE3. Based on morphology and immunophenotype, the favored diagnosis was metanephric adenoma over Wilms tumor, renal cell carcinoma, and nephrogenic rest. However, metanephric adenoma only occasionally occurs in children and has never been reported prenatally. Alternatively, this tumor might be a congenital Wilms tumor that differentiated completely. Although the nature of the tumor remains unconfirmed, resection appears to have been curative; the patient remains disease-free 18 months following surgery alone.

Mini-invasive videoassisted thyroid lobectomy for neonatal hyperfunctioning adenoma related to a somatic TSHr gene mutation.

We report here a case of a paediatric hyperthyroidism due to a micro-macro-follicular thyroid adenoma in the presence of heterozygous point mutation of TSH receptor (TSHr). We describe the case from the initial diagnosis, through laboratoristic examinations and imaging techniques, until the radical surgical treatment made by a mini-cervicotomic videoassisted technique. We also explained the genetic work-up from peripheral blood and thyroid adenoma tissue.

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.

Ultrasound assessment of caudal catheter position in infants.

The positioning of caudally inserted epidural catheters is crucial to their effectiveness. However, level assessment can be difficult and time consuming. We report the use of ultrasound to assess the catheter position in three patients aged between 1 and 10 months. The advantages and disadvantages of this technique are discussed in relation to other methods of assessing caudal catheter placement.

Sporadic nonautoimmune congenital hyperthyroidism due to a strong activating mutation of the thyrotropin receptor gene.

The de novo occurrence of germline-activating thyrotropin receptor (TSHR) gene mutations has been reported as the cause of sporadic nonautoimmune neonatal hyperthyroidism in eight children. We report the case of an Italian infant girl who presented at birth with severe hyperthyroidism and goiter. Ultrasonografic examination of the infant's thyroid showed a diffuse goiter with a normal echogenic pattern. Serum antithyroglobulin, antithyroperoxidase, and antithyrotropin receptor antibodies were undetectable. Treatment with propylthiouracyl, propranolol, and saturated potassium iodide solution started at 44 days of life with the resolution of thyrotoxic symptoms. Once euthyroidism was achieved, the dose of propylthiouracyl was tapered, but hyperthyroidism recurred. Auxological parameters showed an acceleration of linear growth and bone age. DNA was extracted from peripheral white blood cells of the patient, the sister, and the two parents. All of exon 10 of the TSHR gene was amplified by polymerase chain reaction (PCR) and subjected to direct sequencing. In the thyrotoxic infant girl, a substitution of cytosine to thymine was detected, changing isoleucine 568 into a threonine (1568T), located in the second extracellular loop. The normal sequence could also be detected, indicating heterozygosis of the mutated allele. This mutation was previously described as a somatic mutation in a patient with toxic thyroid adenoma. The sister and the parents of the propositus, all euthyroid, showed the wild-type TSHR gene. In conclusion, we describe a case of a de novo germinal mutation of the TSHR causing severe congenital hyperthyroidism.

Management of antenatally diagnosed pulmonary sequestration associated with congenital cystic adenomatoid malformation.

BACKGROUND: Sequestration with associated cystic adenomatoid malformation is rare. A study was undertaken to determine whether pulmonary sequestration associated with congenital cystic adenomatoid malformation has a more favourable natural history than that of sequestration without associated cystic adenomatoid malformation. METHODS: An outline of the postnatal work up leading to the management of extralobar or intralobar pulmonary sequestration with congenital cystic adenomatoid malformation diagnosed antenatally as pulmonary malformation is presented and the indications for surgical intervention are discussed. RESULTS: In five infants in whom an antenatal ultrasound scan had detected a congenital lung malformation at 18-19 weeks gestation a final diagnosis of extralobar or intralobar pulmonary sequestration with congenital cystic adenomatoid malformation was made postnatally. Postnatal ultrasound and computerised axial tomographic scans confirmed the diagnosis of sequestration by delineating anomalous vascular supply. Cystic changes were also observed in the basal area of the sequestration in all patients. Four children remained asymptomatic and one infant presented at 10 months of age with pneumonia. The mean age at surgical resection was 6.8 months (range 2-10). Histopathological examination confirmed intralobar pulmonary sequestration with associated Stocker type 2 congenital cystic adenomatoid malformation in two patients and extralobar pulmonary sequestration with associated Stocker type 2 congenital cystic adenomatoid malformation in three patients. The mean period of follow up was four years (range 1-8). The children remain well and are developing normally. CONCLUSIONS: The importance of seeking an anomalous blood supply in children with congenital lung lesions is emphasised. Pulmonary sequestration and congenital cystic adenomatoid malformation probably share a common embryogenesis despite diverse morphology. The natural history of antenatally diagnosed lung masses is variable. Early postnatal surgical resection of pulmonary sequestration with cystic adenomatoid malformation is recommended. Surgical excision should be conservative, sparing the normal lung parenchyma.

The congenital basal cell adenoma of salivary glands. Contribution to the differential diagnosis of congenital salivary gland tumours.

Congenital epithelial tumours of the salivary glands are very rare. The Salivary Gland Registry maintained in the Department of Pathology. University of Hamburg, contains only three cases among a total of 6,646 salivary gland tumours from the years 1965-1994. The three cases were classified as congenital basal cell adenoma, two of the parotid gland and one of the submandibular gland. Histologically, the three adenomas were similar in structure to the adult counterpart of basal cell adenoma with solid, trabecular or tubular (duct-like) patterns. In some cystic spaces of the duct-like structures PAS- and Astra blue-positive substances were secreted. On immunocytochemistry, the luminal duct-like cells showed membranous expression of cytokeratins 3, 5, 6, 7, 13 and 19. In the isomorphic basaloid cells of the solid and trabecular cell nests few cells expressed cytokeratin. On the outside of the solid cell nests there were smaller elongated myoepithelial-like cells, which expressed cytokeratin 14 and vimentin. Cytokeratins 1, 2, 4 and 18 were not expressed. The pattern of expression reflects the different stages of maturity of the tumour cells and is related to the development of the salivary glands until the end of the 3rd embryonal month with an arrest of further cell differentiation. No acinic cells, invasive growth, recurrence or metastases were observed. The differential diagnosis includes other congenital salivary gland tumours, such as hybrid basal cell adenoma-adenoid cystic carcinoma, sialoblastoma or embryoma, carcinoma, hamartoma and teratoma.

Congenital adenoma of the iris and ciliary body: light and electron microscopic observations.

A 23-year-old man had a lesion in the right inferior iris which appeared to have enlarged since it was first seen when the patient was aged 5 years. The lesion was excised by a partial iridocyclectomy. Histopathologically the neoplasm was composed of both pigmented and non-pigmented cells. Pseudoacini, containing acid mucopolysaccharides, were present throughout the tumour matrix. Electron microscopically the non-pigmented cells were found to possess a convoluted plasmalemma, abundant rough endoplasmic reticulum, and numerous desmosomes and gap junctions. The pigmented cells contained large, round, mature melanosomes, occasional premelanosomes, and desmosomes, which resembled the posterior pigment epithelium of the iris. The intercellular matrix contained fine collagen fibrils resembling vitreous. We believe that this neoplasm represents a congenital adenoma of the ciliary body and iris.

Adrenocortical tumors in childhood: a report of four cases.

In the last 10 years, four children with adrenocortical tumors were treated in our hospital. Three of them had symptoms of adrenogenital virilizing syndrome, and another, nonfunctional, was found during a routine examination. A diagnosis of adrenocortical tumor was established given the symptoms, hormonal tests, and radiologic studies. Two of the tumors were located in the left side, and the histologic diagnosis was pleomorphic cortical adenoma; the ones that affected the right side were adenocarcinomas. All the patients were treated by surgery and none received chemotherapy. At both presurgical and postsurgical stages, the patients were treated with cortisol. All four children have had a favorable course, with normal growth and the disappearance of public hair and hirsutism; however, macrogenitals still persist.

Malformación adenomatoide quística: presentación de un caso / Cystic adenomatoid malformation: report of a case

Se presenta un caso letal de malformación adenomatoide quística acompañada de hidrops y clasificada como variante tipo I. El reconocimiento de los aspectos morfológicos de cada variante permite una mejor comprensión de las características clínicas, radiológicas y ultrasonográficas informadas en la literatura, lo cual posibilita el diagnóstico de esta entidad, cuya patogenia es discutida

Congenital hybrid basal cell adenoma--adenoid cystic carcinoma of the salivary gland.

A congenital parotid gland tumor involving the facial nerve was excised, revealing histologic and ultrastructural features of a basal cell adenoma and adenoid cystic carcinoma. An asynchronous regional metastasis was successfully eradicated with adriamycin. Seven other similar appearing tumors occurring in neonates are documented in the literature and serve to establish this tumor as a clinicopathologic entity. The surrounding parotid gland had "dysplastic" changes attributed to obstruction during morphogenesis.

[Hydrops universalis and respiratory distress due to congenital lung tumor]. / Hydrops universalis und Respiratory distress infolge angeborener Lungengeschwulst.

A case of an immature female newborn child is reported, with a solitary alveolarcell adenoma rising from the left lower lobe of the lung. The consequences of the congenital blastoma of the lung, which is to be regarded as hamartoma, are Hydrops fetalis, a polyhydramnion, respectively a Respiratory Distress not responding to treatment. Finally a survey of the available literature is given on non-immunologic Hydrops fetalis caused by congenital tumors.

Hamartomatous adenoma of the nonpigmented ciliary epithelium arising in iris-ciliary body coloboma. Light and electron microscopic observations.

A 2 1/2-year-old boy had a slowly enlarging mass at the site of a typical iris-ciliary body coloboma for 2 years. The mass was excised partially by iridocyclectomy. By light microscopy, the tumor cells were embedded in a rich mucoid stroma that contained abundant hyaluronidase-sensitive acid mucopolysaccharides. By electron microscopy the tumor showed light and dark cells with interdigitating cell membranes, desmosomes, gap junctions, multilaminar basement membrane, and numerous extracellular collagen fibrils that resembled vitreous fibrils. We believe that the tumor represents a hamartomatous (congenital) adenoma of the nonpigmented ciliary epithelium rather than a conventional (acquired) adenoma, since it developed precisely within a colobomatous defect of the iris and ciliary body.

Monomorphic adenoma of the nasal septum in a newborn (case report and ultrastructural findings).

Salivary gland type adenomas of the nasal septum are rare tumors in adults and even rarer in children. There has been no previous report of such a tumor in a neonate. We have described a tumor of the nasal septum whose light and electron microscopic appearances are consistent with an origin from minor salivary gland or nasal mucous glands. Ultrastructural findings presented do not suggest an origin from the embryonic organ of Jacobson (vomeronasal organ). The biological behaviour of this tumor in the neonate is unknown. A study of similar cases will be necessary to elucidate the incidence and natural history of intranasal adenomas in the neonate.