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Mesenchymal hamartoma of the chest wall (MHCW) is a rare condition. Previously, surgical resection has been advocated with considerable post-operative morbidity. Evidence for conservative management is lacking because the natural history of MHCW is unknown. We present serial measurements of an antenatally detected MHCW (8 antenatal ultrasounds and 2 postnatal computed tomographic scans). The study demonstrates that the relative tumor size peaked at birth and then decreased postnatally. Based on this evidence, we believe that MHCW can be managed conservatively in an asymptomatic patient., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Tuberous sclerosis complex (TSC) is a tumor suppressor gene syndrome in which hamartomas develop in multiple organ systems. Knockout and conditional alleles of Tsc1 and Tsc2 have been previously reported. Here, we describe the generation of a novel hypomorphic allele of Tsc2 (del3), in which exon 3, encoding 37 amino acids near the N terminus of tuberin, is deleted. Embryos homozygous for the del3 allele survive until E13.5, 2 days longer than Tsc2 null embryos. Embryos die from underdevelopment of the liver, deficient hematopoiesis, aberrant vascular development and hemorrhage. Mice that are heterozygous for the del3 allele have a markedly reduced kidney tumor burden in comparison with conventional Tsc2(+/-) mice. Murine embryo fibroblast (MEF) cultures that are homozygous for the del3 allele express mutant tuberin at low levels, and show enhanced activation of mTORC1, similar to Tsc2 null MEFs. Furthermore, the mutant cells show prominent reduction in the activation of AKT. Similar findings were made in the analysis of homozygous del3 embryo lysates. Tsc2-del3 demonstrates GTPase activating protein activity comparable to that of wild-type Tsc2 in a functional assay. These findings indicate that the del3 allele is a hypomorphic allele of Tsc2 with partial function due to reduced expression, and highlight the consistency of AKT downregulation when Tsc1/Tsc2 function is reduced. Tsc2-del3 mice also serve as a model for hypomorphic TSC2 missense mutations reported in TSC patients.

Background: Rhabdomyomas are the most common benign cardiac neoplasms occurring in the fetus and neonate, with most of them identified within the first year of life. Cardiac rhabdomyomas are frequently associated with tuberous sclerorosis., Case: A 25-year-old, pregnant woman with no remarkable personal or family history was referred to us for a suspected fetal cardiac anomaly. Ultrasonographic examination of the fetus revealed multiple solid masses consistent with rhabdomyoma in the ventricular septum and ventricular wall. No other anomalies could be detected. Postnatal echocardiography confirmed the presence of cardiac rhabdomyoma, and periventricular subependymal multiple hamartomas were diagnosed by postnatal magnetic resonance imaging., Conclusion: When fetal cardiac rhabdomyoma is diagnosed, careful evaluation of other fetal structures, including brain and renal parenchyma, should be performed to search for signs of tuberous sclerosis.

Abstract We report on an extremely rare chest wall mesenchymal hamartoma associated with a massive fetal pleural effusion. Prenatal ultrasound examination demonstrated a heterogeneous mass in the right thorax associated with a massive pleural effusion and right lung compression at 29 weeks of gestation. The patient underwent pleuroamniotic shunting at 30 weeks and was delivered at 33 weeks by cesarean delivery secondary to fetal distress. After management of the respiratory distress and evaluation of the mass, surgery was performed at day of life 8. Histological examination confirmed the diagnosis of a chest wall mesenchymal hamartoma.

The hypothalamus is involved in a variety of autonomic, endocrine, neurological and behavioural functions including temperature, osmostatic and autonomic nervous system regulation, pituitary, thyroid, adrenal and gonadal control, thirst, appetite and weight control, memory and emotional behaviour including aggression and laughter, and biological (circadian) rhythms. The functional anatomy of the hypothalamus and its major afferent and efferent neurological connections are described, with particular reference to hypothalamic hamartomas (HH), gelastic seizures, MRI of the hypothalamus, and potential effects of surgery for HH. Normal development of the hypothalamus is reviewed in relation to models of forebrain development, descriptive hypothalamic embryology and the importance of known transcription factors. Potential environmental antecedents to HH development are discussed, and the significance for sporadic, isolated HH of several syndromes associated with HH is explored.

The authors report a case of hepatic mesenchymal hamartoma diagnosed prenatally with ultrasound scan and magnetic resonance imaging (MRI) and confirmed histologically postdelivery. The fetus had a multicystic mass in the left upper abdomen, which showed a rapid enlargement accompanying maternal hypertension and preterm labor. The patient was delivered by cesarian section at 30 weeks and 5 days weighing 1,190 g, and, at birth, a large abdominal mass and severe anemia were noted. Surgical resection and neonatal management were successful, and the patient is alive in a good condition after 3 years follow-up. Although histologically benign, because this lesion frequently results in perinatal complications such as fetal hydrops, maternal toxemia, and preterm labor, early careful fetal ultrasonography should improve the prognosis of this lesion., (Copyright 2003, Elsevier Science (USA). All rights reserved.)

The tail gut is a blind extension of the hindgut into the tail fold just distal to the cloacal membrane. Remnants of this structure may form tail gut cyst. We report a 14-year-old girl with tail gut cyst that presented as acute abdomen. The patient recovered after cyst excision.

Cystic mesenchymal hamartoma is an extremely rare, benign tumor. Rapid growth to a giant size can pose a threat not only in early childhood but also during fetal life. The experience with 2 antenatally diagnosed giant hepatic cysts with widely disparate approaches to management, treatment, and outcome is presented. A giant hepatic cyst was diagnosed on routine screening ultrasound scan. Because of its extremely massive size, the cyst was treated in utero with repeated aspirations, primarily for obstetric considerations. The infant did well, and the lesion was excised laparoscopically during the neonatal period. A second fetus with a giant hepatic cyst was not treated in utero, and the pregnancy continued to term. Nonimmune hydrops fetalis developed, and the fetus was delivered prematurely at 34 weeks. At birth, the infant was noted to have diffuse neurologic injury and no urine output despite normal-appearing kidneys. The lesion was excised during the neonatal period by open laparotomy. Observations at the time of surgery and pathologic studies of the placenta showed aneurysmal dilatation of the placental veins suggesting in utero compression of the fetal intraabdominal umbilical vein. The infant died shortly after birth. The experience with these 2 cases suggests the possibility that giant mesenchymal hamartoma diagnosed in utero may cause umbilical venous obstruction leading to ischemia during fetal life. Decompression of giant hepatic cysts may reverse this phenomenon and allow normal fetal development., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

To determine the biological role of caudal-like homeobox gene CDX2, we constructed knockout mice in which its mouse homologue Cdx2 was inactivated by homologous recombination, placing a bacterial lacZ gene under the control of the Cdx2 promoter. Although the homozygous mutants died in utero around implantation, the heterozygotes were viable and fertile and expressed lacZ in the caudal region in early embryos and in the gut tissues in adults. The heterozygotes developed cecal and colonic villi by anteriorization and formed hamartomatous polyps in the proximal colon. The hamartoma started to develop at 11.5 days of gestation as an outpocket of the gut epithelium, which ceased to express the remaining Cdx2 allele. The outpocket then expanded as a partially duplicated gut but was contained as a hamartoma after birth. In adult mice, these hamartomas grew very slowly and took a benign course. None of them progressed into invasive adenocarcinomas, even at 1.5 years of age. Whereas the cecal and colonic villi expressed lacZ, the hamartoma epithelium did not, nor did it express Cdx2 mRNA from the wild-type allele. However, genomic DNA analysis of the polyp epithelium did not show a loss of heterozygosity of the Cdx2 gene, suggesting a mechanism of biallelic Cdx2 inactivation other than loss of heterozygosity. These results indicate that the Cdx2 haploin-sufficiency caused cecal and colonic villi, whereas the biallelic inactivation of Cdx2 triggered anomalous duplications of the embryonic gut epithelium, which were contained as hamartomas after birth.

An unusual case with Sturge-Weber syndrome is reported. A computed tomography study revealed the presence of gyriform calcifications in the occipital lobe, and discovered a hidden occipital subcutaneous port-wine nevus, instead of the usually expected nevus in the distribution of the first division of the trigeminal nerve. Existence of an occipital port-wine nevus, which was in the distribution of the greater occipital nerve, suggested a variation with respect to the embryogenesis of the Sturge-Weber syndrome.

Enteric duplication cysts of the tongue are unusual lesions that may be confused with dermoid cysts, hemangiomas, lingual thyroid remnants, ranulas, and cystic hygromas. Two cases of lingual enteric duplications are reported in a 5-year-old boy and a 4-month-old boy. In the first case the cyst was lined by gastric-type epithelium, and in the second by colonic-type epithelium. Theories of pathogenesis of enteric duplications include development from small epithelial inclusions trapped during fusion of primordial tissues, from incomplete coalescence of lacunas that form between epithelial cells of the solid core of the developing gut, from persistence of epithelial buds within the wall of the bowel, or from nests of trapped entodermal cells. However, each of these theories presents problems with respect to lingual enteric cysts, as possible trapping of epithelium by fusing primordia does not explain the presence of heterotopic mucosa, and the tongue does not develop in the same manner as the hollow viscera. It becomes apparent therefore that enteric duplication cysts are a heterogeneous group of lesions that share some morphologic features, but perhaps not the same pathogenesis.

Twin fetuses aborted at an estimated gestational age of 145 days were concordant for oral, facial, skeletal, and central nervous system malformations. The twins were discordant for other anomalies including cardiac defects, polydactyly, and malrotated short bowel. The combination of malformations observed overlaps with that of the oral-facial-digital syndrome, hydrolethalus syndrome, and Pallister-Hall syndrome. The problem of phenotypic overlap between these syndromes is discussed.

A unique pigmented lesion, judged to be a hamartoma of neural crest origin, occurring in a female patient, is compared with equine melanotic disease, The characteristic perifollicular arrangement of pigment-laden spindle cells is remarkably similar in both. Previously described patch- and plaque-like blue nevi in humans are also closely related. Light and ultrastructural features showed differentiation toward both nevus cells and Schwann cells, and it is proposed that the lesion be termed pilar neurocristic hamartoma.

Retrorectal cystic hamartomas (RCHs) are uncommon lesions of controversial pathogenesis that arise in the presacrococcygeal space. We describe the clinicopathologic features of RCHs from three adult patients. Two were asymptomatic women; the third was a man who had a pelvic abscess. All three specimens were multiloculated cysts lined by squamous, transitional, and glandular epithelium. Poorly organized collections of smooth muscle were present in the surrounding connective tissue, but no well-formed smooth-muscle coat was seen. Although RCHs possess elements of three germ-cell layers, their histologic features are similar to those of the embryonic tailgut. The male patient also had a perirenal mass that was grossly and histologically identical to the RCH. The associated kidney was malrotated. A portion of the embryonic tailgut may have been pulled cephalad by the developing kidney, inhibiting its rotation. Clinicopathologic features distinguish RCH from other retrorectal cystic lesions, including teratoma, dermoid, epidermal cyst, rectal duplication, anal duplication, and anal gland cyst.

Thirty cases of mesenchymal hamartoma of the liver are presented and compared with 42 previously published cases. The patients, 69% male, range in age from newborn to 10 years (average age 15 months, median age 10 months). Except for occasional cases in which the lesion is an incidental finding at autopsy, most present with progressive abdominal enlargement over a period of days to months. Physical and radiologic examinations are nonspecific except for the demonstration of a mass within or attached to the liver. The masses are large, averaging 1311 g, and frequently contain cysts filled with clear fluid or gelatinous material. Histologic examination shows a mixture of loose mesenchymal tissue, bile ducts, connective tissue, and hepatocytes along with cysts formed either from degenerative areas of mesenchyme or from dilated bile ducts and lympathics. Treatment is partial or total excision of the lesion. Mortality (7-17%) is related to intraoperative or postoperative complications. Recurrence or malignant transformation has not been noted.

Iris hamartomas (Lisch nodules), previously reported in cases of peripheral neurofibromatosis, were found in a 14-year-old girl with segmental neurofibromatosis. The girl was in the 75th percentile for height (168 cm), the 90th percentile for weight (63 kg), and the 50th percentile for head circumference (55 cm). Her blood pressure was 105/70 mm Hg. Her visual acuity (20/20 and J 1), ocular motility, pupillary responses, visual fields, color vision, stereopsis, and intraocular pressure were within normal limits. Biomicroscopy showed several tan elevated nodular hamartomas on the anterior surface of the right peripheral iris but none elsewhere in the right eye and none in the left eye. Café-au-lait spots and freckling were also limited to the right side of the body. The child had no palpable neurofibromas and was in good health and of normal intelligence. There was no family history of neurofibromatosis, multiple café-au-lait spots, axillary freckling, macrocephaly, or learning disabilities. The absence of iris hamartomas has been used to distinguish segmental neurofibromatosis from the peripheral and central or acoustic forms. Thus, their presence in this case is clinically significant. The segmental form not only produces fewer complications but carries less genetic risk. In segmental neurofibromatosis, the Lisch nodules would be expected to be unilateral rather than bilateral, ipsilateral to the side of the cutaneous involvement, and more frequently associated with contiguous cutaneous lesions.

Five cases of a distinctive tumor located in the soft tissues of the lower neck in adults are described. The lesion is characterized microscopically by the presence of four components: cellular areas made up of spindle elements; epithelial islands composed of solid nests, trabeculae and cysts; mature adipose tissue; and lymphocytes, sometimes arranged in a Hassall's corpuscle-like fashion. Electron microscopy and immunostaining for keratin showed that the spindle cell component was of epithelial nature. These tumors were supraclavicular or suprasternal in location, and no local recurrence has developed in any case following local resection. We interpret these lesions as benign tumors arising on the basis of a developmental defect. We think that they are derived from the third branchial arch and that they are composed of abnormal thymic tissue.

Enterocystomas of the head and neck are exceedingly rare lesions; only 21 cases have been reported previously. We describe a case of a newborn infant with an enterocystoma of the anterior tongue. All of the previously reported cases and the three theories of embryogenesis are reviewed. Diagnostic evaluation includes computerized axial tomography and radioiodine thyroid scan, particularly if the tongue is involved. Complete surgical excision is the only appropriate therapy and is curative.