Placental pathology in neonatal stroke.

OBJECTIVE: Neonatal stroke is increasingly recognized, and risk factors have been identified. The placenta has been implicated as a potential contributor to neonatal stroke; however, pathology has not been previously described. This case series systematically evaluates prenatal, maternal, and neonatal risk factors and describes placental pathology in 12 cases of neonatal stroke. PATIENTS AND METHODS: We reviewed the Canadian Pediatric Ischemic Stroke Registry from 1992 to 2006, which consists of 186 neonatal stroke patients. Twelve patients with symptomatic cerebral arterial ischemic stroke or sinovenous thrombosis had their placenta available for pathologic examination. Clinical presentation; maternal, prenatal, and neonatal risk factors for stroke; and patient outcome were collected retrospectively from patient charts. Gross and microscopic placental pathology was described and classified into 4 pathologic categories. RESULTS: Of 12 patients studied, 10 patients were male, 5 patients had arterial ischemic stroke, and 7 patients had sinovenous thrombosis. Maternal risk factors were identified in 5 cases, prenatal risk factors in 10 cases, and neonatal risk factors in 10 cases. Placental lesions were present in 10 cases and were classified as thromboinflammatory process in 6 cases, sudden catastrophic event in 5 cases, decreased placental reserve in 3 cases, and stressful intrauterine environment in 2 cases. CONCLUSIONS: This study reviews detailed placental pathology in a selected cohort of patients presenting near the time of delivery and correlates this with clinical presentation, outcome, and risk factors for neonatal stroke. Our results suggest that multiple risk factors are involved in neonatal stroke, and placental pathology may be a contributing factor. The implications of specific placental lesions remain to be determined with larger, case-controlled studies.

Diagnostic utility of nestin expression in pediatric tumors in the region of the kidney.

Nestin is an intermediate filament that was first identified in neuroepithelial stem cells. During embryogenesis, nestin is expressed in a number of cell types, including neural crest cells and developing myocytes. We have recently shown that nestin is expressed in human podocytes and nephrogenic blastema. We sought to determine the utility of nestin expression in distinguishing pediatric tumors in the region of the kidney. Cases studied included Wilms tumor (n=24), nephroblastomatosis (n=6), renal cell carcinoma (n=19), renal clear cell sarcoma (n=9), mesoblastic nephroma (n=9), neuroblastoma (n=11), malignant rhabdoid tumor (n=8 including 2 renal), Ewing sarcoma (n=16 including 1 renal, 7 soft tissue, and 8 bone), intra-abdominal desmoplastic small round cell tumor (n=5), and rhabdomyosarcoma (n=8, all extrarenal). Nestin expression was assessed semiquantitatively by immunohistochemistry and then scored as positive or negative. All cases of Wilms tumor, mesoblastic nephroma, rhabdomyosarcoma, neuroblastoma, malignant rhabdoid tumor, and desmoplastic small round cell tumor were nestin-positive. In Wilms tumor and nephroblastomatosis, nestin was expressed in blastema and glomeruloid structures, but not tubules. In neuroblastoma, positive staining was detected regardless of degree of differentiation. The majority of Ewing sarcoma and renal cell carcinoma were negative. Expression in clear cell sarcoma was variable with 5 cases negative and 4 cases positive. Thus, nestin is a highly sensitive, but nonspecific, marker of Wilms tumor in the context of tumors that may occur in or around the kidney. Nestin reactivity may be useful in differentiating Wilms tumor from Ewing sarcoma, renal cell carcinoma, or nestin-negative clear cell sarcoma.

Splenic hamartoma in a child in the era of PET-CT.

We present a case of a healthy 7-year-old female with an incidental finding of a growing splenic lesion, diagnosed as a splenic hamartoma after splenectomy. This case highlights the diagnostic challenge of splenic lesions and that the role of positron emission tomography/computerized tomography (PET/CT) in defining splenic lesions in the pediatric population remains to be defined.

Absence of the interstitial cells of Cajal in a child with chronic pseudoobstruction.

Absence or altered distribution of the interstitial cells of Cajal (ICCs) has been described in association with intestinal pseudoobstruction in adults. We report the first pediatric case with regional absence of ICCs in the distal small bowel and colon associated with intestinal pseudoobstruction. This report highlights that abnormalities of the ICCs in intestinal pseudoobstruction should be considered early in the diagnostic workup of children with intestinal pseudoobstruction.

MRI of the fetal eyes: morphologic and biometric assessment for abnormal development with ultrasonographic and clinicopathologic correlation.

BACKGROUND: Currently ocular biometric measurements are defined by US and are measured from the orbital walls. These bony landmarks cannot be seen by MRI, and therefore these measurements cannot be directly applied. OBJECTIVE: To define measurements of normal growth of the fetal eyes using MRI. MATERIALS AND METHODS: Transorbital views were analyzed in 198 fetal MR examinations. The ocular diameter (OD) and interocular and binocular distances (IOD and BOD) were measured and were plotted against gestational age. Fetuses with abnormalities affecting the eyes were evaluated separately. RESULTS: Of 198 scans, 146 had suitable images, 35 of which were abnormal. Normal growth of BOD, IOD and OD were determined, and compared with the respective already established US data. CONCLUSION: Normal growth charts were derived from a cohort of 111 normal fetuses. Because the margins of the vitreous are inside the bony orbit, at the same gestational age measurements of the BOD and OD are always less than the corresponding measurements by US, and those of the IOD are always more. Normal growth charts for MRI can now be used to support suspected diagnoses of orbital and ocular pathologies and the syndromes that give rise to them, and many examples are demonstrated.

Stage III cystic partially differentiated nephroblastoma recurring after nephrectomy and chemotherapy.

Cystic partially differentiated nephroblastoma (CPDN) has low malignant potential. We report a 1-year-old with stage III CPDN of the right kidney that recurred following radical nephrectomy and chemotherapy. There was evidence of tumor spillage pre-operatively and intra-operatively. During chemotherapy the disease recurred in the omentum and the peritoneum. Pathology of the recurrent resected cysts revealed a more differentiated biphasic tumor without blastemal elements. It appears that spillage of CPDN in our patient led to dissemination of disease. Chemotherapy failed to prevent recurrence but only mature elements were present following this treatment. The intensity of therapy required to treat CPDN remains undefined.

The intermediate filament nestin is highly expressed in normal human podocytes and podocytes in glomerular disease.

The intermediate protein nestin is expressed in proliferating embryonic tissues and adult tissues undergoing repair. Recently this protein been identified in rodent podocytes. Its role in this cell is unknown, since podocytes are believed to be terminally differentiated and nondividing. We report the first study of nestin in human kidney. Nestin expression in normal mature human glomeruli was confined to podocytes. In developing kidney, nestin was detected in metanephric blastema and in podocytic cells at all stages of glomerular development. Nestin co-localized with vimentin but not with actin or heavy chain myosin IIA, using a mouse podocyte cell line. Knockdown of nestin in a murine podocyte cell line failed to produce any obvious phenotypic change or alteration in vimentin distribution but was associated with increased cell cycling. A survey of glomerular diseases failed to identify any condition lacking nestin, indicating that the protein is critical for some aspect of podocyte function. Perhaps through an association with vimentin, nestin serves to bolster the mechanical strength of these cells that experience high tensile stress during glomerular filtration. Nestin was also expressed in podocytes that are reported to be 'dysregulated' (lacking podocyte markers). Thus, nestin has a potential as a reliable podocyte marker, even for podocytes that are not completely differentiated (for example, during development) or 'dedifferentiated' in glomerular disease.

Collagenous colitis and eosinophilic gastritis in a 4-year old girl: a case report and review of the literature.

UNLABELLED: Collagenous colitis (CC), a form of microscopic colitis, is characterized by a thick subepithelial collagen layer in the colon in the presence of chronic nonbloody watery diarrhoea and macroscopically normal-appearing colonic mucosa. Typically affecting elderly adults, CC is rare in children with only 12 cases previously reported in the literature. We report the case of a 4-year-old girl with CC associated with eosinophilic gastritis, which was clinically responsive to treatment with ketotifen, a benzocycloheptathiophene derivative, and H(1) class of antihistamine that stabilizes mast cells and potentially impairs eosinophil migration to target organs. We review the published cases of paediatric-onset CC and summarize the links between eosinophils and CC in the clinical and basic science literature. CONCLUSION: CC is a rare cause of chronic diarrhoea in children and may relate to mast cell and eosinophil activity.

The PDAC syndrome (pulmonary hypoplasia/agenesis, diaphragmatic hernia/eventration, anophthalmia/microphthalmia, and cardiac defect) (Spear syndrome, Matthew-Wood syndrome): report of eight cases including a living child and further evidence for autosomal recessive inheritance.

The combination of pulmonary agenesis/dysgenesis/hypoplasia, microphthalmia/anophthalmia, and a diaphragmatic defect (agenesis or eventration) is a rare syndrome presumed to have an autosomal recessive mode of inheritance based on a report of affected siblings born to unaffected parents [Seller et al., 1996]. The condition is known as Spear syndrome and Matthew-Wood syndrome, although genetic heterogeneity cannot be ruled out. We report on eight patients with this condition including a living child, three sibs and three isolated cases. Most presented with fetal ultrasound findings of microphthalmia/anophthalmia, and diaphragmatic eventration/hernia and in five, cardiac abnormalities were also found. The earliest detection was at 20 weeks gestation. This is the second report of sibs affected with this condition, which supports an autosomal recessive mode of inheritance. We present the first and only reported living patient with this condition and expand the intrafamilial, interfamilial, and ethnic variability of this condition. We suggest changing the condition's name to PDAC to reflect the most important components of this condition.

Ganglioneuroma no interior de um névus melanocítico gigante: um mero achado acidental? / Cutaneous ganglioneuroma within giant congenital nevus: mere coincidence?

Ganglioneuromas cutâneos são lesões raramente descritas na literatura médica e, deforma ainda mais especial, em associação com outras lesões. Relatamos o achado de umamassa cervical detectada por exame de ultra-som pré-natal, que regrediu no decorrer dagravidez. Após o nascimento, extensa área pigmentada foi observada na mesma localizaçãoda massa, além de um tumor sólido palpável no seu interior. O diagnóstico diferencialcom outros tumores derivados de células da crista neural é importante, assim como acorrelação entre o névus piloso e o ganglioneuroma cutâneo.

Cutaneous ganglioneuroma have been occasionally reported in the literature. We describea case in which a cervical mass firstly detected by routine prenatal ultrasound examinationregressed throughout the months until delivery. After birth, an extensive area ofpigmentation was found at the same location, with a solid mass was perceptible within.The differential diagnosis between other neural crest tumors should be established, aswell the correlation between congenital nevus and cutaneous ganglioneuroma.

Prenatal detection of microtia by MRI in a fetus with trisomy 22.

Trisomy 22 is a rare chromosomal abnormality infrequently detected prenatally. External ear abnormalities, in particular microtia, are often associated with trisomy 22, but prenatal detection of microtia has not been reported in association with trisomy 22. We report a fetus with trisomy 22, with fetal MRI findings of microtia, craniofacial dysmorphism, and polygyria. Fetal MRI is a useful tool for auricular assessment and might have utility in the prenatal detection of chromosomal abnormalities, especially among fetuses with structural anomalies.

Multifocal lymphangioendotheliomatosis with thrombocytopenia.

Multifocal lymphangioendotheliomatosis with thrombocytopenia is an extremely rare disease. This condition manifests as diffuse congenital vascular lesions in the skin and gastrointestinal tract leading to severe gastrointestinal bleeding and thrombocytopenia. Histopathologic and immunohistochemical studies of vascular lesions demonstrate a lymphatic endothelial cell origin. Treatment often is not satisfactory. We herein describe a 4-week-old infant with this uncommon clinicopathologic entity.

Second-trimester prediction of severe placental complications in women with combined elevations in alpha-fetoprotein and human chorionic gonadotrophin.

OBJECTIVE: The purpose of this study was to determine the ability of uterine artery Doppler and placental ultrasound to identify adverse clinical outcomes attributable to severe placental dysfunction in women with second-trimester unexplained elevated maternal serum screening of alpha-fetoprotein and human chorionic gonadotropin. STUDY DESIGN: Fifty singleton pregnancies with elevated alpha-fetoprotein (3.5 multiples of median [range 2.1 to 10.5]) and human chorionic gonadotropin (5.3 multiples of median [range 2.5 to 21.7]) and a normal fetal anatomical ultrasound were prospectively evaluated with placental ultrasound and uterine artery Doppler at referral between 19 and 23 weeks' gestation. RESULTS: Abnormalities in both placental ultrasound and uterine artery Doppler (n = 24) predicted preterm delivery less than 32 weeks from any cause (n = 24) (75% sensitivity, 75% positive predictive value; likelihood ratio positive 3.3 [1.6 to 6.8]), intrauterine fetal death (n = 12) (100% sensitivity, 50% positive predictive value; likelihood ratio positive 3.1 [2.0 to 5.0]), and intrauterine growth restriction with absent/reversed end-diastolic flow (n = 17) (sensitivity 94%, positive predictive value 67%, likelihood ratio positive 3.9 [2.0 to 6.2]) . Ischemic-thrombotic pathology was present in 88% of placentas examined (n = 32). CONCLUSION: Uterine artery Doppler and placental morphology identified most pregnancies with combined abnormal maternal serum screening destined to result in extremely premature delivery and/or perinatal death. Abnormal maternal serum screening reports could include a recommendation for placental ultrasound testing when no fetal explanation has been identified.

Fetal pericardial teratoma: presentation of two cases and review of literature.

We present the fetal ultrasound and echocardiographic findings and clinical outcome of two fetuses with intrapericardial teratoma encountered in our institution. In the first (diagnosed at 19 weeks of gestation) case there was elective termination of pregnancy; in the second case (diagnosed at 24 weeks), a pericardio-amniotic shunt was placed after reaccumulation of fluid following pericardiocentesis. We review the published experience of intrapericardial teratomas, focusing on the diagnosis, fetal echocardiographic findings, and outcome with and without prenatal intervention.

Association of the t(12;22)(q13;q12) EWS/ATF1 rearrangement with polyphenotypic round cell sarcoma of bone: a case report.

The t(12;22)(q13;q12) chromosomal rearrangement results in an EWS/ATF1 fusion transcript and is associated with clear cell sarcoma (CCS). CCS is an uncommon tumor arising in tendons and aponeuroses of the extremities and shows evidence of melanocytic differentiation at the light microscopic, immunohistochemical, and/or ultrastructural level. Only 5 cases have been reported to arise in bone, none of which had molecular confirmation of the diagnosis. The current report describes a 7-year-old girl with a primary round cell sarcoma of the left humerus showing polyphenotypic differentiation on immunohistochemical analysis. Antibodies directed at melanocytic antigens were negative, and there was no evidence of melanocytic differentiation by light microscopy or ultrastructural analysis. Cytogenetic analysis revealed rearrangement of the EWS locus within 22q12. RT-PCR and sequence analysis revealed the presence of a fusion transcript bringing together exon 7 of EWS with exon 5 of ATF1, consistent with a type 2 transcript reported in association with CCS. However, given the lack of morphologic features usually present in CCS, a diagnosis of polyphenotypic round cell sarcoma was made. This tumor thus expands the spectrum of neoplasms associated with the t(12;22)(q13;q12) rearrangement.

Cutaneous ganglioneuroma within a giant congenital nevus.

Cutaneous ganglioneuroma has only occasionally been reported in the literature. Cutaneous ganglioneuroma is seen even more rarely in association with a giant congenital nevus. Differential diagnosis includes malignancies, especially melanoma and metastatic neuroblastoma. It is essential to rule out malignancy in a solid lesion within a congenital nevus. The present report is possibly the first relating ganglioneuroma and a congenital nevus to a cervical mass detected during routine prenatal ultrasound.

Les neurocytomes cutanés sont peu déclarés dans la documentation scientifique. Ils sont encore plus rares en association avec un naevus congénital géant. Le diagnostic différentiel inclut la malignité, et surtout des mélanomes et des neuroblastomes métastatiques.Il est impératif d'écarter la possibilité de malignité dans une lésion solide d'un naevus congénital. Le présent compte rendu est peut-être le premier reliant un neurocytome et un naevus congénital à une masse cervicale décelée pendant une échographie prénatale systématique.

Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans.

To document the clinical activity of imatinib mesyalte in a child with a dermatofibrosarcoma protuberans (DFSP). An 18-month-old girl presented with a large extremity DFSP. As surgical resection would have caused unacceptable functional defects, imatinib mesylate was administered to induce tumor reduction and or stabilization. After 23 weeks of therapy, magnetic resonance imaging (MRI) of the tumor showed a reduction in the subcutaneous thickness in the transverse plane. The drug was tolerated well without any adverse reactions. Imatinib mesylate offers a non-surgical alternative for the treatment of large DFSP in children.

Is surgery necessary for incidentally discovered adrenal masses in children?

BACKGROUND: There are no guidelines that exist to direct the management of incidental adrenal masses (IAM) in children. The aim of this study was to determine if there is a subset of IAMs that could be safely observed. METHODS: A retrospective analysis was conducted of all adrenal masses that were either resected or biopsied between 1990 and 2002 (n = 91) at the Hospital for Sick Children, Toronto. IAM was defined as a solitary adrenal mass discovered by either physical examination (n = 6; 23.1%) or diagnostic imaging for other indications (n = 20; 76.9%), without metastases or biochemical activity. RESULTS: Twenty-six (28.6%) IAMs were detected (mean age, 4.6 years [range, antenatal to 17 years]; 11 boys, 15 girls). Pathologic diagnoses included neuroblastoma (n = 7), ganglioneuroma (n = 6), adrenocortical adenoma (n = 4), adrenal cyst/pseudocyst (n = 3), adrenal hemorrhage (n = 3), ganglioneuroblastoma (n = 1), nodular cortical hyperplasia (n = 1), and teratoma (n = 1). Eight masses were malignant (30.8%). Two of the 5 masses discovered on antenatal ultrasound scan were neuroblastoma. In comparing the benign with malignant lesions, there was no significant difference in mean size (4.8 cm v 4.3 cm; P =.57), radiologic characteristics, or mode of presentation. Benign lesions occurred more frequently in older children (mean age, 6.5 years v 1.3 years; P =.03). CONCLUSIONS: Clear guidelines cannot be established to predict benign IAM in children. Given the high proportion of malignant lesions, we recommend that all pediatric IAMs should be resected.

Developmental biology of the placenta and the origins of placental insufficiency.

Defects in all the trophoblast-differentiating pathways--endovascular, interstitial and chorionic villous--play a role in the pathogenesis of early-onset intra-uterine growth restriction (IUGR). There are two types of extravillous trophoblast: endovascular trophoblast, that forms the definitive placenta by occlusion of the spiral arteriole at the implantation site, and interstitial extravillous trophoblast, responsible for the anatomical erosion of the distal spiral arteriole and the secretion of angiogenic and vasodilator signals to improve uterine blood flow. Defective endovascular erosion may render the basal plate inadequate to meet the demands of the fetus. Failed interstitial invasion of spiral arterioles could lead to failure of local angiogenic and systemic cardiovascular adaptation signals that could be the underlying basis for early-onset IUGR and pre-eclampsia. As debate persists regarding the relative importance of cord, stem and terminal villous pathology, the study of factors controlling trophoblast turnover from immature intermediate villi to conductance stem villi and gas-exchanging terminal villi, translation of our knowledge from mouse placental genetics into human placental development, and defining causes of thrombo-occlusive damage to the placenta would help our understanding of the pathophysiology of early-onset IUGR.

Retroperitoneal infantile fibrosarcoma: clinical, molecular, and therapeutic aspects of an unusual tumor.

The authors describe a patient with a large retroperitoneal infantile fibrosarcoma that responded well to preoperative chemotherapy, which subsequently facilitated the complete surgical resection of the mass. The patient had an unusual site of metastasis presumed to be to a regional lymph node. The histology on initial core biopsies was not classic but showed a round cell, myxoid pattern. The presence of the t(12;15)(p13;q25) and the fusion transcript ETV6-NTRK3 by RTPCR facilitated the diagnosis.