Showing papers in "Pediatric and Developmental Pathology in 2014"
TL;DR: It is demonstrated that CRir mucosal nerves extend into the proximal 1–2 cm of aganglionic bowel, where their presence in distal rectal biopsies could complicate diagnosis of very short-segment Hirschsprung disease.
Abstract: Absent calretinin-immunoreactive (CRir) mucosal innervation in aganglionic rectal biopsies is considered a useful diagnostic finding for Hirschsprung disease. Analysis of a series of rectosigmoid resections from patients with short-segment (>2-cm aganglionic, n = 9) and very short-segment (≤2-cm aganglionic, n = 9) Hirschsprung disease demonstrates that CRir mucosal nerves extend into the proximal 1-2 cm of aganglionic bowel, where their presence in distal rectal biopsies could complicate diagnosis of very short-segment disease. Indeed, retrospective analysis of preoperative, aganglionic, distal rectal biopsies from 4 of 9 patients with very short-segment Hirschsprung disease revealed CRir mucosal innervation. Accurate diagnosis was possible based on generous histopathological submucosal sampling to exclude ganglion cells and the presence of abundant large-caliber submucosal nerves (more than 4 nerves >30 µm thick/×200 field or more than 2 nerves >40 µm thick/×200 field). Absent CRir mucosal innervation supports the diagnosis of Hirschsprung disease, but the presence of CRir mucosal nerves does not exclude aganglionosis, especially in distal rectal biopsies from patients with very short-segment Hirschsprung disease.
48 citations
TL;DR: With the exclusion of granulomas, cryptitis seems the most distinctive feature of the duodenal lesions associated with IBD, including villous blunting and eosinophilia.
Abstract: Histopathologic lesions of the upper gastrointestinal tract (UGT) are common in inflammatory bowel disease (IBD) patients. Pediatric patients have a higher incidence of IBD-associated gastritis and duodenitis than do adults. This study aimed to identify histopathologic features of duodenal lesions in the pediatric population that are characteristic of IBD, compared to duodenal pathology of different etiopathogenesis. We performed a retrospective analysis of UGT biopsies from pediatric patients with a histopathologic diagnosis of duodenitis (0-18 years of age) over a 7-year period. We identified 40 cases of duodenitis associated with Crohn's disease (CD) and 10 cases associated with ulcerative colitis (UC) and compared the histopathologic characteristics of the duodenitis with age-matched controls consisting of 40 cases duodenitis associated with celiac disease and 40 non-Helicobacter pylori-associated (NOS) etiology duodenitis cases. The histologic features that were evaluated included presence of granulomas, duodenal cryptitis, erosion, lamina propria eosinophils, villous blunting, increased intraepithelial lymphocytes (IELs), and crypt hyperplasia, among others. Additionally, we evaluated the presence of associated gastritis in all of these groups. Statistical analysis to identify significant differences was performed using Kruskal-Wallis testing. Cryptitis was the most distinctive feature of IBD-associated duodenitis. Granulomas were exceptionally rare. The severity of villous blunting and presence of IELs was significantly different in the IBD versus the celiac group. There is a significant overlap with duodenal lesions of different etiopathogenesis, including villous blunting and eosinophilia. With the exclusion of granulomas, cryptitis seems the most distinctive feature of the duodenal lesions associated with IBD.
43 citations
TL;DR: The first case of plexiform fibromyxoma originating in the esophagus is reported, emphasize its occurrence in pediatric patients, and review the related literature.
Abstract: Plexiform fibromyxoma is a distinctive mesenchymal neoplasm usually arising in the gastric antrum. We report 2 cases of this entity in pediatric patients, including the first case arising in the esophagus. The patients were a 16-year-old female who presented with chest pain and was found on computed tomographic scan to have a midesophageal mass at the level of the carina, and an 11-year-old female with a gastric mass. Both patients underwent surgical resection of their tumors, which histologically exhibited a plexiform growth pattern with multiple nodules in the muscularis propria and infiltrative borders. The nodules were composed of a rich myxoid stroma with bland uniform spindle cells, no mitoses or necrosis, and delicate blood vessels in the background. Immunohistochemical studies demonstrated that the tumor cells were immunoreactive with smooth muscle actin and not reactive with S-100, CD34, desmin, and c-kit (CD117). We report the first case of plexiform fibromyxoma originating in the esoph...
39 citations
TL;DR: The age cut-offs for MKI classes in the current INPC are reasonable and effective for distinguishing prognostic groups with increased risk of event/death for older patients and the cut-off of 4 months for H-MKI tumors did not reach statistical significance in the presence of other factors.
Abstract: Prognostic effects of Mitosis-Karyorrhexis Index (MKI) used in the International Neuroblastoma Pathology Classification (INPC) are age-dependent. A total of 4,282 neuroblastomas reviewed at the Children's Oncology Group Neuroblastoma Pathology Reference Laboratory (8/1/2001–3/31/2012) included 2,365 low-MKI (L-MKI), 1,068 intermediate-MKI (I-MKI), and 849 high-MKI (H-MKI) tumors. Cox proportional hazards models were fit to determine age cut-offs at which the relative risk of event/death was maximized in each MKI class. Backward-selected Cox models were fit to determine the prognostic strength of the age cut-offs for survival in the presence of other prognostic factors. The age cut-offs used in the INPC for L-MKI tumors (<60 months, n = 2,710, 84.0% ± 1.0% event-free survival [EFS], 93.8 ± 0.7% overall survival [OS] vs ≥60 months, n = 195, 49.8% ± 4.6% EFS, 71.7% ± 4.1% OS; P < 0.0001) and I-MKI tumors (<18 months, n = 568, 83.8% ± 2% EFS, 93.7% ± 1.3% OS vs ≥18 months, n = 500, 51.4% ± 2.9% EFS, 66.7% ± 2...
35 citations
TL;DR: PE/E is not a single process resulting in a uniform distribution of lesions but, rather, is composed of several different processes manifesting a single clinical presentation.
Abstract: With preeclampsia/eclampsia (PE/E), infants more often are either large or small for gestational age. We explored whether the differences in infant birthweight (BW), placental weights (PW), or time...
29 citations
TL;DR: Measuring serum vitamin D levels postmortem may provide invaluable information on sudden unexplained death in ‘at-risk’ children and vitamin D deficiency may be relevant in childhood asthma and in children with multiple infections and babies with bone fractures.
Abstract: Vitamin D is required for calcium absorption and normal bone mineralization; it has a key role in immune regulation against infections and is believed to be involved in immunomodulation in asthma. We did a retrospective analysis of 52 postmortem cases (aged 2 days to 10 years). Seventeen children had vitamin D deficiency (<25 nmol/L); 24 children had vitamin D insufficiency (25-49 nmol/L); 10 children had suboptimal vitamin D levels (50-79 nmol/L); and only 1 child had adequate levels (≥80 nmol/L). Three infants had fractures. Growth plate histology was abnormal in 10 cases with vitamin D deficiency (59%), but radiology was abnormal in only 3 of those cases. Eight infants (33%) with vitamin D insufficiency had abnormal histology, but radiology was normal in all cases. In 3 children hypocalcemia due to vitamin D deficiency was considered accountable for death; they all showed radiological and histological rickets: 2 babies had cardiomyopathy and a 3-year-old had hypocalcemic seizures. Children from all ethnic groups had a high proportion of low vitamin D levels. Vitamin D deficiency (the most common form of pediatric metabolic bone disease) is preventable and treatable. Profound hypocalcemia due to severe vitamin D deficiency can cause unexpected death in babies and young children. Measuring serum vitamin D levels postmortem may provide invaluable information on sudden unexplained death in 'at-risk' children. Vitamin D deficiency may be relevant in childhood asthma and in children with multiple infections and babies with bone fractures. Postmortem vitamin D levels are stable and easy to measure.
28 citations
TL;DR: An expression of MEIS1 and its binding partner PBX2 in most nephroblastomas is demonstrated, which might point to an involvement of miR-204 in the regulation of Meis homeobox 1 in nephROblastomas.
Abstract: By comparing several studies we identified a possible deregulation of the transcription factors PBX2 (pre–B-cell leukemia homeobox 2) and one of its binding partners, MEIS1 (Meis homeobox 1) in nephroblastomas The regulation of MEIS1 is complex, and its expression is known to be influenced by changes of promoter methylation and binding of microRNA-204 (miR-204) Therefore, in our study, we assessed the expression of MEIS1 and PBX2 and the factors regulating expression of MEIS1 in nephroblastomas MEIS1 and PBX2 messenger RNA (mRNA) and protein levels were investigated by quantitative real-time-polymerase chain reaction (qRT-PCR) and immunohistochemistry Promoter methylation of MEIS1 was evaluated using a methylation-specific PCR assay Expression levels of miR-204 were examined by qRT-PCR Eighteen of 21 nephroblastomas showed a high level of MEIS1 mRNA, and 22 of 26 samples had a specific nuclear protein expression MicroRNA-204 had a statistically significantly lower expression in all nephrob
23 citations
TL;DR: The findings support a pathogenetic model for mesenchymal hamartoma as a consequence of “ectopic” activation of C19MC in hepatic stroma, due to either chromosomal rearrangements or paternal uniparental disomy.
Abstract: Recurrent genetic alterations found in hepatic mesenchymal hamartoma include either androgenetic-biparental mosaicism or chromosomal rearrangements involving chromosome 19q13.4, in the vicinity of ...
22 citations
TL;DR: Although there are known associated characteristics with the polysplenia/asplenia syndromes, correct identification requires a standardized approach for diagnosis and reporting, and great variation in how heterotaxy-associated defects were described, diagnosed, and reported is found.
Abstract: Heterotaxy is a rare disease with high morbidity and mortality. Controversy exists over how to classify these syndromes with most cases stratified into asplenia/polysplenia syndromes or right/left isomerism. In an effort to review comprehensively specific pheonotypes associated with heterotaxy syndromes, we reviewed published cases series, adopted a classification scheme based on spleen status, and evaluated autopsy cases retrospectively with abnormal laterality at our institution. We categorized 116 cases as situs inversus totalis, polysplenia, asplenia, and single right-sided spleen. Cardiovascular abnormalities occurred in 87.1% of polysplenia, 90.5% of asplenia, and all cases of single right-sided spleen. For polysplenia, 48.9% had bilateral bilobed lungs, 87% had right-sided stomach, 58.1% had midline symmetric liver, and 60.4% had malrotated intestines. For asplenia, 51.9% had bilateral trilobed lungs, 86.7% had right-sided stomach, 45.8% had symmetric liver, and 65.5% had malrotated intestines. Atrioventricular septal defects occurred in 91.2% of asplenia compared to 56.8% of polysplenia cases. Eight percent had pulmonary/aortic stenosis or atresia. Double outlet right ventricle was more common in polysplenia (32.6%) compared to asplenia (21.4%). Total anomalous systemic venous return was described in 55.6% of polysplenia and total anomalous pulmonary venous connections in 81% of asplenia cases. Greater than half of the cases had no heterotaxy diagnosis. Although, we found similar heterotaxy-associated characteristics, the frequencies differed from previous studies. We found great variation in how heterotaxy-associated defects were described, diagnosed, and reported. Although there are known associated characteristics with the polysplenia/asplenia syndromes, correct identification requires a standardized approach for diagnosis and reporting.
22 citations
TL;DR: The case of a 6-year-old boy with a deceptively bland spindle cell renal neoplasm found to harbor the EWSR1-CREB3L1 gene fusion, which is an indolent tumor with late metastatic potential and a propensity for long-term disease recurrence.
Abstract: We present the case of a 6-year-old boy with a deceptively bland spindle cell renal neoplasm found to harbor the EWSR1-CREB3L1 gene fusion. This fusion has recently been described as a variant translocation in low-grade fibromyxoid sarcoma (LGFMS), a tumor more typically characterized by a recurrent t(7;16) chromosomal translocation, resulting in the fusion of FUS and CREB3L2 genes. LGFMS is an indolent tumor with late metastatic potential and a propensity for long-term disease recurrence. The tumor is rare in children, with only 33 published cases. In the pediatric population, it has not previously been reported arising in the kidney.
21 citations
TL;DR: Umbilical artery thrombosis is a rare occurrence and is associated with poor neonatal outcomes and carries a poor prognosis, and a series of 7 cases occurring over a 13-year period at the National Maternity Hospital are presented.
Abstract: Umbilical artery thrombosis is a rare occurrence and is associated with poor neonatal outcomes. We present a series of 7 cases occurring over a 13-year period. The National Maternity Hospital is a tertiary referral center with approximately 10,000 births per annum. Cases were identified by a keyword search on the laboratory computer system. Seven cases were retrieved over a 13-year period (from an estimated 116,000 births): 5 cases from 7306 placentas and 2 cases from 1174 autopsies performed. Only cases with isolated umbilical artery thrombosis were included in the study. Placental histology from all cases was examined, placental gross findings were recorded, and clinical information and Doppler findings were obtained. Two infants were stillborn, and an additional 3 of the 7 cases were small for dates. All liveborn infants had a complicated neonatal course: 1 infant had a caudate infarction, 1 was born with partial acrania and schizencephaly, and 1 had a prolonged intensive care unit admission for low birth weight and jaundice. One case had absent end diastolic flow on Doppler ultrasound. Three cases had a cord diameter narrower than that expected for gestational age. All cases showed evidence of placental hypoperfusion. Umbilical artery thrombosis is a rare occurrence and carries a poor prognosis.
TL;DR: The pathologist's role as a partner in a multidisciplinary approach to diagnosis and treatment of this rare pediatric mass is highlighted, potentially the largest Triton tumor in the head reported to date.
Abstract: Benign Triton tumor (neuromuscular choristoma) is a rare mass that most commonly occurs as a multinodular expansion of tissue in or around large nerves. Intracranial occurrence is uncommon. We report on a 4-year-old girl presenting with a right-sided facial mass and trismus. Imaging revealed a large, complex mass extending from the ventral aspect of the pons, along the trigeminal nerve, through the foramen ovale, and into the right infratemporal fossa. The lesion was partially enhancing, invaded adjacent infratemporal musculature, was associated with marked overgrowth of the right coronoid process, and induced bony erosion of the middle cranial fossa. After needle biopsy, a multidisciplinary team, including plastic surgery, otolaryngology, and neurosurgery, performed a combined, multistep, single-day surgical approach for resection. Unique to this case was the resection of the coronoid process, a modified middle fossa intradural and extradural approach, coupled with a transfacial infratemporal approach. Microscopically, the resected tissue showed skeletal muscle, fibrous tissue, and nerve in a disorganized arrangement characteristic of a benign Triton tumor. We present this case to illustrate diagnostic clues and pitfalls in the preoperative evaluation of a benign Triton tumor. We also highlight the pathologist's role as a partner in a multidisciplinary approach to diagnosis and treatment of this rare pediatric mass, potentially the largest Triton tumor in the head reported to date.
TL;DR: Postmortem Diagnosis, and Literature Review of an Intracranial Tumor Detected in Utero
Abstract: Postmortem Diagnosis, and Literature Review of an Intracranial Tumor Detected in Utero STEFAN KOSTADINOV, COREY L. HANLEY, TERAKEITH LERTSBURAPA, BARBARA O’BRIEN, AND MAI HE Department of Pathology & Laboratory Medicine, Women & Infants Hospital of Rhode Island, Providence, RI, USA Department of Pathology, Memorial Hospital, Pawtucket, RI, USA Department of Obstetrics & Gynecology, Women & Infants Hospital of Rhode Island, Providence, RI, USA Alpert Medical School of Brown University, Providence, RI, USA
TL;DR: The incidence and interobserver variation of morphologic findings in a series of 34 term placentas from pregnancies with normal outcome and the value of pathologic examination as a supplement in placental perfusion models are emphasized.
Abstract: This study reports for the 1st time the incidence and interobserver variation of morphologic findings in a series of 34 term placentas from pregnancies with normal outcome used for perfusion studies. Histologic evaluation of placental tissue is challenging, especially when it comes to defining "normal tissue" versus "pathologic lesions." A scoring system for registration of abnormal morphologic findings was developed. Light microscopic examination was performed independently by 2 pathologists, and interobserver variation was analyzed. Findings in normal and perfused tissue were compared and selected findings were tested against success parameters from the perfusions. Finally, the criteria for frequent lesions with fair to poor interobserver variation in the nonperfused tissue were revised and reanalyzed. In the perfused tissue, the perfusion artefact "trophoblastic vacuolization," which is believed to represent dilated transtrophoblastic channels, was reproducible and significantly correlated to the perfusion marker "fetal leakage." In longer perfusions, microscopy of the perfused cotyledon revealed bacteria in the fetal vessels. This finding led to an adjustment in the perfusion protocol with addition of antibiotics to the medium. In the "normal" tissue, certain lesions were very frequent and showed only fair or poor interobserver agreement. Revised minimum criteria for these lesions were defined and found reproducible. This study has emphasized the value of pathologic examination as a supplement in placental perfusion models. Examination of the perfused cotyledon for trophoblastic vacuolization is recommended as an additional quality marker in perfusion models. The study also underlines the need for exact definitions of abnormality in frequent placental lesions.
TL;DR: Evaluating the prevalence of GSTM1, GSTT1, and GSTP1 gene polymorphisms among homozygous sickle cell anemia patients found no significant association between GST genotypes and frequency of Sickle cell–related pain, transfusion frequency, disease severity, or hydroxyurea treatment.
Abstract: Sickle cell disease (SCD) complications are associated with oxidative stress. Glutathione S-transferases (GSTs) are a group of enzymes that protect against oxidative stress. The aims of this study was to evaluate the prevalence of GSTM1, GSTT1, and GSTP1 gene polymorphisms among homozygous sickle cell anemia patients and to investigate the possible association between the presence of these polymorphisms and SCD severity and complications. Genotyping the polymorphisms in GSTT1 and GSTM1 genes was performed using the multiplex polymerase chain reaction (PCR) method. The GSTP1 ILe105Val polymorphism was determined using PCR–restriction fragment length polymorphism. GSTM1 null genotype was significantly associated with increased risk of severe vaso-occlusive crises (VOC) (odds ratio = 1.52, 95% confidence interval = 0.42–5.56, P = 0.005). We found no significant association between GST genotypes and frequency of sickle cell–related pain, transfusion frequency, disease severity, or hydroxyurea t...
TL;DR: It is concluded that malignancy should be suspected in the following conditions: presence of abdominal or multiple symptoms, symptoms duration of 1-6 months, generalized lymphadenopathy, multiple groups of lymph node (LN) involved, LN size > 2 cm, amalgamated, hard, fixed and non-tender LNs, certain abnormal CBC findings, blast cells in blood film and elevated LDH level.
Abstract: Assessment of lymphadenopathy in children represents a diagnostic challenge because of the extensive differential diagnoses including reactive and malignant conditions. Knowledge of the etiologic pattern of lymphadenopathy in a given geographical region is essential for making a confident diagnosis or suspecting a disease. Hence, the present study was carried out to identify different etiologies of lymphadenopathy in children in our region, and assess parameters commonly associated with malignancy, with an emphasis on the role of pathology in the diagnostic workup. One hundred and twenty patients aged one month to 18 years were included in the study. They were sorted into neoplastic and non-neoplastic (Infectious and non-infectious). In only 56 patients, biopsy, whether fine needle aspiration cytology (FNAC), core needle or excision biopsy, was essential to reach the final diagnosis. Sensitivity of FNAC in the differentiation between neoplastic and non-neoplastic lymphadenopathy was 92.3...
TL;DR: In this first neuropathologic report of an infant with 22q11DS, the findings were similar to previously reported manifestations and are likely secondary to perfusion issues, developmental microvasculopathy, and abnormal frontal cortical development.
Abstract: The 22q11 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans and one of the chromosomal conditions most associated with psychosis and autism spectrum disorder. To date, only 2 neuropathologic studies of 22q11DS have been reported. Findings included polymicrogyria, neuronal heterotopias, excess subcortical white-matter (interstitial) neurons, significant white-matter gliosis/hypomyelination, and microvasculopathy. Here, we report on a 3-month-old infant with documented 22q11DS, tetralogy of Fallot, and pulmonary atresia. The brain exhibited tortuous cerebral vessels and proportionately smaller occipital lobes. Histologic examination revealed cerebral white-matter pathology and subtle differences in cortical lamination, including an excess of interstitial white-matter neurons compared with a sample of age-matched controls. There was a 15% increase in DARPP-32+ medium spiny neurons in the anterior-superior caudate. In this first neuropathologic report of an infant with 22q11DS, the findings were similar to previously reported manifestations and are likely secondary to perfusion issues, developmental microvasculopathy, and abnormal frontal cortical development.
TL;DR: The occurrence of choroid plexus carcinoma, Spitzoid melanoma, and myelodysplasia in a child who was found to carry a germline mutation for TP53 and Li-Fraumeni syndrome is reported.
Abstract: Spitzoid melanoma of childhood is a rare malignancy. The histological features are at the upper end of a range encompassing Spitz nevus and atypical Spitz tumor, the unifying features including large oval, fusiform or polygonal melanocytes with abundant homogeneous-appearing cytoplasma and large vesicular nuclei. The presence of a "bottom-heavy" pattern, strikingly enlarged nuclei and nucleoli in both the upper and lower portions of the lesion, and deep mitotic figures are among the findings that distinguish most of the Spitzoid melanomas from Spitz nevi and atypical Spitz tumors. There are no syndromic associations reported for this malignancy. We report the occurrence of choroid plexus carcinoma, Spitzoid melanoma, and myelodysplasia in a child who was found to carry a germline mutation for TP53. While choroid plexus carcinoma and myelodysplasia have relatively frequently been described, melanomas have been very rarely described in Li-Fraumeni syndrome. The association of Spitzoid melanoma with Li-Fraumeni syndrome, especially in a pediatric patient, has not been reported before.
TL;DR: A 21-year-old young man with underlying congenital heart disease who developed Bartonella henselae endocarditis of the right ventricular outflow tract (RVOT) conduit of his Melody transcatheter (percutaneous) pulmonary valve (TPV), with an initial presentation of glomerulonephritis with a dominant C3 pattern, is reported.
Abstract: We report a case of a 21-year-old young man with underlying congenital heart disease who developed Bartonella henselae endocarditis of the right ventricular outflow tract (RVOT) conduit of his Melody transcatheter (percutaneous) pulmonary valve (TPV), with an initial presentation of glomerulonephritis with a dominant C3 pattern, with renal failure and circulating cryoglobulins. There are few reports of a glomerulonephritis with a dominant C3 pattern presenting as a manifestation of B. henselae endocarditis. While most cases of B. henselae endocarditis affect the aortic valve, in this case the valve damage was to the RVOT of the Melody TPV, a percutaneous transcatheter valve delivery system that had previously replaced his pulmonary homograft, which had become dysfunctional as a result of prior Streptococcus viridans endocarditis. The pulmonary homograft had been in place since childhood as a result of a Ross procedure to repair his congenital aortic stenosis. The patient's renal failure significa...
TL;DR: The fetal autopsy findings in FMH are characterized by a eutrophic pale macerated fetus, low liver weight, absent intrathoracic petechiae, increased extramedullary hematopoiesis in the liver and kidney, and increased circulating nucleated red blood cells.
Abstract: Feto-maternal hemorrhage (FMH) is the cause of late fetal death in 1.6%-11% of cases. In spite of this high frequency, its pathological features have received little attention. The definitive diagnosis of lethal FMH requires confirmation of sufficient fetal blood volume loss. This is determined by tests such as the Kleihauer-Betke test, which may not have been obtained or not have been available before the autopsy. The pathologist may offer a tentative diagnosis of FMH from the autopsy findings. The objective of this study was to better characterize the placental and fetal autopsy findings in lethal FMH. This was a retrospective study of 17 cases of FMH proven by a positive Kleihauer-Betke test. The cases were selected from the autopsy files of the Department of Pathology, Centre Hospitalier Universitaire de Bordeaux. The pathological reports as well as the placental and fetal photographs and the microscopic slides of each case were systematically reviewed. The fetal autopsy findings in FMH are characterized by a eutrophic pale macerated fetus, low liver weight, absent intrathoracic petechiae, increased extramedullary hematopoiesis in the liver and kidney, and increased circulating nucleated red blood cells. The placenta shows an increased frequency of intervillous thrombi. Although nonpathognomonic, some of the pathological features are strongly suggestive of FMH. When the latter is present, a Kleihauer-Betke test should be performed, even some days after the delivery.
TL;DR: A case of unsuspected fetal galactosialidosis presenting as severe intrauterine growth restriction and oligohydramnios prenatally and as hyperinsulinemic hypoglycemia in the immediate postnatal period is reported.
Abstract: Galactosialidosis (GS) is a rare autosomal recessive lysosomal storage disease caused by a combined deficiency of lysosomal β-galactosidase and neuraminidase as a result of a genetic defect in the protective protein/cathepsin A gene. We report a case of unsuspected fetal galactosialidosis presenting as severe intrauterine growth restriction and oligohydramnios prenatally and as hyperinsulinemic hypoglycemia in the immediate postnatal period. Placental pathology examination showed striking vacuolations of the villous syncytiotrophoblast, extravillous trophoblast, and villous Hofbauer cells. Electron microscopy revealed numerous membrane-bound electron-lucent lysosomes, mainly within the syncytiotrophoblast. The characteristic histologic and ultrastructural placental findings prompted biochemical and molecular genetic testing for fetal storage disease. Enzyme activity of β-galactosidase was decreased in leukocytes and fibroblasts. Sialic acid content was elevated. Molecular genetic studies revealed 3 variants--c.108, 110delGCT(L37del), c.1045T>A (C349S), and c.1321C>T(R441C)--of the cathepsin A gene, the latter 2 of which have not been previously reported. These findings are consistent with galactosialidosis. We emphasize the importance of following the accepted practice guideline for the examination of the placenta in discovering unsuspected fetal metabolic disorders.
TL;DR: It is indicated that ophthalmopathologic investigation of fetal eyes can be of great value for the further classification of syndromes.
Abstract: We report anterior segment abnormalities in both eyes of a 33-week-old fetus endorsing the diagnosis of MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome. After abortion, the fetus was examined by a standard pediatric autopsy that included macroscopic and microscopic examination of both eyes. Postmortem findings included craniofacial stigmata (such as hypertelorism, a flat nose and low-set ears) and an agenesis of the corpus callosum. Array comparative genomic hybridization revealed a deletion of the short arm of the X chromosome (region Xp22.2 to p22.32). Ophthalmopathologic examination of the eyes revealed microphthalmia with anterior segment developmental anomalies, in particular sclerocornea and Peters' anomaly, respectively. General pathology findings plus the ocular findings allowed the diagnosis of MIDAS syndrome. A discussion of differential diagnoses is provided. This case report indicates that ophthalmopathologic investigation of fetal eyes can be of great value for the further classification of syndromes.
TL;DR: A higher density of MC was found, both in normal-appearing skin and nevus areas of L/GCMN patients, compared with control skin samples from individuals without nevi, suggesting a potential role for MC in the biology of L /GCMN, making them a potential target for therapeutic intervention.
Abstract: Nevocytes (NC) and mastocytes (MC) have different progenitors but share stem cell factor as regulator/activator of NC and for differentiation/proliferation of MC. Both cell types express stem cell factor receptor CD117. We hypothesize that large/giant congenital melanocytic nevi (L/GCMN) may associate with MC hyperplasia. Forty-nine L/GCMN were examined, 12 samples from uninvolved skin of L/GCMN patients and 6 control skin samples studied with Giemsa and immunohistochemistry for CD117 and MC-tryptase. Picrosirius red (PR) was used to assess fibrosis. Digital images were used to count MC/mm2 using ImageJ software. Western blot (WB) for MC-tryptase in 12 GCMN and 12 non-nevus samples was performed. Analysis of variance (Tukey) and Pearson statistical tests were applied. Increased MCs were observed in nevus tissue (75.1 ± 35.3 MCs/mm2) and in uninvolved skin (53.74 ± 27.7 MC/ mm2). P = 0.109 from patients with L/GCMN, compared with controls from individuals without L/GCMN (28.74 ± 8.4 MC/mm2); P ...
TL;DR: This report reports a patient with celiac disease who was not strictly following a gluten-free diet and presented with progressive pallor, fever, and weakness of 1 month's duration, which revealed aplastic anemia.
Abstract: An association between severe aplastic anemia and other autoimmune diseases is rare and has been described in adults for eosinophilic fasciitis, thymomas, systemic lupus erythematosus, and thyroid disorders. Herein we report a patient with celiac disease who was not strictly following a gluten-free diet and presented with progressive pallor, fever, and weakness of 1 month's duration. On investigation, he had pancytopenia, which on subsequent evaluation revealed aplastic anemia. An association between aplastic anemia and celiac disease has rarely been reported. To the best of author's knowledge, only 1 pediatric case of celiac disease associated with aplastic anemia has been published. This is the second report to suggest such an association in children.
TL;DR: Findings point to endothelial damage leading to thrombotic microangiopathy and ischemic tissue injury as the most likely pathogenesis of cyclophosphamide-induced cardiotoxicity.
Abstract: We present a clinicopathologic study of the youngest reported child with lethal cyclophosphamide-induced cardiotoxicity after hematopoietic stem cell transplantation for β-thalassemia major and the 1st pediatric report of the use of extracorporeal membrane oxygenation as a therapeutic modality to bridge the patient to myocardial recovery. Despite improvement in myocardial function while on extracorporeal membrane oxygenation, at autopsy 11 days after the onset of cardiac dysfunction, epicardial hemorrhage and extensive myocardial hemorrhagic infarction were revealed. Histopathologic and ultrastructural examination of the myocardium revealed extensive coagulative necrosis of cardiomyocytes, endothelial damage, fibrin thrombi, and subendothelial and interstitial fibrin. We review the literature on cyclophosphamide-induced cardiotoxicity and describe its clinicopathologic characteristics. Our findings point to endothelial damage leading to thrombotic microangiopathy and ischemic tissue injury as the most likely pathogenesis.
TL;DR: This case of a male newborn with trisomy 21 and transient abnormal myelopoiesis at birth whose placenta showed extravasated fetal blasts in the perivillous (maternal) space is reported, the first report, to the authors' knowledge, documenting maternal peripheral-blood follow-up evaluation of this disorder in the English literature.
Abstract: We report a case of a male newborn with trisomy 21 and transient abnormal myelopoiesis at birth whose placenta showed extravasated fetal blasts in the perivillous (maternal) space. Concern for possible maternal spread of fetal malignancy prompted a Kleihauer-Betke test and flow cytometric analysis of the maternal peripheral blood on postpartum day 2. Notably, no evidence of the persistence of fetal cells in the maternal blood was identified, a finding that likely reflected successful maternal immunologic clearance of the fetal blasts and erythrocytes, and/or blast cellular fragility and limited viability. Ours is the first report, to our knowledge, documenting maternal peripheral-blood follow-up evaluation of this disorder in the English literature. We discuss our case in the context of a comprehensive review of fetoneonatal solid tumor and leukemic proliferative disorders with placental involvement and evidence of maternal metastasis.
TL;DR: The length of the umbilical cord is an important data item, and little is known about the effects of time and fixation on measurement, but studies on cord length should include data on time of measurement and fixation status.
Abstract: The length of the umbilical cord is an important data item, and little is known about the effects of time and fixation on measurement. Such a change has implications for the diagnosis of a long and short cord. This study was conducted to examine the effects of time and formalin fixation on cord length in a routine practice setting. We measured 90 cords from singleton term pregnancies within 5 minutes of delivery, again in the fresh state at 1 to 2 hours, and again after 24 to 48 hours of formalin fixation. The mean cord length was 536.7 mm at delivery. Mean cord shortening was 17.6 mm (3% reduction in length) between delivery and measurement at 1 to 2 hours, and 62.2 mm (12% reduction) between delivery and measurement after 24 to 48 hours fixation. Both values were statistically significant (P < 0.001). Studies on cord length should include data on time of measurement and fixation status.
TL;DR: The case of a 9-year-old girl who had sudden cardiac death as a result of occlusion of the left circumflex coronary artery is reported.
Abstract: Cardiac inflammatory myofibroblastic tumor (IMT) is a rare entity affecting predominantly infants, children, and young adults. Although most tumors have a benign clinical course after complete surgical resection, some have significant clinical effects. We report the case of a 9-year-old girl who had sudden cardiac death as a result of occlusion of the left circumflex coronary artery. A review of 57 cases of cardiac IMTs reported in the literature in terms of epidemiology, clinical presentation, histologic and immunohistologic features, and outcome is presented. Recognition of this rare abnormality is important in order to initiate prompt surgical intervention.
TL;DR: In the cases presented, the utility of postmortem ultrasonography as an adjunct to traditional autopsy following fetal demise is demonstrated.
Abstract: Postmortem evaluation following an in utero fetal demise is essential for determining cause of death and counseling regarding future pregnancies. Severe maceration and fetal size along with patient desires may limit the physician's ability to perform a complete autopsy. In the cases presented, we demonstrate the utility of postmortem ultrasonography as an adjunct to traditional autopsy following fetal demise.
TL;DR: This is the first case of BCM associated with ipsilateral renal agenesis in an adult male and the first male case ofBCM displaying estrogen and progesterone receptor positivity, and reveals the presence of congenital anomalies should be considered in patients with BCM.
Abstract: Benign Cystic Mesothelioma (BCM) is an uncommon peritoneal lesion that usually occurs in reproductive age females with a history of abdominal surgery Occasional expression of estrogen and progesterone receptor in these cells may explain female predilection Reports of BCM in males are rare We describe a case of BCM associated with ipsilateral renal agenesis in a young male without any surgical history The cyst lining stained positive for cytokeratin, Wilms Tumor-1, epithelial membrane antigen, CD10, estrogen receptor, and progesterone receptor, and negative for PAX-8 Only three cases of BCM associated with congenital renal anomalies have been reported To the best of our knowledge, this is the first case of BCM associated with ipsilateral renal agenesis in an adult male and the first male case of BCM displaying estrogen and progesterone receptor positivity Such a case reveals the presence of congenital anomalies should be considered in patients with BCM