PubMed Health⌕ Search

Biomedical subjects

N J Sebire

Publications and source records attributed to N J Sebire.

At least 19 recordsLinked to original sources
PubMed2008

Familial Currarino syndrome presenting with peripheral primitive neuroectodermal tumour arising with a sacral teratoma.

This report illustrates a rare genetic disorder, Currarino syndrome, in association with an unusual malignant transformation to a peripheral primitive neuroectodermal tumour within a sacral teratoma. The triad of features consists of a presacral mass, partial sacral agenesis and anorectal anomalies. The most common presentation is constipation. In this case there was a history of constipation, teratomas and spinal abnormalities in many of the family members over three generations. Detailed family history taken at time of initial presentation may have prevented delay in diagnosis and averted the need for intensive treatment, which may well cause late sequelae.

Child, Preschool↗
PubMed2007

Histomorphometric features of hydatidiform moles in early pregnancy: relationship to detectability by ultrasound examination.

OBJECTIVE: The majority of partial (PHM) and complete (CHM) hydatidiform moles are diagnosed in early pregnancy. About half are identified as molar on ultrasonographic examination prior to evacuation. It is uncertain whether unsuspected cases represent an intrinsically different molar phenotype or are simply dependant on sonographer expertise. We measured a microscopic parameter, average villus diameter, of evacuated PHMs and CHMs to ascertain the cause of non-detection on ultrasound. METHODS: Fifty-four molar pregnancies were examined from the files of the Trophoblastic Disease Unit, in which results of an ultrasound examination prior to evacuation were known. In each, the average cross-sectional diameter of the largest 10 villi was recorded. Maximum villus diameters were compared between gestational age groups (<14 weeks and >or=14 weeks), and ultrasound detection groups (detected (d) and not detected (nd)). RESULTS: The average maximum villus diameter of the largest hydropic villi was significantly less in the first trimester for both PHMs and CHMs that were undetected by ultrasound examination compared to those identified as molar sonographically (P<0.001 and P<0.001, respectively). There was no significant difference in the maximum villus diameter between PHMs and CHMs that were not detected sonographically in the first trimester (P=0.44). Beyond 14 weeks of gestation, there was no significant difference between PHMs detected and undetected sonographically (P=0.88). CONCLUSION: The average diameter of the largest, most hydropic villi, is significantly greater in cases of PHMs and CHMs detected by ultrasound examination in the first trimester compared to that of those not detected sonographically, but beyond 14 weeks such differences are minimal. These findings suggest that, although sonographer expertise could potentially increase ultrasound detection rates somewhat for PHMs and CHMs, a significant proportion of cases demonstrate minimal hydropic change in the first trimester and are therefore likely to remain unidentifiable by ultrasound examination prior to evacuation, even with improved sonographer expertise.

Female↗
PubMed2006

Placental pathology of recurrent spontaneous abortion: the role of histopathological examination of products of conception in routine clinical practice: a mini review.

BACKGROUND: Histopathological examination of products of conception from miscarriages is part of routine clinical practice. The extent of additional clinically relevant information provided by this investigation in the setting of recurrent spontaneous abortion remains uncertain. METHODS: Review of the literature was performed to identify studies reporting on findings of histological examination of routinely obtained products of conception in the setting of recurrent spontaneous abortion. The initial search identified 312 potential references, but 300 were excluded on further examination due to lack of data on specific histopathological findings in routine products of conception specimens from patients with recurrent spontaneous abortion. The 12 included studies indicated that such examination may identify hydatidiform moles, villous dysmorphic features suggesting fetal aneuploidy, chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition and impaired trophoblast invasion. However, in most cases, morphological assessment cannot reliably determine the cause of the miscarriage or distinguish recurrent from sporadic miscarriage. Studies reporting on the use of additional immunohistochemical methods do not currently provide additional clinically useful diagnostic or prognostic information. CONCLUSION: Routine histological examination of products of conception in the setting of recurrent spontaneous abortion can provide important clinical information in a minority of cases.

Abortion, Habitual↗
PubMed2006

Histopathological reporting of paediatric cutaneous vascular anomalies in relation to proposed multidisciplinary classification system.

BACKGROUND: The terminology applied to vascular anomalies has been variable in previously published literature making interpretation suboptimal. The International Society for the Study of Vascular Anomalies (ISSVA) has proposed a revised classification based on clinical features and histopathological findings. This classification is increasingly being accepted as clinically useful and a platform for future studies. AIMS: To examine the extent to which the ISSVA classification can be practically applied to diagnostic histopathological specimens. METHODS: Cutaneous vascular lesions received in a single paediatric pathology unit during a 2-year period (2004-5) were reviewed, including glucose transporter protein 1 (GLUT1) immunostaining where required, and lesions were reclassified according to the ISSVA classification. RESULTS: 144 specimens were identified. Appropriate full clinical information was provided in only 17% of cases at submission. Infantile haemangiomas comprised 46% of cases, 18% of which were regressive type, initially inaccurately identified as vascular malformations before GLUT1 immunostaining. 30% of lymphatic malformations and all lymphovenous malformations were previously classified as vascular malformations, not otherwise specified. CONCLUSIONS: The ISSVA classification of vascular anomalies provides a useful framework for histopathologists to classify vascular anomalies. However, meaningful and appropriate use of such a system is dependent on the adequacy of clinical information provided and routine use of immunohistochemical markers.

Biomarkers, Tumor↗
PubMed2006

Risks of miscarriage and early preterm birth in trichorionic triplet pregnancies with embryo reduction versus expectant management: new data and systematic review.

BACKGROUND: Triplet pregnancies are associated with a high risk of miscarriage and early preterm birth. It is uncertain if the outcome is improved by embryo reduction (ER). METHODS: We examined trichorionic triplet pregnancies with three live fetuses at 10-14 weeks of gestation that were managed expectantly or by ER. The two groups were compared for the rates of miscarriage, defined as pregnancy loss before 24 weeks, and preterm delivery prior to 32 weeks. In addition, systematic searches were performed to identify studies comparing outcomes in expectant management versus ER in triplet pregnancies. RESULTS: We combined data from 365 pregnancies managed in our centre with those of five previous studies. In total there were 893 pregnancies. In the ER group (n=482) compared to the expectantly managed group (n=411), the rate of miscarriage was higher [8.1 versus 4.4%; relative risk (RR)=1.83, 95% confidence interval (CI)=1.08-3.16, P=0.036] and the rate of early preterm delivery was lower (10.4 versus 26.7%, RR=0.37, 95% CI=0.27-0.51, P<0.0001). It was calculated that seven (95% CI=5-9) reductions needed to be performed to prevent one early preterm delivery, while the number of reductions that would cause one miscarriage was 26 (95% CI=14-193). CONCLUSIONS: In trichorionic triplets, ER to twins is associated with an increase in the risk of subsequent miscarriage and decrease in risk of early preterm birth.

Abortion, Spontaneous↗
PubMed2006

Histopathological features of pretreatment neuroblastoma are of limited clinical significance following adjustment for clinical and biological marker status.

Neuroblastic tumours are morphologically classified into broad categories according to defined criteria, with further histopathological features described which may provide prognostic information, such as calcification, mitotic rate and the mitoses-karyorrhexis index; these may be combined with patient age and other factors to indicate high-risk and low-risk groups. However, recently, a range of biological molecular markers have proved to be of major prognostic importance in neuroblastic tumours, including MYCN amplification, 1p deletion, and 17q gain. It is therefore hypothesised that traditional histopathological features are now of limited clinical significance after adjustment for known clinical and biological pregnostic markers. Evidence to evaluate this hypothesis was obtained via a literature search to identify studies reporting on prognostic significance of histopathological features in multivariate analysis after adjustment for biological marker status. Thirteen studies were included of which four (1642 subjects) reported an independent effect of histopathological findings, whereas nine (2385 subjects) reported no significant independent effect. All four studies examining both MYCN and other markers such as 1p, 11q or 17q status, reported no significant independent effect of histological parameters. Histopathological diagnosis remains the gold standard for the diagnosis and evaluation of paediatric tumours but in the evolving era of molecular evaluation of tumours, the role of traditional morphological assessments is likely to become increasingly obsolete, and diagnostic paediatric pathology departments must respond to the changing understanding of the biological basis of childhood malignancies towards routinely providing both diagnostic and molecular prognostic data from these small samples.

Biomarkers, Tumor↗
PubMed2006

Previously unidentified complex cytogenetic changes found in a pediatric case of solid-pseudopapillary neoplasm of the pancreas.

Solid pseudopapillary neoplasm of the pancreas (SPNP) is a rare tumor with low malignant potential found in adolescent girls and young women. The pathogenesis of SPNP remains uncertain and its management is controversial. Genetic changes associated with SPNP have seldom been reported. We describe here the cytogenetic investigation of a case of SPNP in a 13-year-old girl whose tumor cells revealed two unrelated clones: one clone characterized by complex karyotypic changes, including breakpoints in two common fragile sites at chromosome 2, band q33, and chromosome 4, band q31, and the second clone defined by partial monosomy for chromosome X. Loss of heterozygosity for HRAS was also identified by array comparative genomic hybridization (a-CGH). These cumulative changes seem insufficient for activation of cell transformation, but could possibly play a role in priming the cell for future mutagenic events.

Adolescent↗
PubMed2006

Routine pre-evacuation ultrasound diagnosis of hydatidiform mole: experience of more than 1000 cases from a regional referral center.

OBJECTIVES: To examine the accuracy of sonographic findings of routine ultrasound examinations in patients with a proven histological diagnosis of complete or partial hydatidiform mole referred to a supra-regional referral center, and to examine the relationship of sonographic findings to gestational age across the first and early second trimesters. METHODS: Review of consecutive cases referred to a trophoblastic disease unit from June 2002 to January 2005 with a diagnosis of possible or probable hydatidiform mole in whom results of a pre-evacuation ultrasound examination were documented. Ultrasound detection rates for partial and complete hydatidiform moles were calculated and comparison of detection rates between complete and partial mole, and gestational age groups carried out. RESULTS: 1053 consecutive cases were examined. The median maternal age was 31 (range, 15-54) years and the median gestational age was 10 (range, 5-27) weeks. 859 had a final review diagnosis of partial or complete hydatidiform mole (82%), including 253 (29%) complete moles and 606 (71%) partial moles. Non-molar hydropic miscarriage was diagnosed following histological review in 194 (18%). Overall, 378 (44%) cases with a final diagnosis of complete or partial hydatidiform mole had a pre-evacuation ultrasound diagnosis suggesting hydatidiform mole, including 200 complete moles and 178 partial moles, representing 79% and 29%, respectively, of those with complete (253) or partial (606) moles in the final review diagnosis. The ultrasound detection rate was significantly better for complete versus partial hydatidiform moles (Z = 13.4, P < 0.001). There was a non-significant trend towards improved ultrasound detection rate with increasing gestational age, with an overall detection rate of 35-40% before 14 weeks' gestation compared to around 60% after this gestation. The sensitivity, specificity, positive predictive value and negative predictive value for routine pre-evacuation ultrasound examination for detection of hydatidiform mole of any type were 44%, 74%, 88% and 23%, respectively. CONCLUSIONS: Routine pre-evacuation ultrasound examination identifies less than 50% of hydatidiform moles, the majority sonographically appearing as missed or incomplete miscarriage. Detection rates are, however, higher for complete compared to partial moles, and improve after 14 weeks' gestation. Histopathological examination of products of conception remains the current gold standard for the identification of gestational trophoblastic neoplasia.

Adolescent↗
PubMed2006

Myogenin and desmin immunohistochemistry in the assessment of post-chemotherapy genitourinary embryonal rhabdomyosarcoma: prognostic and management implications.

PURPOSE: Posttreatment genitourinary embryonal rhabdomyosarcoma often shows well differentiated rhabdomyoblasts, which are detectable on routine histological staining. Definite areas of residual undifferentiated rhabdomyosarcoma indicate residual/recurrent disease. However, the recent use of immunohistochemical staining with desmin and myogenin in resected specimens and surveillance biopsies following adjuvant therapy may demonstrate scant positive staining cells that appear undifferentiated on light microscopy. To our knowledge the clinical significance of this finding is currently unknown. Therefore, we reviewed our retrospective experience with genitourinary embryonal rhabdomyosarcoma to examine the relationship between immunostain positive undifferentiated cells and subsequent clinical outcome. MATERIALS AND METHODS: A total of 14 children with a median age of 2.75 years (range 8 months to 7 years) with genitourinary embryonal rhabdomyosarcoma were identified in the histopathology database. All had biopsy confirmation of the diagnosis, followed by multi-agent chemotherapy. Two children in whom there was obvious residual active tumor at the resection margins were excluded from further analysis. Histopathological findings in all patients on the resection/posttreatment biopsy were reviewed. All specimens were immunostained with desmin and myogenin to detect residual undifferentiated rhabdomyoblasts. The relation between histopathological findings and outcome was determined. RESULTS: There were 14 cases of genitourinary embryonal rhabdomyosarcoma. In 2 cases (14%) residual embryonal tumor was pathologically confirmed following initial treatment. In 12 cases no obvious residual tumor was present following initial therapy. Rhabdomyosarcoma affected the bladder in 10 cases and the vagina in 2. There were no distant metastases in any child. Ten patients underwent local resection following chemotherapy and 2 underwent followup biopsies only without resection. A total of 11 cases showed well differentiated, posttreatment rhabdomyoblasts that was identifiable on routine hematoxylin and eosin staining with margins apparently free of tumor and 1 showed no morphological evidence of residual rhabdomyosarcoma. However, all cases demonstrated at least scant abnormal desmin and myogenin positive cells in the specimens. Four patients had no further treatment and none had clinical recurrence. All were well 10 years (range 8 to 13) after treatment. Eight patients received further treatment (chemotherapy and/or radiotherapy) based on clinical and pathological findings, followed by further resection in 3. One patient died of disease but 7 were well a median of 7.2 years (range 8 months to 13 years) after treatment. CONCLUSIONS: The significance of undifferentiated myogenin/desmin positive cells in genitourinary embryonal rhabdomyosarcoma in the absence of morphological residual/recurrent embryonal rhabdomyosarcoma remains unclear since such cells can be detected in all cases of posttreatment embryonal rhabdomyosarcoma. In some cases findings are associated with clinical disease recurrence, while others with identical histopathological findings following initial treatment have no clinical sequelae even in the absence of further treatment. In genitourinary embryonal rhabdomyosarcoma close and regular clinical surveillance is essential. Desmin/myogenin immunohistochemistry to detect scattered undifferentiated cells does not appear to provide useful prognostic information.

Child↗
PubMed2006

Renal primitive neuroectodermal tumor in childhood with intracardiac extension.

Primary primitive neuroectodermal tumors of the kidney are exceptionally rare and usually affect children and young adults. We report the first pediatric case of renal primitive neuroectodermal tumor presenting with tumor extension along the inferior vena cava to the right ventricle. This case highlights that when considering a renal tumor with significant intravascular extension in the pediatric age group, although the most likely diagnosis remains Wilms tumor, other rare entities may also demonstrate similar clinical and imaging features.

Child, Preschool↗
PubMed2006

Apparent diffusion coefficient maps of pediatric mass lesions with free-breathing diffusion-weighted magnetic resonance: feasibility study.

PURPOSE: To assess the technical feasibility of apparent diffusion coefficient (ADC) mapping based on free-breathing diffusion-weighted magnetic resonance (DW-MR) outside the CNS in children. MATERIAL AND METHODS: Twelve children with mass lesions of varied histopathology were scanned with short-tau inversion recovery (STIR), contrast-enhanced T1-weighted (CE-T1W), and diffusion-weighted (b=0, 500 and 1000 s/mm2) sequences. ADC maps were calculated. Lesion-to-background signal intensity ratios were measured and compared between STIR/CE-T1W/ADC overall (Friedman test) and between viable embryonal tumors and other lesions (Kruskal-Wallis test). RESULTS: ADC maps clearly depicted all lesions. Lesion-to-background signal intensity ratios of STIR (median 3.7), CE-T1W (median 1.4), and ADC (median 1.6) showed no overall difference (chi-square=3.846; P=0.146), and there was no difference between viable embryonal tumors and other lesions within STIR/CE-T1W/ADC (chi-square 1.118/0.669/<0.001; P=0.290/0.414/1.000, respectively). CONCLUSION: ADC mapping is feasible in free-breathing imaging of pediatric mass lesions outside the CNS using standard clinical equipment.

Adolescent↗
PubMed2006

Absent/reduced glucose transporter-1 protein expression in infantile subglottic haemangiomas.

BACKGROUND: Positive immunohistochemical staining for glucose transporter-1 protein (GLUT1) is a characteristic of cutaneous infantile haemangiomas. OBJECTIVES: To examine GLUT1 expression in subglottic haemangiomas. METHODS: Review of clinical notes and biopsy tissue with immunostaining for GLUT1 in 14 patients with subglottic haemangiomas. RESULTS: GLUT1 immunostaining was negative in 11 cases, and focally positive in three. No subglottic haemangiomas demonstrated the intense diffuse positive GLUT1 staining seen in cutaneous infantile haemangiomas. Five patients had cutaneous as well as subglottic haemangiomas, one of whom had a GLUT1-negative subglottic haemangioma and a GLUT1-positive cutaneous haemangioma of the lip. CONCLUSIONS: Subglottic haemangiomas appear immunohistochemically different from cutaneous infantile haemangiomas, which may reflect differences in endothelial cell differentiation or underlying aetiology.

Glottis↗
PubMed2006

Expression of ETV6-NTRK in classical, cellular and mixed subtypes of congenital mesoblastic nephroma.

AIM: Congenital mesoblastic nephroma (CMN) is the commonest renal tumour of infancy, with classical, cellular and mixed histological subtypes described. A specific ETV6-NTRK3 fusion-gene product is reported in association with the cellular variant. The aim was to investigate the relationship between the presence of this product and morphological phenotype using paraffin-embedded archival material. METHODS AND RESULTS: Cases of CMN from a single centre during a 15-year period (1989-1994) were identified, anonymized and blindly classified using morphological criteria. RNA was extracted from frozen and paraffin sections for both conventional reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. Fifteen samples were analysed; two were non-informative and three expressed ETV6-NTRK3 using both techniques, two showing similar expression, whilst one showed expression two orders of magnitude lower, from a cellular tumour. All fusion positive cases were previously classified as cellular subtype. Six patients had mixed-subtype tumours in which the cellular components, morphologically indistinguishable from cellular tumours, were fusion negative, as were all classical cases. CONCLUSIONS: Real-time PCR Taqman assays, using both fixed and frozen tissue, provide highly reproducible detection and quantification of fusion transcript expression. Differences in expression levels may explain previous conflicting data on fusion gene detection in these tumours.

Humans↗