Dissecting the gray zone between follicular lymphoma and marginal zone lymphoma using morphological and genetic features.

Nodal marginal zone lymphoma is a poorly defined entity in the World Health Organization classification, based largely on criteria of exclusion and the diagnosis often remains subjective. Follicular lymphoma lacking t(14;18) has similar characteristics which results in a major potential diagnostic overlap which this study aims to dissect. Four subgroups of lymphoma samples (n=56) were analyzed with high-resolution array comparative genome hybridization: nodal marginal zone lymphoma, t(14;18)-negative follicular lymphoma, localized t(14:18)-positive follicular lymphoma and disseminated t(14;18)-positive follicular lymphoma. Gains on chromosomes 7, 8 and 12 were observed in all subgroups. The mean number of aberrations was higher in disseminated t(14;18)-positive follicular lymphoma than in localized t(14:18)-positive follicular lymphoma (P<0.01) and the majority of alterations in localized t(14:18)-positive follicular lymphoma were also found in disseminated t(14;18)-positive follicular lymphoma. Nodal marginal zone lymphoma was marked by 3q gains with amplifications of four genes. A different overall pattern of aberrations was seen in t(14;18)-negative follicular lymphoma compared to t(14;18)-positive follicular lymphoma. t(14;18)-negative follicular lymphoma is characterized by specific (focal) gains on chromosome 3, as observed in nodal marginal zone lymphoma. Our results support the notion that localized t(14:18)-positive follicular lymphoma represents an early phase of disseminated t(14;18)-positive follicular lymphoma. t(14;18)-negative follicular lymphoma bears aberrations that are more like those in nodal marginal zone lymphoma, suggesting a relation between these groups.

Macroscopic and microscopic morphology of first trimester miscarriage and subsequent pregnancy outcome - An exploratory study.

INTRODUCTION: Reduced chorionic villous vascularization is associated with first trimester miscarriage and second trimester fetal loss. Differences in villous vascularization have been observed in combination with complications in the third trimester of pregnancy. The aim of this study was to investigate whether abnormal morphology and reduced chorionic villous vascularization in first trimester miscarriages are associated with an increased risk on adverse outcome and/or pregnancy complications in subsequent pregnancy. Secondly, to assess the influence of these parameters on the length of the interpregnancy interval and infertility. METHODS: In a retrospective cohort study 134 consecutive women who underwent dilatation and curettage for a miscarriage were included. The degree of chorionic villous vascularization in miscarriage tissue was determined by a pathologist. Ultrasound details of these miscarriages and clinical data on the subsequent pregnancy of these women were obtained. RESULTS: Neither reduced vascularization nor early embryonic arrest in first trimester miscarriages are associated with an increased risk of a subsequent miscarriage or adverse obstetric and perinatal outcome of subsequent pregnancy. Abnormal morphology of the first trimester miscarriage did not influence the time to subsequent pregnancy. A shorter mean interpregnancy interval between miscarriages was observed after miscarriages with reduced chorionic villous vascularization (5.5 vs. 10.7 months; p = 0.051), showing a trend towards an association. DISCUSSION: Chorionic villous vascularization and morphology have no influence on subsequent pregnancy outcome. Therefore it remains unknown what aspects of miscarriage are causing the increased risk on subsequent miscarriage and complications in the third trimester of the subsequent pregnancy.

Diagnosing perforated appendicitis in pediatric patients: a new model.

OBJECTIVE: Studies have investigated sensitivity and specificity of symptoms and tests for diagnosing appendicitis in children. Less is known with regard to the predictive value of these symptoms and tests with respect to the severity of appendicitis. The aim of this study was to determine the predictive value of patient's characteristics and tests for discriminating between perforated and nonperforated appendicitis in children. PATIENTS AND METHODS: Pediatric patients who underwent an appendectomy at Spaarne Hospital Hoofddorp, the Netherlands, between January 1, 2009 and December 31, 2013, were included. Baseline patient's characteristics, history, physical examination, laboratory data and results of ultrasounds were collected. Univariate and multivariate logistic regressions were used to determine predictors of perforation. RESULTS: In total, 375 patients were included in this study of which 97 children (25.9%) had significant signs of perforation. Univariate analysis showed that age, duration of complaints, temperature, vomiting, CRP, WBC, different findings on ultrasound and the diameter of the appendix were good predictors of a perforated appendicitis. The final multivariate prediction model included temperature, CRP, clearly visible appendix and free fluids on ultrasound and diameter of the appendix and resulted in an area under the curve (AUC) of 0.91 showing sensitivity and specificity of respectively 85.2% and 81.2%. CONCLUSION: This prediction model can be used for identification of 'high-risk' children for a perforated appendicitis and might be helpful to prevent complications and longer hospitalization by bringing these children to theater earlier.

Abnormal development of the vasculosyncytial membrane in early pregnancy failure.

OBJECTIVE: To investigate chorionic villous vasculogenesis (maturation) and development of the vasculosyncytial membrane (margination) using CD34 immunohistochemistry. DESIGN: Case-control study. SETTING: Microscopic analysis of first trimester chorionic villi. PATIENT(S): Twelve patients with anembryonic pregnancies, 12 with embryonic death, and 12 with terminated normal pregnancies. INTERVENTION(S): Quantitative analysis of chorionic villi blinded to group and gestational age using CD34 immunohistochemistry. MAIN OUTCOME MEASURE(S): Vascular parameters (mean functional vascular area, vessels with a lumen, and hemangiogenetic cords, peripherally or centrally located). RESULT(S): Terminated normal pregnancies show significantly more vessels per chorionic villus (maturation) (mean +/- SEM) in comparison with embryonic deaths and anembryonic pregnancies (5.3 +/- 0.3 vs. 1.4 +/- 0.2 and 0.7 +/- 0.1), located mainly peripherally (margination) (3.0 +/- 0.2 vs. 0.9 +/- 0.2 and 0.2 +/- 0.0). Anembryonic pregnancies show significantly more centrally located cords in comparison with embryonic deaths and termination of pregnancies (3.3 +/- 0.2 vs. 2.7 +/- 0.2 and 1.5 +/- 0.1). CONCLUSION(S): A defective chorionic villous vascularization, demonstrating inadequate vasculogenesis and abnormal development of the vasculosyncytial membrane, is seen in pregnancies complicated by embryonic death and is even more pronounced in anembryonic pregnancies. Initiation of placental vasculogenesis is a basic feature in all types of pregnancy and is subsequently modulated directly or indirectly by embryonic signaling.

p16(INK4a) immunostaining as an alternative to histology review for reliable grading of cervical intraepithelial lesions.

BACKGROUND: Histomorphological grading of cervical intraepithelial neoplasia (CIN) is crucial for clinical management. CIN grading is however subjective and affected by substantial rates of discordance among pathologists, which may lead to overtreatment. To minimise this problem, a histology review of CIN lesions by a consensus panel of pathologists is often used. Diffuse strong p16(INK4a) immunostaining has been proposed to aid the identification of true high-grade cervical lesions (ie, CIN2/3). AIM: To assess the value of additional interpretation of p16(INK4a) immunostains for making a more reproducible diagnosis of CIN2/3 lesions. METHODS: The authors used a series of 406 biopsies of cervical lesions, with known HPV status, stained for both H&E- and p16(INK4a). First, in a randomly selected set of 49 biopsies, we examined the effect of additional interpretation of p16(INK4a) immunostained slides, on the agreement of CIN diagnosis among three pathologists. Second, the full series of samples was used to assess the accuracy of p16(INK4a)-supported lesion grading by a single pathologist, by evaluating the degree of diagnostic agreement with the consensus diagnosis of expert pathologists based on H&E-stained sections only. RESULTS: The study shows that the interobserver agreement between three pathologists for the routine H&E-based diagnosis ranged from fair (weighted kappa 0.44 (95% CI 0.19 to 0.64)) to moderate (weighted kappa 0.66 (95% CI 0.47 to 0.79)). The concordance increased substantially for p16(INK4a)-supported grading (mean weighted kappa 0.80 (95% CI 0.66 to 0.89)). Furthermore, an almost perfect agreement was found between the p16(INK4a)-supported diagnosis of a single pathologist and the consensus diagnosis of an expert pathology panel (kappa 0.88 (95% CI 0.85 to 0.89)). CONCLUSIONS: These data demonstrate that additive use of p16(INK4a) immunohistochemistry significantly improves the accuracy of grading CIN lesions by a single pathologist, equalling an expert consensus diagnosis. Hence, the authors advocate the combined use of p16(INK4a)-stained slides and conventional H&E sections in routine histopathology to improve accuracy of diagnosis.

Severe complication after termination of a second trimester cervical pregnancy.

OBJECTIVE: To report a supracervical hysterectomy performed after a life-threatening hemorrhage due to an attempted surgical termination at a gestational age of 18 weeks, which appeared to be a cervical pregnancy. DESIGN: Case report. SETTING: Teaching hospital. PATIENT(S): A 36-year-old pregnant woman, with two previous cesarean sections. INTERVENTION(S): Supracervical hysterectomy. MAIN OUTCOME MEASURE(S): Not applicable. RESULT(S): A stable patient. CONCLUSION(S): By missing a cervical pregnancy in the second trimester, a life-threatening hemorrhage occurred after an attempted surgical termination. In case of failure of the conservative therapy this rare diagnosis should be considered. A supracervical hysterectomy at this gestational age is the only therapeutic option.