Gayatri Ravikumar

Placental expression of the insulin receptor binding protein GRB10: Relation to human fetoplacental growth and fetal gender

INTRODUCTION Imprinted genes play an important role in mammalian fetoplacental growth and development. We have evaluated whether the placental expression of two imprinted genes, growth factor receptor-binding protein 10 (GRB10) and pleckstrin homology-like domain, family A, member 2 (PHLDA2) correlate with human fetoplacental growth parameters. METHODS Placentae (n = 77) were collected from small- (SGA) and appropriate- (AGA) for gestational age full-term singleton pregnancies (n = 36 SGA and 41 AGA). Placentae and neonates were weighed at birth. Realtime quantitative PCR was performed to assess placental transcript abundance of GRB10 and PHLDA2 normalized to a panel of reference genes. RESULTS Placental GRB10 transcript abundance associated positively with placental weight (r = 0.307, P = 0.007), birth weight (r = 0.267, P = 0.019) and neonatal head circumference (r = 0.280, P = 0.014). Placental GRB10 transcript levels were significantly lower in male SGA placentae compared to the male AGA placentae. Placental PHLDA2 transcript abundance did not show any associations with maternal, placental or neonatal parameters. DISCUSSION Placental GRB10 expression was found to be associated positively with placental weight, birth weight, and neonatal head circumference, especially in males. Hence, we speculate that placental GRB10 plays a role in regulating fetoplacental growth and thereby in the pathophysiology of fetal growth restriction in the context of fetal gender.

Beneficiary effect of nanosizing ferric pyrophosphate as food fortificant in iron deficiency anemia: evaluation of bioavailability, toxicity and plasma biomarker

Iron deficiency anemia is a global health issue affecting a significant population worldwide. Fortification of food with iron compounds is a widely used strategy to prevent iron deficiency anemia. To overcome sensory effects, water insoluble and white colored compounds, like ferric pyrophosphate, are used to fortify infant cereals. Ferric pyrophosphate is poorly bioavailable due to its low solubility even in an acid medium. Nanosized iron salts find potential applications in food fortification, since solubility increases with decrease in the particle size. However, limited knowledge exists about the effect of nanoparticles in a biological system. The present study addresses the efficacy of synthesized ferric pyrophosphate in its nano form (10–30 nm) as a potential food fortificant in iron deficiency anemia and measures its toxicity in a rat model. Additionally, the effect of the nanoparticle in vivo has been explored using a mass-spectrometry-based plasma proteomics approach. The relative bioavailability of ferric pyrophosphate nanoparticle, calculated using hemoglobin regeneration efficiency was found to be 103.02% with respect to the reference salt, ferrous sulphate. Histopathological examinations of different organs did not show any significant toxicity attributable to nanoparticle ferric pyrophosphate. However, plasma proteomics analysis showed a decreasing trend in Fetuin-B concentration with increasing dose levels of nanoparticle ferric pyrophosphate. In conclusion, the nanoparticle ferric pyrophosphate could be a promising food fortificant in combating iron deficiency anemia, while Fetuin-B, a negative acute phase protein, might be a potential candidate for detecting biological responses to the nanoparticle exposure in vivo.

Primary Synovial Sarcoma of the Mediastinum : A Case Report

Synovial sarcomas commonly occur in the extremities of young adults. A primary occurrence in the mediastinum is very rare with only a few reported cases in the world literature. This paper is about a 42-year-old male who presented with chest pain and dyspnoea on exertion. Imaging showed an anterior mediastinal mass with adhesions to the lung. Pathological examination of the resected mass showed a biphasic neoplasm with a spindle cell component admixed with gland-like elements. The tumour showed positive staining with cytokeratin, epithelial membrane antigen, and Bcl-2 confirming the diagnosis of a biphasic synovial sarcoma. A wide range of neoplasms, both primary and metastatic, occur in the mediastinum, which pose considerable diagnostic difficulties. A synovial sarcoma should always be considered in the differential diagnosis, and immunohistochemistry is an important adjuvant tool in this situation. This paper highlights the importance of recognizing an unusual presentation of this aggressive neoplasm to aid appropriate clinical management.

Vascular endothelial growth factor expression in ovarian serous carcinomas and its effect on tumor proliferation

Introduction: Vascular endothelial growth factor (VEGF), an endothelial mitogen, acts through VEGF receptors (VEGFRs) on the endothelial cells. During neoplastic transformation, it is hypothesized that the tumor expresses VEGF and also acquire VEGF receptor, enabling VEGF action in an autocrine and paracrine manner with varied effects on the tumor growth and progression. This study on ovarian serous carcinomas (OSCs) was done to determine the expression of VEGF and to correlate it with tumor proliferation. Material and Methods: Forty cases of OSCs were included. Immunohistochemistry was performed for VEGF and Ki-67. The VEGF slides were assigned an immunohistochemical score based on the staining intensity (a) and the percentage of tumor cells staining (b). The sum of both (a) and (b) ranged from 0-6. VEGF was considered positive when the score was more than 2. For Ki-67, maximally immunostained areas were selected; 500 cells counted and positive fraction determined. Mann Whitney test was used to determine the difference in the median value of Ki-67 between VEGF positive tumors and VEGF negative tumors. Results: Of the 40 cases, 32 cases had a VEGF score of >2 (positive) and 8 cases had VEGF score <2 (negative). The Ki-67 score ranged from 2-98%, with mean of 51%. The median Ki-67 index was much higher in VEGF positive cases as compared to VEGF negative tumors (57.5% vs. 40%). However, the difference in the two categories did not reach statistical significance (P = 0.45, Mann Whitney test). Conclusion: Ovarian serous carcinomas express VEGF in a significant number of cases (80% in the present study) although its potential mitogenic effect on tumor cells was not confirmed.

Primary pleural non-Hodgkin lymphoma in a child--an exceedingly rare disease.

Primary pleural lymphomas are very rare. Two types are described in the literature: primary effusion lymphoma, in the setting of human immunodeficiency virus infection, and pyothorax-associated lymphomas, with a strong Epstein-Barr virus association. We report a rare case of a primary pleural lymphoma in a 12-year-old immunocompetent girl who presented with a hemorrhagic pleural effusion and had plaque-like thickening of the pleura. The histologic and immunophenotypic findings conformed to that of a diffuse large B-cell lymphoma (CD20 positive).

CD15 as a marker of fetoplacental endothelial immaturity in IUGR placentas

Abstract Background: Structural or functional defects in the placenta, are the primary cause of growth restriction of the fetus. Morphological examination of such placentas from intrauterine growth restricted (IUGR) fetuses often appears deceptively normal. Evaluation of angiogenesis and fetoplacental vasculature is critical to understand the underlying pathogenesis of fetal growth restriction in both idiopathic as well as cases where it is thought to be secondary to complications like preeclampsia (PE). We analyzed the immaturity of fetoplacental vasculature using CD15, which is a stage specific embryonic antigen known to be expressed in immature endothelium. Material and methods: One hundred and twelve placentas (81 from IUGR and 31 from gestationally appropriate samples (appropriate for gestational age (AGA)) were collected based on stringent inclusion criteria, and subjected to detailed examination of morphology and microscopy along with immunostaining for CD15. IUGR placentas known to have villous immaturity such as those associated with gestational diabetes, Rh negative pregnancies and anemia were excluded. The time of clinical onset of IUGR, associated complications like PE and oligohydramnios along with clinical variables were recorded. CD15 expression was scored in both distal and proximal vasculature and the values in IUGR and AGA pregnancies were compared and correlated with clinical variables. Results: The mean CD 15 scores in both proximal vasculature (PV) as well as distal (DV) vasculature were significantly higher in the IUGR group compared to AGA (17.7 versus 5.16 in PV and 50.8 versus 23.7 in distal vasculature (DV)). Gestational age had no influence on CD15 staining in PV or DV in IUGR group, whereas preterm AGAs expressed higher CD15 only in the distal vessels. PE, oligohydramnios and the time of onset of IUGR did not influence the fetal vascular immaturity, as measured by CD15 scores. Although none of the clinical or obstetric factors influenced CD15 staining in AGA, fetal vessel immaturity in the IUGR group remained high even after adjusting for confounding variables like maternal age, gestational age and birth weight. Histological features suggestive of chronic hypoxia were significantly higher in IUGR placentas, compared to AGA and correlated positively with CD15 expression. Conclusion: Fetoplacental endothelium in both PV and DV is immature in IUGR irrespective of the gestational age or any other associated factors and CD15 immunodetection is a valuable marker for assessment of immaturity.

“The Jelly Belly”: Diagnostic Dilemmas and Current Concepts

BackgroundPseudomyxoma peritonei (PMP) is a rare and poorly understood clinicopathological entity characterized by gelatinous ascites with neoplastic or non-neoplastic mucinous implants in the peritoneum. Although its origin was debated, current evidence in literature favours the appendix as the origin of the disease, over the ovaries. The changing terminologies in the classification of this entity pose diagnostic and management challenges.Case ReportsHerein, we report three cases of PMP in postmenopausal women, their clinical presentation, pathological staging based on the peritoneal tumor deposits and the treatment administered. Two patients recovered uneventfully, while one had recurrence of adenocarcinoma.ConclusionThe rarity of this disease and the diagnostic challenges associated with it are discussed with an emphasis on the current concepts in its origin and management. Appropriate classification and complete removal of the tumor is mandated to prevent disease-related mortality.

Placenta in intrauterine fetal demise (IUFD): a comprehensive study from a tertiary care hospital

Abstract Background: Intrauterine fetal demise (IUFD) is an unpredictable and challenging obstetric complication. Its etiology is multifactorial with more than 60% attributed to the placental cause. The present study was done with a primary objective of understanding the placental lesions underlying IUFD. Methods: In this retrospective observational study, IUFD cases (>22 weeks) between January 2012 and September 2015 were collected from pathology database. The clinical details with ultrasound findings were collected from mother’s charts. The lesions were classified into (A) maternal vascular malperfusion (MVM) including retroplacental hematomas, (B) fetal vascular malperfusion (FVM), (C) inflammatory lesions, and (D) idiopathic. The contributor to fetal death was classified as direct, major, minor, unlikely, or unknown. Placental findings of fetal hypoxia were recorded. Results: The study included 100 cases of IUFD. The mean maternal age was 26 years (18–36 years). Primipara were 46. There were 65 early preterm (PT) (<34 weeks), 20 late PT (34 weeks to <37 weeks) and 15 term (>37 weeks) IUFD. The mean gestation age was 30 weeks. The ratio of male:female fetuses was 1:1.7. Relevant obstetric complications included preeclampsia (n = 39), intrauterine growth restriction (IUGR) (n = 7), pre-gestational diabetes (n = 7), bad obstetric history (n = 6), oligohydramnios (n = 5). The mean placental weight was 256 g. Maternal vascular malperfusion had the highest incidence (30%), followed by combined maternal and FVM (10%). Exclusive inflammatory lesions and FVM were seen in 12 and 6%, respectively. No cause was identified in 18%. Direct contributor to IUFD was identified in 51 cases and major, minor, unlikely contribution in 21, 11 and nine cases, respectively. In nine cases, it was unknown. Lesions indicating fetal hypoxia were noted in 35 cases. In both early and late PT, MVM featured more commonly (23 and 5%). In term placentas, the most common cause was idiopathic. Conclusions: Lesions of MVM were the most common cause of IUFD and served as a direct contributor to fetal demise.

Comparison of clinical diagnosis with histopathology in inflammatory skin diseases: a retrospective study of 455 cases

Background Skin biopsies are performed to support the clinical diagnosis of inflammatory skin diseases. Clinical information is conveyed to the pathologist as a list of differential diagnosis. Aims The aims of this article are to correlate the clinical diagnosis with histopathologic diagnosis and to determine the correlation rank order of differentials with histopathologic diagnosis. Methods Four hundred and fifty-five skin biopsies signed out as inflammatory lesions were identified using the laboratory information system. Clinical differential diagnosis from the biopsy requisition forms were tabulated and compared with the final histopathologic diagnosis. Results Out of the 455 individuals considered, 237 (52.08%) were men and 218 (47.9%) were women. The clinical diagnosis with more than 40 mentions included vasculitis, lichenoid dermatitis, discoid lupus erythematosus, psoriasis and eczema. The histopathologic diagnosis with more than 20 mentions included lichenoid dermatitis, cutaneous vasculitis, pemphigus vulgaris, psoriasis and Hansen’s disease. The median number of differential diagnosis per patient was 3 (range: 1–5). The final diagnosis was included in the differentials in 412 (90.5%) and absent in 43 (9.5%) cases. In 339/412 (82.3%) cases, the final diagnosis was the first differential. In 70/412 (16.9%) cases, the final diagnosis was listed as the second or third differential and in 3/412 (0.007%) cases as the fourth and fifth. Among the 37 discordant cases where the clinical details were available, the clinical description correlated with the final diagnosis in 15 cases; clinical and histopathologic diagnoses fell under the same broad disease category in 19 cases. Only 3/37 cases were truly discordant. Limitations The sample size and the possibility of lesions being overbiopsied are the only possible limitations. Conclusion The overall concordance between the first three clinical diagnosis and histopathology was a good 98%. A longer list of differential diagnosis is not helpful. In situations where a specific clinical diagnosis is deferred, an accurate description of the lesions aids the pathologist.

Expression of adhesion molecule epithelial cadherin and matrix metalloproteinase-9 in squamous neoplasia of the uterine cervix

Background: The objective of the study was to evaluate the expression of cell adhesion molecules [epithelial cadherin (E-cadherin)] and extracellular matrix protease [matrix metalloproteinase (MMP)-9] in preinvasive and invasive lesions of squamous neoplasia of the uterine cervix. Method: The study included 14 cases of cervical intraepithelial neoplasia (CIN) and 43 cases of squamous cell carcinoma (SCC). Immunohistochemistry (IHC) testing was performed for E-cadherin and MMP-9 using the polymer technique. The pathological prognostic parameters, like tumour grade, stage, lymphovascular space invasion and mitosis were compared with the expression of these markers. Results: The mean age of the patients with CIN was 40.1 years, and 50.9 years for those with SCC. Complete uniform membranous expression of E-caherin was demonstrated in the normal epithelium and most CIN (79%). MMP-9 was not expressed in the normal epithelium, whereas 43% of CIN (of which 67% were CIN grade III) were positive. Loss of membranous E-cadherin was shown in 88% of SCC, and MMP-9 with variable intensities expressed in 74%. A statistically significant association was established between the expression of these immune markers in preinvasive and invasive lesions, although there was no significant association with the prognostic parameters. In addition, the loss of E-cadherin was evident in patients with recurrence, while the expression of MMP-9 was demonstrated in 60%. Conclusion: The loss of membranous E-cadherin and the gain of cytoplasmic MMP-9 are markers of neoplastic transformation in squamous neoplasia of the uterine cervix. However, the expression of these immune markers in our study did not relate to the prognostic parameters, indicating the importance of these markers in early neoplastic transformation.