Faisal Qureshi

Amniotic Infection Syndrome: Nosology and Reproducibility of Placental Reaction Patterns

Clinically responsive placental examination seeks to provide useful information regarding the etiology, prognosis, and recurrence risk of pregnancy disorders. The purpose of this study was to assemble and validate a complete set of the placental reaction patterns seen with amniotic fluid infection in the hope that this might provide a standardized diagnostic framework useful for practicing pathologists. Study cases (14 with amniotic fluid infection, 6 controls) were reviewed blindly by six pathologists after agreement on a standard set of diagnostic criteria. After analysis of initial results, criteria were refined and a second, overlapping set of cases were reviewed. Majority vote served as the gold standard. Grading and staging of maternal and fetal inflammatory responses was found to be more reproducible using a two- versus three-tiered grading system than a three- versus five-tiered staging system (overall agreement 81% vs. 71%). Sensitivity, specificity, and efficiency for individual observations ranged from 67–100% (24/30 > 90%). Reproducibility was measured by unweighted kappa values and interpreted as follows: < 0.2, poor; 0.2–0.6, fair/moderate; > 0.6, substantial. Kappa values for the 12 lesions evaluated in 20 cases by the six pathologists were: acute chorioamnionitis/maternal inflammatory response (any, 0.93; severe 0.76; advanced stage, 0.49); chronic (subacute) chorioamnionitis (0.25); acute chorioamnionitis/fetal inflammatory response (any, 0.90; severe, 0.55; advanced stage, 0.52); chorionic vessel thrombi (0.37); peripheral funisitis (0.84); acute villitis (0.90); acute intervillositis/intervillous abscesses (0.65), and decidual plasma cells (0.30). Adoption of this clearly defined, clinically relevant, and pathologically reproducible terminology could enhance clinicopathologic correlation and provide a framework for future clinical research.

Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome

Objective: To determine whether there is a relationship between the presence of histological signs of inflammation in the extraplacental membranes and umbilical cord and the concentrations of fetal plasma interleukin-6 (IL-6). Methods: The study examined a cohort of patients who were admitted with preterm labor or preterm premature rupture of the membranes (PROM) and who underwent cordocentesis. Inclusion criteria included fetal plasma available for IL-6 determination, histological examination of the umbilical cord and placenta, and delivery within 48 h of the procedure. This last criterion was used to preserve a meaningful temporal relationship between fetal plasma IL-6 and the results of histological examination of the placenta. Fetal plasma IL-6 was determined by a high sensitivity ELISA. Forty-five patients were available for study: 18 patients had preterm labor with intact membranes and 27 had preterm PROM. Results: The incidence of funisitis was 44.4% (20/45): 27.8% (5/18) in patients with preterm labor and intact membranes and 55.6% (15/27) in patients with preterm PROM. The median values of fetal plasma IL-6 in patients with funisitis, chorioamnionitis without funisitis, and non-inflamed membranes were 51.4, 18.4 and 5.2 pg/ml, respectively. After log transformation of the fetal plasma IL-6 concentration, the means differed significantly from each other (ANOVA, p < 0.02). There was no difference in log fetal plasma IL-6 concentration between patients with funisitis and those with chorioamnionitis without funisitis. The difference in mean concentration of log fetal plasma IL-6 between patients with funisitis or chorionic vasculitis and those without inflammation was highly significant (post-hoc test, p = 0.01 and p < 0.01, respectively). Fetuses with fetal plasma IL-6 > 11 pg/ml had a significantly higher rate of histological signs of inflammation in the extraplacental membranes and umbilical cord than those with fetal plasma IL-6 < 11 pg/ml (funisitis: 55.6% (15/27) vs. 27.8% (5/18), p < 0.05; chorionic vasculitis: 55.6% (15/27) vs. 12.5% (2/16), p < 0.01; chorioamnionitis only: 25.9% (7/27) vs. 16.7% (3/18), p < 0.05; no inflammation: 18.5% (5/27) vs. 55.6% (10/18), p < 0.05, respectively). Fetuses with funisitis had significantly higher rates of clinical and histological chorioamnionitis, and neonatal infectious morbidity (proven + suspected sepsis) than fetuses without funisitis (40% (8/20) vs. 8% (2/25), 90% (18/20) vs. 36% (9/25), and 40% (8/20) vs. 4% (1/25), respectively; p < 0.01 for each). Fetuses with chorionic vasculitis had significantly higher rates of clinical and histological chorioamnionitis as well as neonatal infectious morbidity (proven + suspected sepsis) than fetuses without chorionic vasculitis (100% (17/17) vs. 42.3% (11/26), p < 0.01; 82.4% (14/17) vs. 50.0% (13/26), p = 0.05; and 41.2% (7/17) vs. 7.7% (2/26), p = 0.01). Conclusion: Fetal plasma IL-6 concentration is significantly associated with the presence of inflammatory lesions in the extraplacental membranes and umbilical cord. Fetuses with fetal plasma IL-6 > 11 pg/ml had a significantly higher rate of funisitis and/or chorionic vasculitis than fetuses with fetal plasma IL-6 < 11 pg/ml. These findings suggest that funisitis/chorionic vasculitis is the histological manifestation of the fetal inflammatory response syndrome.

Ovarian cancer: changes in patterns at diagnosis and relative survival over the last three decades

OBJECTIVE The purpose of this study was to examine patterns of diagnosis and relative survival in women who had a diagnosis of primary invasive epithelial ovarian cancer (EOC) from 1973 to 1997, with follow-up through the end of 1999. STUDY DESIGN From the population-based Surveillance, Epidemiology and End Results (SEER) Program, 32,845 women diagnosed between 1973 and 1997 were used for analysis. The study population was divided in three cohorts based on year of diagnosis and the cohorts were compared with respect to variables of interest by using chi(2) tests and relative survival analysis by the life table method. RESULTS There was an increase in the proportions of minorities diagnosed with EOC, of women 60 years or older at diagnosis, and of women undergoing surgery over time. Survival continuously improved over time, although older patients (60 years or older) and African Americans continued to have the poorest survival. CONCLUSION Over time, relative survival of women who had primary invasive EOC diagnosed improved.

Sequential urinalysis improves evaluation of fetal renal function in obstructive uropathy

OBJECTIVES The purpose of our study was to determine whether sequential vesicocenteses improve the evaluation of renal damage, compared with single urine sampling in obstructive uropathy. STUDY DESIGN A total of 29 fetuses with complete obstructive uropathy underwent a minimum of three sequential complete vesicocenteses at 48- to 72-hour intervals. First and last urine values were analyzed for multiple parameters. The ability of first versus last urine values to detect the presence of renal damage was compared according to postnatal or fetal autopsy information. RESULTS Fetuses with minimal renal damage had patterns of decreasing hypertonicity and last urine values below cutoff thresholds indicative of favorable prognosis. Fetuses with significant renal damage had higher initial values and patterns of increasing hypertonicity. For five of six parameters, last urine samples were more predictive of renal damage than first urine samples. CONCLUSION Last urine values together with pattern-of-change trend analysis after serial vesicocenteses improve diagnostic precision in fetuses with complete obstructive uropathy.

Pre-eclampsia and expression of heparin-binding EGF-like growth factor

BACKGROUND Pre-eclampsia is a disorder of pregnancy associated with poor extravillous cytotrophoblast invasion and above-normal rates of apoptosis in the trophoblast. Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) has strong cytoprotective activity and is an important signalling protein that regulates trophoblast invasion during early placentation. We aimed to establish whether HB-EGF expression is altered in placentae of pre-eclamptic women. METHODS We assessed the expression of HB-EGF mRNA and protein by in-situ hybridisation and immunohistochemical techniques, respectively, in archived placental tissues from pregnancies terminated at around 20 weeks of gestation, and from women delivering between weeks 19 and 35 of gestation with preterm labour, small for gestational age infants, or pre-eclampsia. FINDINGS HB-EGF mRNA and protein were expressed in villous and extravillous cytotrophoblast cells up to week 35 of gestation in placentae from women who delivered preterm. Similar levels of HB-EGF protein were found in the placentae of women who were not in labour. HB-EGF expression was reduced about five-fold (p=0.0001) in pre-eclamptic pregnancies. Fetal growth retardation, which has been linked with shallow trophoblast invasion and moderate apoptosis, was associated with placentae expressing intermediate levels of HB-EGF. INTERPRETATION In pre-eclampsia, deficient HB-EGF signalling during placental development could impair trophoblast survival, differentiation, and invasion, leading to poor placental perfusion and hypertension.

Vulvar vestibulitis subjects undergoing surgical intervention: a descriptive analysis and histopathological correlates

OBJECTIVE We describe here a series of selected patients from an established vaginitis research clinic diagnosed with vulvovestibulitis (VV) who underwent surgical intervention for focal disease. Long-term results of surgical correction are reported and characteristic histopathology findings associated with vulvar vestibulitis are emphasized. STUDY DESIGN A retrospective chart review was carried out to extract relevant clinical, histologic, and outcome data. Tissue blocks of resected specimens were re-examined for specific inflammatory response. RESULTS Complete data and long-term follow up were available in 16 patients who underwent surgical intervention. All were cared for by the same practitioner (CM). The mean (+/- S.D.) age and gravidity on presentation were 26.9 +/- 5.3 years and 0.9 +/- 1.5, respectively. All but one was caucasian, and 70% were nulliparous. Symptoms included entry dyspareunia (100%), discharge (70%), burning (66%), itching (20%) and other (30%). All patients had focal tenderness; other findings were erythema (50%), acetowhite staining (80%), edema (20%), micropapules (20%) and condyloma (10%). After diagnosis, initial duration of conservative management was 9.4 +/- 6.9 months (1-26 months). No patients received interferon therapy. Because of persistent symptoms the 16 subjects underwent targeted partial perineoplasties. Initial histopathology results revealed chronic inflammation, parakeratosis, hyperkeratosis, edema, koilocytosis and acanthosis. When tissue blocks were cut and stained with Giemsa, large numbers of mast cells were identified. Mean postoperative follow up was 42.0 +/- 22.4 months (10-70 months). Follow up after surgery showed an overall improvement in 15/16 patients (93.8%). CONCLUSIONS VV affects primarily white, nulliparous women. In the carefully selected subject, surgical intervention has a high success rate, even on long-term follow up. Although the exact etiology for this condition has yet to be elucidated, the presence of mast cells supports an association with other genitourinary inflammatory syndromes such as interstitial cystitis; and allows for speculation about a possible role played by mast cell activation in the etiology of VV.

Chronic chorioamnionitis: A clinicopathologic and immunohistochemical study

Lymphocytic inflammation of the fetal membranes is unusual and has been termed chronic chorioamnionitis. We report the clinicopathologic and immunohistochemical findings in 31 placentas with chronic chorioamnionitis. The most common histopathologic association was chronic villitis of unknown etiology, which was identified in 22 (71%) of the 31 placentas. The severity of the chronic villitis did not correlate with the severity of chronic chorioamnionitis. Additional placental findings included chronic intervillositis in two, fetal vessel thrombosis in five, hemorrhagic endovasculitis in four, decidual chronic vasculitis in three, and atherosis in one. Maternal history included pregnancy-induced hypertension in six and diabetes in one. Twelve infants were preterm, and five had intrauterine growth retardation. There was no neonatal sepsis or death. Immunohistochemical staining in areas of chronic chorioamnionitis showed CD3+ and CD8+ cells present in moderate numbers, and CD4+ cells in smaller numbers. CD20+ and CD56+ cells were rare or absent. Chronic chorioamnionitis is commonly associated with chronic villitis of unknown etiology, shares similar clinical associations, and may have a related cause, possibly immunologic.

Chronic deciduitis in the placental basal plate: Definition and interobserver reliability

This study tested whether concordance could be achieved for abnormal inflammation in the basal decidua of placental specimens among 6 pathologists experienced in placental pathology. Thirty microscope slides were evaluated by the pathologists for chronic deciduitis. They also scored the severity and extent of inflammation and the presence of plasma cells. No definition of chronic deciduitis was provided. Concordance (5/6 or 6/6 agreement) was achieved in 23 cases (76%). Spearmans rank correlation showed that the diagnosis of chronic deciduitis was almost identical to the assessment of the severity of the inflammation. A regression analysis showed that the perception of severity (and hence chronic deciduitis) was influenced by the other 2 variables, extent and plasma cells. The results were shared with the pathologists, and 25 cases (excluding those with previous 6/6 consensus) were reevaluated. Concordance was now achieved in the 83% of those remaining cases. Using a threshold based on the severity and the extent of lymphocytes, and the presence of plasma cells, pathologists are able to diagnose chronic deciduitis with sufficient concordance to be of value in clinical correlation studies.

Interinstitutional surgical pathology review in gynecologic oncology: II. Endometrial cancer in hysterectomy specimens

SummaryDuring an 8-year period, 76 post-hysterectomy women with endometrial cancer were referred to our institution for evaluation or treatment, and had slides from the hysterectomy specimen sent for review at the request of the gynecologic oncologist (interinstitutional consultation). The original diagnosis was retrospectively compared to the review diagnosis and discrepancies were recorded. The most frequent discrepancy, identified in 24 (31.6%) of the 76 cases, involved assessment of myometrial invasion; 19 of these 24 had an original diagnosis of inner or middle third myometrial invasion and a review diagnosis of no myometrial invasion. The main reason for this discrepancy was irregularity of the endomyometrial junction, or, less commonly, extension of tumor into superficial adenomyosis. Additional discrepancies noted in 11 (14.4%) of the 76 cases included: 1) histologie tumor classification in 6 (7.9%); 2) assessment of angiolymphatic space invasion in 2 (2.6%); 3) identification of meta-static carcinoma in 1 (1.3%); and 4) change in diagnosis from adenocarcinoma to complex atypical hyperplasia and atypical polypoid adenomyoma in 1 each (2.6%). A significant subgroup of patients in this series had modifications in diagnosis; the most frequent discrepancy involved overdiagnosis of myometrial invasion, underscoring the difficulty sometimes encountered in this determination.

Diagnosis of congenital syphilis from placental examination: Comparison of histopathology, steiner stain, and polymerase chain reaction for Treponema pallidum DNA

Congenital syphilis is often a presumptive diagnosis (based on serologies), because confirmation requires identification of Treponema pallidum in fetal/neonatal tissues or in the placenta. Placental histological features associated with congenital syphilis include the triad of enlarged hypercellular villi, proliferative fetal vascular changes, and acute or chronic villitis. The authors blindly evaluated 49 formalin-fixed, paraffin-embedded placentas (38 with positive maternal syphilis serologies; 11 with negative serologies) and compared results of histology, Steiner stain, and polymerase chain reaction (PCR) for T pallidum DNA. Histology was categorized as positive (triad present), suspicious (two thirds of triad present), or negative. Treponemal DNA was detected by amplifying a 189 base pair region of the 47 kd treponemal membrane antigen with 44 cycles of PCR; products were detected by Southern blot. Placentas from the 11 seronegative mothers were all negative by histology, Steiner stain, and PCR. Among the 38 placentas from serologically positive mothers, 4 had positive histology (2 of 4 positive Steiner, 4 of 4 positive PCR); 6 had suggestive histology (0 of 6 positive Steiner; 1 of 6 positive PCR); and, 28 had negative histology (0 of 28 positive Steiner; 1 of 28 positive PCR). PCR identification of treponemal DNA was significantly associated with the triad (P = .0003), proliferative fetal vascular changes (P = .0003), acute villitis (P = .003), chronic villitis (P = .004), and spirochetes on Steiner stain (P = .01). These results (1) confirm a strong association between placental histopathologic features and congenital syphilis; (2) indicate that when such features are present, PCR of placental tissue may confirm the diagnosis of congenital syphilis; and (3) suggest that even when such features are absent, PCR of placental tissue may identify additional cases of histologically unsuspected congenital syphilis.