Philip J. Katzman

Management of gastrointestinal lymphoma

Despite numerous effective chemotherapeutic regimens developed to treat non-Hodgkin’s lymphoma (NHL), it remains the sixth most common cause of cancerassociated deaths in the United States. Estimates from the American Cancer Society project that about 53,000 new cases of NHL will be diagnosed in the United States in 2002 and approximately half of those afflicted will die of their disease. The incidence of NHL has increased greatly since the early 1980s, in large part from increased HIV disease, though ubiquitous environmental and toxic exposures have also been implicated. NHL is more common in men (M/F ratio 1.5/1). The incidence of NHL in younger white men (ages 18 to 45) has stabilized since 1997 but might be increasing in both women and African Americans. Extranodal lymphoma, or lymphoma arising within solid organs, occurs in up to 40% of all cases. The gastrointestinal (GI) tract is the most frequently involved extranodal site, accounting for up to half of all extranodal cases. Lymphomas can involve any part of the GI tract from oral cavity to rectum. Surgical resection can play an important role in the diagnosis and treatment of NHL involving the GI tract. The surgeon should maintain a high index of suspicion for GI lymphomas and appreciate the critical role surgery might play in obtaining an accurate diagnosis and successfully managing these malignancies. This article reviews GI lymphomas with particular emphasis on the role of surgery as part of a multidisciplinary approach to the diagnosis and management of NHL.

Pathologic examination of the placenta and observed practice.

OBJECTIVE: To estimate the percentage of deliveries eligible for pathologic examination of the placenta and compare with observed practice using the College of American Pathologists’ (CAP) 1997 guidelines for examination of the placenta. METHODS: Records were reviewed from all live-birth deliveries 20 weeks or more of gestation in 2001 at Strong Memorial Hospital. The expected number of deliveries with CAP recommended indications was determined and compared with the observed number of deliveries in which the placenta was actually examined. Descriptive statistics, independent t tests, &khgr;2 tests, difference between two population proportions test, odds ratios, 95% confidence intervals, and multiple logistic regression were used to analyze the data. RESULTS: The observed number and percentage of deliveries with CAP recommended indications that had pathologic placental examination, 575 and 18.2% (95% confidence interval 16.9–19.6), was significantly lower (P<.001) than expected, 1,185 and 37.5% (95% confidence interval 35.8–39.2). The placenta was examined less frequently than expected in 9 of 14 categories. Independent predictors of examination of the placenta were gross placental abnormalities, multiple gestation, prematurity, peripartum fever, neonatal intensive care unit care of infant, cesarean delivery, and delivery by a maternal–fetal medicine specialist. CONCLUSION: Using the CAP guidelines for submission of the placenta would result in pathologic examination in 37.5% of all deliveries. Less than one half of all deliveries in which the placenta was eligible for submission were actually examined. Current advances in our understanding of pathologic conditions of the placenta and their relation to infant outcomes may warrant reevaluating policy on placental examination at institutional and national levels. LEVEL OF EVIDENCE: II

Chronic inflammatory lesions of the placenta

The chronic inflammatory lesions of the placenta often run in the shadows of the better-known acute inflammatory processes of the placenta, such as acute chorioamnionitis and acute funisitis. A heterogeneous population of T-cell lymphocytes, plasma cells, and macrophages is the primary player in chronic villitis, chronic chorioamnionitis, chronic deciduitis, and chronic intervillositis, and eosinophils are an added component of eosinophilic/T-cell chorionic vasculitis. The histologic appearance, sites of occurrence in the placenta, and pathogeneses of these entities are reviewed.

Accuracy of signs of clinical chorioamnionitis in the term parturient

Objective:Uniform histopathologic guidelines were applied to diagnose chorioamnionitis and estimate the accuracy of clinical signs in term parturients.Study Design:A retrospective cohort study utilized slides from term parturient placentas with Amniotic Fluid Infection Nosology Committee guidelines as the gold standard. Sensitivity, specificity and accuracy for fever, maternal tachycardia and fetal tachycardia were calculated.Result:Of 641 placentas, 367 (57.3%) had histologic chorioamnionitis and 274 (42.7%) were negative. Fever had a sensitivity of 42%, specificity of 86.5% and accuracy of 61%. Fever, maternal tachycardia and fetal tachycardia had a sensitivity of 18.3%, specificity of 98.2% and accuracy of 52.4%.Conclusion:Histologic chorioamnionitis, frequently asymptomatic, is a common finding in placentas examined from term parturients. Clinical signs are not accurate in the diagnosis. Adoption of uniform pathologic guidelines will facilitate research into the clinical significance of these lesions in the future.

Immunohistochemical Analysis Reveals an Influx of Regulatory T Cells and Focal Trophoblastic STAT-1 Phosphorylation in Chronic Villitis of Unknown Etiology

Maternal T cells and fetal macrophages constitute the primary infiltrate of chronic villitis of unknown etiology (CVUE), but the role of CD25+/FOXP3+ regulatory T (Treg) cells in CVUE has not been examined. Moreover, little is known about the expression of immune markers, such as the major histocompatibility complex (MHC) class II antigen, human leukocyte antigen–DR (HLA-DR), in trophoblasts in this disease. We, therefore, examined CVUE placentas for the presence of Treg cells and aberrant activation of HLA-DR in trophoblasts. Sequential formalin-fixed, paraffin-embedded tissue sections from 8 CVUE placentas and 10 control placentas were stained by immunohistochemistry with antibodies for CD3, CD4, CD8, CD20, CD25, FOXP3, CD56, CD68, HLA-DR, STAT-1, and phosphorylated STAT-1 [P-(Y701)-STAT-1]. T cells and histiocytes were confirmed as the inflammatory infiltrate in CVUE. In areas of CVUE, histiocytes strongly expressed HLA-DR and nuclear P-(Y701)-STAT-1, and the relative numbers of CD25+/FOXP3+ Treg cells were increased, compared with control placentas. In 5 of 8 CVUE cases, there was patchy nuclear expression of P-(Y701)-STAT-1 in syncytiotrophoblast most extensively involved by villitis, but no other marker examined was detected in the trophoblast cell layer. We confirmed the influx of T cells and histiocytes in CVUE. Our results are the 1st, to our knowledge, to identify increased numbers of Treg cells in CVUE vs noninflamed placentas. However, we were unable to verify HLA-DR expression in trophoblasts of placentas with CVUE, suggesting that this does not contribute to the influx of T cells. Our observation that P-(Y701)-STAT-1 expression in a syncytiotrophoblast is restricted to regions of inflammation suggests that the JAK–STAT-1 pathway is aberrantly activated in these cells.

CD30-positive anaplastic large cell lymphoma (ALCL) of T-cell lineage in a 14-month-old infant with perinatally acquired HIV-1 infection.

Purpose: CD30-positive anaplastic large cell lymphoma (ALCL) has been described in adults with HFV-1 infection but is extremely rare in HIV-1 -infected infants and children. Patient and Methods: A 14-month-old girl with congenitally acquired HIV-1 infection presented with fever and a tender, erythematous, cystic mass on the right labium majorum. The mass was biopsied. Histologic examination and immunohistochemistry were performed. Results: Histologic examination showed Touton-like giant cells resembling histiocytes and focally abundant neutrophils obscuring the lymphoid infiltrate. Immunocytochemistry revealed a CD30-positive ALCL of T-cell lineage. Conclusion: Although non-Hodgkins lymphoma is known to be associated with HIV-1 infection in children, large cell lymphomas of T-cell lineage are extremely rare in this population. Early diagnosis should be aggressively pursued in an HIV-1-infected child who presents with a fever and cutaneous mass

Extraskeletal Ewing's sarcoma of primary cardiac origin

SummaryA 13-year-old boy presented with cardiac tamponade. Echocardiography revealed a large mass extending from the right and left ventricles into a large pericardial effusion. Pathology confirmed the first reported case of a primary cardiac extraskeletal Ewings sarcoma.

Preterm cord blood CD4+ T cells exhibit increased IL-6 production in chorioamnionitis and decreased CD4+ T cells in bronchopulmonary dysplasia

BACKGROUND Chorioamnionitis (CA) is associated with premature delivery and bronchopulmonary dysplasia (BPD). We hypothesize that preterm infants exposed to CA have reduced suppressive regulatory T cells (Treg) and increased non-regulatory T cell pro-inflammatory cytokines, increasing risk for BPD. OBJECTIVE To evaluate cord blood CD4(+) T cell regulatory phenotype and pro-inflammatory cytokine production in CA and BPD groups. STUDY DESIGN Cord blood mononuclear cells from infants (GA ⩽32 weeks), with or without placental histological evidence of CA (hChorio), were analyzed by flow cytometry. Clinical information was collected by retrospective chart review. Numbers of putative Treg (CD4(+)FoxP3(+)CD25(+)CD127Dim), CD4(+) non-Tregs, and CD4(+) T cell intracellular cytokine content following in vitro stimulation were compared with CA status and oxygen requirement at 36weeks postmenstrual age. RESULT Absolute Treg numbers were not different in CA and non-CA exposed samples. However, the infants who developed BPD had a significant decrease in Treg and non-regulatory T cell numbers. Greater IL-6 production was observed in hCA group. CONCLUSION A pro-inflammatory CD4(+) T cell status is noted in CA and BPD but the later disease is also associated with decrease in Tregs, suggesting that the development of BPD is marked by distinct inflammatory changes from those of CA exposed infants.

Fetal Inflammatory Response Is Often Present at Early Stages of Intra-amniotic Infection, and Its Distribution along Cord Is Variable

This study investigates the hypotheses that (1) the fetal inflammatory response to intra-amniotic infection can occur in early stages of maternal inflammatory response and (2) a difference in early cord inflammation exists at different sites in the cord. Placentas accessioned in our department over a 4-year period with a differential in umbilical vessel inflammation between proximal and distal sections were evaluated for cord inflammation using a 0 to 4 graded scale. Cases were also evaluated for acute chorionic vasculitis and extent of maternal inflammatory response. Of 5566 placentas, 1004 (18%) had some degree of cord inflammation; 120 (12%) had a differential in inflammation between the 2 cord sites. Greater cord inflammation was divided almost equally between proximal (59) and distal (61) sections. Twenty-two cases had 1 or both arteries involved in 1 cord section only. The proximal section had the greater degree of inflammation in 21 (95%) of these cases. Early or no maternal inflammatory response was seen in 63 of 120 cases (52%). Acute chorionic vasculitis was identified in 57 of 106 cases (54%) with at least 2 chorionic vessels present. Fetal inflammatory response can be seen in early amniotic infection, occasionally without finding maternal inflammatory response. The absence of differences in cord vein inflammation depending on cord site and the finding that arteritis occurs close to the placental cord insertion site suggest that cord vessel blood flow dynamics play a role in neutrophil margination. At least 2 cord sections representing proximal and distal sites are recommended to exclude fetal inflammatory response.

Intrapartum fever, epidural analgesia and histologic chorioamnionitis

OBJECTIVE:Our objective was to determine whether epidural analgesia and histologic chorioamnionitis were independent predictors of intrapartum fever.Study Design:This secondary analysis, retrospective cohort study included term parturients with placental examination during 2005. Logistic regression used fever (⩾38 °C) as the dependent variable. Significance was defined as P⩽0.05.Result:There were 488 (76%) of 641 term parturients with placental examination and epidural. Independent predictors of intrapartum fever were epidural odds ratio (OR)=3.4, confidence interval (CI): 1.70, 6.81, histologic chorioamnionitis OR=3.18, 95% CI: 2.04, 4.95, birthweight OR=2.07, 95%CI: 1.38, 3.12, vaginal exams OR=1.15, 95% CI:1.06, 1.24, duration ruptured membranes OR=1.03, 95% CI: 1.01,1.05, parity⩾1 OR=0.44: 0.29, 0.66 and thick meconium OR=0.35: 95%CI: 0.24, 0.85.Conclusion:Epidural analgesia and histologic chorioamnionitis were independent predictors of intrapartum fever. Modification of labor management may reduce the incidence of intrapartum fever.