Generalized lymphadenopathy with morphologic features of Castleman's disease in an HIV-positive man

In recent years the literature has described a highly lethal "multicentric" variant of classic Castleman's disease (CD) with similar hyperplastic angio-follicular morphologic features. A 44-year-old man who was not known to be part of any established high-risk group for the acquired immune deficiency syndrome (AIDS) presented with clinical and laboratory features similar to "multicentric" CD. Serologic testing revealed antibody to the human immunodeficiency virus (HIV) by Western blot analysis. It is suggested that "multicentric" CD may be part of the clinicopathologic spectrum of HIV infection, and there should be a high index of suspicion for HIV in patients presenting with generalized lymphadenopathy and histopathologic features of CD.     

Incisional hernia and fascial defect following laparoscopic surgery

Complications involving the abdominal wall, particularly incisional hernias, were not expected when laparoscopic procedures were first introduced. With the increasing number of laparoscopies in abdominal surgery, more incisional hernias are observed. The authors report 13 cases of umbilical incisional hernia, which occurred late after laparoscopic cholecystectomy, and one case of omental procidentia through a lateral port, which occurred early after laparoscopic hernia repair with the transabdominal preperitoneal technique. There are 4 men and 10 women (mean age, 59.8 years; range, 40-74 years). Between March 1991 and December 1997, a total of 1,287 patients underwent laparoscopic operations at the Surgical Department of the Gradenigo Hospital in Turin, Italy. Incisional hernia incidence is 1%. Risk factors, such as chronic bronchitis or weight increase, which give rise to endoabdominal pressure, are present in some cases. Malnutrition may have a major role in many cases. Calculi larger than 15 mm are also seen frequently. Postlaparoscopy incisional hernia is generally a minor complication--only once did its occurrence cause a strangulated hernia. All precautions, including fascial suturing, must be taken to reduce the 1% incidence of postoperative incisional hernias.     

Breastfeeding Practices in Relation to Country of Origin Among Women Living in Denmark: A Population-Based Study

The objective of this study was to describe breastfeeding practices and to compare the risk of suboptimal breastfeeding of women living in Denmark according to country of origin, and further to examine how socio-economic position and duration of stay in the country affected this risk. Information on breastfeeding of 42,420 infants born 2002–2009 and living in eighteen selected Danish municipalities was collected from the Danish Health Visitor’s Child Health Database. The data was linked with data on maternal socio-demographic information from Danish population-covering registries. Suboptimal breastfeeding was defined as <4 months of full breastfeeding as described by the Danish Health and Medicines Authority. We used logistic regression to model the crude associations between suboptimal breastfeeding and country of origin, and taking maternal age and parity, and a variety of parental socio-economic measures into account. Suboptimal breastfeeding was more frequent among non-Western migrant women than among women of Danish origin. Women who were descendants of Turkish and Pakistani immigrants had a higher risk of suboptimal breastfeeding as compared to the group of women who had migrated from the same countries, suggesting that acculturation did not favor breastfeeding. For all but the group of women who had migrated from Pakistan, adjustment for socio-demographic indicators (age, parity, education, attachment to labour market, and income) eliminated the increased risk of suboptimal breastfeeding. There was no evidence for differences in the breastfeeding support provided at hospital level according to migrant status. Suboptimal breastfeeding was more frequent among women who were non-Nordic migrants and descendants of migrants than among women with Danish origin.     

Photoprovocation in cutaneous lupus erythematosus: a multicenter study evaluating a standardized protocol

Photosensitivity is an important and distinguishing sign in various subtypes of cutaneous lupus erythematosus (CLE); however, it remains poorly defined. The purpose of this study was to evaluate whether standardized photoprovocation is a reproducible method to assess photosensitivity in subjects with CLE. A total of 47 subjects with CLE (subacute cutaneous lupus erythematosus (SCLE), n=14; discoid lupus erythematosus (DLE), n=20; lupus erythematosus tumidus (LET), n=13) and 13 healthy volunteers underwent photoprovocation at seven European sites. Of these, 22 (47%) subjects (57% SCLE, 35% DLE, and 54% LET) and none of the healthy volunteers developed photoprovoked lesions according to clinical analysis. Of these 22 subjects, 19 (86%) developed lesions that were histopathologically confirmed as specific for lupus erythematosus (LE). In CLE subjects who developed UV-induced lesions, 86% had Fitzpatrick's phototypes I or II, and the mean minimal erythema dose (MED) was significantly lower compared with subjects without UV-induced lesions (P=0.004). No significant differences in photoprovocation results were observed between study sites. Safety parameters showed no clinically meaningful differences between CLE subjects and healthy volunteers after photoprovocation. In conclusion, a standardized, safe, and reproducible protocol for photoprovocation using UVA and UVB radiation induced skin lesions in approximately half of all CLE subjects and showed comparable results across multiple sites. This method may therefore be used for future diagnostic testing and clinical trials.     

Large cell non-Hodgkin lymphoma of childhood: Analysis of 78 consecutive patients enrolled in 2 consecutive protocols at the Memorial Sloan-Kettering Cancer Center

BACKGROUND: The authors report a study of pediatric patients with advanced diffuse large cell lymphoma (DLCL) who were treated with 2 consecutive regimens, LSA2-L2 and LSA4, over a 25-year-period at the Memorial Sloan-Kettering Cancer Center. They also describe a comparative analysis of two subgroups retrospectively identified as having CD30 positive (+) anaplastic large cell lymphoma (ALCL) and CD30 negative (-) DLCL. To the authors' knowledge, this study represents the longest follow-up on the largest series of uniformly treated pediatric DLCL patients reported to date. METHODS: A total of 78 consecutive patients were treated for Stage III/IV DLCL. Immunophenotypic data were obtained retrospectively for 52 patients using a panel of monoclonal antibodies against CD30, CD15, CD45, CD45Ro, CD43, epithelial membrane antigen, CD5, BCL-2, cyclin-D, and p53. RESULTS: A disease free survival rate of 72% in patients with advanced stage DLCL using the LSA2-L2 and LSA4 regimens. Of the 78 treated patients, 56 are alive and without evidence of disease with a median follow-up of 120 months (range, 24-312 months). The recurrence rate was significantly higher in the CD30+ ALCL subgroup (33%) than in the CD30- DLCL group (0.04%). Of 52 patients for whom immunophenotypic data were available, 28 had disease of B-cell lineage, 24 had disease of T-cell/null phenotype, 19 were CD30+ (36. 5%), 18 had disease of T-cell phenotype, and 1 had disease of B-cell lineage. CONCLUSIONS: The CD30- DLCL cases mostly were of B-cell lineage, had a small risk of treatment failure, and did not develop a recurrence off therapy. A distinct clinical pattern was identified for the CD30+ ALCL group; although these tumors were of T-cell lineage and had a significantly higher rate of late recurrences (median follow-up of 24 months) they all were salvageable. Based on the findings of the current study, the authors propose that T-cell CD30+ ALCL be addressed in the future according to equal dose intensity regimens in induction therapy, as is done for B-cell lymphomas; prolonged periods of maintenance chemotherapy, as is done for T-cell lymphoblastic lymphomas; and no central nervous system prophylaxis beyond the induction period unless other recognized risk factors are present.     

Epstein-Barr virus positive large B-cell lymphoma arising in a patient previously treated with Cladribine for hairy cell leukemia

We describe the case of a patient treated with 2-chloro-2'-deoxyadenosine, CdA or Cladribine for hairy cell leukemia who subsequently developed an Epstein Barr virus (EBV)-positive polymorphous large B-cell lymphoma (p-LBCL). The time interval between Cladribine therapy and development of p-BCL was 11 months and morphologically resembled an EBV-positive post transplant lymphoproliferative disorder (PTLD). Molecular genetic studies for EBV-clonality by Southern blot hybridization showed a clonal population of infected cells, implying that this was an EBV induced lesion. The chronology of events suggest that Cladribine, a purine analog which has been previously described to induce long-lasting immunodeficiency, can, in some cases, weaken the host defense mechanism to a level at which an innocuous EBV infection may transform the normal lymphoid cells into an aggressive neoplasm. Unlike most methotrexate-related lymphoproliferative disorders (LPDs), which undergo spontaneous remission after discontinuation of therapy, LPDs secondary to purine analogs often fails to resolve after discontinuation of therapy and requires additional therapy. Our patient was treated with rituximab following the diagnosis of p-LBCL, with the goal of improving the pancytopenia to permit chemotherapy. However, the patient failed to show any dramatic improvements in counts, developed systemic symptoms and progressive ascites. He expired 3 weeks after a second dose of rituximab. Cladribine is a potent immunosuppressive agent and should be included with the list of immunosuppressive agents that may be associated with EBV-related B-cell lymphoproliferative disorders.     

Bcl-2 and bax expression in advanced non-small cell lung cancer: lack of correlation with chemotherapy response or survival in patients treated with docetaxel plus vinorelbine

Surgical series of non-small cell lung cancer (NSCLC) pathologic samples have shown that the expression of the proteins bcl-2 and bax, which regulate cell death, may have prognostic implications. Laboratory data also suggests that these proteins may impact chemotherapy response. In order to determine the rate of bcl-2 and bax expression in advanced NSCLC and assess the impact on chemotherapy response and patient survival, we performed immunohistochemistry on biopsy samples from patients enrolled in a phase I/II trial of vinorelbine plus docetaxel. We chose to study the pathology of patients in this specific trial because both docetaxel and vinorelbine phosphorylate bcl-2 and we hypothesized that this mechanism may affect clinical outcome. The goal of this study was to determine the feasibility of this analysis, and to observe any differences in response rate or survival based on bcl-2 or bax staining results. Unstained slides from paraffin blocks were obtained for 31 patients (55%) on the phase I/II trial. The patient characteristics for this subgroup did not differ significantly from the entire cohort of patients on the trials. Bcl-2 staining was positive in 5/31 samples (16%, 95% CI 3-29%) and bax was positive in 19/28 samples (68%, 95% CI 51-85%). Bcl-2 and bax staining did not correlate with response (p = 0.65 and 1.00 respectively, Fisher's exact test), or survival (by Kaplan-Meier curves). In conclusion, bcl-2 and bax expression was similar in this population with advanced NSCLC to previously reported results for early stage disease, but did not predict response to vinorelbine plus docetaxel in this series.     

Lymphoblastic lymphoma of childhood and the LSA2-L2 protocol: the 30-year experience at Memorial-Sloan-Kettering Cancer Center

BACKGROUND: Until the 1970s, diffuse lymphoblastic lymphoma (DLBL) was considered incurable. With intensive multidrug regimens, the majority of patients can now be cured. In the current study, the authors present what to their knowledge is the longest follow-up presented to date (median, 20 years for survivors) of the largest group of DLBL patients treated with a single protocol at a single institution. METHODS: Between 1971-1990, a total of 95 consecutive patients (age < 21 years) with DLBL were treated with the LSA(2)-L(2) protocol at the Memorial Sloan-Kettering Cancer Center (MSKCC). Patients with Stage I-II disease were treated for 2 years. In 1980, the protocol was modified and patients with Stage III and IV disease were treated for 3 years. In addition, before the modification, patients with Stage IV disease received a cumulative dose of 15,600 mg/m(2) of cyclophosphamide for 3 years; after 1980, these patients received the same dosage as the other patients (i.e., 8400 mg/m(2) for 2 years). Radiation therapy initially was administered to all patients with bulky disease in the primary tumor site. Until 1977, the dose of radiation was 20-55 grays (Gy); from 1977 to 1989, the dose was 20 Gy. After the fifth year of completion of treatment, all patients were evaluated comprehensively every 2 years. RESULTS: The overall survival (OS) of the patients was 79% with a median follow-up of 20 years. The overall event-free survival (EFS) was 75% (71 of 95 patients). Seventeen patients developed a disease recurrence and 15 died of disease. The OS and EFS rates for patients with Stages I-II disease (n = 8) were 87% and 87%, respectively, and the OS and EFS rates for patients with Stage III disease (n = 41) were 90% and 85%, respectively. The OS and EFS for patients with Stage IVA disease (with bone marrow [BM] involvement of < 25%) (n = 19) were 79% and 73%, respectively, whereas the OS and EFS for patients with Stage IVB disease (BM involvement of > 25%) (n = 27) were 74% and 70%. Of the 29 patients with Stage IV disease who were treated with the original protocol, 7 died of disease (1 of 8 patients with Stage IVA disease and 6 of 21 patients with Stage IVB disease). Of the 17 patients with Stage IV disease who were treated with the modified protocol, 3 died of disease (2 of 11 patients with Stage IVA disease and 1 of 6 patients with Stage IVB disease). Six patients developed secondary malignancies, four of whom died. CONCLUSIONS: Long-term EFS can be achieved in the majority of patients with widely disseminated pediatric DLBL. Chemotherapy alone appears to be sufficient prophylaxis against disease recurrence in the central nervous system. No disease-related or treatment-related deaths were reported to occur > 4.5 years after diagnosis in the current study.