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The human breast tumor microenvironment can display features of T helper type 2 (Th2) inflammation, and Th2 inflammation can promote tumor development. However, the molecular and cellular mechanisms contributing to Th2 inflammation in breast tumors remain unclear. Here, we show that human breast cancer cells produce thymic stromal lymphopoietin (TSLP). Breast tumor supernatants, in a TSLP-dependent manner, induce expression of OX40L on dendritic cells (DCs). OX40L(+) DCs are found in primary breast tumor infiltrates. OX40L(+) DCs drive development of inflammatory Th2 cells producing interleukin-13 and tumor necrosis factor in vitro. Antibodies neutralizing TSLP or OX40L inhibit breast tumor growth and interleukin-13 production in a xenograft model. Thus, breast cancer cell-derived TSLP contributes to the inflammatory Th2 microenvironment conducive to breast tumor development by inducing OX40L expression on DCs.

Ovarian cancer is the gynecologic malignancy with the highest number of deaths in the United States. Previous studies had found a decreased incidence of female gynecological malignancies after liver transplantation. In order to estimate the incidence of ovarian carcinoma after liver transplantation, we evaluated 1708 consecutive liver transplant recipients from 1984 to 2001. Of them, 770 (43%) were female. Routine follow-ups were performed at 1, 2, 5, and 10 years after transplantation. There were two cases of ovarian carcinoma. Both occurred in recipients with a previous history of breast cancer. Based on these data, we conclude that the incidence of ovarian cancer is 1:385 among all female liver transplant recipients, and 1:6.5 among those with a history of pretransplant breast cancer. We recommend that regular check-ups should be undertaken, especially in the population at highest risk.

This prospective clinical trial was designed to assess the impact of adjuvant chemotherapy in women with rapidly proliferating node-negative breast cancer. This group has been predicted to have a 5-year disease-free survival (DFS) of 70% without adjuvant chemotherapy. In this study, 449 women with rapidly proliferating breast cancer (91% measured by S-phase fraction and 9% by histochemistry) received adjuvant chemotherapy with doxorubicin/cyclophosphamide (AC) plus tamoxifen for estrogen receptor-positive or progesterone receptor-positive cancer. The 5-year DFS was 90% (+/- 2%) and the 5-year overall survival was 94% (+/- 1%). At a median follow-up of 62 months, the strategy of administering 6 cycles of AC to women with T2 N0 cancer and 3 cycles in those with smaller T1 N0 cancers appeared to eliminate tumor size as a potential prognostic factor. Adjuvant chemotherapy with AC appears effective in reducing recurrence rates for women with rapidly proliferating node-negative breast cancer.

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.

Background: The implementation of new treatment protocols for locally advanced breast cancer is currently limited by inaccurate evaluation of response to neoadjuvant chemotherapy. A recently developed dedicated breast magnetic resonance imaging (MRI) method (RODEO MRI) was evaluated as a tool for determining tumor response and extent of residual disease after neoadjuvant chemotherapy., Methods: Thirty-nine patients with Stage II, III, or IV breast carcinoma were prospectively evaluated prior to and following neoadjuvant chemotherapy by MRI, physical examination, and mammography. Assessment of response determined by the three methods was compared. In addition, detailed pathologic correlation of residual disease was determined by serial sectioning of 31 mastectomy specimens from 30 patients. Nine patients had breast conservation, and were included in the response evaluation only. Estimates of tumor response were made by both surgical and medical oncologists. Independent interpretations of MRI studies without knowledge of clinical response were made by three radiologists., Results: The surgical oncologists assessed complete response (CR), partial response (PR), and no response (NR) in 11, 22, and 7 cases, respectively. The medical oncologists assessed CR, PR, and NR in 12, 21, and 7 cases, respectively. The surgical and medical oncologists' clinical assessment of response agreed with the results of MRI in 52% and 55% of cases, respectively, and with each other in 30 of 40 cases (75%). Mammography correlated with MRI response in only 52% of cases. However, MRI accurately predicted the pathologic determination of residual disease in 30 of 31 cases (97%). There was no disagreement in the assessments of residual disease or response among the three radiologists., Conclusions: RODEO breast MRI accurately estimates residual disease after induction chemotherapy. It assesses response to neoadjuvant chemotherapy better than traditional methods of physical examination or mammography. The information obtained from this MRI technique may be used as an objective tool during clinical trials, and to select patients better for breast conservation after neoadjuvant chemotherapy for locally advanced disease.

Investigators in 13 pediatric nephrology centers reviewed clinical and pathological features in 218 children and adolescents with IgA nephropathy (IgAN), with particular emphasis on 80 patients who had follow-up periods of at least 4 years. Potential prognostic markers in the 80 children were compared between 12 (15%) who developed end-stage renal disease (ESRD) versus 68 who did not. The relationship between clinical and pathological features and the subsequent development of ESRD was examined using stepwise linear discriminant analysis in addition to standard univariate analysis. Seven variables were found to be predictive of ESRD: the presence of glomerular sclerotic changes, especially when this was associated with proliferation or sclerosis in 20% or more of the glomeruli; black race; hypertension at biopsy; proteinuria at biopsy; age at presentation; crescents; male sex. Using the resulting discriminant function, development of ESRD could be correctly predicted in 95% of the subjects. We conclude that ESRD is more common in American children with IgAN than was realized previously. Risk factors previously documented in adult studies have been confirmed, especially the presence of glomerular sclerosis, proteinuria, and hypertension.

Reported is a case of acute fulminant lymphocytic myocarditis with profound circulatory compromise that was successfully reversed by treatment with OKT3 monoclonal antibody. The patient was supported with biventricular assist devices while being treated with the monoclonal antibody. The patient had remarkable recovery of ventricular function, which allowed for the removal of the device after 8 days of support. This case shows the success of combined technologies of monoclonal antibody and mechanical circulatory support to treat a potentially fatal disease process.

In this study, skin-infiltrating cells in psoriasis patients were characterized in biopsies from both involved and uninvolved skin. Histologic examination of biopsies showed the presence of both CD4+ and CD8+ T cells and the lack of B lymphocytes. Skin biopsies were also placed in tissue culture medium supplemented with human serum, interleukin-2 (IL-2), and irradiated autologous blood lymphocytes. T lymphocytes grew from both plaques and univolved skin biopsies and consisted of a heterogeneous population of T-cell subsets. The immunophenotypic analysis of cultured cells was comparable to the histologic examination on frozen section, i.e., there was a greater number of CD4/CDw29+ cells than CD8+/CD45+ cells. Cultures were tested in the primed lymphocyte test (PLT) and cell-mediated lympholysis (CML) assays. All cultures tested demonstrated secondary proliferative but not cytolytic reactivity. The PLT results indicate that the cell cultures generated are autoreactive. This autoreactivity was found to be directed against non-human leukocyte antigens (HLA), i.e., minor HLA with some restriction to major HLA antigens.

A patient with spontaneous remission of nephrotic syndrome (NS) associated with IgA nephropathy is described. The patient presented at the age of 8 years with asymptomatic proteinuria, and at the age of 11 years developed classical features of NS. A percutaneous renal biopsy showed mild mesangial prominence without significant hypercellularity, electron-dense deposits within the mesangium, and 3+ mesangial staining with IgA and IgG. NS resolved 6 weeks after onset without any form of therapy; absence of proteinuria persisted 6 months later. This report demonstrates clearly that patients with NS associated with IgA nephropathy may undergo spontaneous resolution of their proteinuria.

Of 650 eyes with posterior uveal melanomas that were accessioned at the Armed Forces Institute of Pathology from 1975 to 1983, 28 were aphakic and eight were pseudophakic. In ten of these 36 cases, the cataract had been unilateral. Only two patients had been examined with preoperative A-scan ultrasonography to obtain the axial length of the eye. None of the patients had been examined for possible intraocular tumors by either A- or B-scan ultrasonography. We believe that in many of these cases the tumor was large enough to have been detected at the time of cataract surgery. Thus, if the lens is too opaque for the fundus to be viewed, B-scan ultrasonography should be used before cataract extraction.

Two cases of conjunctival rhinosporidiosis were studied by light and electron microscopy. Two distinct phases of the tissue life cycle were present: trophic and endosporulating. Young trophocytes contained a single nucleus. As the trophocyte matured chromatin was dispersed throughout the cyst. During the next phase of the life cycle, sporangial cyst walls acquired a new inner layer that appeared to give rise to endospores. Histochemical and ultrastructural features of Rhinosporidium seeberi are consistent with it being a fungus. Complete surgical excision of the lesion is the only known method to eradicate the infection.

A case report describes the clinical findings of dermal myiasis of the upper eyelid in a 6-year-old girl from South America. Dermal myiasis due to Dermatobia hominis can simulate a common furuncle and is known to occur in world travelers.