Therapy-related acute myeloid leukemia with 11q23 abnormality coexisting with refractory metastatic Ewing sarcoma: report of a case and review of the literature.

Intensified chemotherapy is one of the strategies currently used in the treatment of children with metastatic Ewing sarcoma. However, the increasing dose intensity has not significantly improved the event-free survival. We report a patient who initially presented with localized Ewing sarcoma and later developed metastatic disease that required dose-intensified chemotherapy. The patient's Ewing sarcoma remained refractory to treatment despite continuous intensified chemotherapy and was complicated by a therapy-related acute myeloid leukemia with 11q23 abnormality. Examination of bone marrow at the last clinical follow up demonstrated both acute myeloid leukemia and residual metastatic Ewing sarcoma.

Pseudoangiomatous stromal hyperplasia of the breast in pediatric patients: an underrecognized entity.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign lesion consisting of mammary stromal proliferation with anastomosing slits mimicking vascular spaces. Grossly, it most often resembles fibroadenoma, but may commonly be confused with angiosarcoma and other types of benign vascular proliferations. While PASH has been described in female and male adults since the mid-1980s, there have been only a few accounts in the pediatric population. We present a series of 12 pediatric patients with PASH, including a 3-year-old male, who we believe to be the youngest patient to present with this entity. In our study, PASH was found in 12% of tumors diagnosed preoperatively as fibroadenomas and in 12% of cases diagnosed preoperatively as gynecomastia. Our series documents that PASH is not uncommon in pediatric breast pathology and delineates important differences between adult and pediatric presentations of this entity.

Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia.

Most (up to 71%) of renal cell neoplasms occurring in patients with end-stage renal disease (ESRD), particularly with acquired cystic disease of the kidney (ACDK), have been reported to be papillary renal cell carcinoma (RCC). Our initial experience with tumors in such a setting indicated that many tumors were histologically difficult to classify into the known subtypes of RCC or had features that were different from those in sporadically occurring RCCs. In this study on 66 ESRD kidneys (52 of which showed features of ACDK) removed because tumors were detected in them, we found two major groups of RCC. Overall, there were 261 grossly identified tumors in these kidneys, and many additional tumors were observed on microscopic evaluation in some. Of the two major groups of RCCs, one consisted of tumors similar to those seen in sporadic settings (ie, clear-cell, papillary, and chromophobe RCC), and these formed the dominant mass in 12 (18%), 10 (15%), and 5 (8%) of the 66 kidneys, respectively. The other group consisted of two subtypes of RCC that appear quite unique to ESRD. The more common tumor that we have designated as "acquired cystic disease-associated RCC" was seen as the dominant mass in 24 (36%) of 66 of the kidneys, and it formed the most common tumor type among the smaller nondominant masses, as well. It was characterized by a typical microcystic architecture, eosinophilic cytoplasm with Fuhrman's grade 3 nuclei, and frequent association with intratumoral oxalate crystals. Additionally, these tumors frequently, but usually focally, exhibited papillary architecture, and clear cytoplasm. These tumors occurred only in kidneys with ACDK, and not in noncystic ESRD. The other category was "clear-cell papillary RCC of the end-stage kidneys," present as the dominant mass in 15 (23%) of the 66 kidneys and occurring in both the ACDK and noncystic ESRD. These predominantly cystic tumors showed prominent papillary architecture with purely clear-cell cytology. Immunohistochemical studies in tumors with histology similar to the known subtypes of sporadic RCC showed immunoprofiles similar to that reported in sporadically occurring tumors. The two subtypes of RCC unique to ESRD had distinctive immunoprofiles supporting their separate morphologic subcategorization. Only the acquired cystic disease-associated RCC showed lymph node metastases in 2 cases and sarcomatoid features in 2 more cases. One of the latter 2 died with widespread metastatic disease within 34 months of nephrectomy. Thus, a broad spectrum of renal cell tumors exist in ESRD, only some of which resemble the sporadic RCCs. Acquired cystic disease-associated RCC is the commonest tumor subtype in ESRD, and biologically it appears to be more aggressive than the other tumor subtypes in ESRD.

Proinflammatory cytokine genes are constitutively overexpressed in the heart in experimental systemic lupus erythematosus: a brief communication.

The heart is one of a number of organs that may be affected in systemic lupus erythematosus (SLE), a prototypic autoimmune disease. Potential anatomical sites of involvement include the myocardium, pericardium, endocardium, valves, conduction system and blood vessels that subserve the heart. Typically, the severity of cardiovascular disease in lupus correlates with the degree of systemic inflammation, which is mirrored by the level of C-reactive protein (CRP) in the plasma. C-reactive protein, in turn is regulated by proinflammatory cytokines, such as interleukins (ILs) 1beta and 6. These cytokines have been found in functionally and/or structurally damaged areas of the heart and have been implicated in disease pathogenesis. It has been assumed that the source of these putatively pathogenetically relevant cytokines in the compromised heart is infiltrating mononuclear cells. This study tests the hypothesis that cardiomyocytes per se may contribute to proinflammatory cytokine production in the setting of systemic inflammation. Using as the experimental model MRL/MpJ-Tnfrs6(lpr) (MRL-lpr/lpr) mice, which spontaneously manifest an autoimmune syndrome that has clinical features of SLE, we show that ventricular homogenates and ventricular cardiomyocytes constitutively overexpress genes encoding the proinflammatory cytokines IL-1beta, IL-6, IL-10, and gamma interferon. The results suggest the possibility that proinflammatory cytokines emanating from the heart may actually contribute to the high levels of CRP that appear to aid in predicting subsequent cardiac events. Viewed in this setting, CRP becomes a footprint of an ongoing pathogenic process mediated, in part, by the heart muscle itself.