ABSTRACT
Pulmonary interstitial glycogenosis is an interstitial lung disease of childhood that has been increasingly reported over the past decade. Here, we present a case of pulmonary interstitial glycogenosis associated with trisomy 21, pulmonary arterial hypertension, and congenital heart disease in a 34 week premature infant.
Subject(s)
Down Syndrome/complications , Glycogen Storage Disease/pathology , Heart Defects, Congenital/pathology , Hypertension, Pulmonary/pathology , Lung Diseases, Interstitial/pathology , Down Syndrome/physiopathology , Echocardiography , Fatal Outcome , Female , Humans , Infant, Newborn , Infant, PrematureABSTRACT
Alveolar rhabdomyosarcoma is an aggressive skeletal muscle cancer of childhood. Our initial studies of rhabdomyosarcoma gene expression for patients enrolled in a national clinical trial suggested that platelet-derived growth factor receptor A (PDGFR-A) may be a mediator of disease progression and metastasis. Using our conditional mouse tumor models that authentically recapitulate the primary mutations and metastatic progression of alveolar rhabdomyosarcomas in humans, we found by immunoblotting and immunokinase assays that PDGFR-A and its downstream effectors, mitogen-activated protein kinase and Akt, were highly activated in both primary and metastatic tumors. Inhibition of PDGFR-A by RNA interference, small molecule inhibitor or neutralizing antibody had a dramatic effect on tumor cell growth both in vitro and in vivo, although resistance evolved in one-third of tumors. These results establish proof-of-principal for PDGFR-A as a therapeutic target in alveolar rhabdomyosarcoma.
Subject(s)
Antineoplastic Agents/therapeutic use , Muscle Neoplasms/drug therapy , Receptor, Platelet-Derived Growth Factor alpha/antagonists & inhibitors , Receptor, Platelet-Derived Growth Factor alpha/physiology , Rhabdomyosarcoma, Alveolar/drug therapy , Animals , Benzamides , Cell Line, Tumor , Cells, Cultured , Genes, p16 , Humans , Imatinib Mesylate , Mice , Mice, Knockout , Muscle Neoplasms/etiology , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Rhabdomyosarcoma, Alveolar/etiology , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: This review focuses on current directions in the staging and treatment of melanoma of the vulva. METHODS: All women treated for invasive melanoma of the vulva at the University of Virginia Health Sciences Center from 1980 through 2000 were identified through a retrospective review of the records of the Division of Gynecologic Oncology. Their treatments and outcomes were then analyzed and presented. RESULTS: Over the 20-year study period, 14 cases of melanoma of the vulva were identified. Of the 14 patients treated with curative intent, 6 developed recurrences following the completion of primary therapy, and all are dead from their disease. The mean duration from completion of therapy to recurrence was 7.5 months; the mean survival following recurrence was 17 months. CONCLUSION: One-centimeter skin margins appear adequate for vulvar melanomas <1 mm thick, and 2-cm margins appear adequate for intermediate-thickness melanomas (1-4 mm). In all cases it is necessary to include at least a 1-cm-deep margin extending through the subcutaneous fat to the muscular fascia below. Elective node dissection seems to offer no additional advantage in superficial lesions <0.76 mm thick, and its role in deeper lesions is still uncertain.
Subject(s)
Melanoma/pathology , Melanoma/therapy , Vulvar Neoplasms/pathology , Vulvar Neoplasms/therapy , Aged , Combined Modality Therapy , Female , Humans , Neoplasm Staging , Retrospective Studies , Survival RateABSTRACT
We report the seventh case of angiosarcoma of the heart in a child. The patient was a 23-month-old female who presented for lower extremity limping and underwent open surgical biopsy of the femur. Immediately postoperatively, she developed pericardial tamponade, and a bulky intracardiac mass was discovered as the underlying cause. The mass was composed of highly pleomorphic tumor cells reactive for the endothelial markers CD31, CD34, and factor VIII-related antigen (FVIII-RA). Staging evaluation revealed widespread metastases involving the brain, ovaries, and bone marrow. She died of complications of metastatic disease 8 months following initial presentation. Unusual features of this case include the young age of the patient, left-sided nature of the cardiac tumor, presentation secondary to metastatic disease, and the pattern of metastases. The literature on cardiac angiosarcoma, which is limited to six case reports in the pediatric population, is also reviewed.
