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Platelet-derived growth factor (PDGF)-B is a proto-oncogene capable of transforming fibroblasts. Using adenoviral vectors, we tested whether endogenous PDGF-B expression in human skin xenotransplants leads to changes in the expression of α5 and α2 integrin subunits and whether integrin overexpression leads to PDGF-related changes in the skin. In vitro, transduction of fibroblasts with PDGF-B or the integrin α5 subunit stimulated multilayered growth and spindle-type morphology, both markers of mesenchymal cell transformation. In vivo, PDGF-B transduction of the human dermis was associated with up-regulation of collagen and fibronectin synthesis, increases in α5 and α2 integrin subunit expression, vessel formation, and proliferation of fibroblasts, keratinocytes, and pericytes. A similar stromal response was induced when α5 and α2 integrin subunits were overexpressed in the human dermis, suggesting that integrins play a major role in the induction of a transformed phenotype of fibroblasts by PDGF-B.

Interleukin-8 (IL-8) is a potent chemotactic polypeptide for neutrophils. However, the role of this cytokine during inflammation remains unclear. Skin specimens from patients with pyoderma gangrenosum demonstrated IL-8 overexpression in skin ulcers, which suggests a role for IL-8 in the development of the disease. We therefore constructed a recombinant adenovirus expressing the complementary deoxyribonucleic acid encoding human IL-8 (IL-8/Ad5) that induces a 2000-fold increase in IL-8 expression of infected human fibroblasts in vitro. Human skin engrafted to severe combined immunodeficiency mice and then injected with the recombinant virus demonstrated erythema, an intense perivascular infiltration of neutrophils, and extravasation of erythrocytes after 8 hours. By 12 hours after injection, neutrophils had accumulated beneath the epidermis, which then necrotized, and one or more ulcers that remained for approximately 2 weeks were observed. Clinically and histologically, the ulcers resembled pyoderma gangrenosum. These clinical and experimental findings suggest an etiologic role of IL-8 in the pathogenesis of pyoderma gangrenosum.

Basic fibroblast growth factor (bFGF or FGF-2) is produced by nearly all melanomas in vitro and in vivo but not by normal melanocytes, which require exogenous bFGF for growth. In this study, we transduced normal human melanocytes to overexpress two forms of bFGF: (bFGF-Long and bFGF-Short) using replication-deficient adenovirus 5 vectors. bFGF-Long induced the 17.8, 22.5, 23.1 and 24.2 kDa forms of bFGF, whereas bFGF-Short induced only the 17.8 kDa mature form. Growth of cultured melanocytes transduced with either vector was similar to that of nevus and melanoma cells and was independent of exogenous bFGF and of insulin/insulin-like growth factor 1, and cyclic AMP enhancers, requiring only phorbol ester as an exogenous mitogen. Like primary melanoma cells, transduced normal melanocytes grew anchorage independently in soft agar. When injected into the dermis of human skin grafted to mice, bFGF-transduced melanocytes proliferated for at least 20 days, whereas cells from control cultures showed poor survival and no proliferation. These results demonstrate that bFGF upregulation is a critical component in melanoma progression.

Two cases of lymphangiomatosis of bone, a very rare systemic condition characterized by both skeletal and parenchymal lesions, are presented. The skeletal changes have an appearance similar to haemangiomas in the spine, and soap-bubbly lesions in the flat bones. One case carried the diagnosis of eosinophilic granuloma for 18 years. The findings on MRI, which have not been previously well-established, are discussed.

The frequency of Langerhans cell histiocytosis (LCH) and a malignant neoplasm occurring in the same individual appears to be greater than previously recognized. To define the occurrence and the pattern of these events, a Study Group of the Histiocyte Society initiated a registry of patients in whom this association occurred synchronously or asynchronously. Evaluation of 54 patients detected two patterns of associations between LCH and other disorders. First, it is possible that therapy of LCH promotes a secondary malignancy. Second, it is possible that a genetic predisposition, with or without the immunosuppression associated therapy for the malignancy, plays a role in the development and expression of disseminated LCH. Data collected by the LCH Malignancy Study Group may provide insights into the etiology and pathophysiology of LCH.

Review of Childrens Cancer Group (CCG) randomized trials conducted since 1979 identifies three strategies that have led to incremental improvements in outcome: (a) allogeneic bone marrow transplantation (BMT) in first remission; (b) sequentially timed high-dose chemotherapy and the advent of more effective pre-and post-remission treatment; and (c) attenuation of maintenance therapy. Among patients treated from 1979 to 1983, the 5-year disease-free survival (DFS) following matchedrelated allogeneic transplantation was 45% and between 1983 and 1988, 46%. From 1983 to 1988 intensification therapy with sequentially timed high-dose cytosine arabinoside (ara-C) given on days 0,1 and 7 and 8 achieved a five-year DFS of 38% (p = .06 compared to BMT). Five-year postremission survival with sequentially timed highdose ara-C was 58% compared to 41% with conventionally timed day 0,1 and 28,29 ara-C (p =.05). Five-year survival following high-dose ara-C intensification was significantly lower after 16 months of maintenance therapy compared to no maintenance (44% vs. 68%, p < .01). Since 1979, the remission induction rate has ranged between 74% and 79%, even with kinetically based sequentially timed five-drug chemotherapy. However, post-remission DFS was significantly highr with sequentially timed induction therapy than with conventionally timed therapy: 60% vs. 37% at 3 years (p = .0002). With the combined use of sequentially timed induction therapy, matched-related BMT, and development of the best post-remission regimen from the current study. CCG acute myeloid leukemia (AML) therapy will potentially cure over half the children with (AML) by the year 1999.

There is little information available regarding epidemiologic risk factors for Langerhans cell histiocytosis (LCH). An exploratory investigation was conducted using information obtained from parents of 177 cases of LCH diagnosed before 21 years of age (median 2 years). Utilizing data available from the Children's Cancer Group, LCH cases were compared to two matched control groups including 614 patients diagnosed with a variety of childhood cancers and 318 community controls. Questionnaire data included information on demographics, prenatal and perinatal factors, complications in the neonatal period, environmental exposures, family medical history, and childhood exposures. Factors found to be statistically significantly associated with an increased risk of LCH included: maternal urinary tract infection during the index pregnancy, feeding problems during infancy, and blood transfusions during infancy. Use of supplemental vitamins was associated with a significantly decreased risk of LCH. Results from this exploratory study provide a basis for speculation on potential etiologic risk factors for LCH. Future epidemiologic investigations of LCH need to consider the presenting disease characteristics in assessing possible etiologic factors.

PURPOSE:Nonsurgical treatment of lymphangiomas has shown limited efficacy and often carries unacceptable toxicities, demonstrating the need for a more effective, less toxic therapy. PATIENTS AND METHODS:We describe two patients with lymphangiomatosis treated for 12 to 40 months with recombinant interferon-alpha. RESULTS:Both patients demonstrated stabilization or marked improvement of disease, based on clinical and radiologic findings, with minimal toxicity. CONCLUSIONS:The favorable responses to interferon-alpha therapy in these two cases suggest that this is an effective and well-tolerated treatment for lymphangiomas in children.

A study of 105 patients with childhood malignant germ-cell tumors (MGCT) and 639 community controls was conducted utilizing a large epidemiologic database collected by the Childrens Cancer Group from 25 member institutions in the United States and Canada. This study was designed to explore the risk factors of this malignancy whose etiology remains poorly understood. A structured, self-administered questionnaire was used to collect exposure information, and data were analyzed using an unconditional logistic regression model with adjustment for relevant confounders. Consistent with the findings from studies of adult MGCT, gestational age was associated inversely with risk of MGCT, with a 70 to 75 percent reduction in risk for children born at term compared with those born pre-term. Parental, particularly maternal, self-reported exposure to chemicals or solvents (odds ratio [OR]=4.6, 95 percent confidence interval [CI]=1.9–11.3) and OR=2.2, CI=1.1–4.7 for maternal and paternal exposure, respectively) and plastic or resin fumes (OR=12.0, CI=1.9–7.5.0 [maternal] and OR=2.5, CI=1.0–6.5 [paternal]) were associated with elevated risk of MGCT. New findings, not reported previously, include a positive relationship of MGCT risk with birthweight and prolonged breastfeeding, an inverse association between MGCT risk and number of cigarettes smoked by the mother during pregnancy, and a 3.1-fold increased risk (CI=1.5–6.6) associated with maternal urinary infections during index pregnancy. Although these findings need confirmation from future studies, they suggest a potential influence of in utero exposure to maternal endogenous hormones, parental environmental exposures, and maternal diseases during pregnancy in the development of childhood MGCT.

HomeRadiologyVol. 191, No. 3 PreviousNext ReviewsImaging of Children with CancerMark E. Nesbit, Jr, Beverly P. WoodMark E. Nesbit, Jr, Beverly P. WoodMark E. Nesbit, JrBeverly P. WoodPublished Online:Jun 1 1994https://doi.org/10.1148/radiology.191.3.780MoreSectionsPDF ToolsAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookXLinked In Article HistoryPublished in print: June 1994 FiguresReferencesRelatedDetailsRecommended Articles RSNA Education Exhibits RSNA Case Collection Vol. 191, No. 3 Metrics Altmetric Score PDF download