Primary follicular lymphoma of the testis in children and adolescents.

This study reports 6 cases of primary follicular lymphoma of the testis (PFLT) in children and adolescents correlated with clinical presentation, pathologic features, treatment, and outcome. All 6 patients (age, 3 to 16 y; median, 4 y) had PFLT grade 3 with disease limited to the testis, completely resected and treated with 2 courses of chemotherapy (cyclophosphamide, vincristine, prednisone, doxorubicin). Event-free survival was 100% (follow-up: median, 73 mo; mean, 53 mo; range, 6 to 96 mo). In conclusion, clinical outcome in children and adolescents with PFLT is excellent with treatment including complete surgical resection and 2 courses of cyclophosphamide, vincristine, prednisone, doxorubicin.

Chemotherapy in patients with teratoma with malignant transformation.

OBJECTIVE: Germ-cell tumours (GCTs) with a non-GCT malignant component are a unique and rare phenomenon called teratoma with malignant transformation (TMT). The only published series of patients with TMT treated with chemotherapy comprised 10 patients. We report here our experience in treating 14 patients with TMT. PATIENTS AND METHODS: Sarcoma was identified in 10 of 14 patients, with rhabdomyosarcoma ranking first (n=4). Other histological types included adenocarcinoma (n=3) and bronchoalveolar carcinoma (n=1). Immunohistochemistry was performed to help in identifying the malignant non-GCT component. RESULTS: Primary treatment consisted of surgery alone in 4 patients. The remaining 10 patients received first-line cisplatin-based chemotherapy with resection of residual masses (n=5): 4 patients had a complete response and 5 had a partial response. Overall, 9 patients developed a relapse with a median time of 84 mo (range: 6-168). At relapse, 8 patients received a chemotherapy regimen directed to the non-GCT component. Four of these patients achieved a partial response. With a median follow-up of 59 mo (range: 3-180), 4 of 14 patients are alive, including 3 who are disease-free. CONCLUSION: To our knowledge, this is by far the largest reported European series of chemotherapy in TMT. Although TMT has a poor prognosis compared to GCT, its management may be improved by adapted chemotherapy associated with surgical resection of residual masses.

Negative preclinical results with stealth nanospheres-encapsulated Doxorubicin in an orthotopic murine brain tumor model.

Previous results have shown that PEG-coated poly(hexadecylcyanoacrylate) (PEG-PHDCA) nanospheres displayed a significant accumulation within an orthotopic 9L gliosarcoma model, after i.v. administration to rats. Hence, the aim of the present study was to evaluate in the same model the pre-clinical efficacy of this carrier when loaded with Doxorubicin, an anticancer drug which poorly distributes in the CNS. Free and nanospheres-encapsulated Doxorubicin were administered with a multiple dose treatment. Their maximum tolerated dose (MTD) and increase in life span were respectively assessed in healthy and intracranially 9L-bearing rats. A comparative biodistribution study of Doxorubicin-loaded and unloaded PEG-PHDCA nanospheres was also performed in the tumor-bearing group. The results showed that the cumulative MTD of nanoparticulate doxorubicin was 1.5 times higher than this of free Doxorubicin. Nevertheless, encapsulated Doxorubicin was unable to elicit a better therapeutic response in the 9L gliosarcoma. Biodistribution study revealed that the Doxorubicin-loaded nanospheres accumulated to a 2.5-fold lesser extent in the 9L tumor as compared to the unloaded nanospheres and that they were mainly localized in the lungs and the spleen. Such a typical profile indicated aggregation with plasma proteins as a consequence of the positive surface charge of these loaded particles; this ionic interaction resulting from drug encapsulation was mainly responsible for 9L treatment failure.

In vivo treatment with CPT-11 leads to differentiation of neuroblastoma xenografts and topoisomerase I alterations.

Topoisomerase I inhibitors, such as CPT-11, are potent anticancer drugs against neuroblastoma (NB). Differentiating agents, such as retinoids, improve the survival of children with metastatic NB. To characterize the biological effects associated with exposure to CPT-11 in vivo, athymic mice bearing a human NB xenograft, named IGR-NB8 and characterized as an immature NB with poor prognostic markers, were treated with CPT-11. Prolonged stable disease was observed, resulting in an overall tumor growth delay of 115 days. During treatment, tumors differentiated into ganglioneuroblastomas (GGNB), which reverted into an immature phenotype when treatment was discontinued. In contrast, 13-cis retinoic acid failed to induce differentiation of IGR-NB8 in vivo. Tumor differentiation was associated with decreased N-myc expression, induction of p73 expression in the perinuclear area and cytoplasm, and a dramatic 35-fold decrease in topoisomerase I (topo I) catalytic activity. The full-length Mr 100,000 topo I protein was present in both pre and post-treatment immature NB xenografts. In contrast, differentiated GGNBs did not contain the Mr 100,000 protein but an intense Mr 48,000 topo I fragment. Furthermore, redistribution of the Mr 48,000 and 68,000 forms to the cytoplasm was observed in differentiated tumors. The same pattern of topo I expression and catalytic activity was observed in NBs and GGNBs obtained from pediatric patients. Our data suggest that prolonged in vivo exposure to CPT-11 induces differentiation of NB xenografts, which is associated with truncation of the topo I enzyme, relocation of the degraded forms to the cytoplasm, and decreased catalytic activity.

Dermatofibrosarcoma protuberans, giant cell fibroblastoma, and hybrid lesions in children: clinicopathologic comparative analysis of 28 cases with molecular data--a study from the French Federation of Cancer Centers Sarcoma Group.

The clinicopathologic and immunohistochemical features of 28 dermatofibrosarcoma protuberans (DFSP), giant cell fibroblastomas (GCFs), and hybrid lesions occurring in children are presented, including molecular data for seven of them. There were 19 pure adult-type DFSP (9 male and 10 female patients aged between a few days [neonate] and 13 years, median 7 years), 5 pure GCF (all males aged from 2 to 8 years, median 4 years), and 4 hybrid tumors (all males aged from 1 to 4 years, median 2.5 years). Tumor locations in pure adult-type DFSP included the trunk (6) and lower (11) and upper (2) limbs. Pure GCFs were observed on the trunk (4) and knee (1), and hybrid lesions on the trunk (2) and lower (1) and upper (1) extremities. Tumor size (n = 20) ranged from 0.6 to 5 cm (median 2 cm). Histologically, pure DFSP presented as monotonous and infiltrative, low-grade, dermal/hypodermal storiform spindle cell proliferations, sparing adnexal structures. GCF showed a dense fibrous to myxoid matrix containing slender wavy spindle cells and multinucleated giant stromal cells often lining angiectoid spaces. Hybrid lesions showed varying combinations of DFSP and GCF areas. Mitotic activity ranged from 1 to 3 mitoses per 10 high power fields. All tumors were diffusely positive for vimentin and CD34 but negative for smooth muscle actin, desmin, epithelial membrane antigen, and cytokeratins; one pure adult-type DFSP was also S-100 protein positive; <1% of nuclei were Ki67 (Mib-1) positive. One karyotyped adult-type DFSP showed an unbalanced t(17;22) (q22;q13) translocation. Multiplex RT-PCR analysis and sequencing of PCR products in seven cases showed gene fusion transcripts in two pure DFSP, two pure GCFs, and one hybrid lesion. Results were uncertain in one pure GCF; one adult-type DFSP was negative. Treatment procedures were known for 27 patients, consisting of 16 wide excisions and 11 marginal excisions. Follow-up information on 15 widely excised tumors (median 24 months; range 5-144 months) showed no recurrence. Five of six marginally excised lesions with available follow up recurred 2 months to 6 years (median 2 years) after initial surgery; all but one were cured by wide reexcision. None of the tumors metastasized. In conclusion, this study emphasizes 1) the occurrence of adult-type DFSP in children, 2) the close relationship between DFSP and GCF clinically, histologically, and molecularly, 3) the excellent prognostic of these lesions if widely excised, and 4) the diagnostic usefulness of RT-PCR analyses in detecting the gene fusion transcripts resulting from the t(17;22) (q22;q13) in paraffin-embedded tissues.

[Atypical mesoblastic nephroma: histopathological entity or specific anatomoclinical form?]. / Le néphrome mésoblastique cellulaire ou atypique: entité histopathologique ou forme anatomo-clinique particulière?

Atypical mesoblastic nephroma is a rare kidney tumor mostly which occurred in early infancy. We describe two cases of atypical mesoblastic nephroma diagnosed in infants aged respectively 2 and 3 months. The tumors were completely removed and surgical margins were histologically free of disease. The two patients are well 14 and 9 months after surgery. Microscopically, the tumor was characterized by a densely cellular proliferation, high mitotic levels, cystic degeneration and necrosis. In the literature, the prognostic is good in patients aged fewer than 3 months and in cases in which the surgical removal was complete.