Five-year survival is 92.5% (95% confidence interval [CI], 90%-94%) and eventfree survival (EFS) 91% (95% CI, 89%-93%). EFS is 98% (95% CI, 90%-100%), 92% (95% CI, 89%-95%), and 84% (95% CI, 77%-90%) for group A, B, and C, respectively. In group B, multivariate analysis of prognostic factors showed that a lactate dehydrogenase level more than 2-fold the normal value, no response after COP, and age of at least 15 years were associated with a lower EFS. CNS involvement was the only prognostic factor in group C. (Blood. 2001;97:3370-3379)

Dermatofibrosarcoma protuberans (DP), an infiltrative skin tumour of intermediate malignancy, presents specific features such as reciprocal translocations t(17;22)(q22;q13) and supernumerary ring chromosomes derived from the t(17;22). In this report, the breakpoints from translocations and rings in DP and its juvenile form, giant cell fibroblastoma (GCF), were characterised on the genomic and RNA level. These rearrangements fuse the platelet-derived growth factor B-chain (PDGFB, c-sis proto-oncogene) and the collagen type I alpha 1 (COL1A1) genes. PDGFB has transforming activity and is a potent mitogen for a number of cell types, but its role in oncogenic processes is not fully understood. COL1A1 is a major constituent of the connective tissue matrix. Neither PDGFB nor COL1A1 have so far been implicated in any tumour translocations. These gene fusions delete exon 1 of PDGFB, and release this growth factor from its normal regulation.

Selective avoidance of local therapy is justified in some patients, though further work is required to prospectively identify those for whom this is most applicable. Exclusion of alkylating agents is justified for the most favorable subset of patients. The value of the new six-drug chemotherapy combination is being evaluated further in a randomized study (MMT 95).

The t(2;5)(p23;q35) translocation, associated with anaplastic large-cell lymphoma (ALCL), results in the expression of a chimeric NPM-ALK protein that can be detected by the ALK1 monoclonal antibody. This report describes the morphologic and phenotypic spectrum of 123 cases of lymphoma that all express ALK protein. The results provide strong evidence that the morphologic patterns of ALCL described in previous reports as representing possible subtypes of ALCL, eg, common type, lymphohistiocytic, or small cell patterns, are morphologic variants of the same disease entity. All of these morphologic patterns could be found within this series, and in some patients different subtypes coexisted in a single biopsy or were found in successive biopsies from a single patient. The link between these morphologic subtypes is further reinforced by the presence in all cases of a highly characteristic large cell, with an eccentric nucleus and an eosinophilic paranuclear region. We suggest that this cell can be considered as a major distinguishing feature of ALK-positive lymphomas. Another characteristic of these tumors was the perivascular pattern of neoplastic cell infiltration seen in a significant number of cases. In addition to ALK protein, all tumors expressed epithelial membrane antigen and lacked CD15, features that may be of value in differentiating ALCL from Hodgkin's disease. In the majority of cases (84%), malignant cells showed both a cytoplasmic and nuclear staining for ALK1 and thus presumably carried the 2;5 translocation, but staining was restricted to the cytoplasm in a few cases, suggesting that translocations other than t(2;5) may induce expression of ALK protein. We conclude from this study that ALK-positive neoplasms represent a distinct entity. Because their morphology is often neither anaplastic nor large cell, we suggest that they should henceforward be referred to as ALK lymphomas.

No abstract

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.

Desmoplastic small round cell tumors (DSRCTs) present a reciprocal chromosomal translocation, t(11;22)(p13;q12), that results in fusion of Ewing's sarcoma and Wilms' tumor (WT1) genes. The authors evaluated 15 DSRCTs and 71 other tumors often considered in the differential diagnosis for immunoreactivity using a polyclonal antibody directed against the WT1 part of the chimeric protein resulting from this translocation. WT1 immunostaining was performed on paraffin material using the WT(C-19) antibody after heat-antigen retrieval. All the DSRCTs (15 of 15, 100%) demonstrated strong WT1 nuclear immunoreactivity. Ten of 14 nephroblastomas (71%) disclosed WT1-positive nuclei in accordance with the staining reported by others, and rare and focal nuclear positivity was detected in two of 17 rhabdomyosarcomas. WT1 immunoreactivity was not observed in Ewing's sarcoma/primitive neuroectodermal tumors (zero of 21, 0%), neuroblastomas (zero of 17, 0%), or rhabdoid tumors of the kidney (zero of two, 0%). In nephroblastoma, differential diagnosis with DSRCT was not difficult: Clinical and morphologic data are not similar for these two entities. The current study validates WT1 immunoreactivity as a useful marker to separate DSRCT from other small round cell tumors.

These results suggest that most children with clinical stage I and II HD can be treated with chemotherapy devoid of alkylating agents and anthracycline, followed by low-dose RT.