Cryptic EWSR1-FLI1 fusions in Ewing sarcoma: potential pitfalls in the diagnostic use of fluorescence in situ hybridization probes.

Detection of EWSR1 translocations - particularly t(11;22)(q24;q12) - is of great value in the differential diagnosis of the Ewing family of tumors. We report two cases that highlight the problems and pitfalls of identifying Ewing tumors using conventional chromosome analysis and a commercial EWSR1 fluorescence in situ hybridization (FISH) probe. In both cases, the tumor karyotype was abnormal, but a visible t(11;22)(q24;q12) was not present. The commercial EWSR1 "break-apart" probe was not split in either case. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, however, identified EWSR1-FLI1 fusion transcripts in both tumors, and the gene fusions were corroborated by FISH analysis with "in house" probes and confirmed by sequencing RT-PCR products. The occurrence of cryptic EWSR1-FLI1 fusions mandates that RT-PCR should be performed, particularly in those cases in which the genetic findings are not in agreement with the histologic picture.

Monosomy 3 predicts death but not time until death in choroidal melanoma.

PURPOSE: To study whether monosomy 3 can predict time until death caused by metastatic melanoma, whether life expectancy can be predicted in patients after surgical excision of a melanoma displaying monosomy 3, and to confirm the prognostic value of monosomy 3 and its correlation with tumor histology. METHODS: Archival specimens from 71 patients who died of metastatic melanoma and 40 patients who were living or had died of other causes were identified. The number of copies of chromosome 3 was assessed by chromosome in situ hybridization, and monosomy 3 was compared with clinicopathologic features. RESULTS: Monosomy 3 was detected in 47 of 71 metastasizing melanomas (66.1%) and was significantly associated with metastasis-related death (P < 0.0001). All 40 nonmetastasizing tumors were balanced for chromosome 3 (two copies). In 70% of cases, epithelioid cells and vascular loops in combination predicted the presence of monosomy 3 (P < 0.0001). Among the 71 patients who had died of metastasizing melanoma, there was no difference in time until death between monosomic and balanced tumors. However, a survival curve corrected for age of the patients at the time of surgery suggested that very-long-term survival with monosomy 3 is probably rare. CONCLUSIONS: Monosomy 3 is an important predictor of death in melanoma and is in some cases predicted by histology. However, death of metastatic disease occurs in a significant number of patients without monosomy 3. There is no significant difference in time until death between metastatic melanomas, with and without monosomy 3. However, survival of patients with tumors displaying monosomy 3 is generally short.