CD99 Positivity and EWS-FLII Gene Rearrangement Identify a Breast Tumor in a 60-Year-Old Patient With Attributes of the Ewing Family of Neoplasms

Abstract

Rearrangements of the EWS gene with ETS transcription factor genes as a result of chromosomal translocation and high expression levels of CD99MIC2 characterize the Ewing family of tumors (EFT). This group of rather undifferentiated neoplasms affects bone and soft tissue in children and young adults mostly between 5 and 30 years of age (median, 15 years). This study reports a case of a CD99MIC2 positive small round cell tumor in the breast of a 60-year-old woman in whom a t(11;22)(q24;q12) chromosomal aberration was identified by cytogenetic analysis. Reverse transcriptase (RT)-polymerase chain reaction (PCR) followed by sequence analysis revealed expression of a chimera transcript in which EWS exon 10 was fused to FLI1 exon 6. Previously, this gene fusion has been reported to occur in approximately 3% of EFT. The specific gene rearrangement of EWS intron 10 was confirmed on Southern blot of genomic DNA. This study further contributes to the growing list of unusual neoplasms in adults that carry genotypic and phenotypic traits of the EFT.

Ewing's Sarcoma Family of Tumors: Current Management

“…Individual members of this tumor family are defined along a gradient of limited neuroglial differentiation, with the poorly differentiated Ewing's sarcoma at one end and the more mature pPNETs at the other. With the availability of molecular tools to unambiguously confirm the presence of ews-ets gene rearrangements, the spectrum of Ewing's sarcoma-related neoplasms has recently been expanded to include rare CD99 MIC2 -positive extraskeletal tumors in various anatomic sites including the kidney [40][41][42][43][44], breast [41], gastrointestinal tract [45][46][47][48], prostate [49], endometrium [50], lung [44], adrenal gland [51], and meninges [52]. Although Ewing's family of tumors typically arise during adolescence, there is also an increasing number of adults being diagnosed with a CD99…”

Peripheral Neuroectodermal Tumor (PNET) of the Breast – a 6-Year Follow-Up

“…Although there have been reports of metastatic PNET involving the breast [8,9], a Medline search (1976-2006) revealed only 1 publication on PNET of the breast as a primary tumor [7]. According to our experience with the current patient, the clinical findings first resembled those of a hematoma, which however increased in size.…”

“…The antibody MIB1 stained an inhomogeneously distributed fraction of 10-20%. The cytogenetic examination of 20 metaphases revealed the karyotype 46,XX,t(11;22)(q24,q12) [13] / 46,XX [7]. The t(11; 22) translocation is characteristic for PNET.…”

“…Slides were prepared by conventional technique and G-banding using the trypsin-Giemsa method. Details are described in our publication cited above [7].…”

“…PNET is most often present as a bone or soft tissue mass in the trunk or axial skeleton. Our study group was the first worldwide to publish typical chromosomal aberrations and molecular genetic findings of a PNET arising in the breast as a primary tumor in 1999 (Medline 1976 to December 2006) [7]. Here, we report the clinical symptoms, imaging findings, cytological and histological results in more detail and present the follow-up of this unusual case.…”