Malignant ectomesenchymoma: genetic profile reflects rhabdomyosarcomatous differentiation.
Malignant ectomesenchymoma (MEM) represents a heterogeneous group of tumors, most likely originating from pluripotent primitive neural crest cells. In this report, we present an 8-month-old infant boy with an MEM on the left scrotum. Retrospective review of the incision biopsy showed the presence of a few ganglion cells in an otherwise classic embryonal rhabdomyosarcoma (RMS), whereas in the resection specimen after chemotherapy the combined RMS and ganglioneuroma components were very obvious. Cytogenetic analysis of the residual lesion showed an abnormal karyotype, 49, XY, +2, -6, +11, +20, +mar, with a hyperploidy in a subset of cells. By fluorescence in situ hybridization analysis, the marker chromosome was identified as originating from chromosome 6, and the tumor cells were negative for PAX3/PAX7 disrupting translocations specific for alveolar RMS. Gains of chromosomes 2, 11, and 20, found in the current case, are a common finding in embryonal RMS. These gains probably reflect the myogenic differentiation of MEM and support the genetic link between these 2 neoplasms. In addition to the conventional cytogenetics, array comparative genomic hybridization analysis was performed on the primary and residual tumors. The genomic profiles of both specimens were basically the same including the presence of 2 distinctive chromosome 6p21.32-p21.2 and 6p11.2 amplification regions in the primary tumor, which vanished in the postchemotherapy specimen. The pretreatment biopsy exhibited strong expression of HMGA1 and HMGA2 proteins in immunohistochemistry, with the shift toward the loss of expression of both genes in the posttreatment tumoral tissue. This finding supports the oncogenic properties of the HMGA family of proteins and their role in the process of malignant transformation.
Laboratory for Morphology and Molecular Pathology, University of Leuven, Belgium.
Giuseppe
G
Floris
Maria
M
Debiec-Rychter
Agnieszka
A
Wozniak
Elisabetta
E
Magrini
Guidalberto
G
Manfioletti
Ivo
I
De Wever
Giovanni
G
Tallini
Raf
R
Sciot
D002869:Chromosome Aberrations; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling; D005834:Genital Neoplasms, Male / Q000175:diagnosis* / Q000473:pathology; D025741:HMGA1a Protein / Q000032:analysis; D025743:HMGA2 Protein / Q000032:analysis; D006801:Humans; D007223:Infant; D008297:Male; D008637:Mesenchymoma / Q000175:diagnosis* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor / Q000032:analysis; D051761:Paired Box Transcription Factors / Q000032:analysis; D018233:Rhabdomyosarcoma, Embryonal / Q000175:diagnosis* / Q000473:pathology; D012611:Scrotum / Q000473:pathology
D025743:HMGA2 Protein; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D051761:Paired Box Transcription Factors; D025741:HMGA1a Protein