[1863] Epithelioid Rhabdomyosarcomas: A Clinicopathologic and Molecular Study

Rita Alaggio, Angelica Zin, Angelo Rosolen, Patrizia Dall'Igna, Gianni Bisogno, Roberta Bertorelle. University of Padova, Padua, Italy; University Hospital Padova, Padua, Italy; Padua Hospital, University of Padua, Padua, Italy

Background: Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma is currently classified in 2 principal subtypes: embryonal (ERMS) characterized by variable genetic alterations including TP53, RB1 and RAS mutations; alveolar RMS (ARMS), harbouring a gene fusion between PAX3 or PAX7 and FOXO1, with an aggressive clinical behaviour. Epithelioid RMS is a morphologic variant of RMS recently described in adults.
Design: 150 ARMS enrolled in Italian therapeutic protocols were reviewed in order to identify tumors with features of Epithelioid RMS and investigate their molecular features. Immunostainings (muscle specific actin, Desmin, Myogenin, AP-2β, EMA, cytokeratins, INI-1), reverse-transcriptase polymerase chain reaction (RT-PCR) assays to detect MyoD1, myogenin, and PAX3/7-FOXO1 transcripts were performed. DNA sequencing of TP53 was performed by capillary automated sequencer; RB1 allelic imbalance (gain or loss) and homozygous deletion were analyzed by quantitative real-time PCR.
Results: Five Epithelioid RMS were identified. Clinical features are summarized in the table 1. Histology showed sheets of large cells without rhabdomyoblastic differentiation or anaplasia in 3 and prominent rhabdoid cells in 2; Necrosis in 4, often with a geographic pattern. Immunostainings showed: positive staining for INI, Desmin and Myogenin (scattered cells in 4, 70% in 1); EMA and MNF116 were positive in 2, AP-2β constantly negative. All tumors lacked PAX/FOXO1 transcripts. RB1 and TP53 were wild type in 4 and 3 cases respectively, with mutation at R273H codon in 1.

Table 1
CaseAge/sexSizeSiteLymph-node MetastasisFollow-up
19y/Mu*HN-PM**N1ANED (8yr)
26y/M3.3HN-PMN0ANED (10yr)
313y/F4armN0ANED (8yr)
411y/Fu**armN0u
58y/M8.3orbitN0ANED (4yr)
*unknown, **HN-PM head/neck parameningeal


Conclusions: RMS with epithelioid morphology rarely occurs in children. Lack of ARMS translocations, weak staining for myogenin and negative AP-2β suggest a potential relationship with ERMS, inline with by TP53 mutation found in one case and by the favourable clinical course in the 3 patients with available follow-up.
Category: Pediatrics

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 280, Tuesday Afternoon

 

Close Window