A clinicopathologic study of head and neck rhabdomyosarcomas showing FOXO1 fusion-positive alveolar and MYOD1-mutant sclerosing are associated with unfavorable outcome

Oral Oncol. 2016 Oct:61:89-97. doi: 10.1016/j.oraloncology.2016.08.017. Epub 2016 Sep 6.

Abstract

Background: Based on their distinctive histologic and genetic features, the latest WHO classification of soft tissue tumors includes four pathologic variants of rhabdomyosarcoma (RMS): embryonal (ERMS), alveolar (ARMS), spindle cell-sclerosing (SRMS-ScRMS) and pleomorphic RMS. The aim of this study focused on a detailed clinicopathologic and survival analysis of head and neck RMS (HNRMS) using the latest pathologic and molecular criteria reflecting this new subclassification in a large cohort.

Patients and methods: Patients managed for HNRMS in our institution (1996-2015) were analyzed. The presence of a FOXO1 fusion was required for the classification of ARMS. MYOD1 mutations in SRMS-ScRMS were tested when material available. Univariate and multivariate analyses were performed to evaluate variables related to overall survival (OS).

Results: Ninety-nine HNRMS patients (52 males and 47 females, mean of 16years) were included in the study after pathologic re-review. The most common location was parameningeal (PM) (n=64), followed by non-orbital/non-PM (n=25) and orbital (n=10). There were 53 ERMS, 33 fusion-positive ARMS and 13 SRMS-ScRMS [SRMS (8); ScRMS (5)]. The 5-year OS rate for ERMS patients was significantly higher (82%) compared to ARMS (53%) and SRMS-ScRMS (50%) [SRMS (75%); ScRMS (30%)]. Univariate analysis showed that survival was dependent on histology (P=0.012), tumor size >5cm (P<0.001), regional lymph node involvement (P=0.002), metastasis at initial presentation (P<0.001), stage (P<0.001), and recurrence (P=0.002). Multivariate analysis confirmed histologic subtype to be significant (P=0.043).

Conclusion: Our findings reinforce that HNRMS is a heterogenous disease with ARMS and SRMS-ScRMS having an equally unfavorable outcome.

Keywords: Alveolar rhabdomyosarcoma; Embryonal rhabdomyosarcoma; MYOD1 mutations; PAX3/7-FOXO1 fusion; Sclerosing rhabdomyosarcoma; Spindle cell rhabdomyosarcoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Child
  • Female
  • Forkhead Box Protein O1 / genetics*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Male
  • Middle Aged
  • Rhabdomyosarcoma / genetics
  • Rhabdomyosarcoma / pathology*

Substances

  • FOXO1 protein, human
  • Forkhead Box Protein O1