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



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).



Our findings reinforce that HNRMS is a heterogenous disease with ARMS and SRMS-ScRMS having an equally unfavorable outcome.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, United States.
Adepitan A
AA
Owosho
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States.
Shih-Chiang
SC
Huang
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States.
Sonja
S
Chen
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, United States.
Shruti
S
Kashikar
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, United States.
Cherry L
CL
Estilo
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, United States.
Suzanne L
SL
Wolden
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, United States.
Leonard H
LH
Wexler
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, United States.
Joseph M
JM
Huryn
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States. Electronic address: antonesc@mskcc.org.
Cristina R
CR
Antonescu
D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000473:pathology*
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1
Alveolar rhabdomyosarcoma; Embryonal rhabdomyosarcoma; MYOD1 mutations; PAX3/7-FOXO1 fusion; Sclerosing rhabdomyosarcoma; Spindle cell rhabdomyosarcoma
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