The expanding morphological and genetic spectra of MYOD1‐mutant spindle cell/sclerosing rhabdomyosarcomas: a clinicopathological and molecular comparison of mutated and nonmutated cases

Abstract

Aims

Spindle cell/sclerosing rhabdomyosarcomas (SC/SRMSs) feature spindled and/or rounded rhabdomyosarcomatous cells within variably hyalinized stroma. Only 30%‐67% of SC/SRMSs harbor neomorphic MYOD1 p.L122R mutations, indicating heterogeneity in this RMS type. We compared MYOD1‐mutant and nonmutant cases to characterize the histological and genetic spectra of mutated SC/SRMSs.

Methods and Results

Seventeen RMSs with spindled, sclerosing, or hybrid histology were sequenced to identify MYOD1 and PIK3CA mutations and reappraised to assess histological features and myogenic immunophenotypes. Twelve SC/SRMSs harbored MYOD1 mutations, including homozygous p.L122R (n=8), heterozygous p.L122R (n=3), and heterozygous p.E118K (n=1). MYOD1‐mutant tumors affected 9 females and 3 males aged 8 to 64 years (median, 22.5), had a median size of 4.2 cm (range, 2‐22) and involved the head and neck (n=7), extremities (n=4), and mediastinum (n=1). Fascicular/spindle histology was predominant in 4 cases, including one with heterologous lipoblasts in focally myxoid stroma. Four sclerosing cases mainly comprised rounded cells, including one with multinucleated tumor cells. Four cases were histologically hybrid. The only PIK3CA (p.H1047R) mutation was detected in a predominantly spindled MYOD1‐p.L122R‐mutated case but not in its laser‐microdissected lipoblasts‐containing area. All MYOD1‐mutant cases exhibited diffuse MYOD1 expression but patchy myogenin reactivity. At final follow‐up (median, 13.5 months), recurrences (n=4), metastases (n=2), or both (n=1) occurred in 7 MYOD1‐mutant cases; 1 had died of disease. Five nonmutated cases were reclassified as spindle embryonal (n=3), dense embryonal (n=1), and unclassifiable (n=1) RMSs.

Conclusion

MYOD1‐mutant RMSs, uncommonly comutated with PIK3CA, behave aggressively with expanding morphological and genetic spectra, including lipoblastic differentiation, multinucleated cells, and the alternative p.E118K mutation.

This article is protected by copyright. All rights reserved.

http://bit.ly/2RqEAir