The expanding morphological and genetic spectrum of MYOD1-mutant spindle cell/sclerosing rhabdomyosarcomas: a clinicopathological and molecular comparison of mutated and non-mutated cases
Journal
Histopathology
Journal Volume
74
Journal Issue
6
Pages
933-943
Date Issued
2019
Author(s)
Tsai J.-W.
ChangChien Y.-C.
Kao Y.-C.
Li W.-S.
Liang C.-W.
Liao I.-C.
Chang Y.-M.
Wang J.-C.
Tsao C.-F.
Yu S.-C.
Huang H.-Y.
Abstract
Aims: Spindle cell/sclerosing rhabdomyosarcomas (SC/SRMS) feature spindled and/or rounded rhabdomyosarcomatous cells within variably hyalinised stroma. Only 30–67% of SC/SRMSs harbour neomorphic MYOD1 p.L122R mutations, indicating heterogeneity in this RMS type. We compared MYOD1-mutant and non-mutant cases to characterise the histological and genetic spectrum of mutated SC/SRMS. 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 harboured MYOD1 mutations, including homozygous p.L122R (n?=?8), heterozygous p.L122R (n?=?3) and heterozygous p.E118K (n?=?1). MYOD1-mutant tumours affected nine females and three males aged 8–64?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 four cases, including one with heterologous lipoblasts in focally myxoid stroma. Four sclerosing cases mainly comprised rounded cells, including one with multinucleated tumour 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 lipoblast-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 seven MYOD1-mutant cases; one had died of disease. Five non-mutated cases were reclassified as spindle embryonal (n?=?3), dense embryonal (n?=?1) and unclassifiable (n?=?1) RMSs. Conclusion: MYOD1-mutant RMSs are uncommonly mutated with PIK3CA and behave aggressively with an expanded morphological and genetic spectrum, including lipoblastic differentiation, multinucleated cells and the alternative p.E118K mutation. ? 2019 John Wiley & Sons Ltd
Subjects
alternative mutation; MYOD1; rhabdomyosarcoma; sclerosing; spindle; variant histology
Other Subjects
MyoD1 protein; myogenin; pik3ca protein; protein; unclassified drug; MyoD protein; MyoD1 myogenic differentiation protein; phosphatidylinositol 4,5 bisphosphate 3 kinase; PIK3CA protein, human; adolescent; adult; Article; cancer recurrence; child; clinical article; female; follow up; gene mutation; genetic heterogeneity; heterozygote; histology; homozygote; human; immunophenotyping; lung metastasis; male; preschool child; priority journal; protein expression; rhabdomyosarcoma; school child; spinal cord metastasis; spindle cell sclerosing rhabdomyosarcoma; tumor volume; young adult; comparative study; genetics; middle aged; mutation; pathology; retrospective study; rhabdomyosarcoma; sarcoma; Adolescent; Adult; Child; Class I Phosphatidylinositol 3-Kinases; Female; Humans; Male; Middle Aged; Mutation; MyoD Protein; Retrospective Studies; Rhabdomyosarcoma; Sarcoma; Young Adult
Publisher
Blackwell Publishing Ltd
Type
journal article