The expanding morphological and genetic spectrum of MYOD1-mutant spindle cell/sclerosing rhabdomyosarcomas: a clinicopathological and molecular comparison of mutated and non-mutated cases

Jen Wei Tsai, Yi Che ChangChien, Jen Chieh Lee, Yu-Chien Kao, Wan Shan Li, Cher Wei Liang, I. Chuang Liao, Yi Ming Chang, Jui Chu Wang, Cheng Feng Tsao, Shih Chen Yu, Hsuan Ying Huang

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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.

Original languageEnglish
JournalHistopathology
DOIs
Publication statusPublished - Jan 1 2019

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Rhabdomyosarcoma
Mutation
Histology
Myogenin
Mediastinum
Cell Differentiation
Neoplasms
Lasers
Neck
Extremities
Head
Neoplasm Metastasis
Recurrence

Keywords

  • alternative mutation
  • MYOD1
  • rhabdomyosarcoma
  • sclerosing
  • spindle
  • variant histology

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

The expanding morphological and genetic spectrum of MYOD1-mutant spindle cell/sclerosing rhabdomyosarcomas : a clinicopathological and molecular comparison of mutated and non-mutated cases. / Tsai, Jen Wei; ChangChien, Yi Che; Lee, Jen Chieh; Kao, Yu-Chien; Li, Wan Shan; Liang, Cher Wei; Liao, I. Chuang; Chang, Yi Ming; Wang, Jui Chu; Tsao, Cheng Feng; Yu, Shih Chen; Huang, Hsuan Ying.

In: Histopathology, 01.01.2019.

Research output: Contribution to journalArticle

Tsai, Jen Wei ; ChangChien, Yi Che ; Lee, Jen Chieh ; Kao, Yu-Chien ; Li, Wan Shan ; Liang, Cher Wei ; Liao, I. Chuang ; Chang, Yi Ming ; Wang, Jui Chu ; Tsao, Cheng Feng ; Yu, Shih Chen ; Huang, Hsuan Ying. / The expanding morphological and genetic spectrum of MYOD1-mutant spindle cell/sclerosing rhabdomyosarcomas : a clinicopathological and molecular comparison of mutated and non-mutated cases. In: Histopathology. 2019.
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title = "The expanding morphological and genetic spectrum of MYOD1-mutant spindle cell/sclerosing rhabdomyosarcomas: a clinicopathological and molecular comparison of mutated and non-mutated cases",
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.",
keywords = "alternative mutation, MYOD1, rhabdomyosarcoma, sclerosing, spindle, variant histology",
author = "Tsai, {Jen Wei} and ChangChien, {Yi Che} and Lee, {Jen Chieh} and Yu-Chien Kao and Li, {Wan Shan} and Liang, {Cher Wei} and Liao, {I. Chuang} and Chang, {Yi Ming} and Wang, {Jui Chu} and Tsao, {Cheng Feng} and Yu, {Shih Chen} and Huang, {Hsuan Ying}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/his.13819",
language = "English",
journal = "Histopathology",
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TY - JOUR

T1 - The expanding morphological and genetic spectrum of MYOD1-mutant spindle cell/sclerosing rhabdomyosarcomas

T2 - a clinicopathological and molecular comparison of mutated and non-mutated cases

AU - Tsai, Jen Wei

AU - ChangChien, Yi Che

AU - Lee, Jen Chieh

AU - Kao, Yu-Chien

AU - Li, Wan Shan

AU - Liang, Cher Wei

AU - Liao, I. Chuang

AU - Chang, Yi Ming

AU - Wang, Jui Chu

AU - Tsao, Cheng Feng

AU - Yu, Shih Chen

AU - Huang, Hsuan Ying

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - alternative mutation

KW - MYOD1

KW - rhabdomyosarcoma

KW - sclerosing

KW - spindle

KW - variant histology

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