Extraskeletal Myxoid Chondrosarcomas: The Uncommon Clinicopathologic Manifestations and Significance of TAF15::NR4A3 Fusion

被引：4

作者：

Huang, Shih-Chiang ^{[1
,2
]}

Lee, Jen-Chieh ^{[3
]}

Hsu, Yong-Chen ^{[4
]}

Tsai, Jen-Wei ^{[5
]}

Kao, Yu-Chien ^{[6
,7
]}

Hsieh, Tsung-Han ^{[8
]}

Chang, Yi-Ming ^{[9
,10
,11
]}

Chang, Kung-Chao ^{[12
]}

Wu, Pao-Shu ^{[13
,14
]}

Chen, Paul Chih-Hsueh ^{[15
]}

Chen, Chien-Heng ^{[16
]}

Chang, Ching-Di ^{[17
]}

Lee, Pei-Hang ^{[18
]}

Tai, Hui-Chun ^{[19
]}

Liu, Ting -Ting ^{[18
]}

Wen, Mei-Chin ^{[20
]}

Li, Wan-Shan ^{[21
]}

Yu, Shih-Chen ^{[18
]}

Wang, Jui-Chu ^{[18
]}

Huang, Hsuan-Ying ^{[18
]}

机构：

[1] Chang Gung Univ, Linkou Chang Gung Mem Hosp, Coll Med, Dept Anat Pathol, Taoyuan, Taiwan

[2] Chang Gung Univ, Grad Inst Clin Med Sci, Coll Med, Taoyuan, Taiwan

[3] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Dept & Grad Inst Pathol, Taipei, Taiwan

[4] Taichung Vet Gen Hosp, Dept Pathol & Lab Med, Taichung, Taiwan

[5] I Shou Univ, E Da Hosp, Dept Pathol, Kaohsiung, Taiwan

[6] Taipei Med Univ Hosp, Dept Pathol, Taipei, Taiwan

[7] Taipei Med Univ, Coll Med, Sch Med, Dept Pathol, Taipei, Taiwan

[8] Taipei Med Univ, Joint Biobank, Off Human Res, Taipei, Taiwan

[9] Kaohsiung Vet Gen Hosp, Dept Pathol & Lab Med, Kaohsiung, Taiwan

[10] Triserv Gen Hosp, Natl Def Med Ctr, Dept Pathol, Taipei, Taiwan

[11] Natl Def Med Ctr, Inst Med Sci, Taipei, Taiwan

[12] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Pathol, Tainan, Taiwan

[13] MacKay Mem Hosp, Dept Pathol, Taipei, Taiwan

[14] Mackay Jr Coll Med Nursing & Management, Taipei, Taiwan

[15] Taipei Vet Gen Hosp, Dept Pathol, Taipei, Taiwan

[16] Kaohsiung Med Univ, Kaohsiung Municipal Siaogang Hosp, Dept Pathol, Kaohsiung, Taiwan

[17] Chang Gung Univ, Kaohsiung Chang Gung Mem Hosp, Coll Med, Dept Radiol, Kaohsiung, Taiwan

[18] Chang Gung Univ, Kaohsiung Chang Gung Mem Hosp, Coll Med, Dept Anat Pathol, Kaohsiung, Taiwan

[19] Changhua Christian Hosp, Dept Pathol, Changhua, Taiwan

[20] China Med Univ, Hsinchu Hosp, Div Pathol, Hsinchu, Taiwan

[21] Chi Mei Med Ctr, Dept Pathol, Tainan, Taiwan

来源：

MODERN PATHOLOGY | 2023年 / 36卷 / 07期

关键词：

extraskeletal myxoid; chondrosarcoma; pan-Trk; solid; TAF15; osseous; SOFT-TISSUE; PROTEIN; EXPRESSION; BONE;

D O I：

10.1016/j.modpat.2023.100161

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Extraskeletal myxoid chondrosarcoma (EMC) is an ultrarare sarcoma typically exhibiting myxoid/ reticular histology and NR4A3 translocation. However, morphologic variants and the relevance of non-EWSR1::NR4A3 fusions remain underexplored. Three challenging pan-Trk-expressing cases, featuring cellular to solid histology, were subjected to RNA exome sequencing (RES), unveiling different NR4A3-associated fusions. Alongside RES-analyzed cases, fluorescence in situ hybridization was performed to confirm 58 EMCs, with 48 available for pan-Trk immunostaining and KIT sequencing. Except for 1 (2%) NR4A3-rearranged EMC without identifiable partners, 46 (79%), 9 (16%), and 2 (3%) cases harbored EWSR1::NR4A3, TAF15::NR4A3, and TCF12::NR4A3 fusions, respec- tively. Five EWSR1::NR4A3-positive EMCs occurred in the subcutis (3) and bone (2). Besides 43 classical cases, there were 8 cellular, 4 rhabdoid/anaplastic, 2 solid, and 1 mixed tumor-like variants. Tumor cells were oval/spindle to pleomorphic and formed loose myxoid/reticular to compact sheet- like or fascicular patterns, imparting broad diagnostic considerations. RES showed upregulation of NTRK2/3, KIT, and INSM1. Moderate-to-strong immunoreactivities of pan-Trk, CD117, and INSM1 were present in 35.4%, 52.6%, and 54.6% of EMCs, respectively. KIT p. E554K mutation was detected in 2/48 cases. TAF15::NR4A3 was significantly associated with size >10 cm (78%, P1/4.025). Size >10 cm, moderate-to-severe nuclear pleomorphism, metastasis at presentation, TAF15::NR4A3 fusion, and the administration of chemotherapy portended shorter univariate disease-specific survival, whereas only size >10 cm (P=.004) and metastasis at presentation (P=.032) remained prognostically in- dependent. Conclusively, EMC may manifest superficial or osseous lesions harboring EWSR1::NR4A3, underrecognized solid or anaplastic histology, and pan-Trk expression, posing tremendous chal- lenges. Most TAF15::NR4A3-positive cases were >10 cm in size, ie, a crucial independent prog- nosticator, whereas pathogenic KIT mutation rarely occurred.(c) 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.

引用

页数：14

共 23 条

[21] SMARCA2-NR4A3 is a novel fusion gene of extraskeletal myxoid chondrosarcoma identified by RNA next-generation sequencing
Wei, Shuanzeng
Pei, Jianming
von Mehren, Margaret
Abraham, John A.
Patchefsky, Arthur S.
Cooper, Harry S.
GENES CHROMOSOMES & CANCER, 2021, 60 (10): : 709 - 712
[22] Extraskeletal myxoid chondrosarcoma with a t(9;16)(q22;p11.2) resulting in a NR4A3-FUS fusion
Broehm, Cory J.
Wu, Jin
Gullapalli, Rama R.
Bocklage, Therese
CANCER GENETICS, 2014, 207 (06) : 276 - 280
[23] Extraskeletal myxoid chondrosarcoma: A study of 17 cases focusing on the diagnostic utility of INSM1 expression and presenting rare morphological variants associated with non-EWSR1::NR4A3 fusions
Lenz, Jiri
Klubickova, Natalie
Ptakova, Nikola
Hajkova, Veronika
Grossmann, Petr
Steiner, Petr
Kinkor, Zdenek
Svajdler, Marian
Michal, Michal
Konecna, Petra
Machacova, Dominika
Hurnik, Pavel
Tichy, Michal
Tichy, Frantisek
Kyllar, Michal
Fiala, Ludek
Kavka, Miroslav
Michal, Michael
HUMAN PATHOLOGY, 2023, 134 : 19 - 29

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