杨守京 空军军医大学（第四军医大学）西京医院病理科，西安710032

梭形细胞/硬化性横纹肌肉瘤的过去：

梭形细胞横纹肌肉瘤于1992年首次由Cavazzana等报道[1]，在WHO(2002)软组织肿瘤分类中为胚胎性横纹肌肉瘤的特殊亚型。硬化性横纹肌肉瘤最早由Mentzel和Katenkamp于2000年报道，当时命名为成人硬化性假血管瘤样横纹肌肉瘤[2]，Folpe等于2002年正式将具有丰富玻璃样变基质的横纹肌肉瘤命名为硬化性横纹肌肉瘤[3]。

梭形细胞/硬化性横纹肌肉瘤的现在：

横纹肌肉瘤分为4大类：胚胎性横纹肌肉瘤、腺泡状横纹肌肉瘤、多形性横纹肌肉瘤和梭形细胞/硬化性横纹肌肉瘤。因梭形细胞横纹肌肉瘤预后较非梭形胚胎性横纹肌肉瘤好，且在分子遗传学方面，梭形细胞横纹肌肉瘤亦不同于非梭形细胞胚胎型横纹肌肉瘤和腺泡型横纹肌肉瘤，因此2013年WHO将其独立为一亚型。硬化性横纹肌肉瘤中可见梭形细胞横纹肌肉瘤成分，而部分梭形细胞横纹肌肉瘤中也可见到硬化性区域，提示两者关系密切，故将硬化性横纹肌肉瘤和梭形细胞横纹肌肉瘤归为一类。

最近发现，梭形细胞/硬化性横纹肌肉瘤有三个基因组群：一个是含有VGLL2相关基因融合的梭形细胞横纹肌肉瘤的婴儿亚群 [4]，一个通常与硬化形态学相关的MYOD1突变亚群，以及一个没有MYOD1突变的亚群 [5] [6] [7] [8] [9] [10]。婴幼儿梭形细胞横纹肌肉瘤的间质无明显胶原化，肿瘤呈侵袭性生长，瘤细胞由束状排列的梭形细胞组成，胞质深嗜伊红色，纤维状，可呈席纹状或漩涡状排列，局部区域可见波浪状结构，似神经纤维。 部分细胞内可见横纹结构，有些区域见散在的横纹肌母细胞。瘤细胞间质中有少量胶原纤维。细胞核多为椭圆形，有些细胞核呈纤细波浪状，细胞核异型不明显，核分裂象偶见。该型通常含有VGLL2相关基因融合。MYOD1突变的型，肿瘤间质具有明显嗜伊红色玻璃样变的硬化性间质及黏液软骨样间质，形似原始骨样或软骨样基质。常有MYOD1 (L122R) 突变,约占梭形细胞/硬化性横纹肌肉瘤的55%；仅Chiles等报道1例发现PAX3-FKHR基因融合。免疫表型特征方面，瘤细胞特征性弥漫性强阳性表达MyoD1。相比于其他亚型的横纹肌肉瘤，具有更为明显的侵袭性和更差的预后。

梭形细胞/硬化性横纹肌肉瘤的将来：

因以上三种类型梭形细胞/硬化性横纹肌肉瘤，在其发生年龄、细胞遗传学、临床等方面不同，根据目前的研究进展，有可能在将来分为VGLL2相关基因融合，MYOD1突变型，和MYOD1野生型三种不同的亚型。

参考文献

1.     Cavazzana AO, Schmidt D, Ninfo V, Harms D, Tollot M, Carli M, et al. Spindle cell rhabdomyosarcoma. A prognostically favorable variant of rhabdomyosarcoma. Am J Surg Pathol. 1992; 16(3):229-235.

2.   Mentzel T, Katenkamp D. Sclerosing, pseudovascular rhabdomyosarcoma in adults. Clinicopathological and immunohistochemical analysis of three cases. Virchows Arch. 2000; 436(4):305-311.

3.   Folpe AL, McKenney JK, Bridge JA. Sclerosing rhabdomyosarcoma in adults: report of four cases of a hyalinizing, matrix-rich variant of rhabdomyosarcoma that may be confused with osteosarcoma, chondrosarcoma, or angiosarcoma. Am J Surg Pathol. 2002; 26.

4.   Alaggio R, Zhang L, Sung YS, Huang SC, Chen CL, Bisogno G, et al. A Molecular Study of Pediatric Spindle and Sclerosing Rhabdomyosarcoma: Identification of Novel and Recurrent VGLL2-related Fusions in Infantile Cases. Am J Surg Pathol. 2016; 40(2):224-235.

5.   Agaram NP, Chen CL, Zhang L, LaQuaglia MP, Wexler L, Antonescu CR. Recurrent MYOD1 mutations in pediatric and adult sclerosing and spindle cell rhabdomyosarcomas: evidence for a common pathogenesis. Genes Chromosomes Cancer. 2014; 53(9):779-787.

6.   Tsai JW, ChangChien YC, Lee JC, Kao YC, Li WS, Liang CW, et al. The expanding morphological and genetic spectrum of MYOD1-mutant spindle cell/sclerosing rhabdomyosarcomas: a clinicopathological and molecular comparison of mutated and non-mutated cases. Histopathology. 2019; 74(6):933-943.

7.   Agaram NP, LaQuaglia MP, Alaggio R, Zhang L, Fujisawa Y, Ladanyi M, et al. MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma: an aggressive subtype irrespective of age. A reappraisal for molecular classification and risk stratification. Mod Pathol. 2019; 32(1):27-36.

8.   Rekhi B, Upadhyay P, Ramteke MP. MYOD1 (L122R) mutations are associated with spindle cell and sclerosing rhabdomyosarcomas with aggressive clinical outcomes. Mod Pathol. 2016; 29.

9.   Kohsaka S, Shukla N, Ameur N, Ito T, Ng CK, Wang L, et al. A recurrent neomorphic mutation in MYOD1 defines a clinically aggressive subset of embryonal rhabdomyosarcoma associated with PI3K-AKT pathway mutations. Nat Genet. 2014; 46(6):595-600.

10. Owosho AABCD, Huang SCM, Chen SM, Kashikar SD, Estilo CLD, Wolden SLM, et al. A clinicopathologic study of head and neck rhabdomyosarcomas showing FOXO1 fusion-positive alveolar and MYOD1-mutant sclerosing are associated with unfavorable outcome. Oral oncology. 2016; 61:89-97.