成人梭形细胞横纹肌肉瘤9例临床病理学分析

目的探讨成人梭形细胞横纹肌肉瘤(spindle cell rhabdom yosarcoma,SRMS)的临床病理学特征、免疫表型和鉴别诊断。方法回顾性分析9例成人SRMS的临床资料、病理学形态和免疫组织化学标记结果。结果9例患者中7例男性,2例女性。年龄20～80岁,平均45岁。发生于头颈部4例,包括右下颌、咽部、鼻咽部和左上颌,占总数的44%。前臂、腰部、大腿、小腿、睾丸分别1例。均表现为逐渐增大的肿块。肿块直径2～14cm,平均5.9cm。组织学上主要由具有轻度非典型性的梭形细胞组成,呈交叉的束状排列,散在于梭形细胞之间有少量的梭形或多角形的横纹肌母细胞。在2例局灶区域可见明显的间质硬化,2例局灶区域可见假血管瘤样结构,1例散在少量疏松黏液样区域,在1例可见局灶区域瘤细胞呈轻度的多形性,但不见奇异核的横纹肌母细胞。免疫组织化学标记显示,梭形细胞表达vimentin、desmin、CD99和MyoD1,多数表达myogenin和MSA(分别为6例和7例),均不表达S-100、CD34、CK和HMB-45。术后随访6个月～4年,发生于睾丸患者有腹腔静脉旁转移,发生于小腿者有肝转移。4例复发,2例死亡。结论成人SRMS少见,好发于男性,头颈部是最好发部位,具有较强的侵袭性行为。形态学上应与多种梭形细胞肿瘤相鉴别。     

硬化性横纹肌肉瘤的临床病理学分析

目的探讨硬化性横纹肌肉瘤（SRMS）的临床病理学特征,以及与胚胎性横纹肌肉瘤（ERMS）和腺泡状横纹肌肉瘤（ARMS）之间的关系。方法观察4例SRMS的临床特点、光镜形态,以免疫组织化学染色[En Vision法;波形蛋白、结蛋白、α-平滑肌肌动蛋白（α-SMA）、肌特异性肌动蛋白（MSA）、生肌蛋白、肌调节蛋白（MyoD1）、高分子量钙调结合蛋白（h-CALD）、CD31、CD34、第Ⅷ因子相关抗原、S-100蛋白、细胞角蛋白（AE1／AE3）和问变性大细胞淋巴瘤激酶（ALK1）]确定免疫学表型。结果4例均发生于成年人,平均年龄41．5岁。男性2例,女性2例。肿瘤分别位于左腕部、右大腿、右颊部和右面部,直径大小为2．5—10．0cm,平均5．7cm。镜下以含有大量玻璃样变的基质为特征,类似原始的骨样组织或软骨样基质。瘤细胞主要由原始的小圆形细胞组成,其排列方式呈多样化,包括条束状、索状、列兵样、梁状、微腺泡状和假血管样排列等。除1例可见少量的横纹肌母细胞外,其余3例均未见横纹肌母细胞,也未见花环状多核巨细胞。2例的局部区域还含有梭形细胞成分,其中1例类似梭形细胞横纹肌肉瘤,另1例类似周围神经肿瘤。免疫组织化学标记显示,瘤细胞弥漫强阳性表达MyoD1,而结蛋白多为灶性表达,生肌蛋白多为阴性或仅为灶性阳性。3例表达MSA,2例表达Ot-SMA,但不表达h-CALD。S-100蛋白、CD31和ALK1等标记均为阴性。结论SRMS在形态上和免疫学表型上与ERMS和ARMS均有所不同,但在细胞遗传学上与ERMS关系密切。熟悉SRMS的形态特征和免疫学表型有助于识别这种少见的横纹肌肉瘤亚型及与其他硬化性肿瘤相鉴别。     

先天性梭形细胞/硬化性横纹肌肉瘤临床病理学分析

目的探讨先天性梭形细胞/硬化性横纹肌肉瘤的临床病理学特征。方法收集首都医科大学附属北京儿童医院2017年4月至2022年1月诊断的先天性梭形细胞/硬化性横纹肌肉瘤16例(包括会诊病例10例), 分析其组织形态学特点、免疫表型及分子遗传学特征。结果 16例患儿中, 男患儿9例, 女患儿7例;5例于母孕产期发现, 11例于出生后即发现, 肿物分别位于胸壁、腰背部、腹膜后、四肢及会阴部。肿瘤由束状排列的梭形细胞构成, 局部间质硬化并玻璃样变性, 免疫组织化学显示肿瘤细胞不同程度表达结蛋白、Myogenin、MyoD1、平滑肌肌动蛋白、CD56及间变性淋巴瘤激酶, 其他标志物CD34、CD99、pan-TRK、S-100蛋白、BCOR等均不表达。11例行NCOA2(8q13)及VGLL2(6q22)基因断裂探针检测, 提示4例(4/11)染色体NCOA2(8q13)存在断裂易位;6例测序病例中, 1例(1/6)检测到MYOD1基因p.L122R位点杂合突变;2例行电镜检测, 镜下见束状排列肌丝, 部分有原始肌节形成。5例经单纯性手术切除, 2例活检后仅随诊观察, 9例术后予化疗。有效随访12例...     

硬化性横纹肌肉瘤2例并文献复习

目的 探讨硬化性横纹肌肉瘤(sclerosing rhabdomyosarcoma,SRMS)的临床病理特点,提高其诊断与鉴别诊断水平.方法 对2例SRMS组织进行免疫组织化学染色并文献复习.结果 患者男女各1例,年龄分别为16、28岁,发生部位分别在左颌下及脊柱旁,临床表现均为无痛性肿块.大体均为灰白肿块,质地中等,边界不清.镜下2例组织学形态基本一致,肿瘤内均含有大量嗜伊红色玻璃样变的基质,类似原始软骨样或骨样基质,肿瘤细胞主要由原始小圆细胞组成,呈条索样、梁状、腺管状、微腺泡状和假血管样排列.免疫组织化学示瘤细胞vimentin(+)、MyoD1细胞核(+).结论 SRMS是一种罕见的肉瘤类型,兼具腺泡状横纹肌肉瘤(alveolar rhabdomyosarcoma,ARMS)和胚胎性横纹肌肉瘤胚胎性横纹肌肉瘤(embryonal rhabdomyosarcoma,ERMS)部分形态特点,但与二者又不同.熟悉SRMS病理学特征和免疫表型对诊断和鉴别诊断具有重要意义.     

EWSR1/FUS-TFCP2融合的上皮/梭形细胞横纹肌肉瘤临床病理学研究

目的探讨EWSR1/FUS-TFCP2融合的上皮/梭形细胞横纹肌肉瘤临床病理及分子遗传学特征。方法收集佛山市中医院病理科2019年1月至2022年12月明确诊断为EWSR1/FUS-TFCP2融合的上皮/梭形细胞横纹肌肉瘤会诊病例14例, 对其临床、病理形态学、免疫组织化学特点进行回顾性分析, 利用荧光原位杂交及二代测序技术分析其分子遗传学特征, 并复习相关文献。结果 14例患者中男性5例, 女性9例, 年龄6～36岁(平均22岁), 发生部位分别为头颈部9例, 骨盆2例, 膀胱1例, 左耻骨1例, 腹壁、肱骨及耻骨多发1例。临床表现多为伴有疼痛的占位性病变, 影像学表现多为侵袭性的放射学特征伴有软组织累及。肿瘤平均直径6.6 cm(最大径2～23 cm), 瘤组织界限不清, 镜下主要由比例不等的梭形细胞及上皮样细胞构成。瘤组织分化不一, 分化差的瘤组织异型性明显, 核分裂象活跃, 肿瘤性坏死明显;分化好的瘤组织, 梭形细胞和/或上皮样细胞胞质中等或丰富, 核轻度异型性, 排列呈束状或席纹状。免疫组织化学显示瘤组织表达MyoD1、Myogenin及结蛋白, 程度不等地表达间变性淋巴瘤激...     

前列腺特异性间质肉瘤1例临床病理特征

目的：探讨前列腺特异性间质肉瘤( prostatic special-ized stromal sarcoma, PSS)的临床病理特征、免疫表型、诊断及鉴别诊断。方法回顾性分析1例PSS的临床病理特征、免疫表型、诊断及鉴别诊断等,并复习相关文献。结果梭形及短梭形PSS细胞呈束状、编织状排列,细胞核主要呈卵圆形、短梭形,核仁不明显,可见多角形细胞。免疫表型：肿瘤细胞vimentin、CD34呈弥漫阳性, PR 呈弱阳性。结论PSS起源于前列腺激素依赖性特异性间质细胞,是一种罕见肉瘤。病理诊断主要依靠病理学形态和免疫表型,vimentin、CD34阳性可鉴别诊断,需与肉瘤样癌、平滑肌肉瘤、横纹肌肉瘤等相鉴别。     

儿童梭形细胞横纹肌肉瘤10例临床病理分析

目的探讨儿童梭形细胞横纹肌肉瘤的临床病理特征、诊断及鉴别诊断。方法回顾性分析10例儿童梭形细胞横纹肌肉瘤的临床病理学特征并复习相关文献。结果镜下主要表现为长梭形的肿瘤细胞,部分区域可见典型的胚胎性横纹肌肉瘤区或分化较好的横纹肌母细胞区,肿瘤细胞表达肌源性标记desmin、Myogenin和MyoD1,Ki-67核增殖指数为15%~60%。结论儿童梭形细胞横纹肌肉瘤少见,易漏诊或误诊,需与儿童常见的其他梭形细胞肿瘤相鉴别。     

肾脏横纹肌样滑膜肉瘤1例并文献复习

目的探讨罕见的肾脏横纹肌样滑膜肉瘤的临床病理学特征。方法回顾性分析1例肾脏横纹肌样滑膜肉瘤患者的临床资料和病理学形态,对其原发灶和转移灶行免疫组化EnVision两步法检查及SS18-SSX融合基因检测,并复习相关文献。结果患者男性,31岁,2014年11月影像学检查发现右肾肿瘤,行右肾根治性手术,镜下见肿瘤细胞呈短梭形,弥漫排列,胞质丰富,可见嗜伊红团块样物,初次病理诊断为肾脏横纹肌样瘤。2015年10月影像学检查发现肝脏及膈肌间占位,行肝脏肿瘤及部分膈肌切除,镜下见肿瘤细胞均呈长梭形,细胞密集,交叉束状排列,细胞质较少,胞质内未出现嗜伊红团块样物,该形态学为典型滑膜肉瘤。免疫表型:EMA、TLE1、vimentin、CD56均阳性,INI1阴性。FISH检测SS18-SSX融合基因,原发灶和转移灶均为阳性,最终证实原发灶即为滑膜肉瘤。结论肾脏横纹肌样滑膜肉瘤罕见,易误诊为肾脏横纹肌样瘤,该例肾脏横纹肌样滑膜肉瘤拓宽了肾脏横纹肌样肿瘤的鉴别诊断瘤谱,即使为典型的横纹肌样形态,也需利用分子生物学手段进行鉴别诊断。SS18-SSX融合基因检测阳性是确诊滑膜肉瘤的依据。     

梭形细胞/多形性脂肪瘤7例临床病理分析

目的探讨梭形细胞/多形性脂肪瘤(spindle cell/pleomorphic,SCL/PL)的临床病理学特征、诊断及鉴别诊断。方法回顾性分析7例SCL/PL的临床及病理学特征,并复习相关文献,并将其与脂肪瘤样型孤立性纤维性肿瘤、硬化型脂肪肉瘤、梭形细胞脂肪肉瘤进行对比分析。结果 7例患者年龄41~77岁,平均54岁,均为男性。肿瘤部位:手部2例,颈部3例,肩部2例。病史1~8年。梭形细胞脂肪瘤镜下由温和的梭形细胞、束状排列的胶原纤维及数量不等的脂肪细胞组成。多形性脂肪瘤可见特征性的大的、多形性、花环状细胞。免疫表型:梭形细胞及多形性细胞CD34阳性,脂肪细胞S-100阳性。术后随访5~59个月,未见复发及转移。结论 SCL/PL为较少见的良性肿瘤,应与一些良性、局部侵袭性及低度恶性的软组织肿瘤及肿瘤样病变相鉴别。     

具有TFCP2基因重排横纹肌肉瘤临床病理学特征

目的探讨具有TFCP2基因重排横纹肌肉瘤(rhabdomyosarcomas, RMS)的临床病理学特征。方法收集2例具有TFCP2基因重排RMS的临床病理及分子遗传学检测资料, 同时复习相关文献。结果例1女, 31岁, 肿物位于左上牙龈;例2女, 49岁, 肿物位于右上颌后牙区。镜下形态:例1由条束状、旋涡状的短/胖梭形细胞构成;例2肿瘤与骨组织混杂生长, 长梭形细胞为主伴有少量上皮样细胞。免疫表型, 例1肿瘤细胞部分表达结蛋白及广谱细胞角蛋白, 例2肿瘤细胞弥漫表达结蛋白;2例均MyoD1弥漫阳性, Myogenin阴性, 间变性淋巴瘤激酶Ventana-D5F3部分阳性。间期荧光原位杂交(FISH)检测到TFCP2基因易位。二代测序检测到EWSR1-TFCP2融合基因。例1术后5个月左颈淋巴结转移, 例2术后32个月前腭部肿瘤复发。结论具有TFCP2基因重排RMS是RMS的一组特殊亚群, 好发于骨, 特别是青年患者颅面骨, 表现为上皮样细胞和/或梭形细胞形态, 预后不良。     

Recurrent MYOD1 mutations in pediatric and adult sclerosing and spindle cell rhabdomyosarcomas: Evidence for a common pathogenesis

Sclerosing and spindle cell rhabdomyosarcoma (RMS) are rare types of RMS recently reclassified as a stand‐alone pathologic entity, separate from embryonal RMS (ERMS). Although sclerosing and spindle cell RMS share clinical and morphologic features, a pathogenetic link based on shared molecular alterations has not been established. Spindle cell RMS in children have been associated with a less aggressive clinical course compared to adults. Recently, recurrent MYOD1 mutations were described in 44% of adult spindle cell RMS, but no pediatric tumors or sclerosing RMS were studied for comparison. Thus, we investigated 16 RMS (5 sclerosing and 11 spindle cell) in children and adults for the presence of MYOD1 mutations by targeted Polymerase Chain Reaction (PCR). Remarkably, all 5 sclerosing RMS and 4 of 11 spindle cell RMS showed the MYOD1 p.L122R hot‐spot mutation. Of the five pediatric tumors, 2/2 sclerosing RMS and 2/3 spindle cell RMS showed MYOD1 mutations. Three of nine MYOD1‐mutant RMS showed coexistent PIK3CA mutations, while no MDM2 amplifications were identified. All four pediatric MYOD1‐mutated RMS patients died of the disease at 12–35 months following diagnosis. In conclusion, spindle cell and sclerosing RMS show recurrent MYOD1 mutations, in keeping with a single pathologic entity, regardless of age at presentation. This group however, is distinct from the infantile RMS associated with NCOA2 fusions. Although our study suggests that pediatric MYOD1‐mutant RMS follow an aggressive behavior with high mortality, further studies are required to confirm this finding. © 2014 Wiley Periodicals, Inc.     

Spindle cell/sclerosing rhabdomyosarcoma: case series from a single institution emphasizing morphology,immunohistochemistry and follow-up

Spindle cell/sclerosing rhabdomyosarcoma is a rare skeletal-muscle tumor with distinctive clinicopathologic characteristics. 10 cases (6 cases of spindle cell rhabdomyosarcoma and 4 cases of scleroisng rhabdomyosarcoma) were composed of 6 males and 4 females aging from 5 months to 57 years, with median age 33 years, most of who represented a painless solid mass. Histologically, the tumors were composed of fascicles of spindle cells or primitive round cells embed in sclerotic matrix with presence of rhabdomyoblasts in varying proportion. Immunohistochemically, the tumor cells expressed MyoD1 (10/10), Desmin (10/10), myogenin (6/10), AE1/AE3 (2/10), EMA (2/10), but were negative for SMA, caldesmon, S-100. All of the patients underwent a complete surgical resection without or with chemotherapy (2/10) or radiotherapy (1/10). During the follow-up period (1 to 24 months), 1 patient was succumbed, and 2 cases showed in situ recurrence with 1 of them adopting metastasis. Our cases further demonstrate there do present some clincopathologic relations between spindle cells rhabdomyosarcoma and sclerosing rhabdomyosarcoma, but the latter seems to have a better prognosis. Exact grading and staging contribute to predict the outcome.     

Sclerosing rhabdomyosarcoma of the parotid gland in an adult

Primary rhabdomyosarcoma of salivary glands is an extremely rare neoplasm, mostly seen in children. A newly described subtype of rhabdomyosarcoma, sclerosing rhabdomyosarcoma, has not yet been reported in this location. We report on a parotid gland tumor characterized by infiltrative growth of primitive type of neoplastic cells showing strong and diffuse nuclear positivity for MyoD1 and myogenin and by prominent hyalinized/chondroid matrix with some myxoid foci. The tumor recurred several times, and in recurrent tumors, differentiation into strap myoid cells appeared. There were no distant metastases during the 5-year follow-up.Sclerosing rhabdomyosarcoma may cause differential diagnostic problems because it could be confounded for osteosarcoma, chondrosarcoma, and some other types of sarcoma, and as in our case, for myxofibrosarcoma and myoepithelial carcinoma. Its location in the head and neck is of special interest because 6 of 14 previously described adult cases of sclerosing rhabdomyosarcoma and 7 of 18 pediatric cases also occurred in this region. To our knowledge, this is the first reported case of primary sclerosing rhabdomyosarcoma of the parotid gland.     

Genetic heterogeneity in rhabdomyosarcoma revealed by SNP array analysis

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Alveolar (ARMS) and embryonal (ERMS) histologies predominate, but rare cases are classified as spindle cell/sclerosing (SRMS). For treatment stratification, RMS is further subclassified as fusion‐positive (FP‐RMS) or fusion‐negative (FN‐RMS), depending on whether a gene fusion involving PAX3 or PAX7 is present or not. We investigated 19 cases of pediatric RMS using high resolution single‐nucleotide polymorphism (SNP) array. FP‐ARMS displayed, on average, more structural rearrangements than ERMS; the single FN‐ARMS had a genomic profile similar to ERMS. Apart from previously known amplification (e.g., MYCN, CDK4, and MIR17HG) and deletion (e.g., NF1, CDKN2A, and CDKN2B) targets, amplification of ERBB2 and homozygous loss of ASCC3 or ODZ3 were seen. Combining SNP array with cytogenetic data revealed that most cases were polyploid, with at least one case having started as a near‐haploid tumor. Further bioinformatic analysis of the SNP array data disclosed genetic heterogeneity, in the form of subclonal chromosomal imbalances, in five tumors. The outcome was worse for patients with FP‐ARMS than ERMS or FN‐ARMS (6/8 vs. 1/9 dead of disease), and the only children with ERMS showing intratumor diversity or with MYOD1 mutation‐positive SRMS also died of disease. High resolution SNP array can be useful in evaluating genomic imbalances in pediatric RMS. © 2015 Wiley Periodicals, Inc.     

Recurrent NCOA2 gene rearrangements in congenital/infantile spindle cell rhabdomyosarcoma

Spindle cell rhabdomyosarcoma (RMS) is a rare form of RMS with different clinical characteristics between children and adult patients. Its genetic hallmark remains unknown and it remains debatable if there is pathogenetic relationship between the spindle cell and the so‐called sclerosing RMS. We studied two pediatric and one adult spindle cell RMS by next generation RNA sequencing and FusionSeq data analysis to detect novel fusions. An SRF‐NCOA2 fusion was detected in a spindle cell RMS from the posterior neck in a 7‐month‐old child. The fusion matched the tumor karyotype and was confirmed by FISH and RT‐PCR, which showed fusion of SRF exon 6 to NCOA2 exon 12. Additional 14 spindle cell (from 8 children and 6 adults) and 4 sclerosing (from 2 children and 2 adults) RMS were tested by FISH for the presence of abnormalities in NCOA2, SRF, as well as for PAX3 and NCOA1. NCOA2 rearrangements were found in two additional spindle cell RMS from a 3‐month‐old and a 4‐week‐old child. In the latter tumor, TEAD1 was identified by rapid amplification of cDNA ends (RACE) to be the NCOA2 gene fusion partner. None of the adult tumors were positive for NCOA2 rearrangement. Despite similar histomorphology in adults and young children, these results suggest that spindle cell RMS is a heterogeneous disease genetically as well as clinically. Our findings also support a relationship between NCOA2‐rearranged spindle cell RMS occurring in young childhood and the so‐called congenital RMS, which often displays rearrangements at 8q13 locus (NCOA2). © 2013 Wiley Periodicals, Inc.     

Primary osseous rhabdomyosarcoma with focal matrix formation mimicking osteosarcoma

We present an unusual case of primary osseous pleomorphic rhabdomyosarcoma with focal matrix formation mimicking osteosarcoma. The patient was a 21-year-old man who had suffered from pain and slight enlargement of his left calf for 2 months. A plain radiograph demonstrated a large, predominantly osteolytic mass in the region of the proximal fibula with features typical of malignant primary bone tumor. On open surgical biopsy, the tumor consisted of atypical cells, some of them presenting spindle morphology. Between them, there were bands of densely hyalinized matrix with osteoid appearance, but without definite lacunae or calcifications, and an osteosarcoma was diagnosed. Consequently, the tumor was removed. The postoperative tissue presented more pleomorphic cells with some definite rhabdomyoblasts. Desmin, actin, Myf4, and MyoD1 were positive in tumor cells, and a diagnosis of rhabdomyosarcoma was eventually made. Only few cases of primary pure bone rhabdomyosarcoma have been reported. Other bone tumors with rhabdomyosarcomatous differentiation have been described: dedifferentiated chondrosarcoma, fibrosarcoma, and osteosarcoma. Our case does not meet the criteria for sclerosing rhabdomyosarcoma, as matrix formation is focal and cells are spindle-shaped and pleomorphic. However, it is a further example of a diagnostic error in connection with primary osseous tumor.     

Clinicopathologic features of 300 rhabdomyosarcomas with emphasis upon differential expression of skeletal muscle specific markers in the various subtypes: A single institutional experience

The present study was aimed at evaluating clinicopathologic and immunohistochemical (IHC) features of 300 rhabdomyosarcomas (RMSs), including differential IHC expression and prognostic value of myogenin and MyoD1 across various subtypes of RMSs.IHC expression of myogenin and MyoD1 was graded on the basis of percentage of tumor cells displaying positive intranuclear immunostaining i.e. grade 1 (1–25%); grade 2 (26–50%); grade 3 (51–76%) and grade 4 (76–100%).Clinical follow-up was available in 238 (79.3%) patients. Various clinicopathologic parameters were correlated with 3-year disease free survival (DFS) and overall survival (OS).There were 140 cases (46.7%) of alveolar RMS (ARMS), 90 of embryonal RMS (ERMS) (30%), 61 (20.3%) of spindle cell/sclerosing RMS and 9 cases (3%) of pleomorphic RMS. Most cases, barring pleomorphic RMSs, occurred in the first two decades (228 cases) (76%), frequently in males, in the head and neck region (126) (42%).By immunohistochemistry, desmin was positive in 292/299 (97.6%) tumors; myogenin in 238/267 (89.1%) and MyoD1 in 192/266 (72.2%) tumors. High myogenin expression (in ≥51% positive tumor cells) was significantly associated with ARMSs (95/121, 78.5%), as compared to other subtypes (48/117, 41%) (p value < 0.001). High MyoD1 expression (≥51% tumor cells) was seen in more cases of pure sclerosing, combined with spindle cell/sclerosing RMSs (10/10, 100%), as compared to the other subtypes (91/141, 67.4%) (p = 0.032).There was no significant difference between high myogenin expression and clinical outcomes. Patients without metastasis and harbouring tumors, measuring ≤5 cm showed a significant increase in OS, with p values = 0.01 and <0.001, respectively.ARMS was the most frequent subtype. There was a significant association between high myogenin expression and ARMSs and high MyoD1 expression and spindle cell/sclerosing RMSs. High myogenin expression did not correlate with clinical outcomes. Patients with smaller sized tumors and without metastasis had significantly better clinical outcomes.