双表型鼻腔鼻窦肉瘤临床病理和分子遗传学特征分析

Clinicopathologic and molecular genetic characterizations of biphenotypic sinonasal sarcoma

目的 观察双表型鼻腔鼻窦肉瘤的临床病理以及分子遗传学特征,并对其诊断和鉴别诊断要点进行分析.方法 对3例双表型鼻腔鼻窦肉瘤的组织形态学、免疫组织化学和分子遗传学特点进行观察并结合文献进行总结和分析.结果 2例男性,1例女性,发病年龄分别为45岁、29岁和40岁.CT和MRI检查均表现为鼻腔巨大息肉样占位.镜下观察：肿瘤境界不清,由密集的梭形细胞组成,呈长束状或交错束状排列,常见血管外皮瘤样结构;被覆黏膜上皮呈囊状（2例）、腺样（1例）以及内翻性乳头状样（1例）增生下陷入肿瘤内,局灶可见嗜酸性化生（2例）.瘤细胞核形态温和,核分裂象罕见,未见坏死.免疫组织化学染色3例均显示神经和肌源性标志物的共表达,其中3/3弥漫强表达S-100蛋白,3/3表达平滑肌肌动蛋白（1例弥漫,2例局灶）;1/2弥漫强表达calponin;1/3局灶表达结蛋白;1/1局灶表达MyoD1.此外,1/1局灶核表达β-catenin,3例均不表达角蛋白、SOX10和CD34.Ki-67阳性指数分别为〈5%、10%以及〈2%.荧光原位杂交分析3例均存在PAX3基因易位,其中例3逆转录聚合酶链式反应和转录测序分析提示存在PAX3-FOXO1基因融合.3例随访3~15个月,均未见肿瘤复发和转移.结论 双表型鼻腔鼻窦肉瘤容易与许多良恶性梭形细胞肿瘤混淆,免疫组织化学染色共表达神经和肌源性标志物以及遗传学显示PAX3基因重排可助于其诊断和鉴别诊断.

Objective To investigate the clinicopathologic characteristics, immunophenotypes, molecular genetics, and diagnostic and differential diagnostic features of biphenotypic sinonasal sarcoma （BSNS）. Methods Three cases of BSNS were retrieved, the histomorphology, immunophenotype and molecular genetics were analyzed with review of literature. Results There were 2 male and 1 female patient aged 45,29 and 40 years,respectively.Computed tomography and magnetic resonance imaging examinations showed a large polypoid mass occupying the sinonasal cavity in all 3 patients. Microscopically,these tumors were un-circumscribed and composed of cellular spindle-shaped cells arranged in long and interlaced fascicles. A hemangiopericytoma-like growth pattern was frequently identified. The overlying hyperplastic respiratory epithelium invaginated down into the tumor forming a cystic（2 cases）, glandular（1 case） structures and inverted in a papilloma-like（1 case）pattern, and foci of eosinophilic metaplasia were also noted in 2 of the three cases. The tumor nuclei were bland-appearing,mitoses were scarce and necrosis was absent. Immunohistochemically,the tumor cells showed co-expression of neural and myogenic markers in all the 3 cases,including that 3/3 showed diffuse and strong positivity of S-100 protein,3/3 positivity of smooth muscle actin（1 diffuse and 2 focal）,1/2 diffuse positivity of calponin,1/3 focal positivity of desmin, and 1/1 focal positivity of MyoD1.In addition,1 detected for β-catenin showed focal nuclear positivity. None of the 3 showed positivity to cytokeratin,CD34 or SOX10 in the tumor cells.Ki-67 showed an index〈5%,10%and 〈2%,respectively. Fluorescence in situ hybridization analysis showed rearrangements of PAX3 gene in all 3 cases. In case 3, reverse transcription polymerase chain reaction, followed by Sanger sequencing, demonstrated an in-frame fusion between PAX3 and FOXO1.Follow-up information（range 3-15 months） showed no evidence of local recurrence or distant metastasis in three cases. Conclusions BSNS is a newly described entity which can be readily confused with a variety of benign and malignant spindle cell tumors encountered in the sinonasal cavity; immunohistochemistry co-expression of neural and myogenic markers and PAX3 gene rearrangement can help distinguish this tumor from its many mimickers.