Objective: To study the clinicopathologic features, immunophenotype, molecular genetics and differential diagnosis of biphenotypic sinonasal sarcoma (BSNS), and to evaluate the role of PAX3 and PAX8 immunohistochemical (IHC) antibodies in the diagnosis of BSNS. Methods: Nasal sinus spindle cell tumors surgically treated at the Jinling Hospital from 2000 to 2019 were collected, including three cases of BSNS, 10 cases of acinar rhabdomyosarcoma, eight cases of schwannoma, five cases of hemangiopericytoma, three cases of fibrosarcoma, and one case of triton tumor. The cases were evaluated by histology, IHC by EnVision for PAX3 and PAX 8 (including PAX8 murine monoclonal antibody, clone number OTI6H8, hereinafter referred to as PAX8-OTI6H8 antibody; PAX8 rabbit monoclonal antibody, clone number EP298, hereinafter referred to as PAX8-EP298 antibody) molecular genetic tests. Results: All three BSNS patients were elderly women with clinical manifestations of nasal congestion and bleeding. Imaging showed a soft tissue density shadow of the nasal cavity and sinuses with bone destruction. The boundaries of tumors which were covered with ciliated columnar epithelium were unclear, and mucosal invasion and squamous metaplasia could be seen. Tumor cells were spindle-shaped, arranged in a bundle-like, braided arrangement, with little cellular atypia and occasional atypical mitotic figures. The tumoral interstitial vessels were mostly thin-walled, some showing staghorn-like changes. There was focal striated muscle differentiation in two cases, and bone invasion was seen in two cases. IHC staining showed that all three cases of BSNS expressed PAX3 and PAX8-OTI6H8, but not PAX8-EP298. All eight cases of schwannoma, five cases of hemangiopericytoma, and one case of triton tumor did not express PAX3, PAX8-OTI6H8 or PAX8-EP298. Eight of the ten cases of alveolar rhabdomyosarcoma expressed PAX3 and PAX8-OTI6H8, but not PAX8-EP298. Three cases of fibrosarcoma showed weak PAX3 and PAX8-OTI6H8 expression, but there was no PAX8-EP298 expression. FISH detection showed that PAX3 break apart in the tumor cells from all three patients (four specimens). Conclusions: BSNS is a distinct sinonasal low grade malignancy with dual differentiation which could be readily confused with a variety of spindle cell tumors encountered in the sinonasal cavity. The molecular genetics of PAX3 gene break is the gold standard for diagnosis of this tumor. IHC marker monoclonal PAX3 is 100% expressed in BSNS, while the specificity is limited. PAX8-OTI6H8 is also expressed in BSNS due to the cross reaction with PAX3 antibody, while PAX8-EP298 is all negative for these tumors.
目的： 探讨双表型鼻腔鼻窦肉瘤（BSNS）的临床病理、分子遗传学特征及鉴别诊断，并评估PAX3和PAX8抗体在BSNS诊断中的作用。 方法： 收集2000—2019年东部战区总医院手术治疗的鼻腔鼻窦梭形细胞肿瘤30例（包括3例BSNS、10例腺泡状横纹肌肉瘤、8例神经鞘瘤、5例血管外皮瘤、3例纤维肉瘤、1例蝾螈瘤）。对BSNS标本进行HE、免疫组织化学和荧光原位杂交（FISH）染色，并随访患者。应用免疫组织化学EnVision法检测所有肿瘤标本中PAX3及两种PAX8抗体（包括PAX8鼠单克隆抗体，克隆号OTI6H8，以下简称PAX8-OTI6H8抗体；PAX8兔单克隆抗体，克隆号EP298，以下简称PAX8-EP298抗体）的表达，比较PAX3及两种PAX8抗体在肿瘤组织中的阳性表达率。 结果： 3例BSNS患者均为老年女性，临床多表现为鼻塞，伴出血。影像学显示鼻腔鼻窦软组织密度影，伴骨质破坏。光镜下观察肿瘤组织界限不清，常衬覆纤毛柱状上皮，并可见黏膜内陷及鳞状上皮化生。肿瘤细胞梭形，呈束状、编织状排列，细胞异型性较小，偶见病理性核分裂象。肿瘤间质血管多为薄壁血管，部分呈鹿角样改变。2例肿瘤组织出现横纹肌分化区域，2例可见骨组织侵犯。免疫组织化学标记，3例BSNS均表达PAX3抗体和PAX8-OTI6H8抗体，不表达PAX8-EP298抗体，8例神经鞘瘤、5例血管外皮瘤及1例蝾螈瘤均不表达PAX3、PAX8-OTI6H8及PAX8-EP298抗体，10例腺泡状横纹肌肉瘤中8例有PAX3及PAX8-OTI6H8抗体的阳性表达，而不表达PAX8-EP298抗体，3例纤维肉瘤中1例局灶弱阳性表达PAX3及PAX8-OTI6H8抗体，不表达PAX8-EP298抗体。FISH检测显示3例患者（4份标本）的肿瘤细胞均存在PAX3基因断裂。 结论： BSNS是具有神经和肌源性双重分化的独特的鼻腔鼻窦低度恶性肿瘤，易与其他梭形细胞肿瘤相混淆。PAX3基因断裂是诊断该肿瘤的金标准，PAX3在BSNS中阳性表达，但特异性有限。PAX8-OTI6H8抗体也会在BSNS中表达，PAX8-EP298抗体则均为不表达。.
Keywords: Diagnosis, differential; Immunohistochemistry; Paranasal sinus neoplasms.