睾丸鞘膜间皮瘤--现代泌尿生殖肿瘤杂志

【摘要】目的 探讨高分化乳头样睾丸鞘膜间皮瘤伴对侧非典型间皮增生1例患者的临床表现、病理特征、治疗方法和预后情况。方法 采用10 %中性甲醛固定,常规石蜡包埋,切片,HE 染色,光镜观察。另对石蜡切片采用Envision 法免疫组化染色及特染。一抗为钙网膜蛋白（Calretinin），细胞角蛋白(CK) ,波形蛋白(Vimentin) ,细胞增殖指数( Ki-67) ,均由美国长岛公司提供,染色时设阳性和阴性对照。特染为AB/ PAS染色和网染。结果 患者接受了左睾丸鞘膜切除术，术中见鞘膜腔内淡黄清亮积液约30毫升，睾丸鞘膜腔囊壁见多个实性乳头状突起，单个肿瘤最大直径9mm。组织学上，结节表现为明显的外生性，伴有复杂的乳头状改变，囊壁由增生的纤维组织、平滑肌及小血管构成，表面被覆单层立方上皮，具有成簇的乳头状瘤样新生物突向腔内，乳头间质由血管及迷路上皮样细胞构成。细胞学上，上皮细胞表现为中度非典型增生，罕见有丝分裂。尽管没有表现出恶性间皮瘤的基质侵袭性，但可见由扁平上皮细胞连接的单个小管样结构延伸入睾丸鞘膜浅层下组织。免疫组化Calretinin（+）、CK（+）、Vimentin（++）、EMA(-)。患者拒绝进一步行睾丸和阴囊皮肤切除术。考虑患者双侧睾丸鞘膜发病，术后1个月行右侧睾丸鞘膜切除术，病理回报非典型间皮增生。随防36个月，患者生存良好，每半年行体格检查及阴囊彩超，腹部及盆腔CT检查，肿瘤无复发和远处器官转移。结论 根治性睾丸切除术加患侧阴囊皮肤切除是睾丸鞘膜恶性间皮瘤的推荐治疗方法，对双侧睾丸鞘膜发病的患者，建议行根治性睾丸切除术，本例患者未接受睾丸根治术和术后放化疗等辅助治疗，密切随访36个月患者未见肿瘤复发或转移，说明高分化乳头样睾丸鞘膜间皮瘤是否需要根治性切除治疗仍有待进一步临床观察。

【关键词】间皮瘤；睾丸鞘膜；睾丸切除术。

Well-differentiated papillary mesothelioma occurring in the tunica

vaginalis of the testis with contralateral atypical mesothelial hyperplasia

（case report and literature review）

Yue feng

(Department of Urology, Dalian Municipal Friendship Hospital, Dalian 116001, China;

[Abstract] Objective To review the clinical manifestation，pathological characteristics，treatment and prognosis of well-differentiated papillary mesothelioma(WDPM) occurring in the tunica vaginalis of the testis with contralateral atypical mesothelial hyperplasia. Methods A case of WDPM of the tunica vaginalis testis with contralateral atypical mesothelial hyperplasia was reported and relative literature was reviewed. A 56-year-old man presented with significant asymptomatic scrotal enlargement present for 2 weeks. The patient had a 5-year history of asymptomatic scrotal gradually enlargement that was initially diagnosed as bilateral hydrocele. He was treated conservatively with physical examination and testicular ultrasound on a yearly basis. After 4 years of surveillance, testicular ultrasound revealed multiple bilateral papillary nodules of intermediate echogenicity adherent to the tunica vaginalis bilaterally. The largest of these nodules measured 9.0 mm and 5.1 mm on the left and right testes, respectively. Repeat scrotal examination was unchanged. Beta-human chorionic gonadotropin and alpha fetoprotein were within normal limits. A fine needle aspiration of the left testicular mass was performed and read as mesothelioma. Staging computerized tomography (CT) of the chest, abdomen, and pelvis was negative for metastatic disease. The patient was then referred to our institution for surgical treatment. Results An operation was performed to incise the tumor and tunica vaginalis of left testes under continuous epidural anesthesia．Gross examination revealed multiple tan brown, friable, and pedunculated nodules (up to 9 mm in maximum dimension) adherent to the tunica vaginalis. Histologically, the nodules showed a predominantly exophytic papillary architecture with papillae varying considerably in complexity. The tumor was histologically diagnosed as WDPM of the tunica vaginalis testis. Cytologically, the epithelioid cells showed a mild degree of atypia with rare mitoses. Although the frank stromal invasion associated with malignant mesothelioma was not identified, single tubules lined by bland epithelioid cells were identified extending into the superficial layers of the underlying tunica vaginalis. Immunohistochemical studies shows Calretinin（+）、CK（+）、Vimentin（++）、EMA(-), which proved these lesions to be mesothelial in origin. Given the lack of evidence for significant stromal invasion, a diagnosis of WDPM was made. Radical orchiectomy was refused by the patient and the tumor and tunica vaginalis of right testes was incised one month after the first operation．The patient refused to accept any adjuvant postoperative radiotherapy and chemotherapy. There was no evidence of relapse or distant metastasis during 36 month follow-up after operation．Conclusions Radical orchiectomy plus ipsilateral scrotal skin excision was recommended to malignant mesothelioma of the tunica vaginalis and WDPM of the tunica vaginalis testis patients with bilateral testicular hydrocele disease, but this patient refused to accept radical surgery and postoperative radiotherapy and chemotherapy, long-term follow-up condition is stable, no recurrence or metastasis, indicating paratesticular WDPM must underwent radical orchiectomy is still debatable.

[Key words] Mesothelioma; Tunica vaginalis testis; Orchiectomy

高分化乳头样睾丸鞘膜间皮瘤是罕见的阴囊内肿瘤，需要与恶性间皮瘤相鉴别。本文报道一例超声发现的双侧睾丸鞘膜腔内肿瘤，术后病理证实为高分化乳头样睾丸鞘膜间皮瘤和对侧非典型间皮增生。

临床资料

患者男，56岁，因无痛性左侧阴囊肿大2周入我院。该患既往5年来无症状性阴囊进行性增大，诊断为双侧睾丸鞘膜积液。每年行体格检查和阴囊彩超。入院前1天阴囊彩超发现双侧睾丸鞘膜腔内较多的实性乳头状突起，起源于睾丸鞘膜，左右侧睾丸鞘膜乳头样肿瘤最大分别为9.0 mm和5.1 cm，结节中度回声（图1）。入院查体：阴囊皮肤颜色正常，左侧阴囊肿大，囊性，呈椭圆形，边缘光滑，无触压痛，透光试验阳性，平卧时阴囊不缩小，阴囊内睾丸、附睾均未触及异常，双侧腹股沟淋巴结未触及肿大。β-人绒毛膜促性腺激素和甲胎蛋白检测正常。左侧睾丸鞘膜肿瘤细针穿刺病理为间皮瘤。进一步行胸部、腹部和盆腔CT检查，均未发现肿瘤转移。随后患者在我院接受了手术治疗。

结合临床表现和体格检查，右侧睾丸未触及异常，患者接受了左睾丸鞘膜切除术，术中见鞘膜腔内淡黄清亮积液约30 ml，睾丸鞘膜腔囊壁见多个实性乳头状突起，单个肿瘤最大直径9 mm（图2）。组织学上，结节表现为明显的外生性，伴有复杂的乳头状改变，囊壁由增生的纤维组织、平滑肌及小血管构成。表面被覆单层立方上皮，具有成簇的乳头状瘤样新生物突向腔内，乳头表面被覆立方及扁平上皮，乳头间质由血管及迷路上皮样细胞构成（图3）。细胞学上，上皮细胞表现为中度非典型增生，罕见有丝分裂。尽管没有表现出恶性间皮瘤的基质侵袭性，但是可见由扁平上皮细胞连接的单个小管样结构延伸入睾丸鞘膜浅层下组织。免疫组化Calretinin（+）、CK（+）、Vimentin（++）、EMA(-)，提示肿瘤来源于间皮（图4）。因为基质未受侵袭，病理诊断为高分化乳头样睾丸鞘膜间皮瘤。然而，肿瘤的多中心性和复杂多变的乳头样结构提示该病具有侵袭性。该患鞘膜切缘阴性。

患者拒绝进一步行睾丸根治术和患侧阴囊皮肤切除术。术后1个月行右侧睾丸鞘膜切除术，病理回报非典型间皮增生。随防36个月，患者生存状况良好，每半年行体格检查及阴囊彩超，胸部、腹部及盆腔CT检查，肿瘤无复发和远处器官转移。

讨论

间皮瘤起源于胸膜、心包膜和腹膜，是罕见的肿瘤。Hammar^[1]报道间皮瘤发生于胸膜者约90 %～95 % ,发生于腹膜者约5%～10% ,发生于心包膜和睾丸鞘膜者罕见。人群中患病率约1 ∶1 000 000。只有1 %起源于睾丸鞘膜。首例睾丸鞘膜间皮瘤报道于1957年,当时诊断为恶性，目前看来很可能是高分化乳头样睾丸鞘膜间皮瘤。截止2000年只有93例报道^[2]。恶性睾丸间皮瘤25岁以下发病率仅10 % , 5年存活率小于5 %^[3,4]。该病多发于55岁～75岁^[5]。有报道30 %～40 %的恶性间质瘤与石棉接触有关，机制不明^[4]，其他易患因素为创伤、疝、炎症等,而良性间皮瘤由于发病率低且无特殊病史而病因不明。典型的病灶表现为实性，无痛性睾丸肿瘤，常合并睾丸鞘膜积液^[4，5]。双侧肿瘤极为罕见，双侧肿瘤只占所有病例的3.8 %^[4]。准确的术前诊断对疾病的治疗相当重要，对睾丸鞘膜积液行细胞学检查有助于诊断，彩超和CT也很重要^[4，5]。睾丸鞘膜良性乳头状间皮瘤的临床表现多为无痛性进行性增大的单侧阴囊肿物,而睾丸鞘膜恶性间皮瘤多合并有反复发作的鞘膜积液,晚期可触及腹股沟淋巴结肿大,转移至腹膜可能出现腹痛、血性腹水等症状。

影像学检查对于睾丸鞘膜良性乳头状间皮瘤无特异性,但应常规行B超检查,以多普勒彩色超声观察血流,可准确定位并初步鉴别是炎性病变抑或新生物表现。当有如下特征时应考虑本病:分化好的组织在鞘膜积液中呈现低回声光团,阴囊壁的多发结节状肿物,而睾丸附睾旁肿物或睾丸鞘膜局部增厚。本例B超显示睾丸附睾正常,睾丸旁的鞘膜不均匀增厚,最厚处约1.8 cm x 0.6 cm,未见明显血流信号。

恶性睾丸鞘膜间皮瘤是局部侵袭性肿瘤，对鞘膜下结缔组织和睾丸均有侵袭性，有报道的确诊恶性间皮瘤病例中有34%具有明确的侵袭证据^[4]。一小部分患者表现为转移性疾病，大多数转移到腹膜后、腹股沟或髂窝的淋巴结。睾丸恶性间皮瘤预后差异性很大，在一项大样本研究中，总复发率（包括局部复发和远处转移）为53 %，而有38 %的患者死于疾病进展^[4]。患者接受了目前推荐的睾丸根治术后，局部复发率降为11.5 %，预后远远好于胸膜恶性间皮瘤的复发率，提示低级别间皮瘤病灶可能残留在睾丸旁组织内，根治性手术可以明显提高患者生存期。

2004年，世界卫生组织已经正式将高分化乳头样睾丸鞘膜间皮瘤作为睾丸旁区域的一个临床病理学诊断出现^[6]。典型的高分化乳头样睾丸鞘膜间皮瘤表现为树枝状乳头结构，然而，本例高分化乳头样睾丸鞘膜间皮瘤表现为复杂的病理特征，管状乳头样分化区域和局部实性片状细胞区域^[7]。与真正的恶性间皮瘤相比，高分化乳头样睾丸鞘膜间皮瘤只生长在鞘膜表面，偶有间皮细胞延伸入睾丸鞘膜下方的浅层组织，恶性间皮瘤则有明确的基质浸润表现^[7，8]。

高分化乳头样睾丸鞘膜间皮瘤的生物学行为经过长期随访目前仍无定论。该病的生物学惰性显著高于睾丸恶性间皮瘤。文献报道的6例高分化乳头样睾丸鞘膜间皮瘤完整病例中，只有1例复发并进展为恶性间皮瘤^[7-13]。然而，一旦发现高分化乳头样睾丸鞘膜间皮瘤有机会进展为恶性间皮瘤时，需要对其进行像恶性间皮瘤一样的治疗。辅助放化疗对高分化乳头样睾丸鞘膜间皮瘤或恶性间皮瘤的治疗效果仍不明确。恶性间皮瘤病例中，放疗比化疗有效已经得到公认^[4]。尽管目前的推荐治疗方案中对高分化乳头样睾丸鞘膜间皮瘤的治疗与恶性间皮瘤无异，但是在组织学上区分高分化乳头样睾丸鞘膜间皮瘤和真正的恶性间皮瘤仍很重要，更多的完整的研究需要继续进行，需要大样本的长期随访。

该病临床无特异性，术前诊断方法为依赖术中冰冻切片和术后病理检查确诊。主要应与恶性睾丸间皮瘤相鉴别,以指导治疗。本例患者呈多灶性病变,有明显的鞘膜积液形成,切除局部病灶后,密切随访对于该病非常重要。

根治性睾丸切除术加患侧阴囊皮肤切除是恶性睾丸鞘膜间皮瘤的标准治疗，术后辅助放疗，可以明显延长患者生存期，该例患者同样推荐性睾丸根治术的原因在于，该患双侧睾丸鞘膜发病，虽然一侧为高分化乳头样睾丸鞘膜间皮瘤，一侧为非典型间皮增生，但是均具有恶性倾向，术后患者拒绝接受放化疗等辅助治疗，经过36个月的长期随访，患者病情平稳，未见肿瘤复发或转移。

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