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第八节 汗腺及汗腺肿瘤的免疫细胞化学特点

  目前已有多种PcAb和McAb用于汗腺及汗腺肿瘤的研究,这些不同的抗体对汗腺的不同部位有特异性反应,主要用于探讨汗腺肿瘤的组织发生,分化特点以及诊断及鉴别诊断。同时也可用于外科手术切除时,迅速判断肿瘤是否切除干净。现将不同的抗体分述如下。

  1.癌胚抗原(CEA)  出已证明在大小汗腺的腺体及导管部均有CEA。在各种汗腺的良恶性肿瘤中也有不同的表达形式。CEA在汗腺肿瘤导管样腔隙内及其附近染色最强,汗管瘤及多形性汗腺瘤通常含有丰富的CEA,而实体性肿瘤,例如小汗腺孔瘤、螺旋腺瘤及圆柱瘤中则仅见稀疏灶状沉积,多种汗腺起源的恶性肿瘤中也见灶状CEA沉积,但CEA不能区别是起源于大汗腺或小汗腺。CEA染色不仅可研究肿瘤的发生,还可用于显微镜下的外科手术,用以快速判断肿瘤组织是否切除干净。因Paget细胞也含有CEA,因此也是鉴别Paget氏病的Paget细胞与皮肤原位癌中Paget样细胞以及恶性黑色素瘤中的Paget样瘤细胞的一种简单易行的方法。此外,CEA也存在于胎儿的小汗腺中,因此,可作为汗腺分化的最早标志。

  2.S-100蛋白在皮肤病中,可用以检测Schwann氏细胞、皮肤神经黑色素细胞、痣细胞以及来源于这些细胞或组织的肿瘤。因此可用以区别梭形细胞恶性黑色素瘤与梭形细胞鳞状细胞癌以及恶性纤维组织胞瘤,用以鉴别神经来源的肿瘤与其他纤维性肿瘤,近来也有报告用S-100蛋白染早期麻风皮损中的神经组织,以了解神经的破坏,对麻风的早期诊断有一定的帮助。在小汗腺腺细胞及郎格罕氏细胞,S-100也为阳性,但小汗腺导管及大汗腺则无S-100。因此可以通过S-100染色了解汗腺肿瘤的起源,同时也有助于明确诊断。最近报告汗囊瘤中部分细胞S-100阳性,也说明这些肿瘤的组织发生与小汗腺中含有S-100蛋白的细胞有关。

  3.角蛋白在大小汗腺的导管、腺体以及汗腺肿瘤中均有角蛋白存在。但对不同分子量的角蛋白则有不同的染色形式。近来报告,用识别分子量56kD的Dako-CKl及识别分子量39、43用50kD的Cam5.2二种抗体检测多种汗腺肿瘤,包括汗孔瘤、透明细胞汗腺瘤、螺旋腺瘤、皮肤混合瘤、圆柱瘤、生乳头汗管囊腺瘤及大小汗腺的汗囊瘤等,大多数肿瘤对这二种抗体呈阳性反应。也有用抗角蛋白抗体检测了多种小汗腺瘤的报告,结果所有的瘤均呈形式不同的呈阳性结果。但有些作者的结果表明汗管孔瘤、部分小汗腺孔瘤、螺旋腺瘤及大汗腺汗囊瘤等对抗角蛋白抗体EKH5呈阴性。

  4.上皮膜抗原(EMA)文献报告大小汗腺的腺体部分在EMA抗原,而导管则无该抗原。某些汗腺来源的肿瘤对EMA也呈阳性反应,有报告90%的Paget氏病及乳腺导管癌EMA染色阳性。有人用EMA检测了多种小汗腺癌,包括小汗腺导管癌、透明细胞汗腺癌、乳头状汗腺癌、汗孔癌、腺样囊性癌、微囊性附件癌及小汗腺粘液腺癌等,结果均为阳性。

  5.β2微球蛋白(β2MG)βMG在多种良恶性汗腺肿瘤中可有程度不同的阳性反应。文献报告大汗腺囊瘤、乳头汗腺瘤、透明细胞汗腺瘤、真皮内导管瘤、汗管瘤、螺旋腺瘤及圆柱瘤均为阳性。部分小汗腺癌也含有这种蛋白。

  6.巨囊病液体蛋白(GCDEP)GCDEP主要存在于大汗腺及大汗腺来源的多种肿瘤中,例如大汗腺汗囊瘤、乳头状汗腺瘤、生乳头汗管囊腺瘤、部分圆柱瘤及皮肤混合瘤中,也用于乳房及乳房外Paget氏病的检测。因此,GCDFP可以用于区别大小汗腺分化,有助于了解汗腺肿瘤的组织发生以及诊断及鉴别诊断。

  7.表皮生长因子(EGF)EGF存在于汗腺的腺体及导管部。在某些汗腺肿瘤中也有不同的分布形式。可见于透明细胞汗腺瘤的管状上皮细胞、大汗腺混合瘤的管状及导管细胞的顶端部。

  8.Peptidylarginine deiminase(PD)PD见天大小汗腺的腺体及肌上皮细胞浆中,也存在于乳房外Paget细胞内。认为该酶可作为汗腺肿瘤分类的新的标志。

  9.碳酸酐酶(CA)存在于大小汗腺的腺体细胞及导管上皮细胞。可见于皮肤混合瘤的管状、导管样及囊状结构的管腔细胞。

  10.锌α2糖蛋白(An2GP)An2GP主要存在于大汗腺体及导管部,部分见于小汗腺腺体,小汗腺导管则为阴性。在某些大汗腺肿瘤中多为阳性,例如大汗腺汗囊瘤及生乳头汗和囊腺瘤等。部分螺旋腺瘤及透明细胞汗腺瘤也含有这种蛋白。Zn2GP染色对于了解某些汗腺肿瘤的组织发生及分类有一定的帮助。

  11.乳液脂肪球蛋白(MFG)  MFG位于大小汗腺的腺体,而导管则无此蛋白,有报告90%的乳腺导管及乳房Paget氏病中MFG染色呈阳性反应,认为MFG染色有助于了解某些肿瘤的组织发生。

  12.转铁蛋白(Ft )小汗腺导管外层细胞存在有FT,而末端汗管及小汗腺腺体则无此蛋白。在某些汗腺肿瘤中FT也有不同的分布形式,可见于汗管瘤细胞条索的外层细胞,在末端汗管瘤及某些汗腺癌中可呈弥漫性分布。

  总之,可用于汗腺及汗腺肿瘤标记的分子很多,除上述之外,其他例如抗唾液腺酶、抗α—胰酶蛋白、抗大汗腺上皮抗原(AEA)等,对于了解汗腺肿瘤的起源及分类均有一定的帮助,但目前尚没有一种标记能区别良恶性肿瘤,或区别原发及转移性肿瘤,因此对于汗腺肿瘤的诊断,分类及组织发生,还要结合常规组织病理改变及临床特点等多方面因素进行综合考虑。

  皮脂腺的免疫细胞化学特点。

  目前可用于标记皮脂腺及皮脂腺肿瘤的抗体或酶有多种,包括角蛋白、EMA、MFG、CA及AEA等,但没有一种标记是皮脂腺所特有的。β2MG在皮脂腺痣、皮脂腺腺瘤及皮脂腺癌中也可呈阳性反应。近来报告皮脂腺癌中也存在OKMS抗原、虽然其性质仍不清楚,但OKMS染色有助于该病的诊断。

(孙建方 曾学思 刘季和)

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刘季和 孙建方 曾学思 刁庆春

刘荣卿 聂祝湘 同天文 何威