在诊断有困难的时候，用那些临床病理参数去鉴别？免疫组化标记有没有作用？

想听到更多网友的声音。谢谢！

 如果硬要区分，我倾向毛源性良性肿瘤。理由：有色素、有毛间质、还有突然角化现象、角化囊。

IHC:

图1 BerEP4； 图2 Ki-67； 图3 CK20; 图4 CEA

 等待学习

 BerEP4和CK 20是鉴别基底细胞癌和其它皮肤附件肿瘤的比较好的标志物，基底细胞癌表达前者阳性，其它类型一般为阴性。后者表达的意义则相反。本例标记Ki-67的阳性率在不同区域约45-70%.

请参阅现有的IHC标记结果继续发表意见。谢谢！

MINI-SYMPOSIUM: CUTANEOUS EPITHELIAL TUMOURS

The use of immunohistochemistry in the differential diagnosis of common epithelial tumours of the skin

D.S.A. Sanders ^{, a,} and R.A. Carr^a

^aDepartment of Pathology, Lakin Road, Warwick CV34 5BJ, UK

Available online 25 August 2007.

 

BerEP4

BerEP4 is a monoclonal antibody to a 34/49-kDa glycoprotein on the surface of most epithelial cells, with the exception of superficial layers of squamous epithelia.¹ BerEP4 stains the vast majority of non-cutaneous epithelia and is highly conserved in the tumours derived from them, including non-cutaneous squamous cell carcinomas (SCC).¹ In normal skin, there is reported positivity of the lower part of telogen hairs (secondary hair germ), matrix and outer root sheath (ORS) of vellus hairs, early anagen of terminal follicles (but not any part of mature anagen follicles), and the lower part of the epithelial strand of late catagen follicles.^{[2] and [3]} Similar strong positive staining is seen in lining cells of eccrine and apocrine coils, with more variable staining of sweat duct lining cells and the acrosyryngium.3 F.J. Jimenez, J.L. Burchette Jr, J.M. Grichnik and M.G. Hitchcock, Ber-EP4 immunoreactivity in normal skin and cutaneous neoplasms, Mod Pathol 8 (1995), pp. 854–858. View Record in Scopus | Cited By in Scopus (32)³ The epidermis, follicular mantle, sebaceous glands and all non-epithelial tissues are negative^{[1] and [3]} (Fig. 1A–C).

Figure 1. BerEP4 staining in normal skin and basal cell carcinoma (BCC): (A) weak staining in upper eccrine duct and acrosyryngium; (B) weak staining in lower sweat duct and strong staining in sweat gland coils; (C) outer root sheath telogen and anagen vellus buds (inset showing perifollicular Merkel cells); (D) nodular BCC; (E) metatypical and infiltrative BCC with weaker staining; (F) sebeorrhoeic keratosis (left side negative) in collision with superficial BCC; (G) fibroepithelioma of Pinkus; and (H) perineural invasion from a micronodular BCC.

 

 

Carcinoembryonic antigen

Carcinoembryonic antigen (CEA) is a glycoprotein initially described as a colonic oncofetal antigen,³² but subsequently shown to be expressed in a variety of normal human tissues³³ including squames.³⁴ Anti-CEA antibodies are now designated ‘CD66’ with a subclassification a–e depending on which epitope of the antigen is recognized. In normal skin, membranous CEA positivity can occasionally be seen in suprabasal squamous cells of the epidermis, and on the inner lining of sweat gland coils (including canaliculi), dermal ducts and acrosyringium.³⁵ Monoclonal CEA can be used as a marker of ductal/glandular differentiation in skin tumours, and may also highlight mature squamous differentiation. However, in the authors’ experience, immunostaining is sometimes inconsistent and less sensitive for lumina than EMA.

 

 

Bcl-2, p53 and Ki-67

Bcl-2 is an anti-apoptotic protein residing on the outer mitochondrial membrane. It is implicated in the pathogenesis of several common cancers by inhibiting programmed cell death. In normal skin, Bcl-2 stains the majority of keratinocytes in the basal epidermis, cells of the ORS, mesenchymal cells of the follicular papillae, and clear cells of eccrine glands.⁵⁷ Diffuse cytoplasmic Bcl-2 expression is reported in BCC^{[57] and [58]} and is reported to be useful in the distinction of BCC (diffuse staining) from TE (staining of basal layer only)⁵⁹ and BCC and solar keratosis (latter negative).⁶⁰

p53 is a tumour-suppressor gene and many p53 mutations result in a protein product that is unusually stable and becomes detectable by immunohistochemistry. Ultra-violet light is known to induce both overexpression of wild-type p53 and cause specific mutations in the p53 gene, and a discrepancy between cutaneous tumours with positive immunostaining and those with mutation has been reported.⁶¹ Nuclear accumulation of p53 protein is a feature of the majority of malignant adnexal and epidermal tumours including BCC,⁶² SCC and Bowen's disease,⁶³ and is confined to the areas of basal atypia in solar keratosis.⁶³ Hence, p53 immunostaining may have some utility in the differential diagnosis of intra-epidermal tumours (Fig. 7) and aids the distinction between basaloid proliferations (follicular induction) over dermatofibromas (rarely p53 positive) and the superficial subtype of BCC that they resemble.⁶⁴ p53 immunostaining is of lesser value in differentiating benign from malignant skin tumours, as evidenced by similar staining patterns reported between BCC and TE, and eccrine poroma and porocarcinoma.^{[65] and [66]}

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Full-size image (175K)

Figure 7. Clonal Bowen's: (A) low power of a clonal tumour and (B) high power showing uniform but atypical, acantholytic cells. Negative Cam5.2 is against extramammary Paget's and negative S100 against melanoma. p53 diffusely strongly positive.

View Within Article

 

 

Ki-67 (MIB 1) is a proliferation marker with a pattern of nuclear positivity. Demonstration of the proliferation index in skin tumours, in conjunction with the mitotic index, is used by many pathologists to help differentiate between benign and potentially malignant tumours. p53 positivity in conjunction with Ki-67 positivity is reported to be a feature of malignancy in the differential diagnosis of hidradenoma from hidradenocarcinoma, although histological parameters remain paramount.⁶⁷

 

原文太长，截取部分，希望对大家分析有帮助，继续学习

续上篇

Basal cell carcinoma vs. trichoblastoma (trichoepithelioma)

Immunopanel—BerEP4, CD10, Bcl-2, CD34, CK20, Cam5.2

In trichoblastomas, CD10 typically highlights the peritumoral stroma, including papillary mesenchymal bodies, with minimal patchy staining of basaloid cells. In contrast, in BCC, the stroma is negative and basaloid cells variably strongly positive with CD10. Diffuse Bcl-2 positivity is reported in BCC, whereas the basal layer alone is highlighted in TE. The authors have found this to be variable and unreliable in practice. CD34 may highlight the peritumoural stroma in the desmoplastic variant of TE and not in infiltrative BCC, but this is also an unreliable finding in the authors’ experience. Merkel cells can be highlighted with Cam5.2 or CK20 and are absent from BCC but increased in number in trichoblastoma.

 突击学习，本例形态学集中在基底细胞癌和毛母细胞瘤的鉴别。这两种瘤形态学相似，老师就其鉴别诊断的免疫组化分析提出问题，就BerEP4可以做为基底细胞肿瘤和鳞状细胞癌鉴别的重要marker，但是在基底细胞癌和毛母细胞瘤（Modern Pathology (2008) 21, 178–185; doi:10.1038/modpathol.3801000; published online 7 December 2007，57% of desmoplastic trichoepithelioma）中都有表达，

明天在学习继续写

 BerEP4在汗腺和外毛鞘发生的肿瘤也可阳性，但毛鞘表达BerEP4不如在BCC表达的强。

本例主要是区分BCC和毛母。

谢谢Dr,djdnx.

 有幸请上海著名皮肤肿瘤病理专家—皮肤病理老前辈—孔金诚教授会诊该病例。

孔教授会诊意见：基底细胞癌，伴毛源性分化。

谢谢孔教授！

 这是一位网友对诊断的回答

wang4160  文章：1151 积分：5660 经验：1247 注册：2007-1-31 18:12

发表于 2010-6-11 9:10 {资料} {好友} {短信} {引用} {快回} {编辑} {删除}  第 5 楼        倾向基底细胞癌！ 阿克曼上说：基底细胞癌与毛母细胞瘤的鉴别本身就是个难点，来源与组成差不多，分化方向也差不多，同时也说了一句似乎只有癌会发生浸润现象！也就是说对周围组织的浸润成为诊断的关键！另外从表浅型基底细胞癌来看，似乎基底细胞大多起源于表皮基底层（应该也能起源于附属器基底细胞层），因此与表皮的关系，能否成为一个辅助指标呢？？ 有人提到收缩裂隙，这张片子可以看到，不知道能否作为诊断依据！！！ 个人理解，请各位老师指教！

 这是金主任帮我回答了关于诊断的问题

XLJin8  文章：1290 积分：7265 经验：1608 注册：2009-3-4 3:39

发表于 2010-6-12 8:50 {资料} {好友} {短信} {引用} {快回} {编辑} {删除}  第 17 楼       ......毛母细胞瘤主要发生在头皮, 肿瘤1厘米左右大小。毛胚基样基底样细胞巢和纤维间质二种成分构成.....肿瘤主要位于真皮内，与表皮不相连......基底样细胞巢的周边细胞排列成栅栏状, 与间质紧密相连, 无收缩裂隙......纤维性间质围绕细胞巢,可形成透明胶原带...... ......少数肿瘤的形态与基底细胞癌可有部分重叠, 如鉴别诊断困难, 诊断为”恶性附件肿瘤伴毛囊分化” (Malignant adnexal neoplasm with desc ription of  apparent differentiation)。 参考文献: Lever’s Histopathology of the Skin, 9th edition, 2009;861-862. 参考文献: Lever’s Histopathology of the Skin, 9th edition, 2009;861-862.

谢谢金主任！