10例肛管直肠恶性黑色素瘤临床病理免疫组化研究

目的研究肛管直肠恶性黑色素瘤（简称恶黑）的临床病理特点及免疫组化染色在恶黑诊断中的作用。方法对肛管直肠恶黑的临床资料进行回顾性分析，用免疫组化s—P法作HMB45、S-100、Vimetin等染色。结果10例肛管直肠恶黑临床初步诊断恶黑1例，误诊其它疾病9例。病理形态：上皮样细胞为主7例，梭形细胞为主2例，小细胞似淋巴细胞样细胞为主1例。免疫组化染色：10例HMB-45、s-100均阳性，9例Vimetin阳性，其中1例CK阳性，LCA阴性。结论肛管直肠恶黑临床表现大便带鲜血，无明显黏液，肛门异物及息肉样突出肛门为特征，临床极易误诊。形态观察支持恶黑起源于表皮基底层黑色素细胞，免疫标记提示黑色素细胞起源于神经嵴。HMB45、S-100、Vimetin，三者联合应用能提高恶黑病理诊断的准确性。     

区域注射磷—32玻璃微球对裸鼠移植性人肝细胞癌的形态学影响

目的：研究－３２玻璃微球（３２Ｐ－ＧＭＳ）区域注射对裸鼠移植性人肝细胞癌的形态学影响及其意义。方法：应用光镜、免疫组织化学及电镜观察对照组及治疗组的肿瘤组织学和超微结构特征。结果：对照组中，瘤体长径约３ｃｍ，瘤细胞排列紧密，呈小梁状，富于血窦，约５％瘤细胞坏死。治疗组中，瘤体长径为０．４～２ｃｍ，其中少部分瘤体边缘细胞排列紧密，大部分瘤细胞排列松散，呈网状或假腺样且被纤维血管束分割成巢。４０％～８０％的瘤细胞呈凝固性坏死。７５％以上排列紧密的瘤细胞ＰＣＮＡ阳性，而排列松散的ＰＣＮＡ阳性瘤细胞不足２５％。松散排列的瘤细胞较紧密排列的瘤细胞，桥粒显著减少、细胞变性坏死增多。结论：本研究提示局部内放射３２Ｐ－ＧＭＳ明显具有杀伤癌细胞和抑制肿瘤生长的作用。这为３２Ｐ－ＧＭＳ对肝癌治疗的实验研究和临床应用提供形态学依据。     

36例粘膜原发恶性黑色素瘤临床病理分析及鉴别诊断

目的探讨粘膜原发恶性黑色素瘤的临床病理特点及其鉴别诊断。方法回顾性分析36例粘膜原发恶性黑色素瘤的临床病理资料,对肿瘤进行光镜观察,并做免疫组化染色。结果根据肿瘤细胞形态特点及有无黑色素,36例粘膜恶性黑色素瘤被分为上皮样细胞为主型17例,梭形细胞为主型8例,小痣样细胞型2例,混合型9例;黑色素明显者16例,无或黑色素少者20例。免疫组化染色HMB45、S-100、Vimentin阳性率分别为80%、100%和80%。结论粘膜恶性黑色素瘤的组织结构和病理形态复杂,有不同病理类型,部分病例诊断比较困难,需借助免疫组织化学方法诊断和鉴别诊断。     

S—100蛋白在无色素性恶性黑色瘤诊断和鉴别诊断中的作用

本文应用抗S—100蛋白免疫组化(ABC法)染色对10例无色素性恶性黑色素瘤(恶黑)、11例少黑色素性恶黑、11例色素痣、8例外周神经肿瘤和11例与无色素性恶黑有鉴别意义的肿瘤进行了对比性研究。结果显示恶黑的染色阳性率为100％,瘤细胞的染色强度与其黑色素含量有铰明显的反比关系。这种规律在色素痣中也可观察到,但不含色素的痣细胞,其染色强度与无色素性恶黑细胞何无明显差异。外周神经肿瘤多数也呈S—100染色阳性,但阳性强度一般低于无色素陸恶黑。与无色素性恶黑有鉴别意义的肿瘤除1例恶性间皮瘤的上皮样细胞呈S—100染色弱阳性外,其余肿瘤细胞均呈阴性反应。本文结果提示S—100蛋白对色素痣恶变的确定和对无色素性恶黑与外周神经肿瘤的鉴别帮助不大,但对无色素性恶黑的诊断和鉴别诊断很有帮助,在活检诊断中有较高的使用价值。     

L／H型R—S细胞形态学观察

对２０例淋巴细胞为主型何杰金氏病组织切片应用ＨＥ、酶组化免疫组化及电镜等方法观察了Ｌ／Ｈ型Ｒ－Ｓ细胞的形态学特征。观察结果提示：Ｌ／Ｈ型Ｒ－Ｓ细胞体积大（１２．５～５０μｍ），以单核为主，核膜褶叠扭曲。少数民核或多叶核，有排成马蹄形、花环形或破骨细胞样等形式。核仁小而嗜碱。同时常伴有固缩型Ｒ－Ｓ细胞及瘤型分裂像。部份病例可找到个别诊断型Ｒ－Ｓ细胞。对本型Ｒ－Ｓ细胞的生物学意义，诊断与鉴别诊断进行了     

皮肤真性组织细胞性淋巴瘤的诊断与误诊分析

目的 探讨右大腿皮肤组织细胞性恶性淋巴瘤的诊断、误诊原因及预防对策。方法 对1例皮肤组织细胞性淋巴瘤的标本，采用10％的福尔马林固定，石蜡切片，HE、网状纤维染色及多种免疫组化染色，光镜观察、会诊及病理读片会讨论。结果 临床因早期表现为局部单发肿块，皮肤改变不明显而误诊为皮肤纤维瘤，病理则因组织学上既象淋巴瘤样细胞弥漫分布又有瘤细胞互相粘着不松散而似癌细胞巢，且瘤细胞核大，核仁明显又似恶性黑色素瘤，凭皿切片难以诊断，免疫组化及会诊结果为皮肤组织细胞性恶性淋巴瘤。结论 原发于皮肤的组织细胞性恶性淋巴瘤非常少见。组织学上注意与蕈样霉菌病、美克耳细胞癌、恶性黑色素瘤、恶性组织细胞增生症等鉴别。免疫组化不支持上述病变时要想到本病的可能。误诊的主要原因是早期临床表现不具有特征性，肿瘤发病部位及类型罕见，临床及病理对此类型淋巴瘤认识不深，未能及时进行免疫组化检查。     

女性生殖器官原发性恶性黑色素瘤4例报告

女性生殖器官原发性恶性黑色素瘤（简称恶黑）较少见，作者遇到4例，现就有关临床病理问题进行分析讨论。1临床资料4例中，发生在阴道2例，宫颈2例。年龄42岁～73岁，平均57．5岁，临床表现为：阴道出血流黄水伴胀痛及有坏死组织脱落，病程4个月～4年半。妇检：在阴道或宫颈均可见灰白暗红色或暗褐色肿块，质脆，伴有感染，呈菜花状，肿块大小不等，4例临床全部误诊为癌肿．病理肉眼所见：肿瘤组织呈暗红灰褐色，质脆。镜下主要有以下几种组织类型：上皮样型（2例），小病样细胞型和梭形细胞型（各1例）。2讨论女性生殖器官发生的恶黑，发病…     

无色素性恶性黑素瘤的诊断探讨

本研究收集45例诊断或疑诊恶黑的无色素性组织,通过光镜观察、抗S-100蛋白、波形纤维蛋白、NSE,角蛋白等抗体作免疫组化染色及透射电镜观察,对诊断进行探讨。45例中35例S-100蛋白及波形纤维蛋白均阳性,确诊恶黑。4例免疫组化确诊的恶黑,透射电镜下仅2例找到异常黑素小体。结果提示:(1)多数无色素性恶黑仅通过普通病理即可作出诊断,部分需依赖于免疫组化,透射电镜;(2)在普通病理观察基础上,S-100蛋白及波形纤维蛋白均阳性,能肯定恶黑诊断,两抗体均阴性能否定恶黑;(3)电镜下找到异常黑素小体能肯定恶黑诊断,但未找到异常黑素小体不能排除诊断。     

64例肺癌血清胃泌素和锰超氧化物歧化酶检测结果分析

同时检测了６４例原发性肺癌，３２例肺良性疾病，３２例健康成人血清胃泌素（Ｇａｓｔｒｉｎ）含量和血清锰超氧化物歧化酶（Ｍｎ－ＳＯＮ）活力。Ｇａｓｔｒｉｎ的阳性率为７３．４４％，诊断正确率为７３．４４％，ＭＮ－ＳＯＤ的阳性率为８１．２５，诊断正确率为８６．２５％。Ｇａｓｔｒｉｎ对小细胞肺癌，Ｍｎ－ＳＯＤ对各型肺癌均有较高的阳性检出率。二者的血清水平及阳性率与肺癌病期相关，晚期患者高于早期病人（Ｐ＜０．０１），１５例肺癌患者Ｇａｓｔｒｉｎ和Ｍｎ－ＳＯＤ水平在手术切除肿块后明显下降（Ｐ＜０．０１）。结果提示Ｇａｓｔｒｉｎ和Ｍｎ－ＳＯＤ在肺癌的诊断、判断病期和病理类型，手术疗效监测方面有重要的临床实用价值。     

应用组化及免疫组化方法诊断子宫腺瘤样瘤

目的：子宫腺瘤样瘤发生率低，在临床与病理上均易误诊和漏诊，病理上误诊漏诊的主要原因是其病理形态多样性以及与形态相似的其他肿瘤难鉴别。应用特殊染色和免疫组织化学染色对子宫腺瘤样瘤的诊断与鉴别诊断有重要意义。方法：从本院１０年档案材料１５６０例子宫良性肿瘤中共收集子宫腺瘤样瘤９例，观察其临床病理特征，选用细胞角蛋白（ＣＫ），波纹蛋白（ＶＩＭ），表皮膜抗原（ＥＭＡ），癌胚抗原（ＣＥＡ），血管相关因子（Ｆ８）和ＨＨＦ３５作为第一抗体，应用免疫组化方法（ＳＬＡＢ法），以及特殊染色如糖原染色（ＰＡＳ染色），嗜银染色（Ａｇ染色）和ＡｌｉｃｉａｎＢｌｕｅ染色（ＡＢ染色）。对每例进行染色，观察结果。结果：９例子宫腺瘤样瘤占１５６０例子宫良性肿瘤，其中６例误诊为其他肿瘤。免疫组化结果显示９例子宫腺瘤样瘤瘤细胞ＣＫ及ＶＩＭ均呈强阳性，而对ＣＥＡ，ＥＭＡ，Ｆ８及ＨＨＦ３５均无表达。ＡｌｃｉａｎＢｌｕｅ染色９例均有阳性反应，ＰＡＳ染色阴性，Ａｇ染色见瘤细胞周围银纤维少。结论：本文收集子宫腺瘤样瘤比以前文献报道发生率低，ＣＫ，ＶＩＭ及ＡｌｃｉａｎＢｌｕｅ染色是子宫腺瘤样瘤的阳性标记物，而ＣＥＡ，ＥＭＡ，ＨＨＦ３５，Ｆ８及ＰＡＳ染色瘤细     

Apolipoprotein D expression in cutaneous malignant melanoma

BACKGROUND AND OBJECTIVES: Apolipoprotein D (Apo D) is a protein component of the human plasma lipid transport system, and an androgen-regulated protein in both breast and prostate cancer cell lines. Our goal was to evaluate the expression of Apo D in malignant cutaneous melanomas, as well as to assess its possible relationship to clinical and pathological parameters. METHODS: Apo D expression was analyzed in 32 paraffin-embedded tissues from patients with invasive cutaneous malignant melanomas, in 8 samples from in situ melanoma, and in 10 samples from 10 benign lesions (4 dermal melanocytic nevi, 4 compound melanocytic nevi, and 2 dysplastic melanocytic nevi), using immunohistochemical techniques. RESULTS: The benign lesions were consistently negative for Apo D, whereas 3 of the 8 "in situ" melanomas (37.5%) and 12 of the 32 invasive melanomas (37.5%) showed positive immunostaining for Apo D. The percentage of Apo D-positive tumors was significantly higher in nodular than in superficial spreading melanomas (P = 0.011) and in melanomas with vertical growth phase than in melanomas with radial growth phase (P = 0.02). In addition, the percentage of Apo D-positive tumors was positively and significantly correlated with Clark's level of invasion (P = 0.046). CONCLUSIONS: Apo D may be a new prognostic factor of unfavorable evolution in cutaneous malignant melanoma.     

Immunohistochemical evaluation of uveal melanocytic tumors. Expression of HMB-45, S-100 protein, and neuron-specific enolase

The authors compared the immunohistochemical reactivity of 13 uveal nevi and 20 uveal melanomas for HMB-45, S-100 protein, and neuron-specific enolase (NSE) in formalin-fixed, paraffin-embedded sections. All 33 of the lesions were positive for HMB-45. The false-negative rates for S-100 protein and NSE were 21% and 18%, respectively. If only strongly positive reactions were considered, more than 50% of the tumors would be interpreted as negative for S-100 protein and NSE. Nevi stained with less intensity than melanomas using all three antibodies. The expression of HMB-45 appeared to be greater in active nevi than in inactive nevi. There was a weak association between S-100 protein reactivity and the ability of the uveal melanomas to metastasize (P = 0.1); however, the standard deviation of nucleolar area was a much better predictor (P = 0.02). These results indicate that pathologists will find HMB-45 to be a useful tool in differentiating uveal melanoma from nonmelanocytic tumors.     

Detection of microscopic melanoma metastases in sentinel lymph nodes.

BACKGROUND: Sentinel lymph node biopsy following radioisotope labeling is a recently developed, minimally invasive surgical staging procedure used in the management of primary cutaneous malignant melanoma. If histologic analysis reveals melanoma metastasis in the sentinel lymph node, completion lymphadenectomy is performed and adjuvant therapy considered. The routine pathologic assessment of the sentinel lymph node consists of bisecting the lymph node along its long axis and histologic examination of one hematoxylin and eosin-stained section of each cut surface. METHODS: In this study, the authors reexamined 235 sentinel lymph nodes reported as negative for melanoma metastasis following routine histologic examination, from 94 patients with American Joint Committee on Cancer (AJCC) Stage I and II cutaneous melanoma. RESULTS: Deeper sections into the lymph node and immunohistochemical stains with antibodies to S-100, HMB-45, NK1C3, and MART-1 led to the identification of microscopic metastases in 11 sentinel lymph nodes from 11 patients and capsular nevi in 9 sentinel lymph nodes from 8 patients. CONCLUSIONS: Deeper serial sections and immunohistochemical stains detected microscopic metastases in approximately 12% of cases that would be reported as negative for metastasis by routine pathologic analysis. These techniques also allowed for the identification of capsular melanocytic nevi in the sentinel lymph nodes of 9% of patients. [See editorial on pages 551-2, this issue.] Copyright 1999 American Cancer Society.     

Melanoma cell heterogeneity. A study of two monoclonal antibodies compared with S-100 protein in paraffin sections

Fifty-six formalin, Bouin's, and Carnoy's fixed, paraffin-embedded malignant melanomas (21 primary, 35 secondary), were studied by avidin-biotin complex immunohistochemistry using monoclonal antibodies (MoAb) HMB-45 and B1.1, comparing reactivity with polyclonal anti-S-100 protein. B1.1 (anti-CEA MoAb) was expressed in a minor percentage of cells of the invasive component of some primary melanomas, and weak to moderately in scattered metastic melanoma cells. MoAb HMB-45 prepared against melanocytic tumors reacted with over 90% of all tumors studied, being weakly reactive in one, and nonreactive in four metastases. This antibody stained some primary melanomas and their dysplastic nevus components in a heterogeneous manner, but was largely nonreactive in deep dermal nevus cells that were in association with invasive melanoma, enabling recognition of the deepest penetration of melanoma cells in the dermal nevus component. MoAb HMB-45 appears specific for melanoma cells, with no cross-reactivity with nonnevomelanocytic malignant tumors (unlike polyclonal anti-S-100 protein). MoAb HMB-45 is more sensitive in detecting malignant melanoma cell heterogeneity than anti-S-100 protein.     

Immunohistochemical study of melanocytic nevus and malignant melanoma with monoclonal antibodies against S-100 subunits

Immunohistochemical localization of S-100 protein alpha and beta subunits in the cells of melanocytic nevi and malignant melanomas was studied by using monoclonal antibodies directed against each subunit. Although polyclonal anti-S-100 reactivities have been demonstrated uniformly in all nevus cells and melanoma cells, monoclonal anti-S-100 alpha and anti-S-100 beta reactivities were either absent or rarely found in ordinary junctional nevi or junctional nests of ordinary compound nevi. However, in the junctional nests of dysplastic junctional nevi and junctional components of dysplastic compound nevi, monoclonal anti-S-100 alpha reactivity become more frequent, whereas monoclonal anti-S-100 beta reactivity remains negative. In the superficial variety of melanomas such as superficial spreading melanoma and lentigo maligna melanoma, monoclonal anti-S-100 beta is nonreactive until vertical growth or invasiveness begins. Most nodular melanomas are positively stained with both monoclonal anti-S-100 alpha and anti-S-100 beta. It is suggested that monoclonal anti-S-100 alpha can be an indicator of active junctional nevus of melanocytic nevi and the reactivity with monoclonal anti-S-100 beta may be related to vertical progression of superficial spreading melanomas and lentigo maligna melanomas.     

Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions

Background

Reported data indicate that cancer cells have increased rates of glucose metabolism, as determined by 18FDG-PET imaging in patients with malignancies. The results of many studies have demonstrated that the expression of glucose transporters, especially Glut-1, is increased in a variety of malignancies. This study was undertaken to assess the differential expression of Glut-1 and Glut-3 by benign and malignant melanocytic lesions.

Methods

Immunohistochemical staining for Glut-1 and Glut-3 was performed on paraffin-embedded tissue sections prepared from melanocytic nevi (12 cases), Spitz nevi (12 cases) and primary cutaneous malignant melanomas (20 cases).

Results

We observed immunoreactivity for Glut-1 in all melanocytic nevi, 9 of the 12 Spitz nevi and in 9 of the 20 malignant melanomas, whereas Glut-3 was expressed in all the melanocytic lesions, both benign and malignant.

Conclusion

These findings indicate that the glucose transporters Glut-1 and Glut-3 play a role in the glucose metabolism of melanocytic cells. Glut-1 was present in the majority of benign nevi, whereas its expression was downregulated in 55% of malignant melanomas. Our results suggest that glucose transporter Glut-1 expression can significantly discriminate between human malignant melanoma and benign melanocytic nevi, and support the idea that additional mechanisms other than Glut-1 may contribute to glucose uptake in melanomas.     

Prospective follow-up for malignant melanoma in patients with atypical-mole (dysplastic-nevus) syndrome

A total of 357 white patients who had melanocytic nevi that fulfilled the clinical criteria for the "classic" atypical-mole (dysplastic-nevus) syndrome (100 or more melanocytic nevi; one or more melanocytic nevi 8 mm or larger in diameter; and, one or more melanocytic nevi with atypical features) were followed for the development of cutaneous malignant melanomas. Seventeen patients (4.8%) developed malignant melanomas during an average follow-up period of 49 months. One patient developed two malignant melanomas. Eight of the malignant melanomas detected were in situ and ten were invasive melanomas (less than 0.86 mm in Breslow thickness), implying an excellent prognosis. The number of malignant melanomas detected in these patients exceeded significantly the number expected to occur in age- and sex-matched white controls. All groups were shown to have an increased risk for the development of malignant melanomas. Total-body photographs were helpful in detecting changes in size, shape, and color that led to the diagnosis of malignant melanoma. These data support the concept that patients with this readily regionalized clinical presentation of classic atypical-mole syndrome are at an increased risk for malignant melanomas and, therefore, should be examined regularly.     

Immunohistochemical expression of vascular endothelial growth factor,matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesions

BACKGROUND: Vascular endothelial growth factor (VEGF), an endothelial cell mitogen, plays a hierarchical role in regulating physiologic and pathologic angiogenesis. Moreover, the transformation from noninvasive to invasive carcinomas is accompanied by focal disruption and discontinuity of the basement membrane. Several groups of proteases have been implicated in tumor cell invasion, including the 72-kDa gelatinase A/Type IV collagenase (matrix metalloproteinase 2 [MMP-2]) and the 92-kDa gelatinase B/Type IV collagenase (MMP-9). METHODS: The authors assessed the immunohistochemical expression of VEGF and metalloproteinases MMP-2 and MMP-9 in paraffin embedded biopsy specimens of malignant melanomas (18 invasive melanomas and 10 in situ melanomas); dysplastic nevi with architectural disorder and cytologic atypia of melanocytes; Spitz nevi; and compound or predominantly intradermal, ordinary, benign melanocytic nevi. RESULTS: Strong cytoplasmic staining for VEGF was observed in melanoma cells in as many as 77% of primary invasive melanomas, whereas only 25% of the in situ melanomas exhibited a detectable immunoreactivity for VEGF. It is interesting to note that no immunoreactivity was shown by any nevi; Spitz nevi, in particular, showed negative immunoreactivity to VEGF. Invasive melanomas and in situ melanomas displayed coexpression of MMP-2 and MMP-9, although to a variable extent. In particular, high MMP-2 staining was observed in 14 of 18 invasive melanomas; moreover, strong MMP-2 expression also was observed in 60% of in situ melanomas, whereas the residual 40% of those melanomas showed a moderate level of positivity. CONCLUSIONS: On the basis of the current data showing that malignant melanocytic tumors displayed strong VEGF expression, whereas benign melanocytic proliferations showed no immunoreactivity for VEGF, VEGF also may be used as a discriminating factor to distinguish malignant melanoma from lesions of uncertain histology.     

Nuclear expression of the antiapoptotic protein survivin in malignant melanoma

BACKGROUND: Expression of the antiapoptotic protein survivin has been demonstrated in some melanocytic lesions and is believed to be required for melanoma cell viability. However, its diagnostic value in differentiating melanomas from nevi has not yet been examined. METHODS: Tissue microarray blocks were constructed with paraffin-fixed tissue of 19 nevi, 18 dysplastic nevi, 24 malignant melanomas, and 31 metastatic melanomas. Sections were then reacted with three antisurvivin antibodies (two monoclonal and one polyclonal) assessing labeling intensity (absent or weak, and moderate to strong) as well as the percentage of cells labeled (< 25%, > or = 25%). RESULTS: Of the antibodies evaluated, the polyclonal one was found to be the most sensitive. Nuclear immunoreactivity for survivin (i.e., > or = 25% of cells exhibiting and/or at least moderately intense staining) was seen in a subset of melanomas but not in nevi or dysplastic nevi (P < 0.05). CONCLUSIONS: Survivin is variably expressed in the cytoplasm in the entire spectrum of melanocytic lesions, with nuclear expression detectable only in melanomas. These data may underscore the importance of nuclear survivin in progression to melanoma and may prove useful in the differential diagnosis of melanoma versus nevus.