鼻内镜技术用于鼻腔鼻窦良恶性肿瘤的治疗

目的:评估鼻内镜手术对于鼻腔鼻窦良恶性肿瘤的治疗效果及应用价值.方法:收集我科采用鼻内镜或鼻内镜辅助手术治疗的鼻腔鼻窦良恶性肿瘤共109例,并进行回顾性分析.结果:经随访12-60个月,本组109例患者中,应用单纯鼻内镜下治疗的4例鼻腔鼻窦肿瘤患者术后出现复发,1例失访,复发率为5％;鼻内镜联合柯陆氏入路手术的16例患者中未出现术后复发;2例鼻内镜辅助鼻侧切开手术治疗的恶变内翻乳头状瘤患者术后1年出现局部复发及广泛脑膜侵犯死亡;鼻内镜辅助鼻侧切开手术中的2例恶性黑色素瘤其中1例术前已出现颊部及颈部淋巴结转移,于术后8个月-1.5年中出现远处转移后死亡.结论:鼻内镜手术已经逐渐成为多种鼻腔鼻窦良性肿瘤以及部分恶性肿瘤的首选治疗方式.     

鼻腔鼻窦淋巴瘤相关因素及临床特征研究

目的：探讨早期鼻腔鼻窦淋巴瘤（NHL）相关因素及临床特征。方法：对经我院病理确诊为鼻腔鼻窦NHL的患者及来自同期收治的慢性鼻．鼻窦炎病例各28例,进行回顾性对照研究。统计分析应用SPSS17．0统计软件进行。结果：28例鼻腔鼻窦NHL中,NKfr细胞淋巴瘤18例,外周T细胞淋巴瘤7例,B细胞淋巴瘤3例。统计分析显示,对药物（麻黄素、肾上腺素）收缩反应差OR28．140（1．995．396．972）、发热OR99．366（0．752—13130．619）、粘膜不光滑OR34．665（1．464—820．575）、下鼻甲质地硬oR25．797（1．395-447．001）是鼻腔鼻窦NHL的高危指标。结论：对药物（麻黄素、肾上腺素）收缩反应差、发热、粘膜不光滑、下鼻甲质地硬是早期鼻腔鼻窦淋巴瘤的强危险信号和重要的诊断线索。     

21例变应性真菌性鼻窦炎临床分析

目的探讨变应性真菌性鼻窦炎的诊断以及治疗方法。方法通过临床表现、皮肤激发试验、血清嗜酸性粒细胞、鼻腔真菌涂片、鼻窦CT、鼻内窥镜等专科检查,明确21例变应性真菌性鼻窦炎患者,给予丙酸氟替卡松鼻喷剂喷鼻、151服氯雷他定片10mg（1次／d）、生理海水鼻腔冲洗1～2次／d,治疗1周后,入院行鼻内窥镜鼻息肉切除鼻窦Fess手术,术中彻底清除病变鼻窦内真菌团块或褐色泥砂样真菌泥后,氟康唑氯化钠注射液冲洗窦腔,术后氟康唑氯化钠注射液冲洗清洁术腔,每周1～2次,连续1个月,鼻腔局部继用糖皮质激素3—6个月,获得良好的治疗效果。结果21例变应性真菌性鼻窦炎患者中,单侧鼻窦发病16例,占76．2％,双侧鼻窦发病5例,占23．8％,上颌窦发病16例,占76．2％,上颌窦合并筛窦发病4例,占19．0％,蝶窦发病1例,占4．8％,伴鼻息肉15例,占71．4％,伴有哮喘史8例,占38．1％,术后2例复发,占9．5％。结论变应性真菌性鼻窦炎临床诊断并不困难,治疗以手术为主,但术前糖皮质激素的应用,手术时机选择,术后对鼻腔与鼻窦变应反应的处理,将直接影响预后。     

结膜恶性黑色素瘤3例临床病理分析及文献复习

目的探讨结膜恶性黑色素瘤的临床特点及病理学特征,并进行文献复习。方法回顾性分析3例结膜恶性黑色素瘤的临床特点、病理学特征、免疫表型特点及分子生物学特点。结果老年男性患者多见,病程2个月～1年,有近期肿物增大过快病史。肿瘤细胞呈上皮样细胞型、梭形细胞型或者二者混合型,均可见黑色素沉着。免疫表型:3例HMB45、melan A、S-100、cyclinD1和vimentin均为阳性,只有2例p53阳性,3例Ki-67增殖指数25%～60%。分子病理:3例病例中有1例发生了BRAF V600E突变,均未检测到c-Kit突变。3例患者均进行局部肿瘤切除,随访3个月至5年均未复发、转移。结论结膜的恶性黑色素瘤临床较罕见,镜下形态多样,有时缺乏黑色素,melan-A、HMB-45、S-100、cyclin D1、vimentin等免疫组织化学标记可以辅助诊断,分子检测BRAF V600E和c-Kit也有提示作用,早期发现并进行局部肿瘤切除术,效果较好。     

252例胸膜恶性肿瘤的临床病理分析

目的：探讨胸膜恶性肿瘤的病理类型、肿瘤所占比例、临床病理特征及鉴别诊断。方法：结合病理形态学及免疫组化方法对252例胸膜恶性肿瘤进行诊断及鉴别诊断。结果：252例胸膜恶性肿瘤包括胸膜穿刺活检120例,胸腔镜活检25例,伴有胸膜转移的恶性胸水107例;男性143例,女性109例,年龄19—87岁,平均年龄59．9岁。临床主要症状是胸闷、气短、咳嗽、胸痛等。CT表现为胸膜增厚、胸水（90％）、多发或单发胸膜结节和原发器官占位性病变。活检病例中,转移性癌86例（34．1％）,包括肺腺癌64例（25．4％）,小细胞癌11例（4．4％）,鳞癌11例（4．4％）,恶性间皮瘤47例（18．7％）,滑膜肉瘤9例（3．6％）,非霍奇金淋巴瘤3例（1．2％）;恶性胸水病例病例中转移性癌95例（37．7％）,包括肺腺癌85例（33．7％）,小细胞癌6例（2．4％）,鳞癌2例（0．8％）,乳腺腺癌2例（0．8％）,恶性间皮瘤8例（3．2％）,非霍奇金淋巴瘤4例（1．6％）。结论：胸膜恶性肿瘤中以转移性腺癌多见,其次为恶性间皮瘤,结合形态学及免疫组织化学检测不同标志物的表达有助于诊断胸膜恶性肿瘤的种类。     

肺淋巴管平滑肌瘤病临床病理分析及文献复习

目的：探讨肺淋巴管平滑肌瘤病（PLAM）的临床和病理特征,提高对该病的认识。方法：对1例PLAM患者的临床特点、HE及免疫组化染色结果进行分析,并结合文献进行复习。结果：PLAM是一种持续发展的弥漫性肺疾病,几乎发生于育龄期妇女,主要临床症状为进行性呼吸困难、反复气胸及乳糜胸。病理特征显示未成熟平滑肌样细胞在细支气管壁、肺泡壁、淋巴管壁和血管壁周围增生。免疫组化染色显示增生PLAM细胞Desmin、SMA、Vimentin、HMB45均呈阳性表达,部分细胞ER及PR阳性。结论：PLAM在影像学与病理组织学上有特征性表现,免疫组化HMB-45阳性具特异性。由于肺部广泛病变,预后较差．对PLAM的发病机制和治疗的研究已有了一定的进展,但今后尚需更深入地研究。     

慢性髓细胞白血病急变期MICM分型回顾性分析

目的：探讨慢性髓细胞白血病急变期（CML-Be）患者的细胞形态学（M）、免疫学（I）、细胞遗传学（C）和分子生物学（M）的特征及应用价值。方法：对38例CML．BC患者的MICM分型进行回顾性分析。结果：以FAB分型为基础的形态学确诊率达94．7％;免疫分型结果为：38例CML-BC中CML-AML占71．0％,其中37．0％伴淋系表达;CML-ALL占23．7％,均为B细胞性,其中66．67％伴髓系表达;CML-MAL（混合性白血病）占5．3％,均为B系和髓系混合表达;CD34＋26例（68．4％）,cD7＋10例（26．3％）,均与CD34共表达。细胞遗传学结果显示：CML特征性Ph染色体检出率为94．3％（36／38）,附加异常染色体检出率为60．5％（23／38）,发生频率较高的类型是＋Ph、＋8和i（17q）;FISH检测BCR／ABL融合基因阳性率为100％,der（9）缺失占14．7％。RT—PCR检测20例患者BCR／ABL融合基因均为阳性,其中b2a2型（12／20）,b3a2型（8／20）,1例（1／20）,b2a2和b3a2双阳性（1／20）。结论：CML—BC是造血干细胞疾病,原始细胞分化阻滞在早期阶段,预后差。MICM分型对CML-BC的诊断、治疗和预后判断均有重要价值。     

细菌L型与人乳头状瘤病毒致凹空细胞的比较

应用组织切片革兰染色和免疫组织化学染色等方法,对２４０例有凹空细胞的标本（鳞状细胞乳头状瘤３６例．尖锐湿疣６１例,喉癌８５例,子宫颈鳞癌５８例）进行人乳头状瘤病毒（ＨＰＶ）和细菌Ｌ型检测,比较两者在组织中的检出阳性率、分布及组织病理学表现。结果发现,凹空细胞中ＨＰＶ—Ａｇ检出阳性率（７２．１％）与金葡菌ＣｏｗａｎＩ株Ｌ型－Ａｇ检出阳性率（６５．０％）无显著性差异（Ｐ＞０．０５）;革兰染色有６５．４％的凹空细胞检出Ｌ型菌,ＨＰＶ－Ａｇ与Ｌ型－Ａｇ在组织中的分布和组织病理学表现基本一致。表明细菌Ｌ型与病毒具有相似的病理致病特征。细菌Ｌ型感染是引发上述病变及凹空细胞的重要原因之一。     

肺癌细胞多向分化与异质性的研究

探讨肺癌细胞多向分化与异质性。用光镜、免疫组化方法观察了87例肺癌手术标本组织切片,30例细胞涂片。（1）标本取材块数与病理分型种类多少里显著性正相关。（r=0．407,P＜0．01）;（2）作为单一类型的小细胞癌、鳞癌、腺癌、大细胞癌及类癌仅占27．6％、20％鳞癌、16．7％腺癌、23．3％大细胞癌KER、VIM双表达。66．7％有鳞、腺、神经内分泌三向分化;（3）在混合类型肺癌中,细胞学与组织学分型符合率为56．7％。肺癌细胞类型有明显异质性,其发生分子基础尚待进一步研究。     

VEGF—A和VEGF—C在皮肤恶性黑色素瘤表达的临床病理意义

目的：内皮细胞生长因子（Vascularendothelialgrowthfactor,VEGF）与恶性肿瘤转移密切相关,研究发现VEGF过度表达与恶性黑色素瘤转移有关,在本研究中通过研究VEGF在恶性黑色素瘤中的表达及与临床病理指标的相关性,为以VEGF为靶的抗转移治疗提供依据。方法：应用免疫组织化学技术检测恶性黑色素瘤中VEGF-A和VEGF-C表达,及与临床病理特点和生存状态的关系。结果：VEGF—A在皮肤恶性黑色素瘤中的阳性表达率是83．33％（30／36）,在色素痣中阳性表达率是15％（3／20）,两组间有显著性差异（P〈O．05）。VEGF—C在皮肤恶性黑色素瘤中的阳性表达率是88．9％（32／36）,在色素痣中阳性表达率是10％（2/20）,两组间有显著性差异（P〈0．01）。VEGF-A和VEGF—C表达与年龄、性别、肿瘤形态、肿瘤大小无显著关系,但与淋巴结转移和封闭血管环形成有关,VEGF-A和VEGF—C阳性病例淋巴结转移率和封闭血管环出现率显著高于VEGF-A和VEGF-C阴性病例。有统计学意义。对VEGF-A和VEGF-C表达与恶性黑色素瘤生存状态的关系分析显示,VEGF-A和VEGF-C表达阴性的病例的生存期和生存率均显著高于VEGF-A和VEGF-C表达阴性的病例,有统计学意义。结论：VEGF-A和VEGF-C表达与恶性黑色素瘤的淋巴结转移、血管形成和生存期相关,这两种蛋白过度表达反映黑色素瘤处于进展状态和预后差,可以作为黑色素瘤诊断、预后和复发预测的指标和靶向治疗的靶蛋白。     

Melanoma metastatic to the breast: utility of fine needle aspiration and immunohistochemistry

OBJECTIVE: To describe the morphologic spectrum of metastatic malignant melanoma (MM) cells involving the breast and to explore the diagnostic utility of HMB45, Mart-1, Melan-A and T311 (antityrosinase) antibodies in fine needle aspiration material of MM metastatic to the breast. STUDY DESIGN: Cytologic material from 21 cases (18 women) was reviewed for cytomorphology (epithelioid, spindled, mixed) and immunocytochemical staining attributes for Mart-1, HMB45, T311, Melan-A and cytokeratin based on tissue availability. RESULTS: Seventeen cases (81%) demonstrated epithelioid cell morphology, with 14% exhibiting mixed and 5% spindled morphologies. All 21 cases (100%) were immunoreactive with Mart-1 antibody, with 81% (17/21) immunoreactive for HMB45. In 38% of cases there was a similar percentage of cells immunoreactive for Mart-1 and HMB45, while 48% showed a higher percentage of cells immunoreactive for MART-1 than HMB45. Immunoreactivity with T311 was seen in 8 of 11 cases tested (73%). All six cases tested (100%) were immunoreactive with Melan-A. Staining for cytokeratin was negative in all eight cases tested. CONCLUSION: Because the majority of MM metastatic to the breast shows epithelioid cell morphology, it may mimic primary breast carcinoma. Mart-1 should be part of the immunocytochemical panel utilized to confirm the diagnosis of MM metastatic to the breast.     

Comparison of immunohistochemical labelling of melanocyte differentiation antibodies melan-A, tyrosinase and HMB 45 with NKIC3 and S100 protein in the evaluation of benign naevi and malignant melanoma

A panel of three melanocyte differentiation antibodies has been compared with anti-S100 protein and NKIC3 in an assessment of benign and malignant melanocytic lesions.Anti-polyclonal S100 protein labelled all cases of primary cutaneous malignant melanoma, metastatic melanoma, desmoplastic melanoma and myxoid melanomas. In addition all benign and dysplastic naevi were positive. Conversely, HMB 45 was the least sensitive marker, labelling 24/31 primary cutaneous melanomas, 14/24 metastatic melanomas and only 1/6 desmoplastic melanomas. In the case of naevi, only junctional forms labelled consistently. Results for anti-melan-A and anti-tyrosinase were similar, although anti-tyrosinase proved slightly more sensitive in cases of malignant melanoma. NKIC3 revealed similar results to anti-tyrosinase, but had the disadvantage of reduced selectivity.It is concluded that anti-tyrosinase and anti-melan-A are useful additions to the panel of melanocytic monoclonal antibodies. In addition, both antibodies appear to have greater sensitivity for malignant melanoma than the conventionally used HMB 45 and could be considered as supportive markers to polyclonal anti-S100 protein in the diagnosis of malignant melanoma.     

Fine Needle Aspiration Cytology and Immunocytochemistry of Metastatic Melanoma

The cytological and immunological findings of 81 metastatic melanomas are described. Fine needle aspiration was performed from secondary deposits in lymph nodes (38), subcutaneous and soft tissue (36), abdomen (5), lung (1) from 67 patients with histologically verified malignant melanoma. One patient had disease which had spread into the cerebrospinal fluid. Cytomorphologically the cases were classified as classical (47%), carcinoma-like (22%), spindle cell type (14%), lymphoma like (6%), undifferentiated (6%), myxoid type (3%), and clear cell type (2%). All cases were immunologically characterized using antibodies to S-100, vimentin and cytokeratin. All cases were S-100 positive and the majority (96%) reacted with antibodies to vimentin. A weak heterogenous reactivity to cytokeratin antibody was detected in only eight cases. The HMB45 antibody was applied to 20 cases and 16 (80%) of these tumours were positive. In summary, we found that an immunological characterization was necessary to conclusively diagnose over 50% of metastatic melanomas which presented with an equivocal cytological picture.     

鉴别无色素性恶性黑色素瘤方法的探讨

无色素及少色素性恶黑鉴别诊断时,（１）组织化学铁反应,褪色素和黑色素银染对证实瘤细胞中黑色素是有帮助的,但不能从无色素性恶黑中检出黑色素。因此对无黑色素恶黑的诊断和鉴别诊断帮助不大。网状纤维染色良性病均有增加,而恶黑几乎没有增加或仅极少增加。因此网状纤维染色有助于良恶性的鉴别。（２）免疫组化Ｓ－１００１８例恶黑及６例良性痣均显示阳性,这对无色素恶黑的诊断是有价值的,但对色素痣的恶变帮助不大。１６例恶黑中１４例色素性与１０例无色素性恶黑ＨＭＢ４５均显示阳性,证明两者有共同抗原,总阳性率８７．５％,６例良性痣均为阴性,证明无ＨＭＢ４５抗原。结果提示ＨＭＢ４５免疫组化检测不仅对无色素及少色素性恶黑的诊断与鉴别诊断实用性大,还可以用于对恶黑与良性痣、良性痣恶变的鉴别。（３）本组４例无色素性恶黑电镜下均找到前黑色素小体。因此在其他方法诊断困难时,应用电镜检查对确诊具有决定性作用。     

Anti-melanoma monoclonal antibody HMB45 identifies an oncofetal glycoconjugate associated with immature melanosomes.

The anti-melanoma monoclonal antibody HMB45 is widely used in diagnostic pathology owing to its great specificity and sensitivity in identifying pigmented tumors such as malignant melanoma. However, little is known regarding the nature of the antigen(s) recognized by this antibody. In the observations reported here, the HMB45-defined antigen was identified in another pigmented tissue, the retinal pigment epithelium (RPE). A series of immunocytochemical studies demonstrated transient reactivity of the prenatal and infantile human RPE with antibody HMB45; adult RPE is non-reactive with the antibody. By immunoelectron microscopy, the antibody was demonstrated to react with immature melanosomes. Pre-treatment of deparaffinized tissue sections with neuraminidase completely eliminated HMB45 immunoreactivity, suggesting that the antigen(s) recognized is a sialated glycoconjugate. Mannosidase or N-acetylglucosaminidase pre-treatment had no effect on immunoreactivity. Thus, HMB45 may identify an oncofetal antigen present in cutaneous melanocytes, RPE, and melanoma cells, and changes in immunoreactivity with maturation or malignant transformation may be a function of post-translational modification.     

Collagen XVII is expressed in malignant but not in benign melanocytic tumors and it can mediate antibody induced melanoma apoptosis

The 180?kDa transmembrane collagen XVII is known to anchor undifferentiated keratinocytes to the basement membrane in hemidesmosomes while constitutively shedding a 120?kDa ectodomain. Inherited mutations or auto-antibodies targeting collagen XVII cause blistering skin disease. Collagen XVII is down-regulated in mature keratinocytes but re-expressed in skin cancer. By recently detecting collagen XVII in melanocyte hyperplasia, here we tested its expression in benign and malignant melanocytic tumors using endodomain and ectodomain selective antibodies. We found the full-length collagen XVII protein in proliferating tissue melanocytes, basal keratinocytes and squamous cell carcinoma whereas resting melanocytes were negative. Furthermore, the cell-residual 60?kDa endodomain was exclusively detected in 62/79 primary and 15/18 metastatic melanomas, 8/9 melanoma cell lines, HT199 metastatic melanoma xenografts and atypical nests in 8/63 dysplastic nevi. The rest of 19 nevi including common, blue and Spitz subtypes were also negative. In line with the defective ectodomain, sequencing of COL17A1 gene revealed aberrations in the ectodomain coding region including point mutations. Collagen XVII immunoreaction-stained spindle cell melanomas, showed partly overlapping profiles with those of S100B, Melan A and HMB45. It was concentrated at vertical melanoma fronts and statistically associated with invasive phenotype. Antibody targeting the extracellular aa507-529 terminus of collagen XVII endodomain promoted apoptosis and cell adhesion, while inhibiting proliferation in HT199 cells. These results suggest that the accumulation of collagen XVII endodomain in melanocytic tumors is associated with malignant transformation to be a potential marker of malignancy and a target for antibody-induced melanoma apoptosis.     

Comparative Histopathology of Grey‐Horse‐Melanoma and Human Malignant Melanoma

Equine melanoma shows striking features particularly with regard to clinical development in grey horses: in contrast to malignant melanoma in humans and in solid coloured horses that are characterized by early onset of metastasis, pigment cell tumours display almost benign clinical features in ageing grey horses. Through evolution, grey horses appear to be in a favourable position in regard to the biological behaviour of melanomas. Yet unknown factors inhibiting or retarding early melanoma metastasis may be responsible for this phenomenon. In this study, immunostaining profiles and histopathologic patterns of equine vs. human melanotic tumours were compared. In addition, the expression of melanoma markers currently used in human melanoma detection and characterization were evaluated for their applicability in equine melanoma diagnosis. Immunohistopathologic investigations revealed that benign grey horse melanomas share common features with human blue nevi and with human malignant desmoplastic melanomas, whereas their resemblance to other types of human cutaneous malignant melanomas is less pronounced. Our data equally underline that S‐100, proliferating cell nuclear antigen (PCNA), HMB‐45, Ki‐67, T‐311 and CD44 can serve as reliable markers for horse melanomas. Further investigations aiming at identifying factors retarding metastasis in affected grey horses are needed, as they may contribute to the development of novel treatment strategies for human malignant melanoma.     

Effects of genistein and daidzein on the cell growth,cell cycle,and differentiation of human and murine melanoma cells(1)

Genistein and daidzein are two major isoflavonoids in dietary soybean that have inhibition effect on the cell growth of different tumor cell lines. We previously reported the anti-tumor activities of genistein and daidzein in human co1on tumor (HCT) cells and their different ability to enhance the activation of murine lymphocytes. In the present study, the effect of genistein and daidzein on the cell growth, cell cycle progression, and differentiation of murine K1735M2 and human WM451 cel1s was investigated. It was found that genistein could inhibit the cell growth of two metastatic melanoma cell lines, murine Kl735M2 and human WM45l in a dose-dependent manner. Flow cytometry showed that genistein could cause arrest of both Kl735M2 and WM45l at G(2)/M phase, while daidzein increased the cell numbers at S phase, decreased the cell numbers at G(1) phase. Detection of melanin and morphological observation showed that genistein can induce Kl735M2 and WM45l to produce dendrite-like structure and produce more melanin by 80%. In contrast, daidzein only retarded the growth of K1735M2 and did not induce differentiation in either K1735M2 or WM451. These results suggest that genistein and daidzein in soybean can inhibit certain malignant phenotype of melanoma via different mechanisms and be potential medical candidates for melanoma cancer therapy.