乙酰肝素酶mRNA和蛋白在恶性黑素瘤皮损及A375细胞株中的表达

目的探讨乙酰肝素酶mRNA和蛋白在恶性黑素瘤皮损及A375细胞株中的表达及意义。方法选择恶性黑素瘤30例、黑素细胞痣30例、恶性黑素瘤A375细胞株及15例正常皮肤组织,分别采用原位杂交、免疫组化法检测皮损及细胞株中乙酰肝素酶mRNA及蛋白的表达。结果A375细胞株及19例(19/30,63.33%)恶性黑素瘤皮损中乙酰肝素酶mRNA呈阳性表达,2例(2/30,6.67%)黑素细胞痣皮损中乙酰肝素酶mRNA表达阳性,正常皮肤组织中无1例呈阳性表达;恶性黑素瘤皮损中乙酰肝素酶蛋白的阳性表达率与黑素细胞痣、与正常对照组相比,差异均有显著性意义(χ12=19.200,P=0.000;χ22=25.714,P=0.000)。乙酰肝素酶蛋白在恶性黑素瘤、恶性黑素瘤A375细胞株、黑素细胞痣及正常皮肤组织的表达情况与mRNA相一致。结论乙酰肝素酶mRNA和蛋白的高表达可能与恶性黑素瘤的发生发展有关,有望作为治疗黑素瘤的靶点。     

Bowen病合并恶性黑素瘤1例

患者男,77岁。左侧腰部斑块10年。左中下腹黑褐色斑疹4年,同时全身阵发性皮肤瘙痒15年。皮损组织病理诊断:①Bowen病;②恶性黑素瘤。经手术治疗后好转。     

恶性雀斑样黑素瘤6例临床及组织病理学分析

目的:分析恶性雀斑样黑素瘤的临床和组织病理特点.方法:回顾性分析6例恶性雀斑样黑索瘤患者的临床和组织病理资料.结果:4例患者在老年期发病,其中1例患者有两处皮损,另2例患者在中青年期发病.所有皮损临床上均表现为面部直径较大的边界不规则、颜色不均的黑色斑片,有1例出现溃疡.皮损组织病理学检查:1例为浸润性黑素瘤,其余皮损均为原位黑素瘤.原位黑素瘤表现为表皮内不典型黑素细胞增生,细胞分布不均,有明显异形性,充分进展的皮损可形成小细胞巢.2例发病年龄较早的患者无明显胶原嗜碱性变,其余的组织病理学特征与发生在老年的恶性雀斑样痣无明显差异.免疫组化结果示所有皮损肿瘤细胞S-100蛋白和Melan-A均为阳性.结论:恶性雀斑样黑素瘤是一种老年人多发的多见于面部的黑素瘤,但也可见于中青年患者.其组织病理可表现为原位黑素瘤或浸润性黑素瘤.     

结节性恶性黑素瘤早期转移1例

患者男，39岁。全身出现结节2月。早期出现肝脏、肺和皮肤的多发转移灶。皮肤病理检查：皮下结节示典型的结节性恶性黑素瘤的表现。本文讨论了恶性黑素瘤的预后因素。     

恶性黑素瘤13例临床分析

回顾分析13例恶性黑素瘤的临床表现、病理、免疫组化、血清LDH水平、治疗方法及预后.结果:13例恶性黑素瘤发病年龄为29～83岁,平均58.08岁,好发足部.本组患者生存率低,6个月～5年随访,死亡9例,生存期3个月～5年;存活4例.恶性黑素瘤是一种少见、高度侵袭性肿瘤,易早期转移,多转移到局部淋巴结、肝、肺、骨和颅内,预后差.免疫组化S-100、Vimentin、melan-A和HMB-45有利于辅助诊断无色素性恶性黑素瘤.     

恶性黑素瘤中T-钙粘蛋白的表达

目的:探讨恶性黑素瘤组织中T-钙粘蛋白(T-cadherin)的表达.方法:采用免疫组化SP法对18例恶性黑素瘤组织标本和40例皮肤色素痣组织标本及同一标本的正常表皮、黑素瘤细胞系M14和A375进行T-cadherin的检测.结果:正常表皮均表达T-cadherin,恶性黑素瘤组织中11.1%检测到T-cadherin,皮肤色素痣组织中97.5%检测到T-cadherin(P<0.001),差异有统计学意义;黑素瘤细胞系M14、A375中T-cadherin均呈弱阳性表达.结论:T-cadherin在恶性黑素瘤组织、细胞的表达明显降低或缺失,提示T-cadherin在皮肤恶性黑素瘤的发生、发展中可能起重要作用.     

核转运蛋白基因2的表达在皮肤恶性黑素瘤临床预后中的作用

目的:探讨核转运蛋白基因(karyopherin, KPNA)2在皮肤恶性黑素瘤临床预后中的作用。方法:应用GEO数据库数据分析,比较KPNA2 mRNA在正常皮肤组织、恶性黑素瘤中表达的差异,并进一步利用两种在线数据库进行生存分析,分析KPNA2 mRNA与皮肤恶性黑素瘤的预后之间的关系。结果:KPNA2 mRNA水平在正常皮损组织中明显要低于恶性黑素瘤组织,差异有统计学意义(P0.05);同时生存分析显示KPNA2 mRNA表达水平与皮肤恶性黑素瘤的预后具有的显著相关性,其表达水平高则预后差(P0.05)。结论:KPNA2与皮肤恶性黑素瘤临床预后密切相关,为皮肤恶性黑素瘤治疗提供潜在靶点。     

皮内分析分光光度法在皮肤科的应用

皮内分析分光光度法是一种新型的无创性在体皮肤光学成像技术,通过发射可见光和红外光,可对皮肤内的黑素、血红蛋白和胶原进行快速成像.目前该方法已成为诊断色素性皮损和早期恶性黑素瘤及非黑素瘤皮肤癌等的有用工具.     

恶性黑素瘤细胞周期素D3及增殖细胞核抗原的表达

目的探讨恶性黑素瘤中细胞周期素D3和增殖细胞核抗原(PCNA)的表达及临床意义。方法采用免疫组化SP法检测57例原发性皮肤恶性黑素瘤及37例转移性恶性黑素瘤中细胞周期素D3和PCNA的表达，并以20例良性痣作为对照。结果①原发性皮肤恶性黑素瘤及转移性恶性黑素瘤中细胞周期素D3的阳性表达及PCNA的表达较良性痣均有不同程度增强：转移性恶性黑素瘤中两者的表达较原发性皮肤恶性黑素瘤也有不同程度增强。②两者在原发性皮肤恶性黑素瘤中的表达与病理Clark分级及淋巴结转移状态显著相关。③浅表扩散性恶性黑素瘤中细胞周期素D3阴性组的3年存活率显著高于细胞周期素D3阳性组，浅表扩散性恶性黑素瘤及结节性恶性黑素瘤中PCNA低表达组3年存活率明显高于PCNA高表达组。④浅表扩散性恶性黑素瘤及转移性恶性黑素瘤中细胞周期素D3阳性表达与PCNA高表达呈正相关。结论细胞周期素D3及PCNA的表达可能与原发性皮肤恶性黑素瘤的发生发展有关，对于治疗方案的选择及预后评估都具有重要的临床意义，细胞周期素D3的表达水平可作为浅表扩散性恶性黑素瘤临床预后的预测因子。     

黑素瘤的前期损害

介绍了发育不良痣的临床表现及组织病理改变,并对该病诊断中存在的问题进行了讨论。对家族性多发性非典型性痣—黑素瘤综合征的临床表现,遗传学发病机制、处理以及与恶性肿瘤的关系进行了较为详尽的描述,认为该病的皮损容易转变成恶性黑素瘤,是恶性黑素瘤的前期损害。最后,作者综述了先天性痣(包括巨大型及中小型先天性痣)与恶性黑素瘤的关系,认为巨大型先天性痣与恶性黑素瘤有关,而对中小型先天性痣与恶性黑素瘤的关系则有不同的看法。     

Familial Atypical Mole Syndrome Manifesting as Polypoid Melanoma: A Case Report and Review of the Japanese Literature

A family with atypical mole syndrome which manifested as polypoid melanoma in one member is reported. A 46-year-old man presented with a polypoid tumor on his lower back, which was excised under clinical diagnosis of soft fibroma. The tumor proved to be polypoid melanoma. He was referred to our clinic, and examination revealed that he had the atypical mole syndrome phenotype. The clinicopathological screening of his first-degree relatives confirmed that his 58-year-old sister had the same phenotype. In addition to our discussion of the clinical significance of polypoid melanoma, we also attempted to elucidate the characteristics of the reported Japanese cases of melanomas with atypical moles from a survey of the literature, which revealed the following characteristics: 1) younger mean age than that of total Japanese melanoma cases, 2) sun sensitive skin, 3) unexpectedly and frequently observed familial incidence (Kraemer's D₁ and D₂), 4) frequent site of the melanoma on the trunk and none on the sole of the foot, and 5) high incidence of superficial spreading melanoma and nodular melanoma, and 6) no cases of acral lentiginous melanoma.     

Polypoid Spitz naevus: the benign counterpart of polypoid malignant melanoma

Polypoid malignant melanoma is a peculiar morphological variant of melanoma with a distinct exophytic pattern of growth. This form of melanoma is usually very thick and the prognosis is accordingly poor. We present here a previously undescribed form of Spitz naevus which had a similar polypoid exophytic silhouette and marked cytological atypia. Despite these close morphological similarities, polypoid Spitz naevus evolves in a completely benign manner. Morphologically, polypoid Spitz naevus can be distinguished from polypoid melanoma by the absence of mitoses and by the prominent stromal reaction throughout the lesion.     

Nodular malignant melanoma with Spitz nevus-like pathological features finally confirmed by the pathological feature of the sentinel lymph node

The clinical and histopathological similarities of nodular melanoma and Spitz nevus currently still make a definitive diagnosis difficult. We report here a case of nodular melanoma that was extremely difficult to diagnose both clinically and histopathologically. The primary tumor was a blackish nodule on the scalp and biopsy was performed for pathological diagnosis. Although our first impression was malignant melanoma, we asked two dermatopathologists for second opinions; however, one diagnosed a melanoma and the other a Spitz nevus. Faced with this clinical dilemma, an operation was performed with sentinel node biopsy. Only one sentinel node suggested a metastasis. Histopathological diagnosis to establish whether it was a melanoma metastasis or nodal nevi was also difficult, and we again asked for second opinions from another dermatopathologist in the USA. According to its clinical course and the histopathology of the sentinel lymph node with additional immunohistochemistry, this case was finally diagnosed as a nodular melanoma (T4aN1aM0, stage IIIA). To date, the patient has been given five courses of chemotherapy at 6-month intervals, with no local recurrence or distant metastases so far.     

A comparative study of fluorescence in malignant melanoma and nevocellular nevus using a fluorescence microscope and formalin-fixed specimens

Fluorescence in malignant melanoma cells was investigated. The specimens from 18 cases of malignant melanoma and 26 cases of nevocellular nevus, which were fixed with formalin and embedded in paraffin wax, were studied by the fluorescence microscopic method. On the fluorescence microscope, the malignant melanoma cells emitted intense fluorescence from the cytoplasm. The nevus cells with large amounts of melanin granules showed moderate fluorescence. The tumor cells of melanoma in situ and nevus cells with few melanin granules emitted little fluorescence. Not only malignant melanoma cells but also nevus cells in the formalin fixed specimens had various degrees of fluorescence. Many cases of malignant melanoma emitted intense fluorescence, but this was rarely found in nevocellular nevus. This method is also useful in differentiating melanoma from nevocellular nevus.     

Blue naevus with satellitosis mimicking malignant melanoma

Blue naevus is an acquired benign melanocytic naevus. It is a firm, sharply defined dark blue to grey-black papule or nodule, which is likely to arise from the arrested dermal melanocytes in the dermis. In the last few years, blue naevus has attracted much attention due to the recognition of new entities and to its confusion with malignant melanoma. We report a 69-year-old man who developed a blue-black nodular lesion with satellitosis on his scalp. Although clinically it was thought to be a malignant melanoma, histopathological investigation and conservative methods such as dermatoscopy and power Doppler ultrasonography did not confirm this diagnosis. Histopathological examination excluded malignant melanoma, as there were no cellular atypia and mitotic activity in either the nodular lesion or the satellitosis. Doppler ultrasonography confirmed the benign nature of the lesion. Dermatoscopic examination showed homogeneous steel-blue pigmentation with individual blue globules, dots and some brown veils, and confirmed the histopathological diagnosis. To the best of our knowledge, our case is the third reported case of a blue naevus with satellitosis mimicking malignant melanoma.     

Epidermotropic Metastatic Melanoma Clinically Resembling Agminated Spitz Nevi

Herein, we report a 36-year-old Asian male patient who presented with grouped multiple erythematous waxy papules and nodules on his right medial thigh. He had undergone amputation of the right second toe because of a stage IIa malignant melanoma, 3 years previously. At the time of surgery for the primary tumor, right inguinal lymph node dissection revealed no nodal involvement. Three years after the diagnosis of the primary tumor, crops of multiple erythematous papules and nodules developed. Initial histopathologic evaluation of the papules showed nests of small epithelioid cells similar to compound nevi. However, cytologic features, including high mitotic figures, lack of maturation, and some hyperchromatic nuclei suggested metastatic melanoma. In addition to the pathologic findings, the tumors were on the right thigh, which was the same side as the primary malignant melanoma. The patient underwent wide excision of the tumor and split-thickness skin grafting.     

A case of pedunculated malignant melanoma of the vaginal mucosa.

We report an 84-year-old Japanese woman who presented with a pedunculated malignant melanoma of the vaginal mucosa. Mucosal melanoma is believed to be more common in Japan than other countries, but such tumors of the vulvovaginal region are quite unusual. In our patient, three tumors were connected by a narrow pedicle. Three black tumors measuring 5-10 mm in diameter with a common pedicle were seen on the vaginal mucosa at five o'clock from the cervix. The tumors were hanging from the narrow pedicle. On histologic examination, they were diagnosed as malignant melanoma. Resection was done with a distal margin of 3 cm from the tumors and a margin of 1 cm from the cervix. The patient has had no evidence of local recurrence or distant metastasis. In our patient, the three main tumors had a common pedicle, which seems to be a unique finding. Since pedunculated malignant melanomas are rare, making a clinical diagnosis is difficult. Although pedunculated melanomas are recognized as having a high malignant potential because these lesions are generally thick, a relatively good outcome is sometimes reported. In our patient, there was no tumor infiltration into the dermis of the pedicle, and this may be one reason for the good outcome at present. There has been no previous report of a mucosal melanoma consisting of three tumors like those in the present patient.     

A case of epidermotropic metastatic malignant melanoma with multiple nodular lesions of the scalp

Epidermotropic metastatic malignant melanoma (EMMM) is a form of metastatic malignant melanoma that has dermal cell nests with epidermotropism and specific histopathological features. We report a patient with eight nodular lesions of the scalp with histopathological findings compatible with EMMM. The tumors developed one year before consultation and increased in size simultaneously. The histopathological findings of all eight tumors were very similar. The tumor cells were located mainly in the dermis and partly in the basal layer of the epidermis. They contained melanin pigments and were positive for anti-HMB45 antibody. The tumors did not respond to combination chemotherapy with dacarbazine, nimustine, vincristine, and interferon-beta. Therefore, all the tumors were surgically removed. No local relapse, distant metastasis or re-elevation of plasma 5-S-cysteinyldopa was identified during nine months of follow-up. Histopathologically, all eight tumors lacked apparent vascular invasion, which may be related to a slow clinical course of the present case.     

Giant Metastatic Malignant Melanoma with an Unknown Primary Site

We report a case of malignant melanoma of unknown primary origin which presented with a giant metastatic tumor in his right inguinal region. A 94-year-old man noticed a small subcutaneous tumor in the right inguinal region 3 years earlier, which eventually became as large as 9 cm in diameter without treatment. Although a histological examination of the lesion showed malignant melanoma, extensive examination did not reveal its primary lesion or any metastasis other than that to the right inguinal area. Our case took an interesting course in that this well-growing metastatic tumor was localized in only one region and supported a previous report indicating that malignant melanoma with unknown primary origin has a low tendency to metastasize and a relatively good prognosis.     

Nodular Melanoma in 62 Japanese Patients: Influence of Initial Surgical Treatment on Local Recurrence and Prognosis

The incidence of malignant melanoma is much lower in Japanese than in Caucasians, and the commonest type of melanoma in Japanese is acral lentiginous melanoma (ALM). In contrast to the improved prognosis noted in ALM, it is now of increasing concern that there is a rise in both the frequency and mortality of nodular melanoma. During the 25 years from 1970 to 1994, we observed 190 patients with melanoma, including 62 nodular melanomas and 96 ALM, at the Department of Dermatology, Tohoku University Hospital, Sendai, Japan. We retrospectively reviewed the recurrence and survival rates of nodular melanoma observed. The proportion of nodular melanoma, once comprising only 24% of all melanomas, showed a sharp increase to 40% after 1982. The anatomical sites of the primary tumor were the hands and feet (29%), extremities excluding hands and feet (27%), head and neck (23%), and trunk (21%). Comparison of the stages of nodular melanoma when diagnosed showed that the proportion of stage III remained highest throughout the whole period, but that of stage II melanomas increased after 1982. After treatment, local recurrence occurred far more frequently in nodular melanoma (19%) than in ALM (1%). The prognosis of nodular melanoma was also less favorable than that of ALM, although it slightly improved after 1982; the 5-year survival rates before and after 1982 were 34 and 50%, respectively. Twenty-eight patients with nodular melanoma had underwent simple excision or incisional biopsy of the primary tumor at another institution and were later referred to us for further intensive care or for the treatment of local recurrence and/or metastases. The rate of local recurrence of melanoma in such referred patients was higher than that in those who underwent an initial excision with wide margins in our hospital. Concurrently, the prognosis in the former group was significantly lower than that in the latter group; the 5-year survival rate for the group of narrow initial margin was 22% in contrast to that of wide margin (56%). Combination therapy including initial surgical excision with wide margins as well as the careful follow-up apparently result in a better outcome for the Japanese patients with nodular melanoma.