Therapy-related myelodysplastic syndrome developed by dacarbazine, nimustine hydrochloride and vincristine sulfate (DAV) therapy for patient with malignant melanoma

Therapy-related myelodysplastic syndrome (t-MDS) is mostly attributed to chemotherapeutic agents of alkylating agents. Few studies have evaluated the late effects of chemotherapy for malignant melanoma (MM). To evaluate whether dacarbazine, nimustine hydrochloride and vincristine sulfate (DAV) therapy for MM related to t-MDS or not, a retrospective analysis was performed. We conducted a retrospective case-control study in a cohort of the 217 patients diagnosed with MM from 1989-2007 in Aichi Medical University Department of Dermatology and Nagoya University Graduate School of Medicine Department of Dermatology. One hundred and fifty-five of the 217 patients with MM were prospectively followed after DAV therapy or with or without local injection of β-interferon, of whom two patients developed t-MDS. Cytogenetic abnormalities were found in two of the 35 patients by chromosome banding method - leukemia (G-Banding). The karyotypes were found in the chromosome of -5, deletion (5), addition (7) and 7q-. In conclusion, DAV therapy should be used carefully for older patients with MM after satisfactory operation.     

A case of Werner syndrome with three primary lesions of malignant melanoma

Three primary lesions of malignant melanoma developed in a 44-year-old Japanese woman with Werner syndrome. One lesion was on the right large pudental lip and the others in distinct locations on her left sole. After the wide local excision of these tumors, the wound of the large pudental lip was sutured, and the defects on the sole were covered with skin grafts. After one course of chemotherapy consisting of dacarbazine, nimustine, vincristine sulfate and local injection of Interferon beta were performed, severe myelosupression occurred and continued for two months. Defective production of WRN protein was confirmed by Western blotting, although the three representative mutations in Japanese patients, mutations 1, 4 and 6, which include over 90% of the Japanese patients, were not detected. We also reviewed 26 cases of malignant melanoma associated with Werner syndrome (WS), including ours.     

Antiproliferative effect of hyperthermia and ACNU on cultured human malignant melanoma cells

Human malignant melanoma cultured cells were treated either with ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chlorethyl)-3-nitro sourea hydrochloride), hyperthermia, or the combination of ACNU and hyperthermia. The combination treatment inhibited the cell growth to a slightly synergistic degree compared to the respective single treatments. The present in vitro experimental results support in part the finding of our previous report that the combination treatment with ACNU and hyperthermia have a significantly synergistic antitumor effect to human melanoma transplanted to nude mice. However, the synergistic effect was much less intense in the present in vitro experiment. The difference may have resulted from the environmental differences between in vitro and in vivo experimental systems.     

表现为丘疹和斑块的骨髓增生异常综合征

报告1例以丘疹和斑块为主要表现的骨髓增生异常综合征。患者男,79岁。因胃溃疡,血红蛋白降低住院治疗。入院后3d开始发热,头面部与躯干部出现散在的红色丘疹和班块,外周血及骨髓检查符合骨髓增生异常综合征。额部皮损组织病理检查;真皮中下层弥漫性炎性细胞浸润,以中性粒细胞,组织细胞为主,散在核尘和异形细胞。     

黑素瘤抑制性活性因子在黑素瘤不同阶段及基底细胞癌中的表达

目的：探讨黑素瘤抑制性活性因子（MIA）在黑素瘤及基底细胞癌中的表达及其作用。方法：应用sP免疫组化技术检测38份黑素瘤石蜡标本、35份基底细胞癌石蜡标本以及32份色素痣石蜡标本中MIA的表达水平。结果：MIA在所有色素痣以及基底细胞癌中均呈阴性表达，而在原位黑素瘤、侵袭性黑素瘤、有淋巴结转移的黑素瘤、无淋巴结转移的黑素瘤阳性表达率分别为21．4％、91．6％、94．1％和42．8％。结论：MIA在黑素瘤的发生发展中起重要作用，MIA有可能成为临床诊断、治疗黑素瘤的靶点。     

Rechallenge of programmed cell death 1 inhibitor after an interval with dacarbazine treatment may be effective for advanced malignant melanoma

Immune checkpoint inhibitors (ICI) have been administrated as a standard medication in many cases of malignant melanoma (MM). They may be effective even for MM in advanced stages. However, it is still challenging to reduce the burden of MM, which were or became refractory to ICI, especially those without BRAF gene mutation. Re-administration of ICI after other modalities of treatment may be an option of treatment, but the efficacy and safety of retreatment with ICI have not been well established. We experienced four patients with advanced MM retreated with programmed cell death 1 (PD-1) inhibitor. All cases were refractory to the first PD-1 inhibitor, nivolumab, and then treated with dacarbazine (DTIC), followed by pembrolizumab. Two of the four cases achieved a partial response by switching to pembrolizumab as the second PD-1 inhibitor, and the other two cases resulted in progressive disease. In all cases, no new severe adverse events developed upon PD-1 inhibitor retreatment. Even if the first PD-1 inhibitor proves to be ineffective, it is worth re-administrating PD-1 inhibitor following a bridging therapy with DTIC.     

皮肤黑色素瘤诊治的误区

目的揭示皮肤黑色素瘤诊断和治疗的误区，探讨合理诊断和治疗黑色素瘤的方法。方法结合有关文献，并对15例足部皮肤黑色素瘤的病程和治疗进行分析。结果大多数患者没有及时就医以及医疗单位病检取材不合理。结论正确取材活检，明确切除范围，及时手术以及一期修复组织缺损是有效防止癌肿扩散，提高生存率的关键。     

Acquired streptococcal necrotizing fasciitis following excision of malignant melanoma

Necrotizing fasciitis is an uncommon condition which may complicate any surgical procedure, including 'minor' dermatological procedures. However, it may arise de novo in the absence of any discernible trauma. We report a patient who acquired a fulminant form of this condition following excision of a malignant melanoma. The development of necrotizing fasciitis in association with melanoma has not previously been reported.     

基质金属蛋白酶7在恶性黑素瘤中的表达

目的 探讨基质金属蛋白酶7（MMP7）的表达与恶性黑素瘤浸润、转移的关系。方法 采用免疫组化SP法研究MMP7在恶性黑素瘤（30例）、交界痣（30例）、正常人皮肤（15例）组织中的表达，并观察其在恶性黑素瘤A375细胞株和不同浓度乙酰肝素酶反义寡核苷酸转染的裸鼠体内恶性黑素瘤移植瘤中的表达情况。结果 MMP7在恶性黑素瘤组、交界痣组及正常人皮肤组中的阳性表达率分别为83.33%（25/30）、6.67%（2/30）和0，恶性黑素瘤组与交界痣组MMP7的阳性表达率比较，χ2 = 35.62，P < 0.01；交界痣组与正常人皮肤组比较，差异无统计学意义。10、20、30 μmol/L乙酰肝素酶反义寡核苷酸对裸鼠体内恶性黑素瘤移植瘤MMP7表达表现出不同程度的抑制作用，30 μmol/L组的抑制作用最强，与其他2个组相比，差异均有统计学意义（P < 0.05）。MMP7在A375细胞株中呈强阳性表达。结论 MMP7在恶性黑素瘤中的表达明显高于其在交界痣和正常人皮肤；乙酰肝素酶反义寡核苷酸对裸鼠体内恶性黑素瘤移植瘤中MMP7的表达有显著抑制效应；MMP7在A375细胞株中呈强阳性表达。     

Pagetoid malignant melanoma and lentigo maligna melanoma of toe

Summary Two cases of malignant melanoma on the toe of middle-aged women were examined chiefly by the fluorescence method of Falck and Hillarp. In one of the patients, histopathology of the pigmented tumor on the left middle toe was a Pagetoid (superficial spreading) melanoma in situ, and the subungual granulomatous lesion on the right great toe in the other patient was a lentigo maligna melanoma. On fluorescence microscopy, characteristic findings of the pigment cells lying in the epidermis of both types may be summarized as follows: In the Pagetoid melanoma, the melanoma cells are ovoid, lack dendritic processes, and emit specific yellow fluorescence. In the lentigo maligna melanoma, the pigment cells clearly show dendritic processes, and emit specific green fluorescence.     

Surgical treatment of malignant melanoma: practical guidelines

Melanoma is currently the fifth and sixth most common solid malignancy diagnosed in men and women, respectively. Although accounting for only 4% of cases of all cutaneous malignancies, melanoma accounts for more than 75% of all deaths from skin cancer. This article discusses epidemiology and risk factors, proper biopsy technique, advanced histologic evaluation of biopsy material, assessment of tumor thickness and staging, preoperative metastatic evaluation, excision margin, treatment of regional lymph nodes, treatment of recurrence, and some special clinical situations.     

脱色素技术在恶性黑素瘤HE染色及免疫组化中的应用条件

 目的探索脱色素技术在恶性黑素瘤的HE及免疫组化研究中的最佳适宜条件。方法选取2例恶性黑素瘤的多张组织切片,分别利用不同浓度的高锰酸钾/草酸溶液脱色素处理不同时间,进行HE及免疫组化染色,观察效果及切片脱落情况。结果标本切片脱蜡后使用多聚甲醛进行后固定,以0.25%高锰酸钾溶液及2%草酸溶液进行脱色素处理能得到满意的HE染色;以0.25%高锰酸钾溶液及2%草酸溶液进行脱色素处理,时间分别控制在3 min,在免疫组化染色中获得较好的脱色素结果且同时保持了组织的抗原性。结论0.25%高锰酸钾/2%草酸溶液脱色素法是恶性黑素瘤免疫分子在组织化学表达分析中的最佳合适浓度,脱色时间为3 min。     

Vitiligo associated with malignant melanoma and lupus erythematosus

There exists several reports where malignant melanoma is associated with vitiligo, vitiligo with discoid lupus erythematosus and lupus erythematosus with urticaria. However, there are no reports in which vitiligo, malignant melanoma, lupus erythematosus and urticaria coexist in the same case. Herein, we report a case of a patient who developed lupus erythematosus, malignant melanoma, vitiligo and urticaria simultaneously.     

Four primary malignant tumors, including malignant melanoma and malignant lymphoma, in the same adult patient

We report an 80-year-old Japanese male with four primary malignant tumors: malignant melanoma, prostatic cancer, malignant lymphoma, and renal cell carcinoma, which occurred in that respective order. The combination of malignant melanoma and malignant lymphoma is rare. The patient was treated with BCG after an operation for malignant melanoma. He was also treated with cobalt 60 irradiation after an operation for prostatic cancer. We also discuss other reports of multiple malignant tumors and suggest some possible causes of this patient's primary malignant tumors.     

前哨淋巴结活检技术及其在恶性黑素瘤治疗中的应用

1977年,Cabanas[1]使用阴茎淋巴管造影判断是否存在阴茎癌淋巴系统转移,引入前哨淋巴结(SLN)的概念.1992年,Morton争[2]皮内注射异舒泛蓝进行淋巴管造影(LM),认为该技术对SLN有极高的检出率,假阳性率极低.1993年,Alex等[3]在原发黑素瘤周围注射胶体99mTc后,用影像学或γ探测器检测SLN.由于SLN是肿瘤转移的第一个淋巴结,它的荷瘤状态可以预测局部淋巴结区的所有淋巴结,因此SLN的概念是功能性定位,而不是解剖学位置,其位置取决于患者原发病灶的淋巴引流.     

p-Akt在恶性黑素瘤中的表达及意义探讨

目的 探讨p-Akt（Ser-473）表达水平与恶性黑素瘤的临床和病理学参数的关系。方法 应用免疫组化方法检测21例恶性黑素瘤患者手术切除的肿瘤标本中p-Akt的表达,以21例色素痣作对照,分析其与恶性黑素瘤的临床特征及预后的关系。结果 p-Akt在转移性黑素瘤的表达阳性率（67%）高于原发性黑素瘤（56%）,而在色素痣中表达阴性,三组间的表达阳性率差异有统计学意义（P < 0.05）。肿瘤浸润深度及年龄与p-Akt表达率呈显著正相关（r值分别为0.41和0.53,P均 < 0.05）。p-Akt的强表达与恶性黑素瘤患者的5年生存率显著相关（r = 0.41,P < 0.05）,而高危黑素瘤（浸润厚度 > 1.5 mm）患者中p-Akt的强表达与生存率的相关性更为显著（OR = 2.586,95%可信区间为0.906 ～ 7.382,P < 0.05）。结论 p-Akt的表达随着恶性黑素瘤的浸润程度和进展显著提高,并与患者的5年生存率密切相关。此外,p-Akt可能有利于判断高危黑素瘤患者的预后。     

恶性黑素瘤的诊治进展

皮肤恶性黑素瘤(cutaneous malignant melanoma,CMM)是黑色素细胞的恶性肿瘤,本文对CMM的发病情况、临床分期及目前的治疗方法进行了综述。     

The risk for cutaneous malignant melanoma, melanoma in situ and intraocular malignant melanoma in relation to tobacco use and body mass index

BACKGROUND: The incidence of cutaneous malignant melanoma (CMM) and melanoma in situ (MIS) has been increasing during the last 50 years. Malignant melanoma (MM) is also the most common intraocular malignancy (IMM). Besides ultraviolet radiation, the cause of these tumours is largely unknown. OBJECTIVES: We designed a study to examine the effect of body mass index (BMI) and tobacco use on the risk for MM and MIS. METHODS: Analyses were performed on a nationwide cohort of 339 802 Swedish construction workers. Exposure information was collected prospectively by questionnaires combined with personal interviews. RESULTS: Follow up yielded a total of 7 663 400 person-years during which 1639 workers developed MM/MIS. The risk for MM/MIS was reduced in current or previous smokers compared with those who had never smoked, both when analysing all smoking tobacco products combined and when analysing cigarette and pipe smokers separately. The risk was further diminished with longer duration of smoking and greater quantity of tobacco smoked. The effect was more evident in CMM/MIS than in IMM. Snuff taking conferred a decreased risk for CMM/MIS, and a BMI over normal weight range conferred an increased risk for CMM. CONCLUSIONS: Tobacco smoking was found to be inversely associated with the risk for CMM and MIS. The mechanism of action is unknown but it has been suggested to be due to the immune suppressive effect that tobacco exerts which would be protective against deleterious immune reactions caused by, for example, the sun. Neither is the mechanism behind the higher risk for CMM due to being overweight known. One hypothesis is that it is an effect of a hormonal imbalance. Further studies are required to elucidate these mechanisms.     

Metastatic malignant melanoma presenting with hypercalcaemia and bone marrow involvement

We report a 75-year-old female patient with a background of malignant melanoma who presented with hypercalcaemia to our institution. She was aggressively treated but declined clinically. Computed tomography head and X-ray studies were suggestive of multiple myeloma, but bone marrow examination was significant for metastatic malignant melanoma. Very few patients with melanoma present with these features, and it further exemplifies the importance of close follow-up and the aggressive nature of this disease process.