Cancer risk in patients with earlier diagnosis of cutaneous melanoma in situ.

We calculated the short-term and long-term risks of developing cancer among 3,766 patients with a diagnosis of cutaneous melanoma in situ in Sweden from 1958 to 1992. In total, 393 patients developed a primary cancer at any site compared with an expected number of 177 [standardized incidence ratio (SIR) = 2.2, 95% confidence interval (CI) = 2.0-2.4]. Patients below 60 years of age at diagnosis had the highest SIR (2.7, 95% CI = 2.3-3.2). The overall risks were similar between men and women. The highest risk was seen during the first year of follow-up, though the risk remained elevated also after 15 or more years of follow-up. For specific sites, the highest SIR was found for developing invasive cutaneous malignant melanoma (SIR = 22.2). The risk of subsequent primary non-melanoma skin cancer was elevated 8-fold in men and almost 7-fold in women. An elevated risk was also found for female breast cancer (SIR = 1.4). Especially among women, other sites with increased cancer risk (though not significant) were non-Hodgkin's lymphoma (SIR = 1.9), multiple myeloma (3.2) and cancers of the colon (1.6) and pancreas (1.6). In conclusion, patients with melanoma in situ run a generally increased risk of developing primary cancers, especially cutaneous malignant melanoma and non-melanoma skin cancer. The increased long-term risk of cancer after diagnosis of melanoma in situ may be due to continuing carcinogenic exposure or to intrinsic tumor susceptibility.     

Different manifestations of malignant melanoma in the breast: a report of 12 cases and a review of the literature

BACKGROUND: The breast is associated with a large number of diseases. Besides being the host of many benign and malignant tumors, breast skin and parenchyma are also metastatic sites for various tumors such as leukemia, lung cancer and melanoma. METHODS: Malign melanoma has different manifestations in the breast. All these manifestations are important not only as initial presentations of the disease, but also as indicators of the progression period of the disease. RESULTS: This study reports on 12 cases of cutaneous malignant melanoma in breast skin and tissue. Nine of these cases are primary cutaneous melanomas, while the others are breast metastases from a distant site cutaneous melanoma. In two of the nine primary cutaneous melanomas in-transit metastasis to the breast developed during the follow-up period. CONCLUSIONS: In this paper, the diagnostic and surgical approach to primary and metastatic melanoma of the breast, and the importance of the breast during the follow-up period are reviewed.     

Positron emission tomography to assess hypoxia and perfusion in lung cancer

In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed.     

Preoperative cutaneous lymphoscintigraphy in malignant melanoma

To identify the regional lymph node basins cutaneous lymphoscintigraphy with technetium 99m rhenium sulfide colloid (99mTc-ReS) was performed in 45 patients and with technetium 99m antimony sulfide colloid (99mTc-Sb2S3) in seven patients after excisional biopsy of the primary tumor. All patients had skin tumors located in the face or neck or on the trunk with 47 cases of cutaneous malignant melanoma and 5 cases of benign or premalignant lesions. In 48 patients the scintiscans 1 hour after perilesional injection of the tracer colloid clearly showed the lymphatic drainage patterns from the tumor sites, of them 25 patients demonstrated unidirectional drainage, whereas the remaining 23 patients had multidirectional drainage to two or three lymph node groups. There were technical difficulties in performing the examinations in four patients. The authors recommend cutaneous lymphoscintigraphy as a safe, simple and reliable technique for mapping the lymphatic drainage preoperatively in patients with Stage I cutaneous malignant melanoma of axial localization.     

The tape stripping toluidine blue (TSTB) method in the diagnosis of malignant melanoma: an investigator-blind study.

The cytological investigation of the skin surface with the simple, non-invasive tape-stripping toluidine blue (TSTB) method has been proposed to improve the clinical diagnosis of many dermatological disorders. We carried out an investigator-blind study to estimate the sensitivity and specificity of the procedure for the diagnosis of malignant melanoma. One hundred and fifty pigmented lesions were tested. Positive results were obtained in 22 out of 32 malignant melanomas (sensitivity 68.7%), with three false negatives (two cases of lentigo maligna in premalignant phase and one early melanoma in situ) and seven non-significant findings. Negative results were found in 88 out of 118 non-melanoma conditions (specificity 74.5%), with three false positives (two Spitz's naevi and one dysplastic naevus) and 27 non-significant findings. Thus the TSTB method may be a helpful diagnostic tool, in addition to the ABCDE rule, for the early detection of malignant melanoma.     

Occupational exposure to the sun and risk of skin and lip cancer among male wage earners in Denmark: a population-based case–control study

Objective  

We examined the association between outdoor work and the risks of non-melanoma skin cancer, cutaneous malignant melanoma, and lip cancer in a population-based case–control study.     

The Nordic profile of skin cancer incidence. A comparative epidemiological study of the three main types of skin cancer

The data used for the inter-Nordic comparison of the incidence of skin cancer are based on the material of the national cancer registries of the 5 Nordic countries. It is typical of these countries that the ratio between the incidence of non-melanoma and melanoma skin cancer is much smaller than in regions near the Equator. For the detailed comparative epidemiological study of basal-cell carcinoma (BCC), squamous-cell carcinoma (SCC) and cutaneous malignant melanoma (CMM), the material from the Norwegian Cancer Registry 1955-1988 is used. The etiology of CMM has frequently been debated during recent decades. There are still some obscure points, however, particularly as regards the influence of host factors and UV exposure, and their interaction. The analysis of the incidence trend of CMM on the female breast during the time interval 1970-1988 contributes to the elucidation of these problems. Differences in the epidemiological characteristics of the 2 main types of non-melanoma skin cancer, BCC and SCC, are described. The results indicate that the effect of UV light is not a dominating for BCC as for SCC.     

皮肤黑色素瘤中IDH1基因突变分析

目的:应用癌症基因组图谱(TCGA)数据库分析皮肤黑色素瘤中IDH1基因突变情况.方法:从癌症基因组图谱(TCGA)数据库收集皮肤黑色素瘤数据集,统计患者临床信息、应用cBioPortal网站对数据集进行突变、离散基因、基因共表达、生存期等分析.结果:287个病例中,IDH1基因突变15例,其中,R132C突变10例,R132L突变2例,P33S/E361K突变各1例,X174缺失1例.结论:IDH1基因突变在皮肤黑色素瘤中有一定发生率,占比5.2%,且以R132突变为主,此位点有可能成为靶向药物作用的靶点.     

面部皮肤恶性黑色素瘤整复治疗的临床观察

目的 探讨治疗面部皮肤恶性黑色素瘤切除后皮肤缺损的手术方法 ,并评价其临床疗效。方法 2007年2月至2014年3月本科收治9例面部皮肤恶性黑色素瘤,均采用手术扩大切除病灶;术中常规冰冻切片监测手术切缘,病灶切除后皮肤软组织缺损,分别采用游离皮片移植2例,邻近任意皮瓣6例,游离皮瓣1例,术后常规辅以免疫治疗。结果 9例皮片及皮瓣均成活,伤口Ⅰ期愈合。局部形态较好,术区平整,瘢痕不明显。9例患者获随访3个月~7年,死亡2例,其中1例因其他疾病术后2年死亡;其余病例外形良好,未见局部复发。结论 面部皮肤恶性黑色素瘤手术治疗联合术后辅助免疫治疗疗效肯定,皮瓣修复可取得较为理想的局部外形,术中常规冰冻切片是保证肿瘤根治的一项重要手段。     

Prognostic radiology: quantitative assessment of tumor oxygen dynamics by MRI

It is generally recognized that tumor hypoxia has a strong influence over therapeutic outcome in the clinic. The authors have developed an oximetry approach using 19F echo planar magnetic resonance imaging-FREDOM (Fluorocarbon Relaxometry using Echoplanar imaging for Dynamic Oxygen Mapping), which reveals dynamic changes based on sequential maps of regional tumor PO2. Preclinical investigations focused on diverse sublines of the Dunning prostate R3327 tumor. As expected, intratumoral heterogeneity was considerable. However, large tumors (>3.5 cm3) were significantly less well oxygenated than smaller tumors (<2 cm3). Faster growing, less differentiated tumors were less well oxygenated than size-matched tumors of slower growing sublines. The greatest potential of this technique is the ability to follow the fate of individual tumor regions with respect to interventions. For each subline, there was a significant response to respiratory challenge with oxygen for initially well-oxygenated regions (baseline PO2 > 10 mm Hg). More interestingly, subline dependent behavior was found for initially hypoxic regions that correlated with rate of growth. The authors believe the FREDOM approach is essentially ripe for translation to the clinic. This approach could help to identify patients with hypoxic tumors and indicate the feasibility of manipulating tumor characteristics through adjuvant interventions to improve therapeutic response.     

Nucleolar organizer region count and subjective AgNOR pattern assessment (SAPA) score in skin tumors.

OBJECTIVE: To study the argyrophilic nucleolar organizer region (AgNOR) count and subjective AgNOR pattern assessment (SAPA) score in cytologic and histologic specimens of various skin tumors. STUDY DESIGN: The study group consisted of 37 patients (14 benign and 23 malignant) of various skin tumors. In all cases, cytology by fine needle aspiration cytology (FNAC), and histological specimens were studied by conventional staining and silver staining for AgNOR. RESULTS: The mean count in benign tumors in cytologic specimens was 2.08 +/- 0.01, compared with 5.50 +/- 1.12 in malignant tumors (P<0.001). In histologic specimens, mean count was 2.13 +/- 0.51 in benign, compared with 5.38 +/- 1.10 in malignant tumors (P<0.001). The SAPA score in benign tumors (P<0.001) in cytologic specimens, was 6.07 +/- 0.83, compared with 10.65 +/- 1.27 in malignant tumors, and in histology, it was 6.07 +/- 0.87 in benign, compared with 10.83 +/- 1.15 in malignant tumors (P < 0.001). Melanoma showed the higher AgNOR count compared with squamous cell carcinoma and basal cell carcinoma. The parameters were statistically significant between the grade of tumor in squamous cell carcinoma and the positivity of lymph nodes as demonstrated by SAPA score. No correlation was found between the clinical stage and Clark level of melanoma. Although, AgNOR count and SAPA score showed similar results, the indicators of validity were higher in SAPA than AgNOR count. CONCLUSION: Although, AgNOR count and SAPA score gave similar results, but the indicators of validity were higher in SAPA score than AgNOR count.     

Cutaneous malignant melanoma in association with other skin cancers

A case-control study of 232 cases of cutaneous malignant melanoma and 232 matched controls was performed to assess the association of the disease with nonmelanotic skin tumors--basal cell carcinomas, squamous cell carcinomas, and solar keratoses. There was a fourfold increase in risk of melanoma of all types when actinic tumors were present on the face. The risk was not restricted to the lentigo malignant melanoma class as might be expected but was significantly raised for superficial spreading melanoma and nodular melanoma as well (relative risk, 2.8; 95% confidence interval, 1.1-7.2). This relationship with lesions known to be associated with high-dose solar UV irradiation was supported by quantitative evidence that heavy sun exposure was associated with an increased risk of malignant melanoma.     

Association between dietary fat and skin cancer in an Australian population using case-control and cohort study designs

Background  

Human studies of dietary fat as a possible risk factor for cutaneous malignant melanoma (CMM) and non-melanoma skin cancer (NMSC) – principally basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – have produced inconsistent results. We had the opportunity to examine the association concurrently for all three types of skin cancer in a population-based study in Tasmania, Australia, involving 652 cases of CMM, BCC and SCC and a common set of 471 controls.     

青少年皮肤恶性肿瘤的治疗

目的：总结青少年皮肤恶性肿瘤的治疗经验。方法：分析1991年2月～2003年9月间,收治13例青少年皮肤恶性肿瘤的临床资料,采用病灶彻底切除、皮瓣转移或全厚皮片移植修复术,辅以放射、化学或免疫等方法治疗,对其治疗效果与随访结果进行总结。结果：鳞状细胞癌6例、基底细胞癌2例、恶性黑色素瘤4例和血管内皮肉瘤1例,是本组病例的主要类型,术后随访2～8年,随访12例,失访1例。局部复发与淋巴结转移3例,截肢（指）2例,死亡2例,其余术区外形和功能恢复良好。结论：彻底切除病灶是皮肤肿瘤治疗取得良好疗效的关键,皮瓣、皮片修复有助于术区外形和功能的恢复。放射、化学和免疫等辅助治疗是预防术后复发的有效方法。     

Sentinel node navigation surgery in melanoma and non-melanoma malignant skin tumor

Sentinel node biopsy (SNB) has been performed for melanomas by many researchers since Morton's report in 1992. The technique has been well discussed, however, there have been only few reports about the application of SNB for treatment strategy of melanoma patients. Besides, we have not yet enough information of the clinical significance of SNB for non-melanoma malignant skin tumors. In this paper, we report two new findings of SNB for melanoma patients from the results of a multi-institutional study of SNB in 203 cases of melanoma. Firstly, the incidence of metastasis in non-sentinel node (non-SN) is less than 1% if no metastasis in SN; the identification rate of SN was 97.5%, the false negative rate was 0.98%, and correct diagnosis rate was 99.0%. Secondly, the incidence of metastasis in non-SN is less than 36.4% when patients had pSN 1 or pSN 2 metastasis. That means total removal of lymphnode metastasis can be achieved in 63.6% patients with lymphnode metastasis through SNB. Finally, we studied the usefulness of SNB on 71 cases of non-melanoma malignant skin tumors, and found the SN concept was also applicable for squamous cell carcinoma or invasive case of genital Paget's disease (Paget's carcinoma). Especially, we believe SNB for patients with Paget's carcinoma is as useful as for melanoma patients according our results of 25 cases; the identification rate of SN was 97.6%, the false negative rate was 0%, and correct diagnosis rate was 100%. SNB should be applied for patients with Paget's carcinoma as a diagnostic method of lymphnode metastasis and to determine the indication of lymphnode dissection, and its usefulness must be analyzed in the near future.     

Operative Therapie des malignen Melanoms

The right operative therapy plays a key role in the management of malignant melanoma. If the diagnosis of melanoma is likely, an excision biopsy of the entire pigmented lesion is strongly recommended. After the diagnosis has been confirmed by histology, a safety margin should be excised in accordance with the tumor thickness (a 1-cm safety margin in tumors up to 2 mm in thickness and 2 cm in tumors thicker than 2 mm). In melanoma of the face or genital region, the safety margins can be reduced if the tumors are excised under micrographic control. In patients with a vertical tumor thickness of 1 mm or more, it is recommended to obtain a sentinel lymph node biopsy (SLNB). In the case of unfavorable prognostic factors such as ulceration or regression of the primary tumor or Clark level IV or V, a SLNB is recommended even in primary tumors of less than 1 mm thickness. A radical regional lymphadenectomy is recommended in cases of lymph node metastases. Distant metastases involving only one organ should be excised if possible. If the patient has multiple skin metastases (in-transit or satellite metastases) in only one extremity, isolated limb perfusion (melphalan with or without TNF-α) is an effective treatment combining surgical and oncologic strategies.     

皮肤及眼球外原发性恶性黑色素瘤临床病理分析

研究皮肤及眼球外原发性恶性黑色素瘤的临床与病理特征，以提高临床早期诊断率。方法对１８例皮肤及眼球外原发性恶性黑色素瘤进行临床资料分析，病理组织学、免疫组化及电镜研究。结果本组患者平均年龄５１．６岁，以女性为主。     

Expression of CXCR4 predicts poor prognosis in patients with malignant melanoma.

PURPOSE: CXCR4 receptor and its unique ligand, the CXCL12 chemokine, have been recently implicated in cancer metastasis. Evidence about the role of CXCR4/CXCL12 axis has been reported in several cancers including melanoma. Our goal was to investigate if CXCR4 expression has a prognostic value in malignant melanoma. EXPERIMENTAL DESIGN: Immunohistochemical expression of CXCR4 was evaluated on 71 specimens of primary cutaneous melanoma with a Breslow tumor thickness of >1 mm after radical resection. Associations between baseline patient features and tumors were analyzed by chi(2) test. The prognostic value of CXCR4 expression was evaluated by univariate and multivariate analyses adjusted by age, sex, Breslow tumor thickness, presence of ulceration, and sentinel lymph node metastases. RESULTS: CXCR4 expression was detected in 31 of 71 (43.6%) primary cutaneous melanomas. Membrane or cytoplasmic staining for CXCR4 protein was absent in 56% of the tumors. The positive cases were divided into three score classes according to their staining: low in 15 cases (21%), moderate in 10 (14%), and high in 6 (8%). After a median follow-up of 38 months, 26 patients progressed (16 of 26 expressed CXCR4) and 19 died (12 of 19 expressed CXCR4). The CXCR4 expression on tumor cells was correlated with an unfavorable prognosis with a median disease-free and overall survival of 22 and 35 months, respectively. The hazard ratios of relapse and death, compared with patients with CXCR4-negative tumors, were 2.5 (95% confidence interval, 1.2-6.1) and 3.1 (95% confidence interval, 1.1-7.2), respectively. Median time-to-event (progression and survival) was not reached in patients with CXCR4-negative tumors. In the multivariate analysis, CXCR4 expression, presence of ulceration, and sentinel lymph node status emerged as independent prognostic factors. CONCLUSIONS: This article provides the first evidence that CXCR4 expression could be an independent and powerful prognostic marker in primary cutaneous malignant melanomas.     

Hypoxia in human prostate carcinoma: an Eppendorf PO2 study

The purpose of this study was to characterize the extent of hypoxia in human prostate carcinoma using the Eppendorf PO2 microelectrode. Custom-made Eppendorf PO2 microelectrodes were used to obtain PO2 measurements from the pathologically involved region of the prostate (as determined by the pretreatment sextant biopsies), as well as from a region of normal muscle for comparison. Fifty-nine patients with localized prostate cancer were studied, all of whom received brachytherapy implants under spinal anesthesia. A multivariate mixed effects analysis for prediction of tumor oxygenation was performed including the following covariates: type of tissue (prostate versus muscle), prostatic-specific antigen, disease stage, patient age and race, tumor grade, volume, perineural invasion, and hormonal therapy. Because of differences in patient characteristics, control measurements were obtained from normal muscle in all patients. This internal comparison showed that the oxygen measurements from the pathologically involved portion of the prostate were significantly lower (average median PO2 = 2.4 mm Hg) compared with the measurements from normal muscle (average median PO2 = 30.0 mm Hg), p < 0.0001. A multivariate, linear, mixed analysis demonstrated that the only significant predictor of oxygenation was the type of tissue (prostate versus muscle). This study, using in vivo electrode oxygen measurements, suggests that hypoxia exists in human prostate carcinoma. More patients will be accrued to this study to ultimately correlate the oxygenation status in prostate carcinoma tumors with treatment outcome.     

2 cases of bullous pemphigoid and Bowen's disease associated with esophageal cancer

There are many published reports on the combination of malignant tumors of the digestive tract and various skin diseases. To date, 8 cases with combined bullous pemphigoid and malignant tumor, or Bowen's disease and malignant tumor, have been reported in Japan. In only 2 cases was the esophageal cancer combined with skin disease. The pathophysiological relationship between skin diseases and malignant tumors of the digestive tract remains unknown.