Malignant skin tumours in patients with inherited ichthyosis

Inherited ichthyoses are rare genodermatoses caused by mutations in the genes involved in epidermal development. Although there have been case reports on patients with ichthyosis who developed skin malignancies, it is still unknown whether or not patients with ichthyosis have an increased risk of skin malignancies. Here, we review case series of skin malignancies in patients with ichthyosis and show biological findings which might lead to cancer susceptibility. A survey of the literature revealed 28 cases of inherited ichthyoses with skin malignancy, including 12 cases of keratitis-ichthyosis-deafness (KID) syndrome, seven of autosomal recessive congenital ichthyosis, three of Netherton syndrome and six of miscellaneous ichthyosis. Twenty-four of the 28 cases developed single or multiple squamous cell carcinomas (SCCs). The age at diagnosis of the first skin malignancy ranged from 15 to 54 years. As patients with these particular subtypes of ichthyosis seem to be prone to skin malignancies, including SCC, at an unusually young age, routine cancer surveillance of these patients is strongly recommended.     

Lymphokine-activated killer (LAK) activity against autologous malignant tumors of the skin

When peripheral blood mononuclear cells (PBMC) cultured with interleukin 2 (IL-2) develop the ability to lyse fresh tumor cells, such activity is referred to as lymphokine-activated killer (LAK) activity. In this paper, we examined LAK activity against the autologous skin tumors, malignant melanoma (MM), squamous cell carcinoma (SCC), and basal cell epithelioma (BCE), which have distinct clinical characteristics. Similar levels of LAK activity against Daudi 1A4, an NK resistant cell line were significantly obtained from all cancer patients. However, different levels of LAK activity against autologous tumor cells were found from three kinds of cancer patients using mixtures of autologous tumors and LAK. The levels of cytotoxicity were 29.8 +/- 7.0% in five MM, 15.9 +/- 4.9% in seven SCC, and 4.0 +/- 2.3% in five BCE patients at an effector/target ratio of 50/1. Allogeneic MM targets were lysed by LAK from all three types of cancer patients at similar levels, implying that LAK is not restricted to major histocompatibility complex (MHC) antigens. These results indicate that the levels of autologous LAK activity were significantly associated with the magnitude of clinical malignancy of the tumor targets, and suggested the selective lysis of tumor targets by LAK. NK activity of cancer patients bearing tumors was also examined prior to therapy. The levels of NK activity observed in MM patients were considerably lower than those in two other cancer patients.     

The prognosis of skin carcinoma and malignant melanoma with special reference to their extents as represented in terms of T, N, and M of union internationale contre le cancer (UICC)

The prognosis of skin carcinoma and malignant melanoma was studied statistically. One hundred and one cases of basal cell epithelioma (BCE), 93 cases of squamous cell carcinoma (SCC), and 34 cases of malignant melanoma (MM) were studied. No cases of death due to basal cell epithelioma were found. The squamous cell carcinomas and malignant melanomas were classified according to the TNM system into three classes with different prognoses. The first class represents the initial stage, in which cure is expected if treatment is adequate. The second class is the intermediate stage, in which cure is uncertain and the prognosis depends upon the degree of extension. The third class is the late stage, in which distant metastasis is found and in which cure might not be anticipated. Furthermore, the prognosis of previously treated cases was poorer than that of untreated cases. Our findings indicate that early diagnosis and appropriate treatment in the initial stage results in the best prognosis and that the success or failure of the initial treatment has an appreciable influence on the prognosis of skin malignancy.     

Immunohistochemical localization of ornithine decarboxylase in skin tumors

BACKGROUND: Ornithine decarboxylase (ODC) plays an important role in the biosynthesis of polyamines. Induction of ODC and polyamine synthesis has been demonstrated in neoplastic tumors and is thought to be related to the degree of malignancy. METHODS: In this study, we investigated a series of basal cell epitheliomas (BCE), Bowen's disease, squamous cell carcinomas (SCC), and metastatic tumors of the skin using an antibody against ODC for immunohistochemistry. RESULTS: Eight of 12 cases of BCE failed to show a positive reaction for ODC. In Bowen's disease, 5 of 13 cases diffusely showed positive reaction for ODC. Fourteen of 15 cases of SCC showed ODC expression, the intensity of which was decreased in the peripheral layer. At higher magnification, the distribution of ODC in the positive SCC cases showed granular and heterogenous patterns. Ten of 14 cases of metastatic skin tumors exhibited positive reactions, and well-differentiated adenocarcinomas tended to show more strongly positive than poorly-differentiated ones. CONCLUSIONS: These results support the conclusion that the intensity and the incidence of positive immunohistochemical staining for ODC correlate with the degree of cellular differentiation, and furthermore, that heterogenous distribution of ODC staining may be associated with heterogeneity of tumor cells.     

表皮肿瘤中COX-2与P53的检测

目的了解表皮肿瘤组织环氧合酶-2(COX-2)与P53的表达情况。方法免疫组化法检测脂溢性角化病(SK)15例、Bowen’s病(BD)15例、基底细胞上皮瘤(BCE)20例、鳞癌(SCC)20例COX-2和P53的表达。结果所检测的各肿瘤组织标本均有COX-2的表达,分别为SCC95%,BD73.3%,SK46.6%,BCE68.0%,表达强度以SCC最为显著,周围正常组织未见表达。突变型P53在SCC(80.0%),BCE(75.0%),BD(33.3%)肿瘤组织的阳性率较高,而在SK(13.3%)中基本不表达。SCC和BCECOX-2表达阳性者其突变型P53表达的阳性率较COX-2表达阴性者高(P<0.05)。结论表皮肿瘤存在COX-2的过表达;P53的突变与COX-2的过表达有关,p53突变可能是通过上调COX-2水平发挥抗凋亡作用,从而促进SCC,BCE的形成和发展。     

Mechanisms of metastasis

Metastasis is the process by which a primary malignancy establishes distant and discontiguous disease. It is a dreaded and ominous event that usually portends a worse prognosis, with greater tissue destruction, organ dysfunction, and potential mortality. Fortunately, metastasis is a rare event for nonmelanoma skin cancers (NMSC). Basal cell carcinomas (BCC) comprise the vast majority of NMSC (60-80%) and have a metastasis rate of only 0.0028%. For squamous cell carcinomas (SCC), the rate of metastasis is 2-6% and rises with certain high-risk features. Malignant melanoma (MM) is perhaps the most feared among common skin malignancies. It has a marked propensity for metastasis, and deaths from MM far outnumber the combined mortalities of both BCC and SCC. The 5-year survival of localized stage IA melanoma is 95%. This decreases to 67% for nodal disease and less than 20% for distant metastasis. Even more aggressive than MM are rare cutaneous tumors, such as Merkel cell carcinoma and malignant fibrous histiocytoma. This chapter will discuss the mechanisms of metastasis as they apply to cutaneous malignancies, particularly melanoma.     

MALIGNANT SKIN TUMORS AMONG DERMATOLOGY PATIENTS IN UNIVERSITY HOSPITALS OF JAPAN

A total of 829 patients with squamous cell carcinoma (SCC), 942 patients with basal cell carcinoma (BCC) and 256 patients with malignant melanoma (MM) was encountered among 1,033,678 new dermatology patients in 44 of 46 university hospitals of Japan between 1971 and 1975. The incidences of skin cancers (SCC and BCC) and of MM among new dermatology patients were 0.171% and 0.025% respectively. The incidences had increased 2 to 2.5 times over those of the previous survey between 1956 and 1960. Skin cancers were most frequently seen among those over 60 years of age and on exposed sites. Burn scars, chronic radiodermatitis, traumatic scars and xeroderma pigmentosum were common preceding diseases in skin cancers, although the majority of the cancers were without apparent preceding diseases. The incidence of skin cancers on exposed sites without preceding diseases showed a statistically significant exponential correlation with the decreasing degrees of the Northern Latitude (NL) of the university locations. The incidence of MM was most common on the extremities and showed no such geographic correlation.     

Immunohistochemical expression of cyclooxygenase-2 in skin cancers

BACKGROUND: Cyclooxygenase (COX), also known as prostaglandin endoperoxide synthase, catalyses the conversion of arachidonic acid to prostanoids. There are two different isoforms of COX, referred to as COX-1 and COX-2. Overexpression of COX-2 has been demonstrated in various neoplasms, such as experimentally promoted tumors, gastrointestinal cancers and breast tumors. METHODS: In this study, we used immunohistochemistry to investigate COX-2 expression in a series of basal cell epitheliomas (BCE), Bowen's disease, squamous cell carcinomas (SCC) and metastatic tumors of the skin. RESULTS: Four of 16 BCE showed a positive reaction for COX-2 and the adenoid type of BCE was the most strongly positive. In Bowen's disease, the extent of positive staining for COX-2 was even higher than that in BCE. Eleven of 15 SCC showed a positive reaction for COX-2 and the pattern of staining was heterogeneous with more intense staining in the center of the tumor nests. In metastatic tumors, the percentage of COX-2-positive tumor cells and the intensity of their staining was low compared with Bowen's disease and SCC. CONCLUSIONS: These results indicate that the intensity of COX-2 staining and its heterogeneous distribution are related to the degree of cellular differentiation and the various phenotypes of tumor cells, but the extent of COX-2 staining did not correlate with the degree of malignancy.     

Major Dermatologic Malignancies Encountered in a Teaching Hospital Surgical Department in South Nigeria

Background: Dermatologic malignancies are among the most common form of cancer. However, dark-skinned individuals of African descent are said to be far less likely than fair-skinned individuals to develop skin cancer. Significant differences in the pattern of skin malignancy have also been observed in different regions of Africa. Objective:The aim of this study was to evaluate the pattern, site incidence, and outcome of treatment of major histologically diagnosed dermatologic malignancies encountered in a teaching hospital surgical department in South Nigeria. Methods: We evaluated patients with histologic diagnoses of major dermatologic malignancies that presented to the University of Calabar Teaching Hospital, Calabar, Nigeria between January 2000 and December 2004 and compared our findings with the total number of patients diagnosed with malignancies at the same hospital over the same period. This hospital is located in South Nigeria. Results: There were 63 histologically diagnosed dermatologic cancers, comprising 10% of all histologically diagnosed cancers at the University of Calabar Teaching Hospital during the study period. Squamous cell carcinoma (SCC) was the most common (n = 23; 37%), followed by Kaposi sarcoma (KS) [n = 17; 27%]. Other malignancies included basal cell carcinoma (BCC), melanoma, and dermatofibrosarcoma protuberans (DFSP) [n = 5; 8% each]. The peak age varied with the type of cancer but none was found in patients in the first decade of life. The lower limb was the most frequent site of SCC (Marjolin ulcer), KS, and melanoma, while BCC was most common on the head, neck, and upper limb. Excision surgery resulted in healing of all cases of BCC. Some patients with SCC and melanoma presented late for curative surgery. Some African KS tumors were chemo- sensitive. There was a high recurrence rate for DFSP. Conclusion: This study revealed a similar pattern of dermatologic malignancies in South Nigeria compared with other parts of Africa but also some regional differences (e.g. in Kano, melanoma ranked second). The pattern was, however, in sharp contrast to that seen with Caucasian populations, in whom 80% of the lesions are BCC and 20% are SCC. Public education, implementation of preventive strategies, and early presentation of disease would improve outcomes of dermatologic malignancies in Nigeria.     

Preliminary exploration of the clinical features of Chinese patients with skin malignancies and premalignancies: a retrospective study of 1420 cases from Peking University First Hospital

Background The epidemiological and clinical characterization data of skin malignancies and premalignancies in Chinese population is scarce and inadequate. Objective To systematically investigate the clinical features and the trend of skin malignancies and premalignancies in 1420 Chinese cases. Methods A total of 1398 patients (presenting 1420 skin tumours) were included. Clinical and demographic information for every individual was collected, including age, age of onset, sex, lesion location, disease duration and tumour histology, which was analyzed for each type of skin tumours. Results The number of skin malignancies and premalignancies increased over time, with Basal cell carcinoma (BCC) as the most common type (30.5%). The majority of the patients were above 60 years of age both at onset and at diagnosis (52.8% and 62.9%, respectively), yet around one‐third of patients were between 35–59 years (35.3% and 31.2%, respectively). Skin malignancies and premalignancies were mainly located in the head and neck (58.6%), followed by the trunk (18.3%) and the extremities (15.0%). Of all BCCs, nodular BCC was the most common histologic subtype (62.8%), while 15.8% were classified as aggressive subtypes. Malignant melanoma (MM) comprised the lowest proportion of 3.7%, with 75% located on extremities. The diagnostic accordance rates varied from 49.5% to 90.4%, with BCC being 67.9%. Conclusions The clinical features of skin malignancies and premalignancies in this study showed some similarities with those observed in Caucasian and other Asian populations, with several distinguished features in Chinese patients also being recognized. Closer attention to suspicious lesions in young and middle‐aged people is needed.     

Clinical Features and Association with Visceral Malignancy in 80 Patients with Sebaceous Neoplasms

BackgroundSebaceous neoplasm is a rare subgroup of appendageal tumors that differentiate towards sebaceous adnexal structures of the skin and are known to be associated with visceral malignancy.ObjectiveWe aimed to analyze and compare the clinical data including the past history of associated visceral malignancy in patients with sebaceous carcinoma (SC) and benign sebaceous neoplasms (BSN), such as sebaceous adenomas and sebaceomas.MethodsWe retrospectively reviewed the cases of consecutive patients diagnosed with sebaceous neoplasms. Basic demographic data, past medical history, and clinical data regarding the size, location, and presence of associated visceral malignancies were evaluated.ResultsA total of 80 patients of sebaceous neoplasms (51 SC, 29 BSN) were included. A total of 18 associated visceral malignancies were found in 14 patients (8 SC, 6 BSN). Two patients were diagnosed with subsequent visceral malignancies during the primary work-up process for sebaceous neoplasms. The mean age at diagnosis of the visceral malignancies was 63.9 and 47.5 years for patients with SC and BSN, respectively. The most common site of visceral malignancies was the gastrointestinal (GI) tract. Adenocarcinoma was the most common histologic type of the visceral malignancy noted.ConclusionWe observed associated visceral malignancies in 15.7% of patients with SC and 20.7% with BSN. Our results suggest a need for screening of visceral malignancies, especially of the GI tract, in patients with sebaceous neoplasms.     

Survivin和Ki-67在皮肤鳞癌和基底细胞上皮瘤的表达及相关性分析

目的观察Survivin和Ki-67在皮肤鳞癌(SCC)及基底细胞上皮瘤(BCE)的表达,并探讨其意义。方法采用免疫组化法检测15例皮肤SCC,20例BCE中Survivin和Ki-67的表达情况,并以16份整形手术切除的正常组织作为对照。结果Survivin在皮肤SCC和BCE中的阳性表达率显著高于正常对照组,且在皮肤SCC的阳性表达率也显著高于BCE,差异均有统计学意义(P均<0.05)。Ki-67在皮肤SCC和BCE中的阳性表达也显著高于正常对照组(P<0.05),但在皮肤SCC和BCE组织中的表达比较,差异无统计学意义(P>0.05)。皮肤SCC和BCE组织中Survivin和Ki-67的阳性细胞表达呈正相关(r=0.77,P<0.05)。结论Survivin与Ki-67在皮肤SCC和BCE组织中的表达均升高,且呈正相关,提示两基因有可能共同参与肿瘤的发生和发展。     

CD44在某些皮肤肿瘤中表达的初步研究

目的：探讨CD44在皮肤肿瘤中的表达情况。方法：免疫组化法。结果：在鳞癌和基癌中,癌巢距表皮越近,CD44的表达越强;反之,CD44的表达越弱。在痣细胞痣和恶性黑素瘤（恶黑）标本中,CD44标准型（CD44S）均表达。在其它皮肤肿瘤中,CD44的表达同正常皮肤。结论：在鳞癌和基癌中,CD44的表达与癌巢距表皮的远近有关。CD44S的表达与痣细胞的良性或恶性无关。     

Skin cancer trends in northern Jordan

Background The Jordan Cancer Registry was established in 1996, since which time all cases of cancer have been reported and registered. We have used this registry to perform the first analysis of skin cancer in northern Jordan and to compare our findings with those of published reports from other regions. Methods All histopathologically proven cases of skin cancer, reported during the years 1997 through 2001, were reviewed. Information regarding tumor type, age, gender, and anatomical location was collected. Results A total of 272 cases of malignant skin tumors were diagnosed between the years 1997 and 2001. Basal cell carcinoma (BCC) was the commonest type, representing 52.9% of all skin cancers. Females were more frequently affected than males, with age‐adjusted incidence rates of 23.3 and 19.7 per 100,000 of population, respectively. Squamous cell carcinoma (SCC) comprised 26.4% of the total, its age‐adjusted incidence rate per 100,000 of population being 14.2 for males and 6.18 for females. the incidence rate increased in males and decreased in females during the study period. The incidence of both BCC and SCC increased with age. The head and neck region was the commonest site affected by both types of cancer. Malignant melanoma (MM) comprised 11.39% of all skin cancer cases, with a female to male ratio of 1.2 : 1. The median age at onset for female patients was 49 years while that for males was 70 years, and the commonest site affected was the lower limbs, followed by the trunk. Conclusions In Jordan, sun‐related skin cancers have relatively low incidences and a rather stable pattern, compared with other areas with similar climate and skin phenotypes.     

Cutaneous cancers in the Mosan region and Ardennes of Belgium.

BACKGROUND: The ratios of basal cell carcinomas (BBC) to squamous cell carcinomas (SCC) and to malignant melanomas (MM) have changed over time in the white population throughout the world. OBJECTIVE: To evaluate the incidence of skin cancers in the Mosan region and the Belgian Ardennes over the past 6 years. RESULTS: In contrast with epidemiological data reported by the Belgian National Cancer Registry, cutaneous cancers are the commonest malignancies occurring in humans. At the present time, the ratio BCC:SCC roughly equals 4 to 1. When combined, the incidence of BCC and SCC is about 10 times greater than that of MM. CONCLUSION: The rate of detection of skin cancers does not always correlate with the rate of notification of a national registry.     

Squamous cell carcinoma developing in a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa

We report a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa (nHS-RDEB) who developed two skin lesions of squamous cell carcinoma (SCC) on the left foot. The incidence of SCC in nHS-RDEB is much lower than in the HS-RDEB subtype. Furthermore, this boy is the youngest among 92 previously described patients with DEB to develop SCC. This study emphasizes the importance of vigilance in monitoring the possible development of SCC in DEB patients regardless of age or clinical severity.     

The management of skin malignancy: to what extent should we rely on clinical diagnosis?

BACKGROUND: Cutaneous malignancy forms a major part of the dermatologist's workload. Clinical diagnosis is an important factor in facilitating the urgent excision of squamous cell carcinomas (SCC) and malignant melanomas. OBJECTIVES: To identify the numbers and types of malignant skin tumours managed in an NHS teaching hospital and to assess the diagnostic accuracy. METHODS: Data were collected on every histologically proven malignant skin lesion over a 6-month period. RESULTS: One thousand one hundred and ninety-five malignant skin tumours were identified: 78% were basal cell carcinomas, 14% were SCC, 6% were malignant melanomas and the remaining 2% included Merkel cell tumours, malignant adnexal tumours and lentigo maligna. Eighty-one per cent of the tumours were managed by dermatologists. The correct clinical diagnosis had been made by the secondary care clinician in 84% of cases but an incorrect clinical diagnosis was given in 32% of SCC. Of the 1195 tumours, 916 (77%) had a primary excision and 92% (843 of 916) of these were completely excised. CONCLUSIONS: The majority of skin malignancies (968 of 1195, 81%) were managed by dermatologists. Where primary excision was attempted, this was complete in 91% (767 of 916) of cases. The correct clinical diagnosis was made in 84% of all tumours, but 32% of SCC were not correctly diagnosed prior to surgery.     

Skin findings in internal malignant diseases

PURPOSE: A skin finding may be an indicator of internal malignant diseases. In this report, we investigated the skin findings of the cases who have had internal malignancy within the last 1 month. PATIENTS AND METHODS: Seven hundred cases who were diagnosed as internal malignancy and who did not have any treatment for the malignancy were enrolled in our study between February 2002 and September 2003. A form was completed for all of the cases, including name, surname, and the carcinoma type. All cases were examined in detail, and the observed skin findings or dermatosis was recorded. RESULTS: The most frequent skin findings among the cases were tinea pedis/onychomycosis, followed by xerosis and pruritus. The skin findings in terms of frequency were determined mostly in hematological malignancies (68.96%). CONCLUSION: We would like to emphasize that the skin is an indicator of the functions of internal organs and their disorders.     

Risk of malignancies in psoriasis patients treated with cyclosporine: a 5 y cohort study

This prospective long-term cohort study investigated the incidence of malignancies in severe psoriasis patients treated with cyclosporine. A total of 1252 patients were followed prospectively for up to 5 y. Malignancies were recorded prospectively. Incidence rates for malignancies were compared with the general population using standardized incidence ratios. The effect of duration of exposure to cyclosporine and to previously administered anti-psoriatic treatments on the incidence of malignancies was investigated using Poisson regression models. The mean age of patients was 43 y and on average, patients received cyclosporine for 1.9 y. Malignancies were diagnosed in 47 patients (3.8%), 49% of them had skin malignancies. The standardized incidence ratio in the study cohort was 2.1 as compared with the general population. The higher incidence of malignancies was attributed to a 6-fold higher incidence of skin malignancies, most of which were squamous cell carcinoma. The incidence of nonskin malignancy overall was not significantly higher in this study than in the general population. Duration of exposure to cyclosporine, exposure to psoralen and ultraviolet A, exposure to methotrexate, and exposure to immunosuppressants showed a significant effect on the incidence of nonmelanoma skin malignancies. In conclusion, treatment of psoriasis with cyclosporine is associated with an increased risk of nonmelanoma skin cancer. Patients treated for more than 2 y with cyclosporine were shown to have a higher risk. In addition, exposure to psoralen and ultraviolet A and to other immunosuppressants was shown to contribute to the overall risk.