The Japanese Skin Cancer Society (JSCS) was established in 1986. Since then, the annual meeting of JSCS has attracted many doctors interested in cutaneous oncology. Now, the number of members of JSCS has exceeded 1200. In 2002, the Japanese Society of Cutaneous Lymphomas joined JSCS. This joining made our society much stronger in many aspects. In 2006, the articles of JSCS have been totally revised. The official journal of JSCS, Skin Cancer, was first published in 1986, and now 3 issues per year are published. The epidemiological study of skin cancers affecting the Japanese population has been one of the major concerns of our society. Now, on-line registration systems of patients with melanoma or lymphoma have been prepared. In recent years, our society published clinical guidelines for major types of skin malignancies. The author retired from the presidency of JSCS in May, 2009. Surely, new winds will blow in our society, and the society will go up to the next step.[Skin Cancer (Japan) 2009 ; 24 : 138-144]

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NY-ESO-1 is a cancer/testis antigen identified in an esophageal cancer using SEREX methodology. The antigen is expressed in a variety of tumors at various frequencies and has been shown to be highly immunogenic. We conducted a phase I clinical trial using NY-ESO-1 protein. A complex of cholesteryl hydrophobized pullulan (CHP) and NY-ESO-1 protein was administered subcutaneously every two weeks. The primary objectives were to evaluate safety and to assess immune responses. The secondary objective was to describe tumor response. The results show the material was tolerable and elicited NY-ESO-1 immunity. Furthermore, clinical response was observed in some patients. [Skin Cancer (Japan) 2009 ; 24 : 145-152]

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Dendritic cells (DCs) play a pivotal role in the initiation, programming and regulation of tumor-specific immune responses. However, the DC therapy for malignant melanoma has yielded only limited clinical success. The low efficacy of vaccine strategy against melanoma will be discussed. The combination therapy with novel molecular targeted therapy and vaccine therapy might be promising.[Skin Cancer (Japan) 2009 ; 24 : 153-158]

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Melanoma is one of the most immunogenic tumors. CD8+ cytotoxic T cells play an important role in the rejection of tumor cells in vivo. Many tumor antigens have been identified and used for antigen-specific cancer immunotherapy. In vivo antigen specific immune responses were detected ; however, objective response has remained quite low. Immune regulatory cells, including regulatory T cells, are involved in immune suppression in cancer patients as well as suppressive cytokines secreted from tumors or interstitial cells, induction of apoptosis, antigen loss and MHC molecule loss. In the recent study, control of regulatory T cells improved objective responses of adoptive transfer therapy or antigen-peptide vaccination for melanoma. These results suggested that control of immune regulatory cells may prove useful in the development of cancer immunotherapy.[Skin Cancer (Japan) 2009 ; 24 : 159-163]

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Dendritic cell-based tumor immunotherapy is widely known to elicit protective anti-tumor immune responses, although the safety and effectiveness have yet to be thoroughly explored. We introduce here a novel immunotherapy for melanoma, percutaneous peptide immunization.
A disruption in the stratum corneum barrier results in enhancement of permeability and activation of epidermal Langerhans cells which function as strong antigen presenters for T cells. Topical application of melanoma-associated antigen peptides onto the barrier-disrupted skin specifically induces tumoricidal immune responses in vivo. In addition, percutaneous peptide application has demonstrated a certain degree of effectiveness in patients with stage III/IV melanoma. In the future, control of the regulatory immune mechanism against tumor immunity would improve our strategy.[Skin Cancer (Japan) 2009 ; 24 : 164-173]

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The biological property unique to melanoma cells resides in the biogenesis of melanin pigment (melanogenesis) within the specific compartments, melanosomes. This study showed that melanogenesis can be exploited to develop the tyrosinase-targeted drug delivery system (DDS) and chemo-thermo-immunotherapy (CTI therapy) for melanoma patients. It was concluded a) that NPrCAP/M can develop a novel DDS and anti-melanoma chemotherapy targeted to melanogenesis ; b) that NPrCAP/M with alternating magnetic field (AMF) to C57 BL mice with B16 melanoma inhibited the growth of re-challenged melanoma cells inoculated on to the opposite side of the body after the removal of the initially inoculated melanoma in mice ; c) that NPrCAP/PEG/M with AMF provided thermal heat which resulted in melanoma necrosis and immune reactions generating cytotoxic T cells and regressed distant skin metastases in human clinical trials and d) that novel chemo-thermo-immunotherapy with NPrCAP/PEG/M can, therefore, be developed for melanoma patients by exploiting the melanogenesis cascade.[Skin Cancer (Japan) 2009 ; 24 : 174-180]

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Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope ; HVJ-E) are safe and efficient nonviral vectors for drug delivery as they can incorporate DNA, RNA, proteins, and drugs. We have recently found a novel antitumor immunity of HVJ-E using a colon cancer model. Moreover, intratumoral injection of inactivated HVJ-E solution significantly reduces tumor volume and prevents the occurrence of lung metastasis, conducive to extending overall survival in C57/BL6 mice transplanted with B16/F10 mouse melanoma cells and even immunodeficient mice transplanted with MeWo human melanoma cells. In contrast, no severe adverse events including laboratory data abnormality and anaphylactic reaction were observed. The comprehensive mechanisms of immunologic effect by HVJ-E appear to include not only enhanced effector T cell-and/or NK cell-mediated immunity but also rescue from regulatory T cell (Treg)-mediated immunosuppression, presumably through IL-6 secretion from dendritic cells stimulated by HVJ-E. Since the protocol of this clinical study in malignant melanoma was recently approved by the ethical committee of Osaka University and by the Medical Center for Translational Research in Osaka University Hospital, a phase I/II study for advanced malignant melanoma patients has just started. In this review, we show several favorable results regarding the antitumor effect of HVJ-E and mention the mechanism of this immunity. In addition, we introduce the selection/exclusion criteria and schedule for phase I/II clinical trial.[Skin Cancer (Japan) 2009 ; 24 : 181-191]

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We have established a new registration system for a nationwide survey on cutaneous lymphomas, and prepared a guideline for cutaneous lymphomas, in cooperation with the Japanese Skin Cancer Society. The registration system is designed to achieve two main projects :
1) An annual, nationwide registration system of new patients with cutaneous lymphomas, by collecting minimal essentials of their clinical data : diagnosis, age, sex, treatment, etc.
2) A prospective, follow-up study of patients with cutaneous lymphomas in 10 selected institutes. We have constructed an on-line registration system.
The former project, which had already started in 2007, is expected to give us information on incidences of patients with cutaneous lymphomas in Japan. The latter is to evaluate the prognosis and long-term outcome of each patient treated in line with the standard treatment protocol or clinical trials.[Skin Cancer (Japan) 2009 ; 24 : 192-198]

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Adult T-cell leukemia-lymphoma (ATL) is a distinct peripheral T-lymphocytic malignancy associated with the human T-cell lymphotropic virus type I (HTLV-1). The diversity in clinical features and prognosis of patients with this disease has led to its subclassification into the following four categories : acute, lymphoma, chronic, and smoldering types. Patients with aggressive ATL generally have a poor prognosis despite chemotherapy or hematopoietic stem cell transplantation. The chronic and smoldering subtypes are considered indolent and are usually managed with topical treatment mainly for skin lesion and watchful waiting (WW) policy for systemic chemotherapy, until disease progression. The long-term prognosis of WW for indolent ATL was not good in a large-scale analysis from Japan. As for the treatment of indolent ATL, especially with skin involvement, a combination of zidovudine and interferon alpha was reported to be promising as compared to chemotherapy. However, this combination has not been evaluated in Japan. Several new agents against T-cell malignancies including ATL are now under investigation.[Skin Cancer (Japan) 2009 ; 24 : 199-205]

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Adult T-cell leukemia/lymphoma (ATLL) is a peripheral CD4⁺ CD25⁺ T-cell malignancy caused by human T-cell leukemia/lymphoma virus type I (HTLV-I). The ATLL cells frequently infiltrate into the epidermis and form a Pautrier's microabscess. The expression of CCR4 and its ligands TARC/CCL17 and MDC/CCL22 by ATLL cells may underlie the epidermotropism and microabscess formation.[Skin Cancer (Japan) 2009 ; 24 : 206-211]

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Epstein-Barr virus-associated T/NK-cell lymphoproliferative disorder (EBV-T/NK LPD) of children and young adults generally overlaps with the nosological term of severe chronic active EBV infection (CAEBV). We propose clinicopathological categorization of EBV-T/NK LPD based on pathological evaluation and molecular data into : 1) Category A1, polymorphic LPD without clonal proliferation of EBV-infected cells ; 2) Category A2, polymorphic LPD with clonality ; 3) Category A3, monomorphic LPD (T-cell or NK cell lymphoma/leukemia) with clonality. However, CAEBV with all A1, A2, and A3 is a high-mortality and high-morbidity disease.[Skin Cancer (Japan) 2009 ; 24 : 212-217]

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A 70-year-old male presented with a red macule on the nose, accompanying teleangiectasia. The macule showed typical arborizing vessels on dermoscopy. Histopathological examination confirmed that the macule was basal cell carcinoma. The margin of the tumor was not clinically clear ; therefore, we determined the margins of the macule depending on the dermoscopic signs of arborizing vessels and whitish veil. We removed the tumor with 5-millimeter surgical margins, which was proved to be sufficient by postoperative pathological examinations. Dermoscopic examination is useful for deciding the surgical margins of basal cell carcinoma.[Skin Cancer (Japan) 2009 ; 24 : 218-220]

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We examined the location of sentinel lymph nodes in melanoma (5 cases), squamous cell carcinoma (2 cases) and extramammary Paget's disease (1 case) by using the single photon emission computed tomography/computed tomography (SPECT/CT) combined system. For realizing the anatomical location of sentinel lymph nodes before operating, we could easily and quickly detect sentinel lymph nodes (100%). Therefore the fusion of SPECT and CT images is especially useful for the detection of sentinel lymph nodes.[Skin Cancer (Japan) 2009 ; 24 : 221-224]

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A 59-year-old man presented with a high fever and dyspnea. The patient was diagnosed as having acute respiratory distress syndrome (ARDS). Although he was treated with steroid pulse therapy, ARDS led to multiple organ failure. For critical care, he was transferred to the department of emergency & critical care medicine of our hospital. He was suspected of having severe infection and received antibiotics and continuous hemodiafiltration with no improvement. Since the patient had edema associated with femur telangiectasia on the left and petechial hemorrhage in the skin of his precordium, the patient was sent to the department of dermatology for consultation. Laboratory examination showed an elevated level of sIL-2R (19700 U/ml). A skin biopsy from the telangiectasia revealed the presence of many intravascular, large, atypical lymphoid cells with hyperchromatic nuclei and tumor cell emboli in dermis and subcutis. Immunohistochemical analysis showed that neoplastic cells expressed CD20 but not CD3. These findings were consistent with intravascular large B-cell lymphoma. The patient's clinical symptoms were improved markedly by R-CHOP.[Skin Cancer (Japan) 2009 ; 24 : 225-228]

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We evaluated the efficacy of DAV (DTIC, ACNU and VCR) regimen as adjuvant therapy after surgery in patients with malignant melanoma. We conducted a retrospective comparative study by the presence of DAV, with primary endpoints of relapse-free survival (RFS) and melanoma-specific survival (MSS) with stage II and III melanoma. The Kaplan-Meier method showed that there was no significant difference in RFS and MSS between the two groups. By the Cox proportional hazards model including DAV, sex, age, location, thickness, ulceration, stage and IFN-β as covariates, the presence of DAV had no significant strength of influence on either RFS or MSS. A multicenter, prospective comparative study will be required to continue DAV as a standard adjuvant chemotherapy.[Skin Cancer (Japan) 2009 ; 24 : 229-233]

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We report a case in which a double-bladed scalpel was used for micrographic surgical excision of nasal basal cell carcinoma. This treatment method was found to be more reliable and efficient than conventional methods used in Japan. A 59-year-old Japanese male presented with a 5-year history of an asymptomatic, irregularly shaped lesion from his left nasal ala to the tip of his nose. The lesion was excised by micrographic surgery, a diagnosis of invasive basal cell carcinoma was made, and the excised area was reconstructed by cartilage graft and flap with free surgical margin. The double-bladed scalpel is useful and efficient for the micrographic surgical treatment of high-risk basal cell carcinomas.[Skin Cancer (Japan) 2009 ; 24 : 234-238]

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An 83-year-old woman was referred to our department for evaluation of black nodules on the right eyelid and the left upper lip (near the nasolabial groove). On histological examination, a diagnosis of basal cell carcinoma was made. The tumors were excised under general anesthesia. The defect of the left upper lip was reconstructed with a nosolabial medial advancement flap. The nodule on the eyelid, the anterior lamella, was reconstructed using a cheek rotation (Mustardé) with a tarsoconjunctival transposition flap, and the preserved sclera was used for posterior lamella reconstruction.[Skin Cancer (Japan) 2009 ; 24 : 239-242]

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This report includes two cases of undifferentiated high-grade pleomorphic sarcoma on the back. One is a 70-year-old male with a giant subcutaneous tumor on the left side of the back, and the other is a 75-year-old male with a 2^nd recurrent subcutaneous tumor on the right scapula. Because both cases displayed superficial tumors on their trunks, we were able to resect them with adequate safety margins. They have not shown any evidence of recurrence or distant metastasis for 8 months and 2 years respectively after the operations. We discuss the implications of the cases with regard to clinical issues. Because patients having soft tissue sarcomas on the trunk have less possibility of suffering from functional disorder after an operation than those with head, neck, and/or extremity tumors, we can warrant curative or adequate wide resections for such cases.[Skin Cancer (Japan) 2009 ; 24 : 243-249]

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A 64-year-old man presented with a skin tumor on the outside of the left knee joint in April, 2007. Physical examination revealed that the lesion was a red colored, hemorrhagic, well mobilized and well demarcated tumor measuring 40×40×40mm. Magnetic resonance imaging (MRI) revealed that the tumor showed low signal intensity on T1-weighted image, high signal intensity on the T2-weighted image, and high signal intensity with fat-suppression. The tumor showed enhancement on contrast-enhanced MRI. Histological examination showed proliferation of pleomorphic tumor cells with atypical nucleo and giant cells. The neoplasm contained myxoid stroma and necrosis of tumor cells in part. Lipoblasts with multi-vacuolated cytoplasm and atypical nucleo were identified. Immunohistochemistry revealed that the tumor cells were positive for vimentin, S100, CD68 and negative for SMA, desmin, CD34. We diagnosed pleomorphic liposarcoma. We performed local excision with a 2cm margin and used a full-thickness skin graft. The patient has been free from recurrence and metastasis.[Skin Cancer (Japan) 2009 ; 24 : 250-253]

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Consumption of the epidermis (COE), defined as thinning of the epidermis in areas of direct contact with neoplastic melanocytes, is reported to be found more in melanomas than in Spitz's nevi. Therefore COE is considered a useful criterion in the evaluation of melanocytic neoplasms. We analyzed 59 melanomas and 10 Spitz's nevi for the presence of COE. COE was found in 44/59 (74.6%) melanomas and 3/10 (30.0%) Spitz's nevi. COE in melanomas was associated with increased tumor thickness and ulceration, but not with age, sex, and site as formerly reported. Our study revealed COE was not significantly associated with acral lentiginous melanomas compared to three other histological types, and this result was different from that of former reports.[Skin Cancer (Japan) 2009 ; 24 : 254-257]

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Clinical features and therapeutic survival rate were analyzed in terms of patients' age difference on 2065 malignant melanoma patients in Japan, accumulated during 1987-2001. Nodular melanoma, and especially acral lentiginous melanoma and lentigo maligna melanoma increases in number according to the increase in the patients' age. Superficial spreading melanoma is most frequent in the age range of 40-59 years. Melanomas on sun-exposed areas, which occupy13% of all melanomas, increase in number according to the increase in age. In contrast, melanomas on the trunk, which occupy 14% of melanomas, are most frequent in the age range of 50-59 years. DAV-IFN-β combined therapy results in better survival rates in patients undergoing the therapy than those without it. The survival rate is remarkable in those of the age rage of 40-59 years. This result further supports the recommendation of IFN-β adjuvant chemotherapy for melanoma patients, especially for those who are middle-aged.[Skin Cancer (Japan) 2009 ; 24 : 258-266]

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We report a 74-year-old man with Paget's disease on his left nipple showing remarkable pigmentation. The patient noticed a dark brown patch on his left nipple 10 years before the first of our consultations, and the size of the lesion had been increasing. We could not give a diagnosis of Paget's disease on the histological findings of the first biopsy specimens because of poor specific findings. So a wide excision was performed, and the histological examination revealed relatively large bright cells in the epidermis, positive for cytokeratin-7, CEA, antibody immunochemical stain, which was diagnosed as Paget's disease. For 2 years after the excision and following electron beam irradiation, we found no metastasis or recurrent lesions.[Skin Cancer (Japan) 2009 ; 24 : 267-271]

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In-transit metastases have been reported to have occurred in 5 to 10% of all melanoma, and are known to impair prognosis. This type of metastasis might be the result of adhesion and proliferation of tumor cells within the lymph channel before reaching the lymph nodes. Although the adaptation and the effect are still not yet conclusive, some cases with in-transit metastases which have been treated using subtotal integumentectomy which removes the lymph channel from the primary site to the regional lymph node basin have been reported. In our institute, 4 cases of melanoma with in-transit metastasis were treated using this method, and 3 cases remained free of disease after 7 to 24 months of follow-up. Although the current trend is to use minimal surgery, this method should be discussed when managing cases with in-transit metastasis in the present situation.[Skin Cancer (Japan) 2009 ; 24 : 272-277]

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A caseworker pointed out to a woman in her 80s the presence of erosion of her left nipple. A skin biopsy was performed and she was diagnosed with mammary Paget's disease. Subsequently, she was referred to our hospital. Her left nipple was retracted and caved in. Furthermore, crust and bloody discharge were present at her left nipple. A 2cm×2cm sized elastic hard tumor whose margin was unclear was touchable on the superolateral region of her left breast. Mammography and MRI imaging were performed and then, simple mastectomy and sentinel node biopsy were performed. She was diagnosed with mammary Pagetoid cancer by pathological examination. Because mammary Pagetoid cancer has a worse prognosis than mammary Paget's disease, it is very important to distinguish one from the other.[Skin Cancer (Japan) 2009 ; 24 : 278-282]

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In July 2008, a 98-year-old woman visited Shiroyama-Migita Clinic because of a six-month history of a gradually growing red-colored nodule on her right cheek. Subsequently, she was referred to our hospital. Clinical examination revealed a red-colored, 40mm sized firm ulcerated nodule on her right cheek and a red-colored plaque near the nodule. Clinical diagnosis was SCC. The tumor was excised with a 2cm margin. Histological examination revealed diffuse sheets and solid nests located in the dermis and subcutaneous fat. The tumor was a small blue neoplasm composed of cells of uniform size with round nucleus and scant cytoplasm. The tumor cells showed AE1/AE3-, cytokeratin 20-, chromogranin-and synaptophysin-positive. Therefore, the patient was diagnosed as having Merkel cell carcinoma. Erythematous plaque was diagnosed as actinic keratosis.[Skin Cancer (Japan) 2009 ; 24 : 283-286]

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We report a new method to stabilize the penis during postoperation. A 76-years old man Extramammary Paget's carcinoma (EPC) occurred in genitalia who underwent sentinel lymph node biopsies (SNB) and tumor excision. The invasive of the tumor was whole scrotum skin and the penis skin a half. The patient was underwent sentinel lymph node biopsies from the right and left inguinal region and the result was no metastasis.
The defect after tumor excision was reconstructed by mesh skin graft transplantation. Then, We used the new method for good healing of the postoperative wound region and for improve the mesh skin graft adherence better during postoperation. This new method is very simple device that made from chopsticks and plastic bottle. Postoperatively, the wound healing is good and the mesh skin graft adherence is perfect. After 11 months follow up, metastatic tumors or recurrent lesion have not found and functional and aesthetic result were good.[Skin Cancer (Japan) 2009 ; 24 : 287-291]

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Case 1. A 71-year-old man noticed a reddish nodule of 4 months duration on his left cheek. A biopsy revealed Merkel cell carcinoma. Wide resection of the primary lesion was performed and sentinel node biopsy disclosed no lymph node metastasis. Case 2. An 80-year-old woman noticed a reddish nodule on her upper arm of 3 months duration. Local excision and pathologic evaluation demonstrated Merkel cell carcinoma. Wide resection of the primary lesion was performed and sentinel node biopsy disclosed no lymph node metastasis. These 2 cases were treated with adjuvant radiotherapy to the primary site and regional lymph nodes. The two patients are still alive, without recurrence or metastasis.[Skin Cancer (Japan) 2009 ; 24 : 292-295]

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We present a 69-year-old female patient who developed a malignant fibrous histiocytoma on the upper arm. Ten years earlier a red nodule had been observed on the right upper arm and increased to soybean size. A biopsy was performed, and based on the histopathologic HE and immune staining, a pleomorphic malignant fibrous histiocytoma was diagnosed. Among the immune stains α smooth muscle actin (SMA), CD-1a stained best, allowing observation of poorly differentiated smooth muscles. A total subfascial resection was performed along a line at a distance of 2cm from the circumference of the tumor. Ten months have passed since the surgery, but no local recurrences or distant metastases have been observed.[Skin Cancer (Japan) 2009 ; 24 : 296-300]

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We conducted this preliminary study to determine the feasibility of adjuvant therapy administration schedule of S-1 for locoregionally advanced non-melanoma skin cancers (squamous cell carcinoma, apocrine adenocarcinoma, eccrine porocarcinoma, extramammary Paget's disease). Five patients receiving definitive treatments were enrolled to receive oral S-1 for 2-weeks' administration followed by a 2-week rest for 12 months.
The cumulative rates of the relative total administration dose of S-1 at 100% were 80% (4/5). Adverse events were not severe. The incidences of neutropenia (Grade 1) and skin toxicities (Grade 1) were 60% and 20%, respectively.
A 2-week administration of S-1 followed by a 2-week rest seems to be more feasible in adjuvant chemotherapy for locoregionally advanced non-melanoma skin cancer.[Skin Cancer (Japan) 2009 ; 24 : 301-304]

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In July 2008, a 65-year-old woman visited a clinic because of a nine-month history of a subcutaneous tumor on her right thigh. She was subsequently referred to our hospital. Clinical examination revealed an elastic soft subcutaneous mass on the right thigh. MRI showed a demarcated bulky mass with vasculature, 60mm in diameter, situated between the sartorius and iliopsoas. Laboratory findings showed no abnormal findings. The tumor was excised surgically in July 2008. Histological examination revealed an encapsulated dark brown-colored tumor, exhibiting a characteristic “staghorn” branching vascular pattern. Oval to spindle-shaped tumor cells showed slight atypia, and mitosis was detected in only a small percent of the tumor cells. Immunohistochemical study revealed that the tumor cells stained positive for CD30 and bcl-2, and negative for vimentin, a-smooth muscle actin, desmin, CD31, factor VIII related antigen, S-100 protein and CD99. MIB-1-positive cells accounted for 3 to 5% of the total. Therefore, the patient was diagnosed as having hemangiopericytoma. [Skin Cancer (Japan) 2009 ; 24 : 305-308]

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The patient was a 41-year old male. One year ago a red nodule developed on the ulnar side of the DIP of the right ring finger and became enlarged, reaching a diameter of 12mm and a height of 5mm. Based on the histopathologic HE and CD34 immune staining, a dermatofibrosarcoma protuberans was diagnosed. Imaging findings did not reveal any distant metastases. Following the wish of the patient, a total resection with a horizontal margin of 5mm and a vertical margin reaching down to the tendon followed by a skin graft was performed. The patient has now been free from local recurrence and metastasis for five years after surgery. In the past 46 years only a rare 7 cases with this condition have been reported.[Skin Cancer (Japan) 2009 ; 24 : 309-313]

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