In 1999, new evaluation criteria were proposed by the Committee on Evaluation Criteria for Chemotherapy of Solid Tumors in the International Journal of Clinical Oncology. According to these criteria, the evaluation criteria for malignant tumors of the skin have also been revised. There are various cutaneous malignancies, such as malignant melanoma, squamous cell carcinoma, basal cell carcinoma, tumors of the skin appendages (e.g., sweat gland carcinoma and sebaceous gland carcinoma), metastatic tumors, intraepidemal carcinomas, (e.g., Bowen's disease and Paget's disease), and mesenchymal carcinomas including mycosis fungoides (cutaneous T cell lymphoma).
In consideration of various clinical and thrapeutic aspects of malignant skin tumors, we have established a new evaluation criteria as follows. We measured three different diameters added to the conventional methods which one or two diameter (s) measured in the lesions, and also evaluation of the clinical response of non measurable tumors to chemotherapy considered. [Skin Cancer (Japan) 2001; 16: 143-157]

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As members of the expert committee of the Japan Society of Clinical Oncology for the proposition of guidelines for cancer chemotherapy, we collected and evaluated relevant literatures of chemotherapy of malignant melanoma. Each literature was critically evaluated using an evaluation form and quality of evidence of each study was classified into 4 grades. Summing up all the available information, recommendation statements were described on several issues concerning chemotherapy of malignant melanoma, and strength of each recommendation was evaluated using standardized criteria. Critical response from readers to this paper is welcomed. [Skin Cancer (Japan) 2001; 16: 158-169]

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As members of the expert committee of the Japan Society of Clinical Oncology for the proposition of guidelines for cancer chemotherapy, we collected and critically evaluated relevant literatures of chemotherapy of cutaneous squamous cell carcinoma using standardized criteria. After summing up all the available data, we described recommendation statements on several issues concerning chemotherapy of squamous cell carcinoma and grade of each recommendation was evaluated. Critical response from readers to this paper is welcomed, which helps us to refine these guidelines. [Skin Cancer (Japan) 2001; 16 : 170-173]

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A 59 year old male first noticed black macules at the bottom of right foot in June, 1997. At the initial visit to this dermatology department on Nov 26, 1997 he was found to have a finger-tip sized, rnildly elevated and elastic firm brown nodule in the mid portion of right sole. The nodule was surrounded by several bean sized black nodules. Diagnosis of malignant melanoma was then confirmed. In mid December the patient received wide resection with skin graft and excision of right inguinal lymph nodes. Three times of DAV+IFN were performed. In August, 1999 metastases appeared at the right sole, right leg and the scar area of right groin. After taking the 4th treatment of DAVE-IFN, 5-S-CD level was up to 14.5 nmol/l, lst trial of DACTam was given. In February, 5black macules were found in the inner aspect of right thigh which were prove to be metastases. Ten dose of IFN-β, each containing 3 million units, were given sequentially through local injection. The lesion of cancer metastasis gradually shrinked and disappeared.
Tissue biopsy showed cancer cells degenerated with apoptosis, by the methods of TUNEL, and immunohistochemical staining of p53, FAS and Bcl-2. No sign of recurrence was noted 7 months after the last treatment. [Skin Cancer(Japan) 2001; 16: 174-178]

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A 53-year-old female was admitted to our hospital for multiple brain tumors. One of them was surgically removed and its histological examination showed malignant melanoma. She had multiple lymph node metastasis on the right groin, a blue nevuslike macule on the right sole, and disseminated depigmented macules on the whole body. Although the brain tumors were treated by stereotactic radiosurgery, the patient died of meningeal involvement five month after the admission. The biopsy specimen of the plantar lesion showed no melanocyte in both epidermis and dermis, whereas a number of melanophages were seen in papillary dermis. Intraepidermal infiltration of lymphocytes was also detected. Dermal dendrocyte-like cells were recognized ultrastructually in papillary dermis mixed with melanophages. Those findings suggested that the plantar lesion might be the result of spontaneous complete regression of primary malignant melanoma. [Skin Cancer (Japan) 2001; 16: 179-183]

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We reported two cases of chronic arsenical poisoning diagnosed with multiple malignant skin tumors.
Case 1: A 69-year old man presented Bowen's disease on his right chest and SCC on his left ear. He also had lung and esophageal cancer. He had ingested arsenic as pesticide appoximately fifty years ago.
Case 2 : A 72-year old man from China had noticed diffuse pigmentation on his trunk and extremities since he was twenty years old. He underwent surgery for the removal of a laryngeal cancer last year. Biopsy of the skin lesion on his abdomen revealed SCC and that on his left arm confirmed the diagnosis of Bowen's disease. [Skin Cancer (Japan) 2001; 16: 184-187]

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We reported a case of a 87-year-old male with squamous cell carcinoma (SCC) on the left periauricular area with three months history. Although no lymph nodes and distal metastasis were found, the tumor mass was invasive in the periosteum by CT examination and advanced prostate cancer was also revealed. We gave up the widely surgical removal of the skin tumor in consideration of the tumor invasion, the presence of prostate cancer, the patient's age and also his request. Then we performed partial excision of necrotic tissue and decreased tumor mass followed by electron radiotherapy. A combination therapy of a debulking operation with radiation and thermotherapy controlled tumor very well. There has been no evidence of the recurrence and metastasis for more than fifteen months after medication.
As the low blood flow and/or the hypoxia of the tissues seem to decrease the radiation sensitivity, a debulking operation before radiation may be effective to a patient with SCC, who is relatively contraindicated to widely surgical operation. [Skin Cancer (Japan) 2001; 16: 188-191]

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A 62-year-old male had a subcutaneous hard tumor on the left cheek, which had grown gradually to 3.5 cm in diameter. The tumor invaded into subcutaneous tissue and moderately well-demarcated. Histrogically the neoplastic cells were typically pleomorphic, many spindled, and distributed in fascicles or haphazardly. Atypical mitoses and histiocytoid cells were frequent found. Immunohistochemically, neoplastic cells were positive for vimentin, CD68 and CD74, and negative for α-smooth muscle actin, desmin, CD31, CD34 and factor VIII. Atypical fibroxanthoma (AFX) is histologically similar to malignant fibrous histiocytoma (MFH). It was assumed that MFH differs from AFX only by its deeper location and larger size. [Skin Cancer (Japan) 2001; 16: 192-195]

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The prognosis of the malignant hemangioendothelioma (MHE) on the elderly people's scalp is poor. It is reported that only 23.9% can survive three years or more after diagnosis. We reported a case of a 79 year-old female with MHE of the scalp. She had survived 2 and a half year after the diagnosis. She was treated with the combination therapies of operation and r-IL2 injection. r-IL2 was injected via superficial temporal artery, intravenously and locally around the tumor and into the thoracic cavity. In spite of frequent CT examination of the lung, development of metastasis to the pleura couldn't be identified in the early stage. The pleura metastasis had developed in her right lung and had caused hemothorax three months before she died. This unilateral hemothorax had been continuously compressing her heart and lead to cardiac incompetence which was the cause of her death. In the early stage, r-IL2 was effective to prevent the local recurrence and spreading of the tumor for a while, but it could not prevent the metastasis. As MHE is lethal condition, treatment should be emphasized in the improvement of the patient's QOL. Operation method and the way of r-IL2 injection are discussed. [Skin Cancer (Japan) 2001; 16: 196-200]

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The case of a 54-year-old male with basal cell carcinoma is reported. The patient noticed a nodule on his nose two years ago. On the first visit to our hospital, a 13×5mm-sized nodule with ulcer was observed. This nodule was operated with Evans'flap, that is a method of reconstruction of the nasal ala, using a composite free flap taken from the anterior part of the pinna. [Skin Cancer (Japan) 2001; 16: 201-204]

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We report our experience of sentinel lymph node biopsy in malignant melanoma cousing patent blue V dye, preoperative lymphoscintigrapy and handheld gamma probe. Patients underwent preoperative lymphoscintigraphy with^99mTc-labeled stannous phytate a day before operation. The patients subsequently underwent intraoperative lymphatic mapping and selective lymph node dissection with patent blue dye and radiopharmaceutical agent. A handheld gamma probe determined the radioactive counts over the blue stainned lymph node and the other nodes mapped by lymphoscintigraphy. The single injection of^99mTc-labeled stannous phytate was effective in both preoperative lymphoscintigraphy and handheld gamma probeguided intraoperative determination of sentinel lymph nodes. The dissected lymph nodes were assessed by both intraoperative frozen section investigation and formaline-fixed section stained with hematoxylin and eosin and HMB-45. We failed to detect micrometastases by frozen section in 3 of 3 positive sentinel lymph nodes from 2 patients.
Although the addition of radiopharmaceutical agents serves as a useful adjunct, the blue dye technique remains the criterion standard for selective lymph node dissection. The frozen section analysis is not recommended for determination of subsequent therapeutic lymph node dissection. [Skin Cancer (Japan) 2001; 16: 205-210]

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The incidence of malignant melanoma has increased recently but its prognosis has improved throughout the world, including Japan. The reason for this might be due to advances in intensive treatment and early diagnosis. However, it is still true that advanced malignant melanoma is usually incurable. Correct diagnosis of early malignant melanoma is very important because the prognosis and the treatment are quite different from those of an advanced case. But it is often difficult to differentiate with the naked eye early malignant melanoma from a benign pigmented lesion like a melanocytic nevus. Recent technical advances in dermoscopy (epiluminescence microscopy) have contributed to the early and correct diagnosis of malignant melanoma, allowing us to evaluate the structure of the surface profiles of pigmented skin lesions in detail. In this report I emphasized that early diagnosis was very beneficial for the treatment of malignant melanoma. [Skin Cancer (Japan) 2001; 16: 211-221]

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To identify factors that are prognostic for survival in patients with stage IV malignant melanoma, a retrospective analysis was performed at the authors' institutions between 1976 and 1999. The median survival time of 53 stage IV patients was 7.1 months. Univariate analysis showed that initial site of metastasis (p=0.05) was significant prognostic factor. Conversely, the stage of disease preceding distant metastasis (p=0.59), disease free interval before distant metastasis (p=0.66), times at distant metastasis (p=0.92), and treatment modalities (p=0.17) were not significantly prognostic for survival. The response rates to DAV (dacarbazine, nimustine, vincristine), CDV (cisplatin, dacarbazine, vindesine), and DACTam (dacarbazine, nimustine, cisplatin, tarnoxifen) regimens were 22.2%, 9.1%, 0%, respectively. There was no statistically significant difference in response rates among the treatment arms (p=0.23). Although a variety of chemotherapeutic drug combinations have been explored over the years, they have not proven to be superior to dacarbazine alone. We need to develop new strategies for the treatment of stage IV melanoma. [Skin Cancer (Japan) 2001; 16: 222-227]

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A trapezius musculocutaneous (MC) flap was used for the defect after excision in an advanced squamous cell carcinoma on the left occipital region in a 75-year-old female, and in a multiple recurrent liposarcoma on the left shoulder in a 90-year-old female, respectively, and a trapezius cutaneous perforator flap was also used in a multiple recurrent soft tissue sarcoma (unclassified type) on the posterior cervical region in an 85-year-old male. A trapezius MC flap may be indicated for reliable coverage for head and neck, and shoulder defects, especially in an advanced and/or difficult malignant tumor with bleeding, odor, or obstinate pain. [Skin Cancer (Japan) 2001; 16: 228-232]

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The auther report two cases arising of skin cancer on the burn scar. A 72-year-old Japanese woman got burnt in the frontal scalp, when she was 3 years old. The tumor was an easiely bleeding nodule measuring 14×14×8 mm in size. Histological examination revealed a keratotic Basal Cell Carcinoma. Wide excision of the lesion and local skin flap were performed. Second case was an 86-year-old woman who had a burn on the left thigh during a neonatal period. It has grown up to the intractable ulceration in 1995 and it became hemorrhagic. The biopsy specimen showed that the ulcer is a squamous cell carcinoma. It was removed widely under the general anesthesia, and the skin graft was carried out in 1999. [Skin Cancer (Japan) 2001; 16: 233-236]

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We report a case of lung metastasis of angiosarcoma of the scalp treated with irradiation and docetaxel. The patient was 67-year-old Japanese man, who had large purpura and hemorrhegic nodule on his forehead. He was treated with irradiation to head, surgical excision, and chemotheraphy (Carboplatin, Ifosfamide, Vindesine) .However 8 months after our first visit, lung metastasis was developed. Lung metastasis of angiosarcoma was diagnosed by thoracoscopic lung biopsy. Chemotherapy (Carboplatin, Ifosfamide, Vindesine) and intravenous rlL-2 injection was not effective, and pneumothorax occurred. After irradiation to lung (total 60Gy), air leakage stopped and the tumor was not shown in CT scan and chest radiography, and he could discharge from our hospital. However multiple new metastasis in bilateral lung were appeared, we performed intravenous docetaxel injection a week in outpatient. Docetaxel injection was effective, and multiple metastasis were disapeared in radiography. We suggest that irradiation and docetaxel will be useful for treatment of lung metastasis of angiosarcoma. [Skin Cancer (Japan) 2001; 16: 237-241]

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A 81-year-old man with apocrine adeno-carcinoma arising in the scalp was reported. The lesion of alopecia had been noticed since birth but had enlarged progressively during the past several years. A tumor measuring 32×32×4mm was excised. A histological examination revealed adenocarcinoma composed of atypical cells with abundunt eosinophilic cytoplasm and a finding of decapitation in some parts of the tumor. The tumor cells were PAS (+) (with resistance to diastase), CEA (±), EMA (±), GCDFP-15 (+), cytokeratin 7 and 19 (+) .
Electronmicroscopically, the cells had polygonal nuclei with many clefts and clumped chromatins. The cytoplasm contained moderate amounts of enlarged roughendoplasmic reticulum cisternae, a varying number of secretary granules, and many pleomorphic mitochondoria. Based on these findings, typical apocrine adenocarcinoma was diagnosed. We considered that this tumor was probably of apocrine origin associated with organoid nevus. [Skin Cancer (Japan) 2001; 16: 242-246]

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Growth dependence with androgen (Nishi J Natl Cancer Inst 84: 519, 1992) and frequent expression of structurally unaltered androgen receptor (Fujimoto Lab Invest 80: 1465, 2000) in Extramammary Paget's disease (EMPD) may provide arational basis for hormone therapy. We report the first attempt of total androgen blockade (TAB) therapy in a 78-year-old man with advanced EMPD. The TAB therapy, which is widely used for prostate cancer, consisted. of oral administration of chlormadinone acetate 100mg daily and subcutaneous injection of leuprorelin acetate 3.75mg every month. Although skin metastases on his lower abdomen gradually progressed, para-trachial lymphadenopathy disappeared and para-aortic lymph nodes decreased in size by more than 60%. He died of the disease one year after starting the TAB therapy. Future clinical trial is required to establish the role of TAB therapy in the management of advanced stage EMPD patients. [Skin Cancer (Japan) 2001; 16: 247-250]

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We reported a case of spindle cell squamous cell carcinoma.
The patient was a 73-year-old man who developed an ulcerated nodule, 2.8×2.0cm in size, on the burn scar of the head. Histologically, the tumor was composed of disorderly arranged atypical spindle cells, and mitotic figures were often found. Immunohistological studies showed positive reaction of these cells for vimentin and CAM5.2. [Skin Cancer (Japan) 2001; 16: 251-254]

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The patients with advanced malignant melanoma are difficult to treat because the response rate to chemotherapies is low. We have treated eight patients of advanced malignant melanoma (stage III & IV) by combination chemohormonal therapy with dacarbazine, nimustine hydrochloride, cisplatin, and an anti-estrogen agent tamoxifen (DAC-Tam therapy). Three patients who received this treatment as postoperative adjuvant therapy showed complete response for more than 4 weeks, but in 5 patients progressive disease existed. [Skin Cancer (Japan) 2001; 16: 255-261]

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To examine whether the local injection of interferon-β (IFN-β) affects systemic immunity in post-surgical melanoma patients, several immunological parameters were measuredbefore and 24-hours after the local inj ection of IFN-β (3×10⁶ IU) in 14 patients. Immunological parameters included NK cell activity, production of IL-2 and interferon-γ (IFN-γ) in mitogen stimulated peripheral blood lymphocytes, and percentages of CD4+/IFN-γ+ (Th1) and CD4+/IL-4+ (Th2) lymphocytes measured using flow cytometry. No statistically significant change was observed in any parameters exarnined before and after the local injection of IFN-β. [Skin Cancer (Japan) 2001; 16: 262-264]

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We performed subtotal sacrectomy for squamous cell carcinoma on the sacral area of a 48-year-old man suffering paralysis of lower extremities for 28 years. Although the resection of the total mass of carcinoma including most part of sacrum (S2-5) was successfully performed, the patient suffered from protracted bacterial infection of the pelvic cavity and osteomyelitis of iliac bone. He died of respiratory failure due to distant metastasis of the tumor to the lung 248 days after surgery. [Skin Cancer (Japan) 2001; 16: 265-2691]

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