A-61-year-old man, sheet metal worker, of epidermodysplasia verruciformis (EV) with malignant changes was reported. There was no similar disease on his family. Since 16 year old, he notised erythematous flecks with no symptom on his back, chest and hands. At 55 years old, he was operated for squamous cell carcinoma on left eye-lid. The physical examination showed two tumors on his face and neck, egg-sized pigmented fleck with erythema on his chest and numerous been-sized erythema and hypopigmented flecks on his chest and back.
The histological features of the bean sized erythema showed large clear cells in the granular layer. The nucleus of these cells positively stained with anti-human papillomavirus antibody. The lesion was diagnosed as EV.
Histopathologically the tumors of his face and trunk were diagnosed as followings: the tumor on his left eye-lid was squamous cell carcinoma, the tumor on his neck was basal cell carcinoma with actinic keratosis, the egg-sized pigmented fleck was Bowen disease.
Treatment with 5-FU cream for EV was effective.

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Two cases of reconstruction with a reversed forearm flap of the defect in which the bone was exposed were reported.
Case 1: A 77-year-old male had a malignant melanoma on his right thumb. The nail had completely fallen off and an ulcer on the irregularly pigmented nail bed tended to bleed markedly (Fig. 1) .
Regional or systemic lymph node swelling was not noticed and no signs suggestive of metastasis were found. The tumor was widely resected with 4 to 5mm free margin and the right thumb was amputated at the level of the interphalanx joint (Fig. 2) . The defect in which the thumb proximal phalanx was exposed was reconstructed with a right reversed forearm flap (Fig. 3) . Pathologically, the tumor was a completely resected malignant melanoma with Clark level III, 1mm tumor thickness (Fig. 4) . Prophylactic right axillary lymph node dissection was performed thereafter. Pathologically, the right axillary lymph nodemetastsis was not revealed. TNN classification of the tumor was _pT₂, _pN₀, M₀; stage I a.
Case 2: An 81-year-old male had a malignant melanoma on his right index finger. On the volar side of the finger a wide brown to black pigmented lesion with central painful ulceration was noted (Fig. 6) . One small right axillary lymph node was palpable. No signs suggestive of metastasis were found. The tumor was widely resected with 5mm free margin and the index finger was amputated at the level of distal 1/3 of the second metacarpus (Fig. 7) . The defect in which the stump of the second metacarpus was exposed was reconstructed with a right reverse forearm flap (Fig. 8) . Pathologically, the tumor was a completely resected malignant melanoma with Clark level IV, 3.10mm tumor thickness (Fig. 9) . TNN classification of the tumor was _pT_3b, _pN₀, M₀; stage II.
In the above two cases, the reversed forearm flaps completely survived and the reconstructed hands have both satisfactory function and appearance (Figs. 5 and 10) .
We believe that a reversed formed flap is the best choice of treatment for defects in which the bone, nerve or vessels are exposed after resection of the malignant skin tumors on the hand, because this flap is able to be elevated easily and safely and therefore shortens operating time. These reasons are beneficial all the more in cases of aged patients with many complications. In addition, a reversed forearm flap is able to be transplanted with nervus cutaneus antebrachii lateralis, musculus palmaris longus or radius involved. In cases doubtful of any regional lymph node metastasis, however, a reversed forearm flap should not be used.

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Four cases of Bowen's disease associated with early gastric cancer were reported.
Case 1. A 60-year old man visited our department in June, 1985, with a 17×19mm sized erythema on the penis. Bowen's disease was histologically diagnosed. Soft X-ray therapy cured the lesion. Examination of internal organs demonstrated lung cancer in February, 1986. A combination of chemotherapy and radiation exerted a complete remission. In December, 1987, X-ray examination of upper gastro-intestinal tract revealed multiple early gastric cancer (IIa+IIc, IIa, IIc, IIc). The patient underwent surgery.
Case 2. A 79-year old man visited in September, 1987 with pigmented macules on the waist, abdomen and left axilla, sized 59×75mm, 20×18mm and 21×31mm respectively. Bowen's disease was histolocally diagnosed for the waist lesion and basal cell carcinoma were diagnosed for the others. Examination of internal organs revealed multiple early gastric cancer (I+IIa, IIc+IIa) in October, 1987. One month after the gastrectomy, the skin lesions were removed in December, 1987.
Case 3. A 65-year old man visited in October, 1990 with a 10×15mm sized ulcer on the left index. The lesion was histologically diagnosed as Bowen's disease. The lesion was totally removed. Examination of internal organs showed an early gastric cancer (IIc) in January, 1991. So that gastrectomy was curried out.
Case 4. A 73-year old man visited in January, 1991 with a 30×34mm sized pigmented macule on the left arm. The lesion was histologically diagnosed as Bowen's disease and totally removed. Examination of internal organs disclosed an early gastric cancer (IIa) in January, 1991. The patient refused our proposal of surgical operation.
From January, 1985 to December, 1992, 43 patients with Bowen's disease visited our hospital. Sixteen patients of them were examined for the malignancy of internal organs. Eight patients (50%) of them were associated with malignant tumor, including 6 patients (37.5%) with internal malignancy. This study includes 3 patient who would have been killed by the tumor, if the internal examination were not suggested by their Bowen's disease. This result suggest the importance of internal examination in the patients with Bowen's disease.

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A case of apocrine adenocarcinoma is reported. The patient was an 82-year-old Japanese man who complained of a nontender mass in his right axillary cavity. On examination, multiple asymptomatic subcutaneous nodules were also found bilaterally in the axillae.
On the basis of histological and immunohistochemical examination, the unilateral axillary tumor was diagnosed as an apocrine adenocarcinoma, and the bilateral multiple subcutaneous nodules were identified as apocrine adenomas.
This rare case demonstrates the possibility of apocrine adenocarcinoma arising from benign apocrine tumors.

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A case of sebaceous carcinoma was reported. The patient was a 59-year-old man who had a reddish nodule on his left hypochondriac region. Histopathologically, the tumor was non-capsulated but relatively circumscribed reaching the subcutaneous tissue. It consisted of variably sized lobules of undifferentiated cells and sebaceous cells with abundant foamy vacuolated cytoplasm. This is the first case which has occurred on the chest or abdomen in Japan.

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Aesthetic units and subunits of the face have been previously described. The upper lip has been divided by some commisures and dimples as a philtrum or nasolabial folds in topography. Burget reported the topographic subunits of the upper lip; lateral and medial unit, and the excellent refinement replacing Abbe flap belong lateral subunit. These principles are also extremely beneficial to get natural contour and symmetry in the upper lip. There is no question that replacing as a subunit brings superior result than as a patch. However sometimes the defect is too small to replace whole subunit. In such cases, we have applied miniunit principles that was instituted as individual wrinkles, commisures, highlight and shadow to get natural contour. We call such lines that make miniunit “potential wrinkle line”. As a result, we have achieved reasonable symmetry, good contour and no conspicuous facial scarring in every patient whose defect was small in upper lip. We have presented herein its description and evaluation of the advantages of subunit and miniunit principle with 2 typical cases.

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Spitz nevus is a rare form of benign melanocytic nevus, which is sometimes confused with malignant melanoma by the presence of bizarre nevus cells. We experienced such a difficult case.
Our patient was a 15-year-old young man who suffered from a nodule on the left ankle joint. The greyish brown nodule was 8mm in diameter and grew rapidly during the past one year. Histopathologically, it showed features of a dermal nevus. The nevus cells were composed mainly of epithelioid cells. The cytoplasm was large and pleomorphic. The nucleus was atypical and occasionally showed multiplicity. In spite of the pleomorphism and loss of maturation, we diagnosed the tumor as a Spitz nevus because of the relative uniformity of tumor cell size, the sparcity of mitotic feature, the sparcity of melanin, the sharp lateral margins, and the symmetry of the architecture. In order to confirm the diagnosis, immunohistochemical studies were performed with anti-PCNA antibody and anti-P53 antibody. The result supported our estimation that the case was not malignant melanoma.

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Urinary excretion level of 5-S-cysteinyldopa (5-S-CD) has been used as a biochemical marker of efficacy of therapy in malignant melanoma.
We reported a case of 53 year-old female with multiple metastatic melanoma treated with interferon-β-DAV combination therapy. Before treatment, urinary excretion level of 5-S-CD was 1093.2μg/day and its level decreased after a each single course of the treatment and increased thereafter.
The level decreased gradually over the course of the treatment and further decreased to the minimum level, 77.5μg/day after the surgical resection of the tumors.
Our case supported the usefulness of urinary excretion level of 5-S-CD as a marker for monitorring the disease activity of malignant melanoma.

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A 72-year-old male with metastatic melanoma was administered intravenously with Cisplatin (CDDP, 60mg/m²), Dacarbazine (DTIC, 400mg/m²) and Vindesine (VDS, 2mg/ m²) every 4 weeks for threetreatments.
Responses to treatment were histopathologically assessed in excised spesimens of the skin. Tumor nests, which decreased in size after the second cycle of the chemotherapy, apppeared divided int several parts and surrounded with collagenfibers.Some tumor cells showedballooning, pyknosis and eosinophilic degeneration. These changes are tumor cells necrosis presumably induced by the chemotherapy.
The computed tomography demonstrated the pleural mass decreased in size after the third treatment.
These findings show that CDDP, DTIC and VDS therapy is effective for metastatic melanoma.

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During the last two decades, the recommended margin for primary cutaneous melanoma has consistently become more narrow. In the past, a 5cm margin in all directions from the tumor was recommended, but in practice, narrower or conservative excision was selected when the lesion located in cosmetically sensitive or in functionally critical area. Our clinical experience has shown that local recurrence is an infrequent problem, and conservative operation contributed the QOL of patient. Recently, prospective, multi-institutional, randomaized trials (Veronesi, et al. and Balch, ) were conducted to clarify controversies concerning surgical margins. These results showed that <1mm, 1cm and, 1-4mm, 2cm margin could be safely available. Collected clinical data would suggest that exceeding 3cm dose not improve either local control or ultimate patient survival, and that the histpathologic features of the primary lesion, for the most cases, dictate patient disease free interval. After this time, arbitrarily wide excision should be avoided to preserve the QOL of melanoma patient.

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We report a case of angiosarcoma of the left lower extremity arising from lymphedema of the left foot.
A 42-year old Japanese woman visited our clinic for the evaluation of a toroser lesion on the dorsal of her foot and restiform subcutaneous nodules on her lower leg. Intralesional injection and intravenous drip of recombinant interleukin 2 (rIL-2) were partically effective.

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A 68-year-old woman developed a scalp nodule measuring 7×5× 2cm in the cranial vault. The nodule, having been present for 3 years since she had got a bruise on the head, had increased gradually in size for the past 3 months. On physical examination, a pea-sized subcutaneous nodule was found in the left temple. Biopsy specimen of the scalp nodule showed malignancy. Both nodules were resected operatively and were examined histologically. Light microscopic examination of the scalp nodule demon-strated the proliferation of atypical polygonal and spindle shaped cells in the dermis and subcutis. The temple nodule showed metastasis in the lymph node with prolifera-tion of atypical cells corresponding to those in the scalp nodule. Hematoxylin-eosin and Fontana-Masson stains revealed no melanin pigment in the tumor cells. By immunohistochemistry, the tumor cells were positive for NSE and HMB-45, but were negative for S-100, keratin, EMA, CEA, Factor VIII and UEA-1. Electron microscopic examination revealed oval granules similar to stage II or III melanosomes in the cytoplasm of a tumor cell. This tumor possibly represents an amelanotic melanoma of the scalp soft tissue accompanied by a lymph node metastasis, although no definite diagnosis can be made. The reasons against the diagnosis of melanoma were as follows: (1) Tumor cells were negative for S-100 protein. (2) There was no irregular junctional activity. (3) Only a small number of melanosomes could be detected in the tumor cells.

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A 72-year-old male fisherman who referred to our department in October 1993, because of a two years history of erosion on the right Achilles' tendon and a fifty year history of porokeratosis over his entire body. The patient underwent total gastrectomy and splenectomy for gastric cancer at the age of 52, and also had high anterior resection of rectal cancer at the age of 55. A biopsy sample taken from the erosion on the right Achilles' tendon showed squamous cell carcinoma, and a sample taken from the erythematous skin on the right forearm showed soler keratosis. The patient arearted by surgical excision in November 1993 and has been free of disease up to the time of writing, April of 1995, a period of about sixteen momth.

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We present two cases of metastatic skin carcinomas, both resulting from mammary carcinomas. Tumor cells in the dermis had not contained mucin, whereas mucin had depositted in the stroma around the tumor nests. In case 1, tumor cells including mucin in the cytoplasms had sporadically indurated into the epidermis. These results consisted with those previously reported on extramammary Paget's disease. It is suggested that proliferation and differentiation of tumor cells in the epidermis is inhibitted. The lesions in the metastasis in the scalp showed mucin deposition around the degenerated hair follicle. Mucin is known to cause a degeneration of the external root sheath cells, as seen in alopecia mucinosa. The findings of previous reports and of our study suggest that mucin derived from mammary carcinoma may be the cause of hair loss in alopecia neoplastica.

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We reported a case of squamous cell carcinoma (SCC) arising in a burn scar on the scalp. The patient, a 45-year old man, had sustained a burn injury two years old. He noticed a tumor on the burn scar one year ago. The tumor had increased in size and reached to 10cm. This lesion widely excised with margin of 2cm and the skin defect was cover with a free radial forearm flap measuring 13×20cm.
The postoperative course was unevenful and there has been no sign of recurrence for about a year.

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The frontonasal flap procedure is a useful method for the repair of relatively larg defects of the central part of nose. Not only the central defect but also the alar defect could be reconstructed by our modified frontonasal or extended frontonasal flap which is composed of the frontonasal flap and the continuous nasolabial flap. The modified frontonasal flap covers alar defects with the nasal tip skin, while the extended frontonasal flap covers large alar defects with both the nasal tip and the opposite alar skin. The donor ala is reconstructed by the continuous nasolabial flap. Four patients underwentthe modified frontonasal flap repair and in two patients the defect was covered by the extended frontonasal flap. All of them were more than 70-years-old. Half of the patients were operated under regional anaesthesia. In all cases, cosmetic results were excellent. One patient complained of nasal obstruction during the first four weeks after operation.

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The questionaire about truth telling to skin cancer patients and informed consentwas underwent at the 8th annual meeting of the Japanese society for skin cancer, 1992. Ninety physicians replied the questionaire. Main results; only 17% (15/90) of subjectshad a policy of informing the correct diagnosis to the patients, while 93% (85/90) of subjects have informed the diagnosis to the family of the patients. 76% (68/90) agreedthe necessity of informed consent and truth telling theoretically but 49% (44/90) feltthe difficulty to do it practically. 29% (26/90) of the subjects approved the promotinof informed consent to the skin cancer patients, while 63% (57/90) took a prudentattitude to this problem. There were a variety of opinions concerned with informedconsent and additional problems. We may need a further discussion about theseproblems.

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The case was a 38 year-old male who had a subcutaneous nodule on his left axillarregion. There was no malignant sign with computed tomography, Ga scintigraphy, and endoscopy. Histopathologically, the tumor consisted of atypical tumor cellsthroughout the dermis and subcutaneous fat and partially showed tubular pattern. Inimmunohistochemical study, tumor cells showed EMA (+), cytokeratin10 (+), cytokeratin19 (+), WGA (+), RCA-1 (+), ConA (+), S-100 (-), α₁-antitrypsin (-), α₁-antichymotrypsin (-), lysozome (-), desmin (-), LCA (-), and PSA (-) . Furthermore, tumor cells revealed high PCNA labeling index and a remarkable increase of FINORs not only in number but also in volume which were compatible with malignant tumor. On ultrastructual examination, there were desmosome like structure and tubular likestructure with microvilli between tumor cells. From these results, we diagnosed this case as primary malignant tumor with sweat gland differentiation.

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A 86-year-old Japanese man had a Merkelcell carcinoma on his left instep. The lesion was a nodule, 28×25×10mm in size, surrounded by a reddish plaque measuring 52×35mm. Histologicalexamination of the nodule revealed proliteration of small basophilic neoplastic cells in the dermis.
The cells were immunohistochemically positive for NSE and electoron microscopic study detected dense core granules in their cytoplasm.
The epidermis of the plaque lesion histologically showed features of Bowenoid changes. In addition, eccrine fibroadenomatous changes of the epidermis were found in the epidermis neighboring the nodular lesion. Association of Merkel cell carcinoma and Bowen's disease has been well documented in the literature. However, the present case was unique because three components of Merkel cell carcinoma, Bowen's disease and eccrine fibroadenomatous lesion coexisted within a single lesion.

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A dome-shaped tumor on the face of an 89-year-old woman revealed findings identical to Merkel cell carcinoma by both histopathology and immunohistochemistry. A cervical lymph node biopsy showed metastasis of the tumor cells. Perilesional injections of interferon (IFN)-β were tried to damage the original tumor and also the metastatic tumor cells of the regional lymph nodes. The tumor completely regressed after 21 times daily injections of IFN-β. In the excised materials no tumor cells were observed histologically. No recurrence and metastasis were found within 8 months until the death by heart failure. Perilesional injections of IFN-β may be a treatment of choice for Merkel cell carcinoma.

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A 65-year-old man visited the dermatology with complaint of a cutaneous nodule on his right chest for more than 20 years. Physical examination showed a 26×24mm sized, dome-shaped, firm, somewhat yellowish cutaneous nodule with fine telan-giectasia. Microscopically, irregularly shaped tumor nests were present from just beneath of the epidermis to the deep cutis. Palisading arrangement was not seen on the periphery of each lobules. The anaplasia of each cell was prominent and large round cells with foamy cytoplasm were intermingled with the tumor cell nests. The cytoplasm of the foamy cells was positive for Sudan III stain.

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A 80-year-old woman with basosquamous cell carcinoma is reported. The lesion began as a black flat nodule on the left side of the arm near the elbow 10 years ago. The lesion gradually enlarged to the size of 26×20mm, forming like a rosary at first examination. Histopathological findings showed that the tumor was composed of three different figures; Firstly, the solid BCE-like lesion that the tumor was consisted of basaloid cells with uniform oval basophilic nuclei and relatively little cytoplasm. The peripheral cell layer showed a palisade arrangement. Secondary, the intermedi-ate type lesion that the tumor showed the rough retiform construction, which was made up mainly of basaloid cells and showed transition to squamoid cells. Thirdly, SCC-like lesion that was composed of squamoid cells with relatively large nuclei and abundant cytoplasm. Many whorls of keratinocytes like squamous eddies were seen in this lesion. Immunohistochemically, the cells of intermediate type lesion and SCC-like lesion were positive for MA903, a monoclonal antibodyagainst cytokeratin. In contrast, MA904 showed a positive staining in the cells of individual cell keratiniza-tion and focal areas like squamous eddies. Cell proliferating activities using cytofluor-ometry. Argyrophilic Nucleolar Organizer Regions (AgNORs) and immunostaining using MIB-1 were also examined. Each three different lesions showed cytofluor-ometric histograms exhed diploid pattern (normal nuclear DNA content), high positive rates of AgNORs and %MIB-1.

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Serum 5-S-cysteinyldopa (5-S-CD) was evaluated as a biochemical marker of malignant melanoma. Serum samples were collected at 66 institutions throughout Japan from melanoma patients receiving a combination therapy of IFN-β and chemotherapy using DAV. This report summarizes a two-year follow-up of the ongoing project. Serum 5-S-CD values prior to treatment increased progressively with the increase of stage; stage III patients (n=40) showed a significantly higher 5-S-CD level of 7.4 nmol/l vs. 4.3 nmol/l of the control (n=33). Cumulated survival rate of patients who had exceeded the normal range of 10 nmol/l prior to treatment was 70.7% (9/12), which was significantly lower than that of 89.4% (86/92) observed for patients with normal values. Serum 5-S-CD values in stage III patients with lymph node metastases were increased significantly from 4.8 nmol/l to 8.5 nmol/l after the pre-operative combination therapy. Serum 5-S-CD values were elevated to the abnormal level significantly earlier than the clinical detection of distant metastases in 4 patients who progressed to stage IV and died of the disease. Serum 5-S-CD value thus appears to reflect well the progression of melanoma and the efficacy of the IFN-β-DAV therapy, and the prognosis.

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A case of multiple malignant trichilemmoma on the left forehead and the right chest in a 74-year-old man is reported. The lesion on the right chest was the annular tumor measuring 40×35mm in size with a granular surface. Histopathological examination revealed that no cancer cells were found in the atrophic epidermis on the central area of the annular tumor and that several lymphocytes surrounded and attached to cancer cells on the inner boundary of the annular tumor. Pigmentary incontinence and many mononuclear cell infiltrates were observed in the upper dermis of the central area. A recent review of 73 cases of malignant trichilemmoma reported in Japanese literatures revealed that the lesion in multiple forms was presented in four cases (5.5%) and the annular lesion was presented in only one case (1.4%) in which cancer cells existed in the central area.

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We reported a case of multiple Bowen's disease with adenocarcinoma and squamous cell carcinoma of the lung. He had three brownish erythematous plaques on his left lower leg, left dorsum of the foot and left forearm. The histopathological examination of the lesions showed typical Bowen's disease. He was treated by surgical excision.
It is not solved whether Bowen's disease is a skin marker for internal malignancy, however, we think patients of multiple Bowen's disease are preferably examined their internal malignancy.

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MY-1 is a new biological response modifier, which consists of heat-denatured nucleic acids, extracted and purified from Mycobacterium bovis BCG. A multi-center clinical phase II study of this drug was performed at 10 institutes on patients with Adult T-cell leukemia (ATL) . All the patients were anti-HTLV-I antibody positive and had the cutaneous type ATL. The drug was administered by a subcutaneous injection with a daily dose of 15 or 30mg. Efficacy was evaluated by using the criteria of the Japanese Society for Skin Cancer.
Of a total of 24 eligible cases, complete response (CR) was observed in 5 and partial response (PR) in 7. Then, overall response rate was 50% (12/24) .
Adverse reactions, such as fever, leucopenia, and hepatic disorder were rarely observed. In cases where they were observed, none were serious and all were reversible.
In conclusion, MY-1 was considered to be a useful drug in the treatment of cutaneous type ATL.

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The effect of OCT-43 on mycosis fungoides was immunohistochemically evaluated using skin obtained from 13 patients, 5 responders and 8 non-responders, bybiopsies performed before and after treatment with OCT-43. Pretreatment examination of the skin showed no significant differences in infiltrating cells between the 5 responders

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