A 65-year-old Japanese man presented with an asymptomatic tumor in his left cheek, apart from the parotid area. The tumor had slowly increased in size over fifteen years. In physical examination, a firm, 2 cm sized in diameter, subcutaneous nodule was observed. Dark red erythema without erosion was seen on the overlying skin (Fig. 1) . Regional lymph nodes and superficial lymph nodes on the body were not palpable. CT and ultrasonography of the face and neck revealed that the tumor was so clearly separated from the surrounding tissues not to suggest any invasion to muscles and bone and that there was no clear lymph node swelling in the face and neck. Further examinations including gastrointestinal fiberscopy, CT, and garium scintigraphy ruled out a metastatic tumor.
Wide local excision was performed 5 cm apart from the tumor margin and on the periosteum of the zygoma and the fascias of the masseter and expression muscles. Because the zygomatic and buccal branches of the facial nerve were invaded, they were also excised with enough free margin. Pathological examination could not completely deny any residual tumor on the bottom of the excised specimen. Accordingly 2 weeks later, additional excision was done more 5 cm apart from the previous margin and involving the periosteum of the zygoma and a portion of the masseter and expression muscles and the raw surface was covered by split thickness skin (Fig. 2) . Pathological examination demonstrated no residual tumors.
Histologically, tumor cells were arranged in a cribriform pattern from the upper dermis to subcutaneous fatty tissue (Fig. 3) . Some of the tumor cells were found continuous to the hair follicles and sebaceous glands (Fig. 4) . Perinural extension was noted (Fig. 5) .
Immunohistochemically, keratin and epithelial membrane antibody were immunoreactive with the tumor cells, whereas S-100 protein, vimentin, and carcino-embryonic antigen were not.
On electron microscopy, the tumor cells were arranged in a luminal structure. Most of them, however, were pseudolumina containing fine stellate granules, basal lamina, and collagen fibers (Fig. 6) although some were true lumina with numerous microvilli and junctional complexes nearby where the tumor cells were connected to the hair follicles and subcutaneous glands (Fig. 7), which suggests that the tumor originates from a sweat gland. On the above-mentioned, the tumor was diagnosed as a primary cutaneous adenoid cystic carcinoma.
After 14-month-follow, the tissue defect of the cheek was reconstructed by the transfer as a free flap of the secondary vascularized musculocutaneous flap composed of the anterior seratus muscle, of which the volume is almost equal to that of the excised muscles of the cheek, and the anterior chest skin, of which the color and texture are matched to that of the cheek skin (Fig. 8) . The use of expander promoted the secondary formation of vascular network between the anterior seratus muscle and the anterior chest skin and made the primary closure of the flap donor without free skin graft possible.
No recurrence or metastasis of the tumor has been observed in the course of 27 months' follow and the patient is very satisfied with the restored cheek.

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We reported a case of trichilemmal carcinoma (TLC) on the left cheek in a 79-year-old man. He developed a submandibular lymph node metastasis after the operation of the primary lesion. The simple excision of that lymph node was followed by Linac irradiation on both sides of his neck. One year and two months after the operation, he had no recurrence and no metastasis. Keratin NCL-5D3 was positive in TLC cells, although another follicular tumors also showed positive staining. Squamous cell carcinoma was negative for NCL-5D3. We think that this antibody may be useful for the diagnosis of some types of follicular tumors.

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A case of eccrine porocarcinoma is reported. An 89-year-old woman had a pigmented tumor with ulceration and crust on her left medial crural region, which had enlarged up to 2cm in diameter during two years. Histologically, the tumor composed of two types of atypical cells, one with dark nucleus and the other with clear nucleus, which showed tubular structure in part. Cytoplasm of the tumor cells contained PAS-positive and diastase-sensitive granules. These findings were compatible with eccrine porocarcinoma.
Taking into account the patient's age, we chose combination therapy of radiation with hyperthermia. She received a cource of 10MeV electoron irradiation in a total dose of 60 Gy. Hyperthermia was given one time a week for 5 weeks. After the end of the treatment, the tumor disappeared clinically and the biopsy specimen showed inflammatory cell infiltrate taking place of tumor cells. It is supposed that this combination therapy is beneficial for carcinoma of eccrine glands as well as other skin tumors.

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A patient, 71-year-old male, with extramammary Paget's disease showing erythematous and depigment lesions was discussed. The lesions were bilaterally extending from the scrotum to the perianal region. Histology revealed Paget's cells invated to the rectal mucosa. The patient was also noted to have a sigmoidcarcinoma. Hence, we have done rectsigmoidectomy and widly local excision due to the sigmoidcarcinoma. A year after the treatment, he has not any evidence of recurrence.

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We present a case of a 47-years-old woman who first noticed a miliary-sized skin tumor on the right buttock about 3 years ago. Two years ago the size increased gradually and it became tender. The patient was admitted to our hospital because a biopsy suggested a basal cell epithelioma (BCE) . At the first visit in our clinic a pale red-violet protruding tumor of 23×20mm size, which showed partial ulceration on its surface, was observed on the right buttock 2 cm from the anus. Under palpitation a slight movability of the 35×47mm subcutaneous mass was observed but on the anal mucous membrane there were no abnormalities. Preoperative CT scanning and sonography showed an extensively spreading tumor that invaded also the subcutaneous fatty tissue, but there were no signs of an infiltration into the sphincter ani. Histological examination after total resection revealed that basal cell-like tumor nests were partially attached to the epidermis an proliferating into the subcutaneous fatty tissue. In this tumor aspect of a solid type as well as aspect of adenoid and keratotic types of BCE were observed. There was no staining of the tumor cells with PAS, Alcian-blue, CEA and S-100 protein. Moreover, there were no significant findings in enzyme histochemical analyses. We reported this BCE case revealed specific clinical feature which developed comparatively rare on the buttock referring some references.

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Two patients with subungal malignant melanoma on the right thumb were treated by amptation of the thumb and successfully reconstructed by pollicization using the index finger.
Fourtyone year-old woman with stage II (pT_3aN₁M₀) melanoma (case 1) and 78-year-old woman with stage III (pT_3aN₁M₀) melanoma (case 2) were presented.
Amptation of the thumb, pollicization, and axillar lymphadenectomy were perfoumed.
No recurrence or metastasis has been found at two years (case 1) and three years (case 2) after operation. And followed-up evaluations of function and appearance of the thumb are quite good.
We think that pollicization benefits patients of thumb melanoma.

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We presented 14 cases who had skin metastases by internal malignancies between these 11 years. Among the 14 patients, 8 were males and 6 were females. Mean age at their first visit was 62.5 years old. Lung was the most frequentt primary tumor of skin metastases. Clinically, nodules were most frequent and histologically, adenoid type were the comonnest.
The mean prognosis was 4 months except for 4 live cases.

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A 76-year-old woman visited our department for the granulomatous tumor on her nose on October 6, 1992. She noticed a papule on her nose 5 months ago and it had gradually grown. A 16×12×3mm sized, oval shaped, ulcerated, pale pink colored, granuromatous tumor with slight bleeding was seen on her first visit. Spindle cell squamous cell carcinoma was diagnosed histologically for the tumor. The tumor was composed of mainly spindle-shaped cells with large, atypical, round nuclei and tumor cells arranged like a stream. Immunohistological staining of the tumor showed anti-keratin antibody positive, anti-melanoma antibody and vimentin both negative. The tumor cells was S-100 negative, however, plenty of S-100 positive dendric-shaped cells infiltrated among the tumor cells.

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In our clinic, we encountered 4 patients (3 men and one woman, 42-76 years old) with malignant melanoma during an 18-year period from 1975 to 1992. Acral lentiginous melanoma was observed in 3 patients, and nodular melanoma in one. Wide surgical excision was done in all cases, and right inguinal lymphadenectomy was added in one patient (case 1, pT₄N₁M₀. Stage III) . One patient (case 1) died 3 years and 2 months after the first visit due to metastasis to the lung. Another patient (case 2, pT_3aN₀M₀. Stage II) died 5 years and 1 month after surgery due to pneumonia without metastasis or recurrence. One patient (case 3, PT_3aN₀M₀. Stage II) is still alive without metastasis or recurrence 1 year and 10 months after surgery. In the remaining patient (case 4, pT_3aN₀M₀. Stage II), left axillar metastasis was found 8 months after surgery, despite DAV and IFN-& combination therapy. Although chemotherapy was not done in cases 1, 2 and 3, IFN-& therapy was added in case 3.

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Clinical and statistical study of 20 patients with malignant melanoma (MM) of the heel, seen at Department of Dermatology, Yokohama City University School of Medecine during 23 years from 1970 to 1992 was reported. The frequency of the patients with MM of the heel was 14.8% of patients with of the skin. The sex ratio of the patients was male 9: femal 11. The ages of the patients at the time of the first medical examination ranged fro 39 to 88 years (mean. 62.8 years) . A granulomatus lesion was observed in 9 patients with MM of the heel. The patients of stage III. was predominate. 11 out of eighteen (55%) and the patients with level V lesion was also predominate 11 out of eighteen with MM of the heel. The prognosis of the patients was relatively better than that of patients with MM of the skin.

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Fourty seven patients with malignant melanoma (MM) at Tsukuba University for the past 15 years (1978-1992) was statistically analyzed. The frequency of the patients with MM in all newly visiting outpatients had increased since 1978. The sex ratio was 25/22 (male/female) . The age peak of the patients was in the 6th decade. The most frequent type was acral lentiginous melanoma, which arose on the feet, fingers and toes. The following was influenced the survival rate and had prognostic value: sex, type, stage, level, whether biopsied or not before the surgery, period between biopsy and surgery, lymph node dissection in pT3, 4N0, chemotherapies in pT3, 4N0. In our study, tumor thickness did not influence the prognosis between 1.5mm and 7mm.

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Four of the 24 patients with malignant skin tumors treated by proton beams developed ulcer in the radiation field 6 months to 2 years after the irradiation. To determine adequate fractionation regimen, we plott on logT-logD and logN-logD planes the total dose (D), the overall treatment time (T), and the number of fractions (N) of 16 patients, whose radiation field could be observed for longer than 6 months. The regression curves of the 4 patients who developed ulcer were regarded isoeffective as to radiation-related skin damage in late phase. The fractionation schedules should be chosen in the area under the isoeffect curves, especially when skin tumors are treated by proton beams alone. And, this is an important point to be considered, when we seek the appropriate dose-fractionation of proton irradiation to improve local control rate of malignant melanoma.

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A case of genital Paget's disease in a 79-year-old female treated with intralesional recombinant interferon-α-2a (rIFN-α-2a) is reported. The tumor cells disappeared histopathologically after injection of 132, 000, 000 IU of rlFN-α-2a. Leukopenia was noted with 5 times/week administration, while not noted with 3 times/week administrations. No other side effect was noted. At 9 months after the end of rIFN-α-2a administration, local recurrence was seen. Deeper cut of the specimen obtained at the end of rIFN-α-2a injection revealed rests of Paget's cells.

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It has become clear that mutation and subsequent accumulation of nuclear p53 protein is an almost universal step in the development of human cancers. We have immunohistochemically studied p53 expression in 112 benign and malignant epidermal neoplasms using monoclonal anti-p53 protein antibody DO7. p53 immunoreactivity was not detected in any benign epidermal tumors including verrucae vulgaris, seborrheic keratoses, and keratoacanthomas. In contrast, positive staining was observed in 5/13 (38%) of squamous cell carcinomas, 2/10 (20%) of basal cell carcinomas, 14/32 (44%) of Bowen's disease, as well as 8/13 (62%) of solar keratoses. p53 expression was absent in all 10 cases of extramammary Paget's disease thus far examined. The results suggest that the mutation of p53 gene and an abnormal expression of nuclear p53 protein may be a common event in malignant and premalignant epidermal neoplasms.

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146 patients with chronic arsenical poisoning at Toroku, Miyazaki were studied, especially the causes of death among them. At present, 40 male (mean age 75.2 years) and 30 females (mean age 74 years) have died. The top killer disease of male patients was malignant neoplasm, especially lung cancer and it was heart diseases in females. As malignant tumors, Bowen's disease was present in 16 patients (11%) and lung cancer in 15 patients (10%) and tumors in the urinary system in 2 patients among 146 patients. Concerning the relationship between lung cancer and smoking, 6 (28.6%) patients developed lung cancer among 21 smoker patients, while 4 (4.5%) patients developed lung cancer among 88 non-smoker patients. The mean age of death among female patients with chronic arsenical poisoning was significantly shorter than that of the mean age of death in Miyazaki female inhabitants, and it is assumed that this was due to the heart diseases of the female patients.

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A 12-year-old boy presented a slowly growing 3×2.5mm black, flat lesion on the right sole of 8 months' duration. There were junctional nevus cell nests and transepidermal elimination of melanin and dopa-and HMB-45-positive single melanocytes.
Differential diagnosis from acral lentiginous melanoma in situ was discussed.

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Two cases of basal cell carcinoma of the nose were reported.
Case 1: A 82-year-old woman presented defect of the nose with a basal cell carcinoma. Following excision of the tumor, nasal reconstruction was performed with bilateral naso-labial flaps, a median forehead flap and a scalping forehead flap.
Case 2: A 83-year-old man presented with a recurrent basal cell carcinoma of the It. nasal ala. Following excision of the tumor, a naso-labial flap and a median forehead flap were used for reconstruction of alar defects.
It is useful to combine pedicle flaps for reconstruction of full-thickness nasal defects.

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A 81-year-old man noticed red papules and subcutaneous tumors on his face and trunk about 2 months ago. He had biliary system cancer about 1 year ago and received conservative therapy. The tumors were well-demarcated, 7 to 15mm in diameter with crust on its surface. The specimen had been obtained from the right postauricular subcutaneous tumor.
On light microscopic findings, tumorr cells were observed in the dermis and subcutaneous tissue. There were variously sized glands lined by columnar cells. The lumina contained a various amounts of mucinous material. Various atypical tumor cells were also seen.
On electron microscopic findings, in tumorr cells, small intracytoplasmic lumina lined by microvilli were observed. Cell organelles such as mitochondria and rough endoplasmic reticula had relatively increased in number.
Immunohistochemical examination showed that tumor cells were positive for keratin, EMA, CEA and CA19-9.
From these findings, the characteristics of tumor cells resembled that of the epithelium of biliary system. It was difficult to determine whether the tumor arose from the bile duct or from the gallbladder.

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We investigated the expression of proliferating cell nuclear antigen (PCNA/cyclin) in human melanocytic tumors, using the anti-PCNA monoclonal antibody (clone PC10) and compared the results with previous findings with clone 19A2, another monoclonal antibody. The expression of PCNA in formalin-fixed and paraffin-embed-ded pathological tissues increased in accordance with the progression of tumor. In normal tissues, PCNA-positive cells were mainly in basal and suprabasal layer by PC10, whereas nuclear labeling of 19A2 was found in suprabasal layer of epidermis. The population of PCNA-positive cells in common melanocytic nevi were significantly higher than 19A2-positive cells. There were, however, no significant differences between PC10 and 19A2 in the number of cells they recognized in malignant melanomas. The antigen recognized by clone PC10 appears to be a more common epitope in PCNA/cyclin than that of 19A2. Therefore, application of other markers for cell proliferation and a careful interpretation of the results are necessary to evaluate the correlation between immunoreactivity of clone PC10 and to establish the degree of malignancy in the diagnosis of tumors of melanocytic origin.

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Malignant fibroush istiocytoma usually involves the soft tissue of the trunk or extremities, and epidural metastasis of this tumor is unusual, but the following report describes such a case.

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A late phase II study of OH-6000 consisting of two phases, one to find the optimal dosage and regimen and the other to evaluate the clinical efficacy at the optimal dosage and regimen, was performed in patients with mycosis fungoides. This study was a multicenter study including 42 medical institutions nationwide. The drug was administered by the intramuscular route at a daily dose of 1×10⁶ or 2×10⁶ IU, 3 times a week on alternating days or 5 consecutive days a week.
The optimal dosage and regimen was determined to be 1×10⁶ or 2×10⁶ IU, adjusted for adverse reactions and severity of symptoms, administered at least 5 consecutive days a week, for 8 or more successive weeks. Therefore, the latter phase of the study was performed with this dosage and regimen.
Of a combined total of 38 completed cases in both study phases, complete response (CR) was observed in 3 and partial response (PR) in 19, for an overall response rate of 57.9%. The response rates in the individual study phases were 41.2% (7/17) in the dosage and regimen-finding phase and 71.4% (15/21) in the efficacy-evaluation phase.
Adverse reactions were those commonly observed with other IFN-γ; none were serious and all were reversible.
In conclusion, OH-6000 was considered to be a highly useful drug in the treatment of mycosis fungoides.

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