The authors report a case of malignant rhabdoid tumor arising from soft parts in the lower abdominal wall in a 53-year-old man. The tumor metastasized to lung and was increased in size very progressively. An extrarenal malignant rhabdoid tumor is very rare, and in addition this case is also unusual with regard to the age of onset.

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Squamous cell carcinoma (SCC) of the lip has its characteristics on the points of its preceeding diseases, therapies and prognosis.
Especially, its way of operation may include the cosmetic and functional problems of the lip. At present, the Abbe's flap method should be one of the best to disolve the problems.
We report 6 cases of lip SCC that were experienced in our Department of Dermatology for the past 2 years, mainly about their clinical pictures, histopathology, methods of operation and prognosis.
The ratio of male v.s. female was 5: 1. All occured on the lower lip.
Five were clasified as papillomatous carcinoma. All belonged to stage I or II. Three cases belonged to grade 2. All 5 cases that underwent the Abbe's flap method are still alive at present. The case of grade 3 that could not undergo any operation because of a serious lung disease, and died of tumor after all, had the history of the longest course as long as 7 yeras untill the first visit.

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Sixty-six year old house wife developped a large ulcerative mass on her left tigh and left groin. Histopathologically differentiated squamous cells with atypical nuclei proliferated and invaded into surrounding muscles.
Immunohistochemically, tumor cells were CAM5.2, MA903 and thrombomodulin positive, but HMB45 and vimentin negative.
Considering with no indication for curative surgical treatment and poor general condition, we choosed the continuous intra-arterial 5FU infusion with irradiation. She complaind no symtom by side effect of chemotherapy. Biopsy of tumor lesion after treatment could not detect any alive tumor cells. Eight month following up showed no organ metastasis and lesional recurrence.

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A 74-year old man developed 2 squamous cell carcinomas, 2 Bowen carcinomas, 4 Bowen's disease and multiple senile keratoses on his lower legs and genitalia. Immunohistochemistry for p53 protein revealed that 20 out of 30 (67%) excised lesions expressed mutant p53 protein. Although the patient had no history of arsenic ingestions, tar was suspected as a carcinogenic agent.

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One hundred forty malignant melanomas of the skin excluded LMM were treated at the Department of Dermatology, Chiba University, between January 1967 and December 1992. Fifty of these tumors were located on the sole of foot (ALM), 16 ungual area (ALM), 43 extremity (NM and SSM) and 21 trunk (NM and SSM) . Forty-seven patients died of metastatic disease until August 1993. Of 140 patients, 78 were stage III, 3 were stage IV, and stage III not decrease even in recent years. Patients with advenced stage tumor were done frequently previous inadequate treatment. Most frequent previous treatment is small excision of NM or SSM, and incision or small excision of ALM on the sole of the foot or ungual area under the clinical diagnosis of clavus or whitlow. It is important to recognize clinical course of malignant melanoma for treat adequatly on the first chance and improve the prognosis of this disease.

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A statistical study of 43 patients with malignant melanoma treated at Department of Dermatology, Tokyo Medical and Dental University during 1959 to 1991 was reported. We have confirmed TNM classificaton, Clark's level, tumor thickness and prophylactic lymph node dissection as siginificant factors to decide prognosis of malignant melanma.
1) Our cases consisted of 49% of acral lentiginous melanoma, 14% of superficial spreading melanoma, 14% of nodular melanoma, 2% of lentigo maligna melanoma, 5% of unknown cases. Our cases consisted of 16% of Stage I cases, 30% of stage III cases, 19% of stage IV cases, 5% of unknown cases.
2) The five years survival rates of each stage were as follows: stage I 100%, stage II 92%, tage III 53%, stage IV 0%. Prophylactic lymph node dessection of cases of stage III showed improvement of prognosis.
3) Analysis of 12 patients who had prophylactic lymph node dissection showed that three patients had histological regional metastasis whose thickness was over 1.5mm and levels was IV or V of the primary lesion. Prophylatic lymph node dessection appeared to necessary and useful in the patients with primary lesion having over 1.5mm thickness and IV or V level.

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We reported a case of a 13-year-old girl with malignant melanomo and her elder brother had dysplastic nevus. A small papule on the right dorsal hand had been appeared since a few years ago and growed rapidly up to tip of little finger size. Excisional biopsy was done and histological examiation revealed nodular melanoma. The lesion was widely excised and reconstructed with groin flap and axillary lymph node dissection was done. Post-operative course was good and no recurrence was found so far.

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Reconstruction of a heel has been difficult in terms of producing favorable results due to the unique characteristics of the heel's function and structure. Because of this, to date a large number of procedures have been devised. Under the circumstances, we have succeeded in obtaining good results by means of medial plantar flaps for the reconstruction of heels in five patients after extensive resection of malignant heel tumor.
We used to reconstruct the heels either with cross leg flaps or with the combination of muscle flaps and skin grafts. However, these methods would often involve disadvantages such as the development of ulcer and difficulties in accomplishing stable reconstruction of the heels. As a result, the patients would often complain of difficulties in walking after surgery.
Therefore, in order to reconstruct heels, it is desirable to use flaps which have similar structure and sensation to those of the heels. Medial planter flaps satisfy such requirements.
Postoperative disorders often lead to the limitation of patients' life. Needless to say, priority should be given to the radical treatment of malignant tumors, but is essential that due consideration should be given to the functional prognosis from the standpoint of “Quality of life.” Based on all this, we have reconfirmed the superiority of medial planter flaps

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We reported a case of 60-year-old man of extramammary Paget's disease with Paget's cells in the nipple epidermis histologically. Clinically, he had a skin lesion only on the genital region, and no lesion at axilla and nipple. We didn't have any abnomal laboratory findings including serum tumor markers. When we operated genital lesion, we carried out biopsy of bilateral axillae and nipples, and histologically recognized clear cells at the right side nipple epidermis.
These clear cells were stained by digestion-PAS, Alcian blue, CEA, EMA and GCDFP-15. These staining findings were almost the same as genital lesion, but not the same as Toker's clear cells of nipple epidermis in 1969.
For these above reasons, we thought clear cells at the nipple epodermis of our case as subclinical Paget's conditoin, and considerd extrammary Paget's disease may occur multicentric at the apocrine gland rich areas, but further study will need.

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We would like to describe and report a 72-yrars-old Japanese male patient case with extramammary Paget's disease. The clinical course commenced with the appearance of exanthema on the pubic region and three and a half years later, systemic and multi-organ involvement was observed. The patient passed away due to respiratory failure caused by Paget's cell embolism which originated from the male external genitalia.
Autopsy results revealed metastasis to both lungs, liver, both adrenals, superior sagittal sinus, vertebrae, sternum, ribs and lymph nodes: both pulmonary hili, paraaortic and both inguinal regions. Examination of pulmonary histopathological preparations revealed the presence of metastatic cells in the pulmonary vessels (various sizes), within the alveolar walls and in some regions thrombus was observed.
The patient sought medical attention for exanthema on the external genitalia but was observed to have respiratory failure, elevated levels of myoenzymic activity and bleeding tendencies. The patient passed away 14-days after the initial examination and during hospitalization, the changes in blood gases (deterioration and/or improvement) due to metastatic cell embolism or thrombosis were observed. Embolism and/ or thrombosis is suggestive as the cause of DIC and in addition, increase in myoenzymic activity was simultaneously observed with deterioration of blood gases due to metastatic embolism and/or thrombosis with this particular case. It is suggested that metastatic thrombosis occured within the vascular vessels of the skeletal muscles even thought we were unable to determine this from the autopsy findings.
Conclusively, it is suggestive that cases with metastatic intravascular embolism, simultaneously increases the probability of concurrent occurrence of multi-organ metastatic embolism.

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A case of 77-year-old man with extramammary Paget's disease of the bilateral axillae was reported. 9 years ago, he was affected by urinary bladder carcinoma (transitional cell carcinoma, grade 1) and was treated by TUR.
At first, he noticed erythema of the bilateral axillae, and subsequent some nodules on the right. As the nodules increased in number, swelling of the right arm appeared. The course had been quite rapid, and his death was caused by bacterial pneumonia after a year and a half since the first clinical appearance. In autopsy, metastasis were observed in lungs, liver, vertebral bodies, spleen, several lymph nodes and so on. It will be the first report in Japan which was died of extramammary Paget's disease of the axillae.

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Expression of the p53 gene in basal cell carcinoma (BCC) was immunohistochemically examined using frozen sections and two different antibodies against p53 protein (CM1 and DO7) . Out of 15 BCCs examined, all the BCCs were CM1-positive and 14 BCCs were DO7-positive. Out of the 15 cases of BCC, 13 cases were informative on the p53 expression in the epidermis and/or the hair follicle adjacent to tumor nests. The two other cases were not informative because of lack of the epidermis and the hair follicle in tissue sections. Out of the 13 informative cases, 11 cases were CM1-positive and 8 cases were DO7-positive in the epidermis and/or the outer root sheaths of hair follicles. Out of 7 specimens of normal facial skin, 6 were CM1-positive and two were DO7-positive in the epidermis and/or the hair follicle. On the other hand, all of 4 specimens of normal skin from sun-protected regions were negative. Since all the BCCs examined here developed on faces, the facial skin frequently overexpressed p53 protein, suggesting induction of p53 protein by sun light. The presence of immunohistochemically detected p53 protein may not necessarily mean the presence of p53 gene mutations.

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The true route of contamination of the Namikata arsenical poisoning incident in Shikoku, which took place in 1933-1935, has remained unclarified, in spite of intensive on-the-spot investigations. The Toroku mine in Miyazaki, Kyushu, had produced arsenicals for scores of years until its complete discontinuance of operations in 1962. The arsenious acid produced there increased between 1921 and 1941, most of which was transferred to Ohkunojima, an islet in Tadanoumichou, Hiroshima Prefecture as materials for lewisite [ (CHCl: CH) ₂ AsCl], a poisonous gas, it has been disclosed.
Marine shipping agents in Namikata and nearby towns, well aware of the Inland Sea, transported various things in small boats carrying only 2 to 4 persons, often family members from Kyushu to Osaka and Kobe areas. We assume that this was the route of contamination in the Namikata arsenical poisonig incident because of the following reasons: Most of the patients were young 20 to 30 year-old seamen, most of them were family members, such as a man and his child, man and wife, man and cousins, no aged persons or children had been affected. An episode which was told one of us (Kubo, who has worked in Namikata where the incident took place) was that there was a strong demand of a man that there should be no mention of the death in connection with her job when a 47 aged wife died of lung cance in 1956 and her death certificate was prepared, because it would inform her relatives that poisonous materials had been sent with them.

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We reported a case of Bowen carcinoma complicated of Bowen disease, Actinic keratosis, Basal cell epithelioma and gastric cancer in his course. A 78-year-old man was operated by BCE of I-III finger six years ago, and operated gastric cancer 1 year ago.
He noticed the tumor and plaqu on his left back of foot 3 years ago. We operated these lesions, and diagnosed Bowen carcinoma and Bowen disease histologically. Further examination revealed multiple actinic keratosis on the face and scalp. It is well known that Bowen disease related internal malignancy and multiple Bowen disease is due to Arsenics. We cosidered that Bowen disease concerned not only internal malignancy and Arsenics but also malignant skin tumors. We considered that Bowen disease concerned not only internal malignacy and Arsenics but also malignant skin tumors.

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A case of Bowen carcinoma on the vulva was described. The patient was 39 years old female and had a history of cervical carcinoma at the age of 35. She noticed a cutaneous lesion on her vulva about one year ago. It was growing slowly and became hemorrhagic. On examination, a 45×40mm sized erythematous lesion with greish white margin was found on the left side of her vulva. There were two granulomatous nodules, sized 13mm in diameter and bright red in color, in the lesion. Some blackish pigmented spots were distributed on the margin. A biopsy specimen was histolpgically diagnosed as a Bowen disease showing anaplastic epidermal cells containing multinucleated cells and dyskeratotic cells. Intradermal invasion of the same tumor cells was observed at the site of the nodules. Then the lesion was diagnosed as a Bowen carcinoma (squamous cell carcinoma (SCC), grade III, T₃N₀M₀) . The tumor was removed with 10mm excision distance.
Immunohistochemical stain using anti human papilloma virus (HPV) antibody was negative in the tumor cells of the Bowen carcinoma. Further, in situ hybridization using HPV type 6/11 and type 16 DNA probes was negative in both the Bowen carcinoma and the cervical carcinoma.
There were 4 Bowen carcinomas and 13 Bowen diseases at our division in the years of 1983-1992. Therefore, 24% (4/17) of Bowen diseases became invasive Bowen carcinomas. On the other hand, out of 29 SCCs operated at our division for these 10 years, 5 SCCs deveroped on scar lesions, 4 developed on Bowen diseases and 3 deveroped in a patient with xeroderma pigmentosum variant.

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We report a case of trichilemmal carcinoma. A 47-year-old Japanese man had a 7-year history of a slowly progressive reddish tumor on the left lateral side of trunk. The initial eruption was reddish papule. This lesion gradually enlarged and became elevated to form ulcerated tumor. The classification of malignant outer root sheath cell tumors is still controversial. This problem may be due to the differing diagnostic criteria for these tumors used different authors. Histology of present case was highly pleomorphic and some lobules showed cystic degeneration with amorphous eosinophilic material in the cystic space, which were consistent with malignant proliferating trichilemmal tumor. In this report, we discussed the classification of malignant outer root sheath cell tumor.

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We reported a case of undifferenciated adenocarcinoma which was suggested to be possibly of apocrine origin. It occurred on the left axilla of the 44 year-old-man as a subcutaneous elastic hard nodule. It has gradually developed up to 2×3cm in size for two years. No palpable lymph node was detected.
Histologically the tumor was composed of clear cells in various shape and size, which had large oval nucleus and abundant cytoplasm with eosinophilic granules. It was suggested to be an undifferenciated adenocarcinoma of unknown origin. Metastatic tumor, aberrant breast cancer and sweat gland carcinoma were suspected.
Findings of clinical examination and laboratory data showed no visceral involvement indicating metastasis. And we could not find out normal mammary gland in contact with the tumor tissue, though one could usually do in case of aberrant breast cancer. So sweat gland carcinoma of eccrine or apocrine origin was suggested.
We studied further histopathologically using specific staining and electron microscopy. The tumor was negative for S-100 staining like an apocine gland. In electon microscopy, the findings were more compatible with apocrine gland than with eccine gland.
In conclusion, we considered that this tumor was probably of apocine origin.
The tumor was exicised and radical axillar dissection was performed. No tumor invasion or lymph node metastasis was detected.
We consider that the present case should be followed up as a case of undifferenciated type of apocrine adenocarcinoma paying attention to focal recurrence and metastasis.

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An 82-year-old woman presented a 5.0×4.5cm, well-demarcated, partially brownishblack, erythematous plaque in the left abdomen of about 15 years' duration. There were slightly raised portions in the plaque. No apparent regional lymphadenopathies were present. Histologically the center of the plaque showed tumor cell nests invading into the dermis and connected with the epidermis. The tumor cells consisted of diastase-labile, CEA-negative, clear cytoplasms with large, atypical nuclei surrounded by peripheral basaloid cells. There were duct-like structures within the nests. The overlying epidermis also showed clear cell nests without atypical nuclei. The plaque was excised in toto with lcm margins. There were no recurrences or metastasis 12 monthe later.

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The patient was a 32-year old housewife, noticed a few symptomless small nodules on her left wrist in October 1992. They gradually increased their size and number, Her past history revealed that her left middle finger was amputated in April 1992, due to progressive ischemia. Biopsy specimen of the nodule showed that there were irregular foci of collagen degeneration with mucin in the dermis, surrounded by spindle cells. A few mitotic figures were observed among them. These findings were quite similar to those observed in granuloma annulare. But, both cytological atypia and infiltrative pattern of the spindle cells into the peripheral nerve suggested us that this case represented an epithelioid sarcoma. Her left arm was amputated. Pathological studies showed an epithelioid sarcoma of the hand with multiple metastases to the skin. Axillary lymph nodes were also involved. Clinicians as well as pathologists should be aware that epithelioid sarcoma sometimes masquerades as a benign granulomatous disease.

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A case of apocrine adenocarcinoma arising in the scalp is reported. A 69-year-old male presented with an ulcerated nodular reddish firm mass in his scalp and two subcutaneous nodules in the left side of his neck. The biopsy suggested a metastatic adenocarcinoma, but a whole body CT, Ga scintigram and other examinations revealed no evidence of malignant tumor in other organs. Therefore we diagnosed it as sweat gland carcinoma and the wide resection and total neck dissection were done. The histopathology of the resected tumor showed adenocarcinoma with varying degrees of differentiation, composed of cords and nests which occasionally formed branching lumina. Atypical epithelial cells had abundant eosinophilic cytoplasm and only rarely showed projections from the apical cytoplasm consistent with decapitation secretion. Some tumor cells and luminal eosinophilic material were PAS positive, diastase-resistant, and were also alcian blue and CEA positive. By electron microscopy, the epithelial cells showed enlarge and rounded mitochondria and electron dense secretory granules, but no tonofilaments in the cytoplasm. Microvilli were seen along the luminal membrane. Infrequently apical membranes protruded in the lumen and showed typical dividing membrane. In addition, myoepithelial cells were seen along the basal epithelial membranes that led us to the final diagnosis of apocrine adenocar-cinoma.
It is difficult to make a diagnosis of carcinoma of sweat glands, especially in poorly differentiated cases, because of the histological similarity to metastatic adenocarcinoma in the skin. Apocrine adenocarcinoma that usually occurs in axilla or wherever apocrine glands normally exist and has high risk of regional lymph nodes metastasis is an uncommon neoplasm. Our case of apocrine adenocarcinoma of the scalp is the 4th reported case in Japan. Immuno-histochemical stainings are likely to be overused to make a diagnosis of sweat gland carcinoma. We should be reminded that some basic histological features such as decapitation secretion or myoepithelial cells which are elongated cells surrounding tumor nests and positive for smoothmuscle actin are still very contributory to define these tumors.
Mishima and Morioka suggest sweat gland tumors can be classified according to their anatomical origin and malignancy that provide us relatively clear-cut concept of these tumors. Using Mishima and Morioka system, we classify this tumor as an apocrine spirocarinoma because of the presence of decapitation secretion and myoepithelial cells, and the absence of tonofilaments.

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A 66-year-old female case of BCE associated with Apocrine carcinoma developed from organoid nevus on her scalp was reported.

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A 85-year-old Japanese woman visited our clinic for the treatment of a giant dome-shaped node, 35×45×5mm in diameter on her left frontal scalp. The histopathology of the lesion showed malignant hemangioendothelioma. She was treated with an intralesional injection of recombinant interleukin 2 (rIL-2; Celeuk®) at 4×10⁵JRU a day, 5 days a week. On day 8 after the start of injection, the tumor began to reduce in size. On day 50 when the tumor was 25×35×2mm in diameter, it was surgically excised, because of no further effect of the injection, followed by the intravenous injection of rIL-2 at 4×105JRU a day, twice a week for 3 weeks. There was no evidence of local recurrence or metastasis 7 months after the surgical excision. Although the intralesional injection of rIL-2 was very effective, the lesion was too large to be completely cured with rIL-2 alone. We guessed that the combination therapy of rIL-2 and surgical excision should improve the cure rate of malignant hemangioendothelioma.

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Two cases of metastatic skin cancer referred to our clinic were reported.
Case 1: A 61-year-old female had a subcutaneous induration on her chest. Pathological findings of this induration showed many adenocarcinoma cells in the edematous stroma of the dermis. This lesion was judged to be due to metastasis of poorly differentiated adenocarcinoma of the stomach, because gastric carcinoma excised six years previously. This case was considered a delayed cutaneous metastasis of the gastric carcinoma.
Case 2: A 43-years-old male had an extensive erythematous plaque on his left chest, back and arm. Histological findings from the chest lesion showed the accumulation of tumor cells within the dermal vessels. He was referred for the endoscopy and there was a malignant ulcer in his stomach. This case was diagnosed as an inflammatory type in cutaneous metastasis of the gastric cancer.

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A Phase II clinical study to evaluate the efficacy and safety of a BRM, Whole peptidoglycan (WPG), was conducted in 104 patients with malignant tumors of skin. All patients received WPG by intratumoral injection. Ninety patients were evaluable for the efficacy. Overall response rate on malignant tumors of skin was 57.8% (52/90) . The satisfactory result was obtained in patients with mycosis fungoides (5/5: 100.0%), solar keratosis (11/15: 73.3%), Bowen's disease (13/18: 72.2%) and squamous cell carcinoma (4/6: 66.7%) . WPG was also effective on metastatic malignant melanoma (6/12: 50.0%) and CTCL (4/8: 50.0%) and ATLL (3/6: 50.0%) . The main adverse reactions were fever, anorexia and local pain at the injection site, but which were tolerable and reversible. These results suggest that local therapy using WPG is useful for the patients with malignant tumors of skin, particularly malignant melanoma and malignant lymphoma.

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A late phase II study of CPT-11 was conducted to evaluate for antitumor activity and safety in patient with squamous cell carcinoma of skin (SCC) and malignant melanoma (MM) by 22 multi-institutional study group in Japan. Forty-two patients in SCC and 38 in MM were enrolled from June 1990 to November 1992. Patients were administered at a dose of 100 mg/m² weekly by intravenous infusion.
The characteristics of 41 eligible patients with SCC were median age: 67 yr. (43-86), male/female: 31/10, P.S. 0-1/2-3: 35/6, no prior therapy: 27. Thirteen patients including 2 complete responses (CRs) responded to CPT-11. The response rate was 39.4% (13/33) . Two CRs were confirmed histologically. Out of 11 partial responses (PRs) 7 was able to resect completely tumor site after the treatment. Antitumor activity was observed not only in primary site but also in distant metastases such as lungs and lymph nodes.
The characteristics of 35 eligible patients with MM were median age: 55yr. (29-81), male/female: 20/15, P.S. 0-1/2-3: 32/3, prior therapy: 30 (chemotherapy 26) . Three patients were achieved PR for a response rate of 9.4% (3/32) . Out of them 2 were recurrence patients with lung metastases, having received prior chemotherapy, DAV.
Major adverse reactions were nausea/vomiting, diarrhea, anorexia, leukopenia and anemia for the incidence (≥ grade 2) of 47.4% (36/76), 36.8% (28/76) and 52.6% (40/76), 56.6% (43/76) and 26.3% (20/76), respectively. These adverse reactions were well tolerable and reversible. It was thought that CPT-11 should be given carefully after confirming laboratory data and patients conditions.
Inconclusion, CPT-11 is very effective against SCC, but less effective against MM in this study. Further clinical studies of CPT-11 combined with other agents are warranted.

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