A case of extramammary Paget's disease with underlying anal carcinoma of a 52-year-old female patient is presented in this study. She had pruritis around her perianal skin 15 years ago. The histological exammination then revealed presence of anal Paget's disease, and she received the electron beam therapy. Ten years later, the recurrence of Paget's disease was observed. But there was no evidence of anal carcinoma by romanoscopic exammination. When she visited us, the histological exammination showed that Paget's cells invaded the dermis, and signetring cell were present within the epidermis. Immunohistochemical staining of the Paget's cells by monoclonal anti-CEA was positive. The electron microscopic study revealed that Paget's cells posessed mucinous secretory vacuoles. It was diagnosed, therefore, as carcinoma in situ, according to the classification of Ohyama, whose cells originated from either epithelium of anal gland or mucinous gland, and later developed into the anal carcinoma as a result of infiltration of lamina propria.
We usually perform wide local excision of the primary lesion and prophylactic lymph node dissection on stage III1 cases, while wide local excision and radical lymph node dissection were performed on stage III2, 3 cases. When the lesion is found on the toes and the anterior half of the sole, we usually perform the amputation at the proximal third of the lower leg. Concerning the subungual melanoma, amputation is performed at MP joints. When the lesion is found on the posterior half of the sole, we usually perform the wide local excision. In some cases of stage III2, 3 subtotal integmentectomy or muscles flap technique was applied occasionally. When intransit metastasis are found we do wide local excision of the primary lesion and the subtotal integmentectomy. The primary lesion being found on the axilla, we perform the wide local excision and the axillary lymph node dissection simultaneously. Then we use the latissimus dorsi muscles flap to cover the axillary veins, arteries and nerves, and to make the good bases for the skin graft. When doing the groin dissection, we usually use the sartorius muscles flap to protect a femoral artery, vein and nerves.
A statistical observation of 59 patients with squamous cell carcinoma (SCC) seen at Department of Dermatology, Yokohama City University School of Medicine during the past 10 years (1981-1990) was reported. The frequency of the patients was 0.09% of all newly visiting outpatients. The sex ratio was male 1.81: female 1. The highest peak of the age was 7th decades of life and average was 69.7 years old. The average age of the patients with SCC derived from burn scars and chronic radiodermatitis was younger than the others. The tumors were located mostly on faces (24 cases) and then on lower extremities (12 cases). The ratio of recurrence, metastasis and death became higher when the tumor was poorly differentiated or when the tumor invaded deeply. As for the stage classification, the prognosis became poorer in the stage III or IV.
We studied the cells in S-phase in various benign and malignant skin diseases such as psoriasis, seborrheic keratosis, actinic keratosis, Bowen's disease, extramammary Paget's disease, basal cell carcinoma, squamous cell carcinoma, malignant lymphoma, and malignant melanoma. Small pieces of excised skin tumor were incubated with 5-bromo-2'-deoxyuridine (BrdUrd), thymidine analogue, under three atmospheres of pressures in 95% O2 with 5% CO2. Anti-BrdUrd monoclonal antibody stained the nuclei which incorporated that substance. We analyzed labeling pattern as well as the counting of labeling indices. Malignant diseases such as squamous cell carcinoma, basal cell carcinoma, and Bowen's disease showed higher labeling indices than non-malignant specimens. As for the labeling pattern, malignant diseases lost the polarity of labeling and labeled cells were scattered randomly without forming germinative layers. On the other hand, non-malignant specimens showed the germinative layers. Therefore, high labeling indices together with the loss of polarity seemed characteristic for the malignancy.
We reported a case of humoral hypercalcemia of malignancy (HHM) in association with squamous cell carcinoma of the skin. The term HHM describes the condition in which the hypercalcemia is due to the production by the cancer of some substance which acts generally upon the skelton to increase bone resorption. The patient was a 51-year-old man. He became aware of asymptomatic tumor, on his lower back, measured about 2×2cm in 1971. From June, 1992, the lesion enlareged rapidly and ulcerlated. At the same time, both inguinal lymph nodes metastases were found. When he was addmitted our hospital on September, 1992, the size of the lesion on the lower back was 18×10cm. Histopathological examination of the lower back and inguinal lymph nodes revealed an infiltrating, well differentiated squamous cell carcinoma of the skin with involvement of the lymph nodes. The cell masses showed keratinization, horn pearls were present. Laboratory studies on admission showed as following: the WBC count was 8, 600/ mm3, with a normal differential cell count. The hemoglobin level was 15.6g/dl, and the hematocrit reading was 45.7%. The liver function tests, urinalysis were normal. The total protein level was 7.3g/dl and an albumin level was 4.0mg/dl. The serum calcium level was 13.4mg/dl, the phosphate value was 2.1mg/dl. The serum parathyroid hormone (PTH) level was lower than 100 pg/ml (normal: 180-560pg/ml) . The serum calcitonin level was 5lpg/ml (normal: 0-100pg/dl) . Bone scintigram, computed tomography (CT), and X-ray examination showed no evidence of metastatic bone lesion. Culture from his wound revealed Staphylococcus aureus. We treated him for hypercalcemia with sodium chloride infusion and calcitonin. However, the serum calcium level was not significantly decreased. Then, we treated with aminohydroxyprolidene diphosphonate (APD) 30mg. Two days after this treatment, the serum calcium level fell to normal (10mg/dl) . APD is a kind of bisphosphonates which are analogues of pyrophosphate. They have high affinity for bone. The precise effects of bisphosphonates on bone and bone cells are not known in detail, however, they are thought to be taken up by osteoclasts and appear to inhibit the action of these cells. The tumor of lower back and inguinal lymph nodes were excised and skin graft wasapplied. And we administered doxorubicin hydrochloride and cisplatin. However, because of recurence, the serum calcium level rose again and his condition deteriorated. He died on Jan. 23, 1992. Parathyroid hormone related protein (PTH-rP) is one of the substance which cause HHM. Recently, cDNAs coding for a PTH-rP has been cloned. PTH-rP shares 80% homology with the first 13 amino acids of PTH in the resion responsible for binding to the PTH receptor. Whether PTH-rP has a physiological role is uncertain, but the compound seems to be primary associated with epithelium. Very high concentrations have been found in breast milk, and immunocytochemical studies have demonstrated high concentrations of PTH-rP in mammary epithelium. It is also abundant in skin, and most squamous cell carcinomas contain PTH-rP. During his hospitalization, we studied his serum level of PTH-rP. The normal level was from 13.8 to 55.3pmol/l. The patient's was 728.4pmol/l. So, we thought the secretion of PTH-rP from SCC was responsible for his hypercalcemia.
A case of polypoidal malignant melanoma, arisen from the black pigmented spot on the face of 48-year-old female was reported. Two years ago, the patient noticed the pigmented spot on the right side of the jaw, and it has extended with scratching. The tumor has elevated rapidly on the pigmented spot, and recently bleeding was observed. Present illness: There was black, partially dark red, and elastic hard polypoidal tumor, sized 18×15×7 mm on the pigmented spot. The easy-bleeding erosion and crust were observed on the surface of the tumor. Pathologic findings: Tumor cells were composed of different sired atypical epitheloid cells chiefly, and they contained clear nuclei. Aboundant melanin granules were observed in the cytoplasm of the tumor cells. At the site of peripheral part of the tumor, the incleasing of atypical melanocytes were observed in the basal layer. Therapy: After DAV and IFN-β therapy, wide spread surgical excision and cervical lymphadenectomy were done. Metastasis was observed in the part of cervical lymph nodes. After the operation, DAV and IFN-β therapy were added.
In 7 patients the primary lesion of malignant melanoma was treated with proton beams in Proton Medical Research Center, University of Tsukuba. Four cases were male and the other 3 were female. Five cases were acral lentiginous melanomas and the other 2 were superficial spreading melanomas. Two cases received 3 to 8Gy fractions administrated 15 or 16 times in 24 or 44 days to a total dose of 90 or 91Gy. The other patients received even higher single doses than them, i.e. large fraction radiotherapy. They received 10 to 13Gy fractions administrated 7 to 11 times in 9 to 18 days to a total dose of 91 to 110Gy. Clinically the tumor reacted to the irradiation and in 6 cases showed partial regression of the size with erosive reaction, and in one case showed complete regression with complete healing of moist desquamation. Histological examinations were performed in 4 cases and they showed many melanoma cells degenerated. Electromicroscopic examination revealed that the organelle and the nucleus highly degenerated. Results indicated good local effects were obtained by proton beams, although additional modalities were requested to manage the remaining tumors. Malignant melanoma is considered unresponsive to conventional radiation therapy in part due to a large shoulder on the radiation survival curve and higher dose fractions might be beneficial. The superior dose distribution of proton beams allows high-dose exposure to the target area with lesser dose to the surrounding normal tissues. And it enables one to treat malignant melanomas with as high single doses as 10 Gy like in the 5 cases, expecting that repair process of melanoma cells would be overcome. It is postulated that proton therapy should allow malignant melanoma to be treated with even higher doses resulting in improved local control rates.
In this paper, we present a 27-year-old female of metastatic melanoma treated with interferon-β-DAV combination therapy, and in addition, the course of urine 5-S-cysteinyldopa excretion level was analyzed. Pretreatment urinary excretion level of 5-S-cysteinyldopa was 4, 118.7μg/day and declined immediately after dose. Every after dose, urinary excretion level increased and then decreased rapidly. This fluctuation continued throughout the treatment and the maximum urinary excretion level reached 8, 388μg/day. In comparison of previous reports, this case achieved long-term survival in spite of remarkable high urinary excretion level of 5-S-cysteinyldopa.
A 62-year-old man exhibited a 3.0×2.5cm sized, sharply circumscribed and irregular shaped black macule on his left hipochondriac region. In the center of the lesion, there was a slightly concave and depigmented area. This area had contained a polypoid tumor which was resected by his family physician. A 1.5cm sized lymphnode was palpable in his left axilla. After one course of DAV therapy, a tumorectomy and an axillary lymphadenectomy were performed. We concluded that a clinicopathological subtype of this case was a superficial spreading melanoma. After that, DAV and PAV therapy were performed and his clinical course was satisfactory. But 2 years and a half later, liver, bone marrow and skin metastases were detected. Five months after that, the patient died from liver failure. Urine 5-S-cysteinyldopa excretion level was remarkable high (1951.3 μg/day) when the metastasis was detected.
A 30-year-old man with malignant melanoma of the left foot arising in a small congenital nevus was reported. Histopathologically, an expansile nodule was observed, which pushed the residual congenital vevus, in the dermis. The nodule was composed of monomorphic spindle cells with fine melanin granules and vesicular nuclei. Although no mitotic figures were found, we considered the nodular lesion as a nodular melanoma. In 3 out of 18 inguinal lymph nodes, there were nevus cell aggregates. They were situated mostly in the capsule and trabeculase. However, atypical large cells with melanin granules were found, intermingling with nevus cells, not only in the capsular area but also in the node parenchyma.
In a female patient with non-bullous type, congenital ichthyosiform erythroderma, who was 55 years old at first examination, pseudocarcinomatous hyperplasia was noted in the refractory ulcer portion of the right toe and Mishima et al.'s plantar premalignant melanosis in the right sole, and both lesions were resected. Four years later, squamous cell carcinoma resulting from Bowen's disease developed on her right forearm, of which amputation was performed. Furthermore, 13 years later, this patient developed ALM on her right heel and Bowen's disease on her left forearm. This is a very rare case. The sequential onset of Bowen's disease is not uncommon, but there has been no report on the sequential onset of ALM on the same side of body. There also seems to be no case report on malignant tumor of the skin secondary to non-bullous type, congenital ichthyosiform erythroderma. Duplication and sequelae of two kinds of cutaneous malignant tumors seem to be very rare. The possible involvement of trauma (physical stimuli) in the development of malignant tumor has been accepted. In this case, the involvement of trauma such as desquamation repeated on hyperkeratotic skin was suspected for the development of ALM and SCC. Additionally, it was considered that an abnormal immunity of the host was involved in plural sequelae of cutaneous malignant tumors. Retinoids could not inhibit the development of these cutaneous malignant tumors, but may have inhibitory effects on metastasis.
A case report of malignant schwannoma Twenty six-year-old woman had noticed a coin sized tumor on the upper part of her left breast from about 11 years ago. This tumor had gradual growth since that time. When she visited our hospital, the tumor had dome shaped appearance with erythema and the size was 3cm in diameter. In her physical examination, our diagnosis was hemangioma immediately treated by simple resection. In light microscopic study, the tumor contained of spindle shaped cells with herring bone pattern in arrengement. Immunohistochemically, these tumor cells did not react with anti-vimentin, -desumin, -factor VIII, -S-100, -NSE, -myoglobin, -CEA, -keratin and -lysosome. In the electron microscopic study of the tissue, we could detect some projections from the tumor cells which surrounded by a basement membrane like structure and adhered to a desmosome like structure. According to these findings our diagnosis was malignant schwannoma. Since then we removed the first and second recurrences of the tumor, afterward the patient was treated by chemotherapy by Farmorubicin. There was no recurrence in her follow up of about 1 year.
A 53-year-old female patient with myxoid liposarcoma on the left foot is reported. The patient underwent local excisions before visiting to our hospital. The tumor had been diagnosed as benign. Physical examination revealed a 25×40mm soft cutaneous tumor which was located on the forth toe and the adjacent region of the dorsum of left foot. Light microscopy of excised lesion revealed that there were many tumor masses consisting of spindle or oval shaped cells with pleomorphic nuclei and cytoplasm containing numerous small vacuoles in the dermis and subctaneous tissue, and that tumor masses were embedded in an abundant mucoid matrix stained with Alcian blue. It was also shown that tumor masses were not completely removed at the margin of the specimens. The patient received postoperative irradiation with fast neutrons at dose of 17.1Gy. When last seen, 49months post-operatively, the patient had no evidence or recurrence or metastasis.
We presented a 58-year-old female with malignant fibrous histiocytoma developing in a burn scar. She had sustained thermal burn on the right side of her head when she was a baby. An atrophic scar with loss of hair had been present since that time. For the last 10 years, she had suffered from a recalcitrant ulcer in the burn scar. In 1982, the ulcer was resected and covered with a local skin flap. The histologic section showed large, atypical tumor cells with slit-like spaces among them, and extravasation of erythrocytes. A tentative diagnosis of malignant hemangioendothelioma was made. After 9 years of a disease-free period, a small ulcer recurred after minor trauma near the previous lesion. In the following 2 months, a fist-sized, easily bleeding tumor developed rapidly. Examination by CT-scan and MRI revealed the tumor destroyed cranial bone and invaded dura mater. A course of extensive radiotherapy consisting of 80Gy of 15MeV electron-beam was instituted and the tumor regressed clinically. The remaining ulcerative lesion was excised, including bone and dura underneath. The histological examination of this lesion revealed proliferaton of atypical, spindle cells in a storif orm pattern. Immunohistochemical stainings of specimens obtained before and after irradiation showed that the tumor cells were positive for α1-antichymotrypsin, while negative for factor VIII related antigen and UEA-1. Pulmonary metastases were detected in a short time. In spite of a combination chemotherapy (CYVA-DIC) and X-ray irradiation to lung lesions, the patient's condition rapidly deteriorated and she died of respiratory failure. Extensive irradiation in combination with excision may be the choice of treatments for primary lesions of malignant fibrous histiocytoma. This is the tenth case of malignant fibrous histiocytoma developing in a burn scar among Japanese.
An 88-year-old Japanese man presented with 4 lesions of malignant trichilemmoma on the scalp and face. Histopathological examination revealed typical malignant trichilemmoma in all 4 nodules and actinic keratosis around one of them. This suggested that the malignant trichilemmoma had developed from actinic keratosis in this case. The patient died due to pneumonia 14 months after radical surgery with skin grafting. No metastasis was found.
A case of sweat gland carcinoma with von Recklinghausen's disease were reported. We considered this case syringoid eccrine carcinoma that had reported by Mehregan A.H., in 1983. A 61-year-old man had a complaint of asymptomatic eruption on the vertex of the scalp on July 1991, that had increased in size slowly since resection of the traumatic scar on January 1990. Physical examination revealed a 15×15mm erosive lesion with crust on the vertex of the scalp and a lot of neurofibromas on the whole body. A 15×15mm red nodule was close to the scalp lesion. Examination of the hematoxylin-and-eosinstained specimens showed many variously sized cysts extended in upper dermis and a lot of branching tubular structures embedded in a fibrous stroma of lower dermis. Tumor cells consisted by cystic and tubular structures were moderately atypical basaloid cells and did not form palisading. There was evidence of perineural and periarterial invasion. Evident connection between the tumors and neurofibromas was not found. Immunohistochemical stain with Avidin-Biotinylated-Peroxidase-Complex method showed that luminal cells of cysts stained positive with carcinoembryonic antigen (CEA) and S-100 protein and tubular structural cells staind positive with CEA negative with S-100 protein. CAM5.2, antihuman cytokeratin, was reactive to the both structures. Vimentin showed negative activities. Enzyme histochemical examination revealed tumor structures gave positive reactions for succinic dehydrogenase and negative for β-gluculonidase. Electron microscopic findings were numerous intracellular ducts with prominent microvilli were present and tumor cells connected with desmosomes. Immature tonof filaments were found in some cytoplasmes. In July 1991, the tumor was totally excised and skin-grafted. But the remnants of tumor cells were found at the margin with histological examination. In spite of a 40Gy electron radiation therapy, it recurred on previous skin graft in September 1991. The patient had wide surgical excision. It has not recurred in 11 months. In 1983, Mehregan, studied 35 patients diagnosed in the past 20 years and classified eccrine adenocarcinomas the following 4 distinct variants histologjcally: eccrine porocarcinoma, syringold eccrine carcinoma, mucimous eccrine carcinoma and clear cell eccrine carcimoma. Syringoid eccrine carcinoma (SEC) occurred on the scalp in four instances, on the extremities in four, on the back in two, on the ear and the cheek in each one. The lesions were single in all cases and measured from 1.5 to 4cm. Local lymphnode metastasis was rare. Histologically, SECs were characterized by cystic and tubular structures resembled syringoma were composed by basaloid cells and invasively prolifetared in a fibrous stroma. Tubular structures were lined by a single layer of luminal cells and one or more rows of cells. Mitosis were often found. In some cases, tumor nests showed connections with the overlying epidermis. Perineural or perivascular invasion may be present. Enzyme histochemical showed positive reactions for succinic dehydrogenase and leucine aminopeptidase and negative for alkaline phosphatase. Basal cell carcinoma has no activity to CEA that SECs react. Syringoma does not exhibit the aggressive infiltrative growth seen in the SECs. Cylindromas have more classic basaloid nests arranged in a jigsaw puzzle pattern. Primary cutaneus adenoid cystic carcinomas have its characteristic cribriform patterns. We concluded our case differentiated into dermal duct through secretary portion by our immunohistochemical exmanination. In Japan, 63 cases of non-neurogenic malignant neoplasms were reported among 2, 513 cases of von Recklinghausen's disease. It's rate was 2.5%. These complications may be accidental but a mutation theory is proposed that von Recklinghausen's disease patient may be given a tendency of occuring malignant neoplasms by gene mutation.
A case of apocrine adenocarcinoma is reported. The patient was a 81-year old man who had an asymptomic tumor for three years in his right axillary cavity. From the histopathological and enzyme histochemical examination of the tumor, we diagnosed this tumor as apocrine adenocarcinoma. The following points were distinct for the case; (1) Its clinical course and the location of lesion were typical. (2) Histologically, decapitation secretion was found evidently in the tumor cells that were arranging in adenoid pattern. (3) The cytoplasma of the tumor cells contained PAS-positive, diastase-resistant granules. (4) The tumor cells show strong activity of apocrine enzymes, such as acid phosphatase and beta-glucuronidase.
A 52-year-old woman was admitted to our hospital in February 1991 with an intracutaneous tumor on the left axilla which was noticed as a small mass at the age of 20 and began to enlarge for the last 4 months. On admission, the tumor was firm, approximately 2.4cm in diameter, purplish red and showed radial folds on the surface. Histologically, the tumor was located in the dermis and subcutaneous tissue. The overlying epidermis was papillomatous. Numerous degenerated elastic fibers were seen in the upper and middle dermis. The tumor cells with eosinophilic cytoplasm tended to form tubular structures. Tubular luminal cells often showed decapitation secretion in the central part of the tumor. In the peripheral portion, the cells were atypical in part and showed invasive proliferation to the adjascent, along with vascular and nerve tissues. Transitional form of cells were seen between cetral and peripheral part of the tumor. A few apocrine glands were found in the stroma. Immunohistochemical studies revealed that all tumor cells were positive for EMA and keratin, negative for S-100 protein but CEA was pratially reactive in the periph-eral portion. Electron-microscopic study revealed apocrine and merocrine secretion. Widespread radical excision was performed and lymph node metastasis was found. There was no recurrence or metastasis at follow-up 16 months later. The tumor was diagnosed as apocrine carcinoma arising from axillary apocrine apparatus, however a possible diagnosis of carcinoma derived from accessory mamma remained to be ascertained.
A case of malignant eccrine poroma is reported. The patient, a 73-year-old woman, had a granulomatous tumor on her right sole during the last 10 years. Histological examination revealed solid tumor nests were composed of mainly poroma like cells. However, some of them were atypical cells suggested malignant tumor. Immunohistochemical studies showed that tumor cells, around the duct like structures, were especially stained with anti-CEA antibody.
A case of malignant trichilemmoma occured on the lesion of poroepithelioma folliculare was reported. A 81-year-old man was admitted to our clinic with a red nodule measuring 12×10mm in size on the right side of lumbar region in July 1991. This oval shaped nodule with the erosive surface was located in the central area of brown colored pigmentation mesuring 21×26mm in size, which had been present for about ten years. The clinical impression of this nodule was that of squamous cell carcinoma. In July 1991, this lesion was completely excised. No recurrence or metastasis were noted after a year of follow up. Histologically, the nodule on the pigmentation was the tumor to consist of irregular masses of epidermal cells that proliferated downward into the dermis. This tumor had some clear cells and bizzare keratinocytes with trichilemmal keratinization in the surface of the nodule, mitotic figures, many dyskeratotic cells and some squamous eddies. Partially, tumor masses were poorly demarcated from the surrounding stroma, because some atypical cells had no recognizable intercellular bridges and invaded into the dermis. The dermis around the tumor showed a marked inflammatory infiltration composed of lymphoid cells and plasma cells. This feature was confirmed to be a typical malignant trichilemmoma. In the other hand, the pigmented lesion had many rounded nests of epithelial cells, well defined from the surrounding epidermal keratinocytes. These nests were composed of chiefly small cells with round basophilic nuclei, which sometimes showed mild cytological atypicality and mitotic figures. In the nest, there were some pigment blockade melanocytes, clear cells and squamous eddies but no tubular differentiation like sweat gland tumors. This lesion were considered as a case of so-cared intraepthelial epithelioma and these findings were consistent with those of poroepithelioma folliculare. Poroepithelioma folliculare is one of precancerous tumors first recognized by Morioka in 1976. This tumor has been interpreted as a type of follicular intraepidermal epithelioma, which is divided into five histopathological types. Five histological patterns were a trichilemmoma-like, inverted follicular keratosis-like, tumor of follicular infundibulum-like type and the clonal type of seborrhoeic keratosis in addition
A 76-year-old female patient with Merkel cell carcinoma was reported. The tumor presented at the left neck and chest wall. Tumor cells were stained by antibodies to neuron specific enolase and keratin. Electron microscopy revealed dense core granules. Thirty cases reported sine 1988 were reviewed.
A 64-year-old Japanese male presented multiple lesions of basal cell carcinoma (BCC) on the face on a poikilodermic basis. The lesions numbered nine, and two were reddish, erosive, dome-shaped, thumb-finger-sized tumors located on the nose and left upper eyelid and the other seven were blackish flecks, one of them had ulceration. Histological examinations revealed nodular BCC, a part of which was differentiated into sebaceous glands, and the flecks showed either adenoid or superficial BCC. Although the tumoral lesion of the eyelid was complicated by MRSA infection, calcification, foreign body granuloma and infiltration with plasma cells and lymphocytes were found around the tumor nests and a local immunodeficiency was not confirmed. The poikiloderma on the face was probably due to a single exposure to poisonous gas, composed of yellow mustard gas (Yperite), difenylcyanarsine, hydrocyanicacid and chloracetophenone, and resulting chemical burn at age of 18 or some therapy (probably radiation therapy) for psoriasis vulgaris at age 32. Multiple BCC was, therefore, probably due to the combination of the poisonous effects of the gas, chemical burn scar and radiation therapy for psoriasis, but the true cause could not be determined. Wide excision of the lesions and skin grafting were performed. For the prevention of developement of new lesions and the treatment of psoriasis, an aromatic retinoid is being given.
We reported a typical case of nevoid basal cell epithelioma syndrome (NBCES) . 40 year-old man, no similar disease and no consanguinity of his family history. He had large ulcerated black lesion on the r-cheek and multiple black plaques of basal cell epithelioma on the trunk and extremities. He had all the five symptoms, i.e. multiple basal cell epithelioma, jaw cysts, keratotic pits on the palm and sole, ectopic calcification and skeletal abnormalities. Diagnostic criteria of NBCES was still confused and unclear. We considered to regard the five symptoms as important for diagnosis of NBCES.
We present 2 cases of unusually large squamous cell carcinoma (SCC) on the face in aged patient. Case 1: A 95-year-old woman had a dome shaped tumor sized 55×50×30 mm on her left cheek. The tumor was dark red in color and had a irregularly ulcerated surface. The histological examination specified it as a poorly differentiated SCC (Grade III, T3 N0M0). Case 2: A 88-year-old woman developed a pedunculated tumor measuring 60×45×20 mm on her middle portion of lower forehead. The tumor was bright red in color and had a granular surface with keratinization. It was histologically diagnosed as a well differentiated SCC (Grade I, T3N0M0) Both tumors were removed with 15-20 mm excision distance and the defects were covered with split thickness skin grafting. Out of 25 SCCs operated at out division for these 10 years (1982-1991), 9 SCCs were developed in facial region. Among the 9 SCCs, the present 2 cases were characterized by their largest size of the tumor and highest age of the patient.
Malignant melanoma in situ of the mucous membrane has been rarely reported, although the mucous membrane including oral mucosa is the favorable predilection site of malignant melanoma among Japanese. A 66-year-old Japanese woman visited us with a 6-year history of a pigmented macule on her lips. Physical examination evaluated that the pigmented macule continuously spread from the left oral angle to the buccal mucosa, upper and lower lips, and the inner side of nasolabial fold. The pigmented macule showed haphazard combination in color ranging from tan to brown black. Most of the sections through the brown-black macule showed an increased number of melanocytes in the basal layer in part associated with the nest formation. In addition almost all of the basal layer was composed of pleomorphic melanocytes with bizarre nuclei. Such atypical melanocytes scattered even within the spinous layer. A section of the pigmented macule on the nasolabial fold also showed a lentiginous proliferation of melanocytes associated with solar elastosis of the upper dermis. Based on the clinical and histopathologic findings we concluded a deagnosis having with malignant melanoma in situ of the mucous membrane, but not with lentigo maligna.
Skin metastases from internal malignancies are rare, particularly those originating from carcinoma of the cervix uteri. A 58-year-old woman with cutaneous metastases from the cervix on her right buttock is described. She presented to our hospital with postmenopausal bleeding in 1982. Biopsy showed squamous cell carcinoma in situ of the cervix uteri. She was treated by total hysterectomy with bilateral lymphoadenectomy. She came to our clinic on Dec. 2, 1991 with a red-colored, hard, painful, dome-shaped nodule on her right buttock of one year's duration. Histopathological and clinical examination revealed that the tumor was metastatic squamous cell carcinoma from the cervix uteri.
Natural killer cells are large granular lymphocytes, which do not express CD3 surface antigen, nor rearrange (α, β, γ or δ) T cell antigen receptor (TCR) genes. This report covers a case of cutaneous natural killer cell lymphoma, followed by the occurrence of acute leukemia. In March, 1991, a 43-year-old male complained of the skin tumor on his back. The histopathological examination showed diffuse large cell lymphoma. Grenz zone was not recognized. The tumor cell's surface phenotypes were: Pan T-, Pan B-, CD2+, 3-, 4-, 8-, 19-, 20-, 16-, 57-, HLA-DR+. Laboratory findings on admission indicated no abnormal findings. (Hb 13.9g/dl, Platelet 227, 000/μl, WBC 3, 600/μl with 0% abnormal lymphoid cells.) Anti-HTLV-1 antibody was negative. Bone marrow aspiration, chest X-P, abdominal echo, whole body CT revealed no abnormalities. He was diagnosed as cutaneous non-T, non-B cell lymphoma. Electoron beam therapy was effective for the skin lesion. In October, 1991, he visited us again, complaining of high fever and night sweating. His leukocyte count was found to be 1, 900/μl, with large granular lymphocyte occupying 15% of peripheral blood, and 85% of bone marrow. Large granular lymphocytes were characterized by a presence of azurophilic granules in the cytoplasm. Two color analysis was performed using the flow cytometric method, 75.4% of the cells from the bone marrow examined under that method proved to be double-positive for both CD2 and CD56. Tumor cells were found to have the expression of CD 2+, 3-, 8-, 16-, 56+, 57-. They did not rearrange (β, γ) T cell antigen receptor gene. Based on those findings, the case was finally diagnosed as cutaneous natural killer cell lymphoma accompanied with acute leukemia. Although a combination chemotherapy using MACOP-B was performed, the patient died of sepsis within four months after the start of the therapy. Natural killer cell leukemia is classified into two types; one type with good and mild prognosis, the other with a poor. The latter type is characterized by a symptom of high fever, hepatosplenomegaly and lymphnode swelling, and does not express CD16, 57. These findings suggest that the examination of the surface antigen on natural killer cell is necessary for the diagnosis of the lymphoma with skin lesion of increased large granular lymphocytes.
An early phase II study of CPT-11 involving patients with several malignant skin tumors was conducted at 6 institutions in Japan. The following four administration schedules were used: a weekly dose of 100mg/m2 (Arm A), a biweekly dose of 150mg/m2 (Arm B), 200mg/m2 every 3-4 weeks (Arm C) and 50mg/m2 once or twice a week (Arm D) . An antitumor effect was observed against squamous cell carcinoma (SCC), malignant melanoma (MM), Paget's disease (PD) and Bowen's disease (BD), with the response rates being 36.4% (4/11), 11.1% (1/9), 20.0% (1/5) and 100% (1/1), respectively. The response rate was 25.0% (3/12) in Arm A, 0% (0/1) in Arm B, 14.3% (2/14) in Arm C, and 50.0% (2/4) in Arm D. Major adverse reactions consisted of leukopenia, anemia, nausea/vomiting, and diarrhea, with the incidence being 52.9%, 41.2%, 61.8%, and 29.4%, respectively, all reactions were tolerable. Nausea/vomiting and diarrhea were common just after starting the Arm C regimen and the incidence of diarrhea was high in Arm D. In conclusion, CPT-11 was effective against malignant skin tumors such as SCC, MM, DC, and PD. MM and SCC show a high level of malignancy and no satisfactory chemotherapy has yet been established for them. Therefore, a late phase II study seems to be justifiable for SCC and MM at a dose of 100mg/m2 weekly.
With Interferon Alpha-2a (Recombinant), a multi-centered clinical study was performed at 24 institutes in patients with such skin cancers as mycosis fungoides. In the most patients with mycosis fungoides, the interferon was administered intramusclary. On the other hand, in some patients with papulor- or tumor-type mycosis fungoides as well as those with skin metastatic malignant melanoma and epidermal cancers, the interferon was administered to all of their tumor lesions. The dosage regimen was as follows; 3 to 18 million (International Unit: IU) for intramuscle administration, or 3 to 9 million (IU) for local administration to the tumor lesions. Including 28 patients with mycosis fungoides, enrolled were total 40 patients with skin cancers such as ATL, skin metastatic malignant melanoma, epidermal cancers (extramammary paget disease, Bowen's disease, solar keratosis), of which 39 patients were eligible for safety evaluation and 35 were eligible for efficacy evaluation. As for mycosis fungoides, 11 of 23 patients who were eligible for efficacy with systemic administration (22 with intramuscle and 1 with subcutaneous administration) showed PR, and the efficacy rate of the interferon was 45%. In the cases of the other cancers, the intramuscle administration could lead PR in 2 of 2 eligible patients with ATL, and the local administration could lead PR in 2 of 3 with epidermal cancers and CR in 1 of 1 with malignant f olliculoma. With any route of the administration, such subjective and objective symptoms were observed mainly as fever, malaise, anorexia, headache, nausea/vomiting, and itching/ rash. As laboratory abnormalities, leucopenia thrombocytopenia, and SGOT/SGPT elevation were also seen. These adverse events were not irreversible nor clinically significant with any concerns. It was concluded that Interferon Alpha-2a is effective and tolerable for treatment of mycosis fungoides.
The antitumor effects of CPT-11, a derivative of camptothecin, on human squamous cell carcinoma (SCC strain) transplantable in nude mice were studied. The results indicated that CPT-11 has antitumor effects when administered either intravenously or subcutaneously. These effects were dose-dependent, and inhibitory effects continued even after completion of administration. In a histopathological examination, increased cornification and degeneration of the tumor cells (especially increased eosinophilia of the cytoplasmic element appearance of giant cells, pyknosis and disappearance of the nucleus) were observed. These findings appeared to be related to the inhibition of DNA synthesis, the main action of CPT-11. From the results of this study, it was evident that clinical application of CPT-11 should be successful in the cases of squamous cell carcinoma.