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Biomedical subjects

T Shimoda

Publications and source records attributed to T Shimoda.

At least 19 recordsLinked to original sources

Intracortical osteoblastic osteosarcoma with oncogenic rickets.

Intracortical osteosarcoma is the rarest variant of osteosarcoma, occurring within, and usually confined to, the cortical bone. Oncogenic osteomalacia, or rickets, is an unusual clinicopathologic entity in which vitamin D-resistant osteomalacia, or rickets, occurs in association with some tumors of soft tissue or bone. We present a case of oncogenic rickets associated with intracortical osteosarcoma of the tibia in a 9-year-old boy, whose roentgenographic abnormalities of rickets disappeared and pertinent laboratory data except for serum alkaline phosphatase became normal after surgical resection of the tumor. Histologically, the tumor was an osteosarcoma with a prominent osteoblastic pattern. An unusual microscopic feature was the presence of matrix mineralization showing rounded calcified structures (calcified spherules). Benign osteoblastic tumors, such as osteoid osteoma and osteoblastoma, must be considered in the differential diagnosis because of the relatively low cellular atypia and mitotic activity of this tumor. The infiltrating pattern with destruction or engulfment of normal bone is a major clue to the correct diagnosis of intracortical osteosarcoma. The co-existing radiographic changes of rickets were due to the intracortical osteosarcoma.

Bone Neoplasms

Clinicopathologic and immunohistochemical study of early colorectal cancer with liver metastases.

Seven (3.3%) of 213 patients who underwent surgery for early colorectal cancer (invasion limited to no deeper than the submucosa) at the National Cancer Center Hospital, Tokyo, between 1986 and 1995 had synchronous (2 patients) or metachronous (5 patients) liver metastases. The average period from surgical resection of the primary colorectal cancer to the diagnosis of liver metastases was 25 months (range, 0-52 months). The clinicopathologic and immunohistochemical features of the primary lesions in these patients were compared with these features in the lesions in consecutive patients with early colorectal cancer who had no evidence of liver metastases within at least 5 years after colorectal resection. Venous invasion was more frequent in the primary lesions with liver metastases than in those without liver metastases (57% vs 0%; P = 0.0035). Expression of p53 and CD44v9 was more frequent in the primary lesions with liver metastases (71% and 100%) than in those without metastases (56% and 72%). In contrast, MUC2 expression was more frequent in the primary lesions without liver metastases (72%) than in those with metastases (43%). Venous invasion is considered to be closely related to liver metastasis, and the immunohistochemical expression of p53 and CD44v9 provides useful information for identifying those patients with early colorectal cancer who have a high risk of developing liver metastases.

Adenocarcinoma

In vitro responses to antigen stimulation: comparison between human lung parenchyma resected from asthmatic patients and non-asthmatic patients.

BACKGROUND: The airway of asthmatic patients is hyperresponsive to various stimuli in vivo. There are, however, only a few reports that compared the in vivo responsiveness of asthmatic patients and non-asthmatic subjects to those of lung parenchyma in vitro. OBJECTIVES: To compare the contractile response, release of various chemical mediators, and responsiveness to drugs in samples of lung parenchyma excised from asthma patients with those of non-asthmatic subjects. METHODS: Human lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to mites. The strip was suspended in a magnus bath containing a buffer solution. Parenchymal contraction was induced by PGF2 alpha. After washing, the baseline concentrations of thromboxane B2 (TXB2), leukotriene (LT), and histamine were measured in each bath and then contraction was induced by the addition of a mite antigen. The concentrations of TXB2, LT, and histamine were measured after contraction. The inhibitory effects of TXA2 synthetase inhibitor (DP-1904) and TXA2 receptor antagonist (AA-2414) were also evaluated in both tissue samples. RESULTS: There were no significant differences between lung parenchymal tissues of asthmatic and non-asthmatic patients with regard to PGF2 alpha-induced contraction, antigen-induced contraction, release of chemical mediators, and the response to drugs. CONCLUSION: Unlike the response in vivo, there are no differences in the response to stimuli in vitro between lung parenchymal tissues of asthmatic and non-asthmatic patients.

Aged

Sensitivity to the house dust mite and airway hyperresponsiveness in a young adult population.

BACKGROUND: The pathogenic mechanisms of airway hyperresponsiveness (AHR) in asthma are unknown and only a few studies have examined the importance of sensitivity to antigens in AHR in young adults. OBJECTIVE: We investigated the correlation between AHR and sensitivity to specific antigens, atopy, history of childhood asthma and spirometry in a young adult population. METHODS: Based on the results of interviews with 447 students at our university, 308 non-smoker students were classified into six groups. Group 1 comprised subjects with intermittent mild bronchial asthma; group 2, subjects with history of childhood asthma; group 3, subjects with atopic disease, and a RAST score for Dermatophagoides farinae (Def) of > or = 2; group 4, normal subjects with a RAST score for Def of > or = 2; group 5, subjects with cedar pollinosis; and group 6, normal subjects. We measured AHR to methacholine (MCh), spirometry, immunoglobulin E-radioimmunosorbent test (IgE-RIST), IgE-radioallergosorbent test to six common antigens, eosinophil cationic protein (ECP), and eosinophil count in peripheral blood in each subject. RESULTS: Airway hyperresponsiveness to MCh did not correlate with IgE-RIST, eosinophil count, or ECP. The highest AHR to MCh was present in groups 1 and 2 and lowest in groups 5 and 6. Multiple regression analysis showed that sensitivity to Def was the only factor that significantly influenced AHR to MCh. Airway hyperresponsiveness to MCh of groups with a RAST score for Def of 0/1 was lower than groups with a RAST score of 2 to 6. Airway hyperresponsiveness to MCh did not correlate with the degree of positivity to Def antigen among positive sensitized groups (RAST score 2 to 6). CONCLUSIONS: Sensitivity to mite antigen may be important in the pathogenesis of AHR and Def is a major contributing antigen in young adults in Japan. Once asthma occurs, AHR remains positive for a long time even after the disappearance of asthma-related symptoms.

Adult

Corticosteroid resistance in mild asthma: markers of persistent inflammation.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is an important feature of asthma. Glucocorticosteroids (GCS) reduce BHR, probably by suppressing allergic inflammation. There are, however, two groups of asthmatics with either GCS-responsive or non-responsive BHR to methacholine. We investigated the mechanism of non-GCS-responsive BHR in mild asthma. METHODS: Non-GCS-responsive BHR asthma was defined as failure of reduction of BHR to methacholine after a 2-week course of oral prednisolone (30 mg/day). The expression of interleukin (IL)-4, IL-5, IFN-gamma mRNA in peripheral blood mononuclear cells, eosinophil count, serum cortisol, eosinophilic cationic protein (ECP), and spirometry were measured in five non-GCS-responsive BHR asthmatics and six patients with GCS-responsive BHR asthma before and after prednisolone therapy. RESULTS: With the exception of serum ECP and expression of IL-5 mRNA, no significant differences were observed between GCS-responsive BHR and non-GCS-responsive BHR asthma. The mean ECP level was significantly higher in non-GCS-responsive BHR than in GCS-responsive BHR asthma before and after prednisolone therapy. Interleukin-5 mRNA was detected in all asthmatics before prednisolone therapy; however, after prednisolone therapy, IL-5 mRNA was only detected in non-GCS-responsive BHR asthmatics. CONCLUSIONS: Our findings suggest that activation of eosinophils appears to persist in some asthmatics with non-GCS-responsive BHR due to continuous IL-5 production by lymphocytes.

Administration, Oral

Inhibitory effects of azelastine hydrochloride in alcohol-induced asthma.

BACKGROUND: Alcohol-induced bronchoconstriction is due to high blood concentrations of acetaldehyde, a metabolic product of ethanol, which lead to the release of histamine from basophils and mast cells. OBJECTIVE: We examined the inhibitory effects of azelastine hydrochloride, which inhibits histamine release and blocks H1 receptors, in alcohol-induced asthma. METHODS: Subjects were 13 Japanese asthmatic patients. We measured the change in FEV1 after ingestion of 30 g of pure ethanol. Blood ethanol, acetaldehyde, histamine, leukotriene C4 (LTC4), and thromboxane B2 (TXB2) concentrations were also measured. Alcohol challenge test was repeated in responders after administration of azelastine for 1 week at 4 mg/day. RESULTS: Of 13 asthmatic patients, five (38.5%) tested positive during an ethanol challenge test, represented by a fall more than 20% in FEV1. The responders had a high blood ethanol, and showed a rise in blood acetaldehyde and histamine concentrations, but not in LTC4 or TXB2. After azelastine treatment, there was no significant fall in FEV1 among responders. Neither the rise in blood ethanol nor blood acetaldehyde levels were blunted by treatment with azelastine, but the rise in blood histamine was blunted by this treatment. CONCLUSION: Our results suggest that antihistamine agents may be effective against alcohol-induced asthma by both blocking H1 receptors and inhibiting histamine release.

Acetaldehyde

Mucin histochemical analysis of minute gastric differentiated adenocarcinoma.

Fifty-six surgically resected intramucosal differentiated adenocarcinomas (DA) of the stomach with a maximum diameter of less than 5 mm were analyzed by mucin histochemistry. Gastric type phenotypic expression was observed in 41.1% of cases, intestinal type in 28.6% and gastric-intestinal type in 28.6% of all cancers. Gastric type phenotypic expression was the most frequent. As the tumor diameter increased, the incidence of DA with gastric phenotype tended to decrease. Intestinal metaplasia of the cancer's surrounding mucosa was absent or slight in DA with gastric phenotype, but moderate to severe in DA with gastric-intestinal phenotype and intestinal phenotype. Morphologically and mucin histochemically, intestinal metaplasia surrounding DA with gastric phenotype was immature and incomplete compared with DA with gastric-intestinal phenotype or intestinal phenotype. It is suggested that a large amount of DA with gastric phenotype is histogenetically derived from the gastric gland proper without intestinal metaplasia. However, as the tumor grows and intestinal metaplasia progresses, intestinal type phenotypic expression appears and then DA with gastric phenotype changes into DA with gastric-intestinal phenotype or intestinal phenotype.

Adenocarcinoma

Heterotopic sebaceous glands in the esophagus: histopathological and immunohistochemical study of a resected esophagus.

A resected esophagus with numerous heterotopic sebaceous glands was examined in an attempt to determine whether esophageal heterotopic sebaceous glands are the result of a metaplastic process or a congenital anomaly. The present case concerns a 79-year-old Japanese man with numerous esophageal heterotopic sebaceous glands accompanied by superficial esophageal cancer. The resected esophagus possessed numerous heterotopic sebaceous glands, which could be seen clearly as slightly elevated, yellowish lesions. Histological examination of these glands, all of which were located in the lamina propria, revealed lobules of cells that showed characteristic sebaceous differentiation. Bulbous nests of proliferating basal cells showing sebaceous differentiation were occasionally observed in the esophageal epithelium. Of the antibodies against six different keratins used, only anti-keratin 14 labeled both the heterotopic sebaceous glands and the bulbous nests. Acquired metaplastic change of the esophageal epithelium is probably the pathogenetic mechanism involved in these unusual lesions.

Aged

Paraneoplastic vasculitis associated with esophageal carcinoma.

We report a case of esophageal carcinoma associated with paraneoplastic vasculitis. A 69-year-old man suffered from low-grade fever and numbness of the lower limbs for 3 months before esophageal and gastric carcinomas were detected. Concurrent infection or collagen disease was ruled out following clinical and laboratory examinations. In April 1996, the gastric carcinoma was completely removed by endoscopic mucosal resection, but the symptoms remained. Three weeks later esophagectomy was performed for esophageal carcinoma after which time the fever and numbness disappeared. The esophageal carcinoma was a well-differentiated squamous cell carcinoma invading into the submucosal layer. Twenty-two lymph node metastases were found in 68 resected lymph nodes. Latent thyroid cancer was found. Histologically, vasculitis was detected in the esophagus, stomach and serratus anterior muscle. The distribution and degree of vasculitis were most pronounced in the esophagus. The concurrent onset and spontaneous resolution of fever and numbness after the removal of the esophageal carcinoma suggested a paraneoplastic origin. The majority of patients with malignant neoplasm-associated vasculitis had hematologic neoplasms. Cases of esophageal carcinoma associated with paraneoplastic vasculitis are extremely rare.

Aged

Histologic and immunohistochemical analysis of early submucosal invasive carcinoma of the colon and rectum.

To investigate the development and progression of colorectal carcinoma, submucosal invasive carcinoma (SMC) with residual intramucosal neoplasm was studied histopathologically. Intramucosal neoplasm was confirmed by immunohistochemical staining against anti-alpha-smooth muscle actin antibody. Submucosal invasive carcinoma was classified into polypoid growth-type carcinoma (PGC) and non-polypoid growth-type carcinoma (NPGC), depending on the presence of intramucosal tumor proliferation. Tumors were > 15 mm in size in 78.2% of the PGC lesions studied, but the degree of submucosal invasion was minimal (invasion of the upper 500 microm of the submucosal layer) in 52.9% of the PGC lesions. Conversely, 64.4% of NPGC lesions were 15 mm in size and the degree of submucosal invasion was moderate or severe (involving the middle and deeper layer of the submucosa) for 72.9% of NPGC. In other words, lesions of NPGC were significantly smaller in size but showed deeper infiltration than PGC lesions. Furthermore, PGC was derived from intramucosal polypoid carcinoma (including carcinoma with adenoma) and was morphologically identical to polyp cancer as reported previously. However, NPGC was derived from the flat and/or depressed type of intramucosal carcinoma classified not as polyp type, but as the superficial type. Typical NPGC was, therefore, also of the superficial type. In addition, approximately 25% of PGC lesions were identified as having an adenoma-carcinoma sequence. There was no coexistence with adenoma in the NPGC lesions, suggesting de novo development. When the degree of histologic atypia in the two types of intramucosal carcinoma was compared, 74.7% of PGC lesions showed low-grade carcinoma, regardless of tumor size, while 62.7% of NPGC lesions showed high-grade carcinoma in the intramucosal lesion. Approximately 25% of carcinomas with low-grade atypia were positive for p53 (as were the high-grade lesions), but it was not expressed in the adenoma. Therefore, tumor development and the degree of invasion differed significantly between the two types of carcinoma.

Actins

A case of menstruation-associated asthma: treatment with oral contraceptives.

A menstrual rhythm has been documented for exacerbations of asthma, which may have important clinical relevance to the patient with severe asthma. We report the case of a 26-year-old patient with menstruation-associated asthma who showed a dramatic response to oral contraceptives. It was noted that falls in peak respiratory flow rate coincided with ovulation. We concluded that oral contraceptive therapy is useful in this particular group of asthmatic patients.

Adult

Infrequent somatic mutation of the adenomatous polyposis coli gene in aberrant crypt foci of human colon tissue.

BACKGROUND: The authors examined somatic mutations of the adenomatous polyposis coli (APC) gene in 84 human aberrant crypt foci (ACF) to determine whether APC gene mutations were involved in the histologic progression of ACF. METHODS: Mutation cluster regions of the APC gene were subjected to polymerase chain reaction single-strand conformation polymorphism analysis and direct sequencing. RESULTS: Four kinds of deletion were detected in the mutation cluster regions of APC gene in five ACF. APC mutation was detected in 1 of 18 ACF with Stage I abnormalities (6%). Four of 10 adenomatous ACF (40%) harbored the mutation. There were no mutations in 56 hyperplastic ACF. CONCLUSIONS: These results suggest that APC mutations may be involved initially in only a limited number of adenomas in ACF.

Adenomatous Polyposis Coli

The clinicopathologic significance of small areas unstained by Lugol's iodine in the mucosa surrounding resected esophageal carcinoma: an analysis of 147 cases.

BACKGROUND: Small areas unstained with Lugol's iodine are often observed in the mucosa surrounding esophageal carcinomas. METHODS: For light microscopic evaluation, the histologic features of 131 small areas unstained by Lugol's iodine in 12 selected cases were investigated. For clinicopathologic evaluation, the numbers of small areas unstained by Lugol's iodine in the mucosa surrounding 147 consecutively resected esophageal carcinomas, including these 12 cases, were counted. The relation between the incidence of such areas and the development of multiple primary cancers in the upper aerodigestive tract was examined together with data on the patients' tobacco and alcohol consumption. RESULTS: Ninety-two percent (131) of the small areas unstained by Lugol's iodine contained dysplastic lesions. Seventeen (12%) of the 147 resected specimens contained fewer than 5 small unstained areas, whereas 52 (35%) had 6-10 and 78 (53%) had more than 11 such areas. The incidence of multicentric cancer in the upper aerodigestive tract and the average alcohol index scores were significantly higher for patients who had more than 11 unstained areas than for patients who had fewer than 5 such areas (P < 0.01). CONCLUSIONS: Lugol's iodine staining method is useful for detecting groups at high risk of multicentric cancer in the upper aerodigestive tract.

Adult

Differences in the diagnostic criteria used by Japanese and Western pathologists to diagnose colorectal carcinoma.

BACKGROUND: In view of the many studies of early stage colorectal carcinoma from Japan, it is essential to know whether the criteria for the histologic diagnosis of colorectal carcinoma are similar in Japan and Western countries. METHODS: Eight expert pathologists from Japan (4), North America (2), and Europe (2) individually reviewed microscope slides of 20 colorectal lesions from Japanese patients who had undergone endoscopic mucosal resection or surgery because early stage carcinoma and/or adenoma was suspected. The pathologists indicated the pathologic findings on which they based each diagnosis. RESULTS: For 11 slides that showed adenoma according to the Western pathologists with low grade dysplasia according to at least half of them, the Japanese diagnosed definite carcinoma with or without adenoma in 4 cases and adenoma in 5, and in 2 cases they were equally divided between a diagnosis of adenoma and carcinoma. For five slides showing adenoma with high grade dysplasia according to the Western pathologists, the Japanese diagnosed definite carcinoma with adenoma in three cases and adenoma in one, and in one case they were equally divided between a diagnosis of adenoma and carcinoma. For one case in which the Western pathologists were equally divided between a diagnosis of carcinoma and adenoma with high grade dysplasia, all the Japanese pathologists diagnosed definite carcinoma with or without adenoma. Three slides showed definite carcinoma with or without adenoma, according to both the Western and the Japanese pathologists. The presence of invasion was the most important diagnostic criterion of colorectal carcinoma for the Western pathologists, whereas for the Japanese the nuclear features and glandular structures were more important. CONCLUSIONS: In Japan, colorectal carcinoma is diagnosed on the basis of nuclear and structural criteria, even in cases considered by Western pathologists to be noninvasive lesions with low grade dysplasia. This diagnostic practice may contribute to the relatively high incidence of early stage colorectal carcinoma reported in Japan as compared with Western countries.

Adenoma

Correlation between alcohol-induced asthma and acetaldehyde dehydrogenase-2 genotype.

BACKGROUND: Alcohol-induced asthma, a phenomenon characteristic of Asians, is due to differences in alcohol metabolism, particularly acetaldehyde metabolism. We investigated the effect of polymorphism in acetylaldehyde dehydrogenase 2 (ALDH2) gene on the response to alcohol challenge testing in a group of Japanese asthmatic subjects and normal subjects. METHODS: Subjects were 32 asthmatic subjects and 30 healthy individuals. We measured the change in FEV1 after ingestion of 30 gm of ethanol. Blood ethanol, acetylaldehyde, and histamine concentrations were determined. ALDH2 gene type was established by polymerase chain reaction. RESULTS: Ethanol provocation test results were positive in 15 (47% responders) asthmatic subjects. The blood ethanol concentration was similar in responders and nonresponders. The fall in FEV1 was associated with a rise in blood acetaldehyde and histamine concentrations. The response to oral ethanol challenge was positive in three (19%) of 16 patients with normal homozygote ALDH2 genotype, 10 (71%) of 14 patients with type mutant heterozygote, and two (100%) of two patients with type mutant homozygote ALDH2 genotype. CONCLUSIONS: Alcohol-induced asthma is probably caused by increased blood acetaldehyde concentration resulting from abnormalities of ALDH2 enzyme activity based on ALDH2 genotype differences.

Acetaldehyde

Effect of synthetase inhibitors and receptor antagonists in antigen-induced contraction of human lung parenchyma.

BACKGROUND: Chemical mediators induce bronchoconstriction, enhance vascular permeability, and promote inflammation. The use of synthetase inhibitors and receptor antagonists of these mediators may be useful in the treatment of asthma. OBJECTIVES: We evaluated the role of chemical mediators in mite antigen-induced contraction in resected human lung parenchyma using synthetase inhibitors and receptor antagonists for these mediators. METHODS: Resected human lung parenchymal specimens were passively sensitized with serum obtained from patients with asthma showing an IgE RAST score for mites > or = 5. The specimens were suspended in Magnus bath filled with buffer. After confirmation of contraction using PGF2 alpha, buffer or synthetase inhibitors or receptor antagonists of various chemical mediators were added. Contraction of parenchyma was induced by the addition of mite antigen, and the concentration of thromboxaneB2 (TXB2), leukotriene (LT), and histamine was measured before and after contraction. RESULTS: Thromboxane A2 (TXA2) synthetase inhibitors significantly inhibited TXB2 release but not contraction. Leukotriene synthetase inhibitors significantly inhibited both LT release and contraction. The magnitude of the inhibitory effect was in the order of LT receptor antagonist > 5-lipoxygenase inhibitor > TXA2 receptor antagonist > PAF antagonist, TXA2 synthetase inhibitor, antihistamine > cyclooxygenase inhibitor. CONCLUSION: Among chemical mediators, LT appears to be the most closely involved in the immediate antigen-induced contractile response in resected human lung parenchyma. Receptor antagonists produced a more marked inhibition of antigen-induced contraction than synthetase inhibitors.

Aged

Comparison of three treatment regimens of inhaled sodium cromoglycate in the management of adult patients with severe, steroid-dependent asthma.

BACKGROUND: Asthmatic patients whose asthma remains poorly controlled despite treatment with high doses of inhaled corticosteroids and co-administration of oral corticosteroids are a difficult problem in therapeutics. OBJECTIVE: To investigate the relative efficacy of three treatment regimens of inhaled sodium cromoglycate in the treatment of adult, severe, corticosteroid-dependent patients as determined by the reduction in the dose of oral corticosteroids and change in lung function. METHODS: Open, randomized, group comparative trial of 12 weeks duration in asthmatic patients attending a hospital outpatient department. Patients whose asthma is (1) severe according to the classification of the Japanese Society of Allergology, (2) stable, and (3) needing treatment with at least 1600 microg of inhaled beclomethasone dipropionate and 5 mg or greater of oral prednisolone per day. The three treatment regimens of inhaled sodium cromoglycate were group A received sodium cromoglycate powder at a dose of 16 mg/day administered by a metered dose inhaler. Group N received sodium cromoglycate aqueous solution at a dose of 80 mg/day administered by a nebulizer. Group C received sodium cromoglycate aqueous solution (80 mg/day) combined with salbutamol (3 mg/day) administered by a nebulizer. The main outcome measures were a change in the daily dose of oral corticosteroids and in lung function with twice daily measurements of peak expiratory flow (PEF) recorded in the morning (PEF AM) and in the evening (PEF PM). RESULTS: Mean reduction in oral corticosteroid dose/day was group A, 3.68 mg (95% CI 1.35,5.95); group N, 3.59 mg (95% CI 0.73,6.45); and group C, 3.97 mg (95% CI 1.81,6.13). The dosage reductions are all significant but with no differences between the groups. The mean increase in PEF over the last 4 weeks of treatment compared with baseline values was significant in all groups. The increases in group C are significantly greater than those in the other groups. These changes are all significant and the increases in group C are significantly greater than those in the other groups. CONCLUSIONS: Inhaled sodium cromoglycate may be a useful additional treatment in the management of adult patients with severe, oral steroid-dependent asthma. Of the three methods of administration compared in this trial the most useful immediate results were obtained when the drug was administered as an aqueous solution mixed with salbutamol and delivered by a powered nebulizer.

Administration, Inhalation

Eccrine porocarcinoma with melanocyte colonization.

We describe a 74-year-old Japanese man with a pigmented eccrine porocarcinoma (malignant eccrine poroma). The patient had a brown-black nodule measuring 9 x 7 mm on his leg. Microscopically, the tumour, which had invaded the reticular dermis, was composed of poroid cells with large and small intracytoplasmic lumina. The tumour cells showed cytological pleomorphism and frequent, often abnormal, mitotic figures. Many dendritic melanocytes containing melanin were intermingled with the tumour cells. The poroid cells were diffusely positive for cytokeratin, while the dendritic cells containing melanin were positive for S-100 protein and HMB-45. Ten months of follow-up revealed no recurrence or metastasis of the tumour.

Acrospiroma