Characteristics of incompletely excised basal cell carcinomas of the skin

OBJECTIVES: To determine the proportion of basal cell carcinomas (BCCs) treated by excision biopsy that extended to the margins of surgical excision (incompletely excised tumours) and to identify their characteristics. DESIGN: Case series of BCCs submitted to a single pathologist in the first six months of 1995. SETTING: Rural and metropolitan (Perth) Western Australia. PATIENTS: 268 patients with 353 histologically confirmed BCCs. OUTCOME MEASURES: Age and sex of patients; discipline of referring doctor; anatomical site of BCC; macroscopic features; histological growth pattern; and completeness of excision. RESULTS: Sixteen per cent of BCCs (58/353) extended to the margin of surgical excision. Most of these were situated on the head or neck (43/58; 74%) and were flat (47/58; 81%); a high proportion of incompletely excised BCCs (21/58; 36%) had an infiltrative growth pattern. Recurrent BCCs (28/353; 8%), categorised from the history or because of histologically identified surgical scarring, were even more likely to be flat (26/28; 93%) and to show a microscopic infiltrative growth pattern (18/28; 64%). Seven of the 28 (25%) recurrent BCCs were incompletely excised; all seven were on the head and five had an infiltrative growth pattern. CONCLUSION: Incompletely excised BCCs are those most likely to recur. Because most recurrent tumours are situated on the head and neck and have an infiltrative growth pattern, we recommend that: Pathologists report on the microscopic growth pattern of BCCs as well as on completeness of excision. Clinicians attempt to excise head and neck BCCs with wide margins initially, where possible. Tumours extending to the margin of excision which are infiltrative in pattern and located on the head and neck may be particularly likely to recur, and immediate re-excision should be considered in these patients.     

Immunohistochemical staining of ovarian granulosa cell tumors with monoclonal antibody against inhibin

Inhibin is a peptide hormone produced by ovarian granulosa cells and by granulosa cell tumors. Serum inhibin measurements have been used as a biochemical marker of the presence or progression of ovarian granulosa cell tumors and their metastases. In the current study, an antibody against the alpha-subunit of human inhibin was used to stain 16 cases of ovarian adult granulosa cell tumors, 15 cases of other ovarian sex cord-stromal tumors, and 51 cases of a range of ovarian and extraovarian neoplasms, many of which may mimic granulosa cell tumor. There was diffuse strong cytoplasmic staining of all cases of adult granulosa cell tumor. Diffuse positive staining also was observed in all Leydig cell tumors, and there was focal staining in a proportion of fibrothecomas. There was focal weak staining of one case of ovarian clear cell carcinoma but no staining of other ovarian and extraovarian neoplasms. Immunohistochemical staining with antibodies against inhibin is of value in the diagnosis of granulosa cell tumor and in the distinction of this neoplasm from others that may mimic it. The antibody also may be useful for the confirmation of late metastasis of granulosa cell tumor, especially when the previous history is not known.     

Immunohistochemical localization of granzyme B in peritumoral infiltrates of basal cell carcinoma

We report a case of eosinophilic cystitis the onset of which was characterized by acute peritonitis secondary to a spontaneous intraperitoneal rupture of the vesical cupula. The patient was treated with urgent partial cystectomy in another hospital and 3 months later he underwent endoscopic diathermic coagulation of a residual inflammatory lesion at our institution. After an 18 month endoscopic follow-up no further signs of recurrent eosinophilic cystitis have been pointed out. The non-traumatic bladder perforation and the absence of any other bladder pathology might indicate that eosinophilic cystitis can be responsible for complete bladder rupture.     

Effect of cell differentiation in prostatic cancer on basal PSA

The effect of cell differentiation on PSA production in patients with prostate cancer has been evaluated. With this intention 70 patients were included and were analyzed for age, T stage, cell differentiation, bone scan involvement and PSA level prior to therapy. In well-differentiated tumours mcan PSA was 31.3 ng/mL, 56.6 in those with moderate differentiation and 31.6 in poorly differentiated ones (p > 0.05). Multivariate analysis shows no significant differences between both variables, but and inverse relationship between cell differentiation and PSA production (r = -0.27, p > 0.05) can be seen. The most influential variable on PSA levels was de extent of bone scan involvement. Cell differentiation as confusion variable to interpret PSA values in poorly differentiated tumours deserves further study to know the exact role of this protein as a treatment response criterion in prostate cancer.     

Results of the treatment of bladder tumors infiltrating the muscle

The results of PUVA treatment for severe alopecia areata (AA) were reviewed in 102 patients. Fifty-three per cent had greater than 90% regrowth of hair. Although these results appear to be encouraging, they differ little from what would be expected with no treatment. We consider that PUVA is not an effective treatment for AA.     

Expression of retinoic acid receptor proteins in basal cell carcinomas: an immunohistochemical analysis

We analyzed immunohistochemically the expression of RAR proteins in basal cell carcinomas (BCCs; n = 15) in situ. The labeling pattern for the different types of RARs was compared with the staining pattern of the proliferation marker Ki-67 in the same tumors. We found strong immunoreactivity for RAR-alpha and moderate immunoreactivity for RAR-gamma in all BCCs analyzed, whereas no or very weak staining for RAR-beta protein was detected. In contrast to RAR-gamma, which revealed no or only marginal differences in staining intensities, RAR-alpha immunoreactivity was consistently stronger in BCCs compared to adjacent unaffected epidermis. In general, labeling of BCCs for RAR-alpha and RAR-gamma was pronounced in cells of the palisade and peripheral cells, whereas staining in the center of the tumors was heterogeneous. Eleven of the 15 BCCs analyzed revealed no visual correlation in comparing labeling patterns for RAR-alpha and RAR-gamma with the labeling pattern for Ki-67. In four specimens, expression of RAR-alpha, RAR-gamma, and Ki-67 proteins was confined to peripheral tumor cells. Our findings indicate that (a) RAR-alpha and RAR-gamma proteins are, in contrast to RAR-beta, strongly expressed in BCCs; (b) expression of RAR-alpha is upregulated in BCCs compared to keratinocytes of uninvolved epidermis; and (c) BCCs may be targets for potentially preventive or therapeutic treatment with RAR-alpha- or RAR-gamma-selective retinoic acid metabolites.     

Influence of neoadjuvant treatment on bladder infiltrating tumors treated with radical cystectomy

Retrospective study of 107 patients diagnosed with infiltrant tumour of the bladder in stage T3-T4 N0-N1, treated with radical surgery. Eighty-four (84) received neoadjuvant therapy with radio- and/or chemotherapy. The neoadjuvant treatment was seen to provide significantly better survival, but the specific type of neoadjuvant treatment appears to have no influence. The multivariate study evidenced that the two most influential variables for survival are the complementary treatment and the clinical stage.     

Immunohistochemical analysis of proliferation and differentiation in organotypic cultures of cervical tumor cell lines

Researchers have previously demonstrated that organotypic cultures of cervical tumor cell lines exhibit morphological characteristics similar to the in vivo biopsies from which they were derived (Rader et al., 1990). Both the in vivo biopsy and organotypic culture appeared undifferentiated. We have extended these studies with immunohistochemical analysis using the proliferation and differentiation markers, proliferating cell nuclear antigen (PCNA) and involucrin, respectively, to evaluate in more detail the ability of cervical tumor cell lines to differentiate in organotypic culture. An HPV-immortalized keratinocyte cell line, PE-4, expressed PCNA in the lower half and involucrin in the upper half of the organotypic culture which is consistent with the characteristics of a preneoplastic lesion in vivo. The CC-1 cell line, derived from an invasive squamous cell carcinoma, appeared undifferentiated, but expressed involucrin in the upper half of the organotypic culture. This is the first observation of expression of a differentiation marker in an organotypic culture of a cervical tumor cell line. The other cervical tumor cell lines, SiHa and HeLa, derived from a squamous cell carcinoma, and an adenocarcinoma of the cervix, respectively, did not express detectable levels of involucrin or mucin. All three cervical tumor cell lines, CC-1, SiHa and HeLa, expressed PCNA throughout their entire thickness. The majority of nuclei in SiHa and HeLa cultures were PCNA-positive, while the CC-1 cell line exhibited a lower growth fraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical study on the expression of carbohydrate antigens in normal squamous epithelia and squamous cell carcinomas of the uterine cervix

The expression of 4 kinds of carbohydrate antigens, CA50, CA19-9, sialyl SSEA-1, and DU-PAN-2 was studied immunohistochemically in 15 normal cervical squamous epithelia and 49 cervical carcinomas. (1) In normal epithelia, CA50 and CA19-9 were expressed in all cell layers and all cell layers except for the basal layer, respectively, and a gradual decrease in the intensity of staining was observed in the upper layer. Sialyl SSEA-1 was expressed only in the superficial layer, but DU-PAN-2 was not found in any normal epithelia. (2) In cervical carcinomas, CA50, CA19-9, sialyl SSEA-1 and DU-PAN-2 were observed in 51.0%, 49.0%, 55.1% and 26.7%, respectively. (3) The number of Ki67 positive cells tended to be lower in the area with sialyl SSEA-1 immunostaining. (4) In the cases in which sialyl SSEA-1 positive cells were distributed diffusely in cancer nests, the incidence of lymph node metastasis was significantly higher. These result suggest that the expression of CA50, CA19-9 and sialyl SSEA-1 is related to the differentiation of normal squamous epithelial cells, and sialyl SSEA-1 may be related to cell differentiation also in cervical carcinomas, and the features of its expression may be useful in predicting the biologic properties of cervical carcinomas.     

p21WAF1/Cip1 expression is associated with cell differentiation but not with p53 mutations in squamous cell carcinomas of the larynx

The anti-metastatic effect of Z-100, an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis, was investigated in mice bearing B16 melanoma cells. Treatment of BF10 mice implanted with high metastatic B16F10 melanoma cells with a 10 mg/kg dose of Z-100 resulted in the reduction of experimental pulmonary metastasis as compared with that of BF10 mice treated with saline. The number of pulmonary metastatic colonies in BF1 mice (mice implanted with low metastatic B16F1 melanoma cells) was greatly increased after the inoculation of CD4+ CD11b+ CD281+ TCR alphabeta+ type 2 T cells (F10-Th2 cells) derived from BF10 mice, while only a few metastatic colonies were demonstrated in lungs of BF1 mice inoculated with naive CD4+ T cells. However, the numbers of metastatic colonies in BF1 mice were not increased when they were inoculated with the F10-Th2 cell fraction derived from Z-100-treated BF10 mice and the generation of F10-Th2 cells in BF10 mice was effectively suppressed by the Z-100 treatment. These results suggest that Z-100 inhibits pulmonary metastasis of B16 melanoma through the regulation of tumor-associated Th2 cells, which are a key cell in the acceleration of tumor metastasis.     

Definitive surgery for duct cell carcinomas of the pancreas

BACKGROUND AND DESIGN: As changes in the health care system aim to reduce the cost of medical care, physicians need to understand and be able to justify their reasons for referring patients. To learn the basis for making referrals, we asked 116 referring physicians why they made referrals to one university-based physician. We also assessed the referring physicians' satisfaction. RESULTS: A total of 112 of the 116 physicians responded in reference to 114 patients. The responses fit into five categories. Fifty of 114 patient were referred for therapy; 16 patients, for a diagnosis; and 16, for a combination of diagnosis and therapy. Other reasons in descending order of frequency were (1) a nondermatologist referring the patient to a dermatologist, (2) self-referral, ie, the patient was not referred by the physician, and (3) the patient's personality was difficult. The referring physicians were satisfied in 94 instances. CONCLUSIONS: The most frequent reason for referral was for therapy. This observation may be generally true for many physicians, since it is consistent with results of two other studies, in different fields, that we were able to find. Eighty-two percent of referrals were satisfactory to the referring physicians. Most of the physicians who were unsatisfied with the referral process stated they had not received a follow-up letter from the consulted physician.     

Immunoreactivity for LN2 and LN3 distinguishes small cell carcinomas from non-small cell carcinomas in the lung

The hydrolyzing activities of O-hexyl O-2,5-dichlorophenyl phosphoramidate (HDCP) and p-nitrophenyl butyrate (p-NPB) in chicken serum had been found to copurify in the same protein, identified as albumin. The hydrolyzing activities of both chicken serum and commercial serum albumins from different species were inhibited in a dose-dependent manner by short chain fatty acids. On simultaneous incubation of chicken serum with HDCP and p-NPB, a competitive interaction was detected between the two substrates. This behavior suggests that both are hydrolyzed in the same albumin active site. When chicken serum was preincubated with one of the substrates, and the latter were withdrawn by large dilution, the hydrolyzing activities with both substrates were found to be reduced. This reduction was in turn dependent upon the time of preincubation with the first substrate. These results suggest that HDCP and p-NPB are hydrolyzed by the same albumin active site, via a mechanism based on transient phosphorylation/acylation of the active site. The proposed hydrolysis mechanism would account for the hydrolytic kinetics of both substrates.     

Improving state Medicaid contracts and plan practices for children with special needs

The purpose of this study was to investigate the actions of intraperitoneal macrophages and aortic endothelial cells (EC) as the cause of proliferation of primary cultured smooth muscle cells (SMC) of the aorta in non-insulin-dependent diabetes mellitus (NIDDM) models, including spontaneously diabetic GK and streptozotocin-diabetic Wistar rats. Conditioned medium derived from macrophages of GK rats increased proliferation of SMC in Wistar rats to a greater extent when compared to normal Wistar rats in conditioned medium. Serum of both GK rats and of Wistar rats which was previously exposed to 16.7 and 25 mM glucose (glycated serum) activated normal macrophages, enhancing SMC proliferation. However, glycated serum and high concentrations of glucose did not affect directly the proliferation of SMC. Conditioned medium from EC of streptozotocin-Wistar rats enhanced SMC proliferation. The enhancing activity of EC in diabetic rats was mimicked by conditioned medium from glycated EC but not from EC treated with the diabetic rat serum nor glycated bovine serum albumin. Cholesterol (39 microg/ml) potentiated the action of glycated serum on macrophages, but neither the action of normal macrophages nor the direct action of SMC was affected. Both the actions of glycated serum and cholesterol were inhibited by a polyclonal platelet-derived growth factor-BB antibody. However, low density lipoprotein (LDL), acetylated LDL and oxidized LDL (25 microg/ml) did not potentiate the action of glycated serum. These results demonstrate that glycated serum in the NIDDM model predominantly activated macrophages, resulting in proliferation of SMC by the release of platelet-derived growth factor-BB. Cholesterol potentiated the actions of glycated serum on macrophages.     

Epithelial tumors with thymus differentiation of the thyroid gland and the neck

A total of 1100 samples of prepared foods purchased in restaurants and delicatessen shops in the city of Barcelona was examined for the presence of Listerio. L. monocytogenes was more frequently isolated from foods intended to be consumed without further cooking (9.3%) than from foods intended to receive further cooking prior to consumption (2.9%). A quantitative study, carried out with 773 samples, yielded 1% of samples with numbers of L. monocytogenes higher than 100 CFU/g. Strains of L. monocytogenes belonged to serovar 4b (36.3%), 1/2a (29.5%), 1/2b (22.7%) and 1/2c (11.3%). L. monocytogenes serovar 4b phagevar 3274: 2671 (6 of 11) was prevalent among the strains studied.     

Role of electron microscopy and other special techniques in the diagnosis of childhood round cell tumors

A series of case presentations show unique challenges associated with childhood round cell tumors and the role of ancillary techniques in diagnosis. Electron microscopy is shown to be the most powerful individual technique. Immunohistochemistry is less effective but also essential. Other ancillary techniques may provide needed additional diagnostic information. Because this is an area where it is of great importance to secure the most rapid, accurate, and specific diagnosis possible, an integrated multimodal approach is recommended--incorporating light microscopic, electron microscopic, and immunohistochemical studies as a matter of routine, and providing for cytogenetic and/or molecular diagnostic studies as indicated.     

CCNU chemotherapy in adult patients with tumors of the basal ganglia and brain stem

The present investigation evaluates those few patients of our series with basal ganglia and brain-stem tumor who refused either surgical decompression and biopsy or radiation therapy. Four patients were suffering from tumors of the basal ganglia and three from brain-stem tumors; all the tumors were diagnosed by classical neuroradiological investigations and computerized tomography. The patients were given CCNU by mouth, 13 mg/sq m every 6 weeks. No toxicity was recorded. Mean survival was 19 weeks for patients with basal ganglia tumors and 48 weeks for those with brain-stem tumors. All patients were evaluated with respect to the quality of survival. Results were compared with those obtained in a control group of patients who received methylprednisolone therapy only.