HSP-70, C-myc and HLA-DR expression in patients with cutaneous malignant melanoma metastatic in lymph nodes.

HSP-70, C-myc and HLA-DR were examined in patients with cutaneous malignant melanoma metastatic to lymph nodes. Lymph-nodal fine-needle aspiration biopsies (FNABs) were analyzed and the results were correlated to other variables, such as the gender of the patients, Clark level and Breslow thickness of the primary tumor. Thirty cases of metastatic melanoma in lymph nodes from 30 patients with cutaneous malignant melanoma were studied. All patients (100%) had microscopic regional nodal metastasis and a recurrence of the lesion during the first two years. The HSP-70, C-myc and HLA-DR expressions were investigated immunocytologically, using the APAAP (alkaline phosphatase) method on the FNAB samples. The immunocytochemical expressions of HSP-70 protein, C-myc oncogene, and HLA-DR antigen were found in 18 cases (60%), in 14 cases (43.3%) and in 12 cases (40%), respectively. Clark levels were significantly associated with HSP-70 protein (< 0.01), C-myc oncogene expression (< 0.05) and HLA-DR antigen (< 0.01) expression. The HLA-DR antigen was also found to be related (< 0.05) to higher Breslow thickness (> 1.5 mm). The clinical course of malignant cutaneous melanoma is related to the expression of these indices, which seem to play a significant role in the metastasis and prognosis of this aggressive tumor. The immunocytochemical expression of HSP-70 in the malignant melanoma tumor could be of particular value in the identification of patients with poor prognosis.

Cell proliferation and DNA fragmentation (apoptosis) on FNABs of breast invasive ductal carcinomas and their relationship to clinicopathological variables and prognosis.

The purpose of this study was to investigate cell proliferation and apoptosis in ductal breast invasive carcinomas and their relationship to prognosis. Fifty cases, from the same number of operable female patients, were diagnosed cytologically on FNA biopsies as invasive ductal breast carcinomas and confirmed histologically after oncectomy. In the same cases, to evaluate the cell proliferation and apoptosis, the MIB1 and the TUNEL method were used respectively. Furthermore the relationship between proliferative activity and apoptosis to other factors such as menopausal status, tumor size, axillary lymph node status and tumor grade was studied. Cell proliferation and apoptosis were found to be significantly related to the menopausal status of the patients (p < 0.001) and to the grade of the tumor (p < 0.01), while no significant relationship to axillary lymph node status and tumor size was found.

Bcl-2 expression as an apoptotic index in non small cell lung carcinomas.

To evaluate the bcl-2 protein expression in non small cell lung carcinomas (NSCLC) as an index of apoptosis of these tumors, in fine needle aspiration biopsies (FNABs) of the lung, we studied thirty-eight cases of NSCLC (25 bronchogenic adenocarcinomas and 13 squamous. carcinomas. Bcl-2 protein was used as the primary antibody (monoclonal, DAKO) by Alkaline-phosphatase method. Very light haematoxylin was performed as the counterstain. The results were compared and confirmed histologically. A cytoplasmatic expression of the bcl-2 protein was found in 72% (18 out of 15) of the bronchogenic adenocarcinomas while 61.54% (8 out of 13) of squamous carcinomas showed bcl-2 expression. For the quantitative analysis of our results, we used the t-test and the difference between those two histologic types was regarded as statistically significant with p < 0.001.

Nuclear grading in invasive ductal breast carcinomas.

Nuclear grade (NG) was studied in cytologic material obtained from 120 fine-needle aspiration biopsies of breast lesions and compared with the NG observed in the nuclear grade of surgical biopsies of the same lesions. All lesions included were invasive breast carcinomas diagnosed cytologically and confirmed histologically. Cytologic aspirates and tissue sections were graded by cytologists and pathologists, respectively, using a multiheaded microscope. Fisher's modification of Black's NG scheme was used. An agreement was observed between the NG of cytologic material and that of surgical biopsies in 93.33% of tumors, and an interesting exercise would be to correlate the NG with other significant factors for the prognosis of breast carcinomas. The purpose of this study was to assign and correlate the NG of ductal carcinomas of the breast in fine-needle aspiration biopsies and tissue specimens from the same patients.

P53 expression in patients with malignant and benign breast diseases.

Immunohistochemical expression of p53 protein was studied in FNA specimens of 20 breast ductal carcinomas, 20 fibroadenomas and 20 atypical ductal hyperplasia of the breast. Nine cases of breast carcinomas (45%), five fibroadenomas (25%) and four atypical ductal hyperplasia (20%) were found to be p53-immuno-positive. A statistically significant difference was found among p53 staining index of breast carcinomas (mean 72.55%), fibroadenomas (mean 41.2%) and atypical ductal hyperplasia (mean 34%). Variations in p53 expression among individual breast carcinomas was found, and these variations may correlate with prognosis.

Quantitative cytology in ovarian carcinoma ascitic fluids.

OBJECTIVE: To assess the value of quantitative methods in the differential diagnosis between ovarian carcinoma cells and mesothelial cells in ascitic fluids. STUDY DESIGN: Ninety ascitic fluid samples, previously reported as positive for ovarian carcinoma (30 cases), suspicious for malignancy (30) and negative for malignancy, containing only reactive mesothelial cells (30), were retrieved from the files. In each of these specimens the nuclear area, perimeter, roundness and shape coefficient of 100 cells were determined at 630 x magnification. Statistical analysis was performed using analysis of variance and, for multiple comparisons, the Student-Newman-Keuls technique. RESULTS: Mean values for nuclear area and perimeter were higher in malignant cells as compared to reactive mesothelial cells, whereas those for roundness and shape coefficients were lower. All differences were statistically significant, the former two at a .05 level and the latter at the .001 level. CONCLUSION: Quantitative methods can reliably support the differential diagnosis between ovarian carcinoma cells and mesothelial cells in ascitic fluid specimens.

Cytological diagnosis of malignant mixed müllerian tumor of the uterus in ascitic fluid.

The malignant mixed Mullerian tumour (MMMT) is a rare and aggressive neoplasm of the uterus, seen in postmenopausal women. In this case, an uncommon neoplasm was diagnosed cytologically in the ascitic fluid of a woman 58 years old and was confirmed histologically after hysterectomy and bilateral adnexectomy.

Nuclear morphometry of the myocardial cells as a diagnostic tool in cases of sudden death due to coronary thrombosis.

Sudden cardiac death due to underlying coronary artery thrombosis is one of the leading causes of death. However, in a significant percentage of individuals who died suddenly, no indication of myocardial infarction is found during post-mortem examination, especially when the time interval between appearance of symptoms and death is short. In the present study, we have evaluated certain nuclear morphometric parameters, such as, minimum, maximum, mean and standard deviation of perimeter and area in 20 individuals who died of coronary artery thrombosis, within 1 h from symptoms onset. Furthermore, the above parameters were compared with those of a control population of 20 individuals whose sudden death was caused by traffic accidents. Statistical elaboration of the results by means of t-test, Mann-Whitney (U-test) and analysis of covariance (adjusting for age), showed a statistically significant difference for all variables except for the minimum area. With stepwise discriminant analysis method, the mean perimeter was selected as the best predictor of cardiac death. Mean perimeter achieved a correct reclassification percentage (based on Fisher's linear discriminant function) of 92.5% (85% and 100% for cases and controls, respectively). Moreover, by applying the cut-off of 172 microns, we could identify the individuals who died suddenly because of coronary artery thrombosis with a specificity of 100% (sensitivity 85%, P < 0.001). Our results show that nuclear morphometry of the myocardial cells is a reliable diagnostic tool for the diagnosis of coronary thrombosis based lesion in cases of sudden death, even when methods trying to verify the presence of infarction fail to do so.

Quantitative pathology in uterine smooth muscle tumours: the case for the standard histologic classification criteria.

A number of nuclear morphometric factors (longest and shortest axis, perimeter, area, roundness coefficient) as well as the number of mitoses per 20 high power fields with an x40 objective (mitotic index) and the volume corrected mitotic index (VCMI) have been assessed in 33 uterine smooth muscle tumours (14 leiomyomata, 5 leiomyosarcomata, 9 atypical leiomyomata and 5 tumours of uncertain malignant potential). Multivariate analysis showed the VCMI and nuclear roundness coefficient to be the two most significant prognostic factors achieving, by means of Fisher's linear discriminant function, a high percentage of correct reclassification of the tumours into their respective groups. Furthermore, VCMI was shown to be a more accurate prognostic factor than the simple mitotic index. The results uphold the traditional classification histologic criteria and demonstrate the significance of VCMI as a reliable index of mitotic activity.

The prognostic value of morphometry in advanced epithelial ovarian cancers.

The relationship between morphometric and clinical data was assessed in a series of 60 advanced ovarian carcinomas. Morphometric parameters included nuclear area, nuclear perimeter, shortest and longest nuclear axis, roundness coefficient, volume percentage of epithelium (VPE) and mitotic index. All patients had at least 5 years of follow-up. Univariate survival analysis showed that FIGO stage (P < 0.001), VPE (P < 0.001), mean nuclear area (P < 0.001) and size of residual tumour (P < 0.001) are significantly associated with survival. When the response rate of these patients to cisplatin combination chemotherapy was evaluated, variables with good prognostic outcome were residual tumour size (P = 0.01), mean nuclear area (P = 0.0006) and s.d. of nuclear area (P = 0.0019). We conclude that morphometric parameters are able to support diagnostic and therapeutic decisions.

Metastasis of malignant melanoma to a transitional cell carcinoma of the urinary bladder.

A case of malignant melanoma metastatic to a transitional cell carcinoma of the urinary bladder in a 28-year-old female is reported. This is the sixth reported case involving malignant melanoma metastasis in another neoplasm. The pertinent literature is reviewed.

Gliosarcoma cerebri with a myxoid matrix of the sarcomatous component.

A case of a cerebral gliosarcoma in a 63-year old female located in the left parietooccipital area of the brain is herewith described. Histology showed the tumour to consist of two components: a gliomatous resembling glioblastoma, and a sarcomatous with a prominent myxoid intercellular substance, a feature reported only thrice before in the medical literature. We report the histochemical and immunohistochemical characteristics of our case, and compare them with those of previous case reports.

Nuclear morphometry as a prognostic factor in laryngeal squamous cell carcinomas. Preliminary study.

A preliminary report concerning the prognostic significance of certain nuclear morphometric parameters in laryngeal squamous cell carcinoma (SCC) is presented. 18 cases of primarily glottic laryngeal SCC were graded according to the criteria outlined by Jakobsson et al., and assessed for the presence of infiltration of laryngeal cartilage. Nuclear width (short axis) and perimeter were found to be smaller in the "favourable prognosis" group than in the "unfavourable prognosis" one, on an indicative basis only, due to the small number of cases. The nuclear perimeter was furthermore found to be larger in cases with carcinomatous infiltration of the laryngeal cartilage than in cases without, on a statistically highly significant basis. The clinical utility of these results in a biopsy report of a laryngeal SCC is discussed.

Vascular density and the response of breast carcinomas to mastectomy and adjuvant chemotherapy.

Using morphometric analysis of histological preparations, in a retrospective study vascular indices, expressing the extent of vascularisation, were determined for a number of mammary carcinomas. The indices were found to be related to the survival of the patients treated with modified radical mastectomy in combination with pre- and postoperative chemotherapy, the cases with low indices having the shorter survival. The impaired access of the cytotoxic agents to cells in the deficiently vascularised tumours was considered as an explanation. It was concluded that determination of vascular density in tumours may have a prognostic value in regard to the treatment response, and may be helpful in choosing the appropriate treatment.

A case of gonadoblastoma in a normal woman with tubal pregnancy.

Gonadoblastoma is a rare tumor arising usually in a dysgenetic gonad. The commonest karyotypes seen in patients with this neoplasm are 46XY and 46XY/45XO mosaicism. The occurrence of gonadoblastoma in pregnant or normal (46XX karyotype) women is extremely rare. A case of gonadoblastoma in a pregnant eukaryotic (46XX) woman is reported.

DNA distribution pattern and comparison of quantitative data in breast tumours.

Aspiration cytology smears from 24 breast alterations were subjected to cytophotometry and TV image analysis. The smears were grouped according to histological diagnosis and cytological pattern. Cell cycle parameters and DNA indices were calculated from the decomposition of the DNA histograms. Based on quantitative morphometric features the TV image analyser distinguished the benign cells from the malignant ones. In benign cases its diagnostic accuracy is of 80%. Cytological Grades 1, 2 and 3 are also identifiable by this system. Cytophotometric measurements were also performed with 22 invasive breast cancers with known 5-year survival. The cell cycle parameters were related to the survival data. From the point of view of survival only the ratio of the S plus G2 phase cells of all the parameters examined proved to be significant.

Correlation of histoenzymological studies with the response to chemotherapy and survival in breast cancer patients.

The enzyme activity of cancerous tissue and the adjacent normal epithelium of 40 patients with breast cancer was determined. This enzymatic activity was correlated with the responsiveness of those tumors to the chemotherapy. It was found that the presence of cytochrome oxidase and alkaline phosphatase and the absence of leucine aminopeptidase, beta-glucuronidase and dehydrogenases in cancerous tissues was related to good response. On the contrary, the absence of alkaline phosphatase and cytochrome oxidase and the presence of leucine aminopeptidase, beta-glucuronidase and dehydrogenases in the cancerous tissues was related to poor response and therefore to poor survival.

Carcinosarcomas of the skin--report of two cases.

Carcinosarcomas of the skin are extremely rare. Two such cases have been recorded in the literature. In the two cases reported, the epithelial component consisted of a well differentiated squamous cell carcinoma and the mesenchyma of a malignant fibrous histiocytoma. Immunohistochemistry was applied for the confirmation of the diagnosis.

Vascularization and curability of stage III and IV nasopharyngeal tumors.

In a retrospective study the capillary density was determined in biopsies from 25 cases of nasopharyngeal tumor, stages III and IV. Determinations were made on stained histological sections by counting the capillaries within a standard field size and at standard magnification. A statistically significant correlation was found to exist between capillary density and eventually with chemotherapy. No correlation between survival and age or sex of the patients, or stage of tumor, was noted. It is concluded that capillary density in nasopharyngeal tumors has a predictive value.