DNA content and proliferation activity in superficial transitional cell carcinoma of the bladder.

The identification of new prognostic parameters in Superficial Transitional Cell Carcinoma of the Bladder (STCCB) is important since conventional methods are often insufficient for prognostic purposes. We studied the proliferation activity and the DNA ploidy status of 60 pTa and pT1 Superficial Transitional Cell Carcinoma of the Bladder in relation to grade and recurrence rate. The proliferative activity was investigated by measuring the PCNA expression in paraffin embedded tissue sections. The DNA content was studied in Feulgen stained imprints by image analysis technique using a SAMBA 2005 analyser. According to our measurements a statistically significant difference was found in PCNA expression among tumors grade I, grade II, grade III (F = 5.43, p < 0.001), between tumors of the same grade with, and without recurrence (p < 0.001); and between recurrent and non-recurrent tumors (T58 = -6.03, p < 0.001). A statistically significant difference was also observed concerning the DNA-index among grade I, grade II and grade III (F = 4.81, p < 0.01), and between recurrent and non-recurrent tumors concerning the DNA DNA ploidy status (DNA-euploid vs. DNA-aneuploid tumors) (X2 = 24.96, p < 0.001). The recurrence status is also strongly influenced by the proliferation rate and the DNA ploidy status of tumors (X23 = 41.19, p < 0.001). No cases recurrence were found in the group of DNA-euploid tumors with PCNA. expression lower than 30%, in contrast a very high percentage of recurrence in patients with DNA-aneuploid tumors with PCNA expression higher than 30%. Although a small proportion of cases could not be included in me previous categories, STCCB may be classified in to main groups concerning the risk of recurrence. In keeping with this view of proliferation rate and DNA ploidy status could provide useful information, on the potential malignancy of Superficial Transitional Cell Carcinoma of the Bladder. However further studies are required to establish the clinical utility of these parameters.

Curschmann's spirals in sputum: histochemical evidence of bronchial gland ductal origin.

Curschmann's spirals from 30 patients suffering from chronic bronchitis were examined histochemically by periodic acid-Schiff (PAS), Alcian blue (AB), PAS-AB, high-iron diamine (HID), and HID-AB stains. Their central core and fibrillar component were found to be rich in neutral mucins and in sulfated and nonsulfated acid mucins, while their outer mantle was rich in neutral and nonsulfated acid mucins only. Curschmann's spirals consist of mucus of high viscosity. Histochemical and morphological evidence suggests that, in addition to their origin in the lumen of smaller bronchi and bronchioles, they are also formed in the ducts of the seromucous bronchial glands.

Immunodetection of neuron-specific enolase and keratin in cytological preparations as an aid in the differential diagnosis of lung cancer.

The results of neuron-specific enolase (NSE) and keratin immunodetection in cytological specimens of sputum secured from 41 patients with lung cancer are presented. All 19 cases of small-cell carcinoma showed intense immunoreactivity for NSE. No such immunoreactivity was found in 21 of 22 cases of non-small-cell carcinoma. The single positive result was from a case of large-cell undifferentiated carcinoma. All 10 cases of squamous-cell carcinoma showed immunoreactivity for keratin. The 19 cases of small-cell carcinoma showed no such reactivity. Our findings indicate that immunostaining for NSE and keratin is a valuable aid when a definite diagnosis of small-cell carcinoma of the lung can not be made on the basis of conventional cytologic features.

Efficacy of the Isaacs Endometrial Cell Sampler in the cytologic detection of endometrial abnormalities.

The efficacy of the Isaacs Endometrial Cell Sampler to obtain specimens for cytologic examination to detect both hormonal disturbances and precursors of malignancy of the endometrium was assessed in 120 symptomatic women. Correlation of the cytologic results with the histologic diagnosis on curettage specimens showed a diagnostic accuracy of 96.3%. The cytologic criteria for diagnosing samples obtained with the Isaacs device are presented.

Detection of benign or malignant origin of ascites with combined indirect immunoperoxidase assays of carcinoembryonic antigen and lysozyme.

The indirect immunoperoxidase method was used to study the presence of the intracellular carcinoembryonic antigen (CEA) and lysozyme (LZ) in alcohol-fixed cytologic smears of peritoneal fluids from 2 patients with chronic active hepatitis, 31 patients with liver cirrhosis and 7 patients with malignant liver disease. In the two patients with hepatitis, LZ was positive in both CEA was positive in one and negative in the other. Of the 31 patients with liver cirrhosis, 21 (67.5%) were LZ positive, 27 (87%) were CEA negative and only 4 (13%) were CEA positive. Of the seven patients with malignant disease, six were CEA positive and six were LZ negative. It is of interest that 23 of 24 (96%) LZ-positive results and 28 of 29 (97%) CEA-negative results corresponded to negative cytologic diagnoses for malignancy. Cytologic diagnosis of "reactive mesothelial cells" seemed to correlate better (71%) with CEA-negative and LZ-positive results. The data suggest that the investigation of CEA and LZ in the cells of peritoneal fluids appears to have promise as an adjunct to cytology in differentiating benign from malignant origins of the fluid.

Digital imagery/telecytology. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Optical digital imaging and its related technologies have applications in cytopathology that encompass training and education, image analysis, diagnosis, report documentation and archiving, and telecommunications. Telecytology involves the use of telecommunications to transmit cytology images for the purposes of diagnosis, consultation or education. This working paper provides a mainly informational overview of optical digital imaging and summarizes current technologic resources and applications and some of the ethical and legal implications of the use of these new technologies in cytopathology. CONSENSUS POSITION: Computer hardware standards for optical digital imagery will continue to be driven mainly by commercial interests and nonmedical imperatives, but professional organizations can play a valuable role in developing recommendations or standards for digital image sampling, documentation, archiving, authenticity safeguards and teleconsultation protocols; in addressing patient confidentiality and ethical, legal and informed consent issues; and in providing support for quality assurance and standardization of digital image-based testing. There is some evidence that high levels of accuracy for telepathology diagnosis can be achieved using existing dynamic systems, which may also be applicable to telecytology consultation. Static systems for both telepathology and telecytology, which have the advantage of considerably lower cost, appear to have lower levels of accuracy. Laboratories that maintain digital image databases should adopt practices and protocols that ensure patient confidentiality. Individuals participating in telecommunication of digital images for diagnosis should be properly qualified, meet licensing requirements and use procedures that protect patient confidentiality. Such individuals should be cognizant of the limitations of the technology and employ quality assurance practices that ensure the validity and accuracy of each consultation. Even in an informal teleconsultation setting one should define the extent of participation and be mindful of potential malpractice liability. ONGOING ISSUES: Digital imagery applications will continue to present new opportunities and challenges. Position papers such as this are directed toward assisting the profession to stay informed and in control of these applications in the laboratory. Telecytology is an area in particular need of studies of good quality to provide data on factors affecting accuracy. New technologic approaches to addressing the issue of selective sampling in static image consultation are needed. The use of artificial intelligence software as an adjunct to enhance the accuracy and reproducibility of cytologic diagnosis of digital images in routine and consultation settings deserves to be pursued. Other telecytology-related issues that require clarification and the adoption of workable guidelines include interstate licensure and protocols to define malpractice liability.

Detection of c-Ha-ras oncogene expression in pleural and peritoneal smear effusions by in situ hybridization.

This study was undertaken to determine the presence of the c-Ha-ras protooncogene in pleural and peritoneal effusions. Cells from 40 pleural and peritoneal fluids from patients with malignant and nonmalignant diseases were studied by in situ DNA hybridization utilizing a biotinylated probe. The results were correlated with those obtained by conventional cytological methods. A cytological diagnosis of metastatic carcinoma was established in 67% of the patients with malignancy and effusion, and in 6% of the patients with benign disease accompanied by effusion. On the other hand, a relatively high proportion of ras expression was observed in 38% of the cases representing benign and reactive effusions and as high as 88% in the cases with malignant tumor and effusion. These results suggest that the ras oncogene may have an important role in differentially diagnosing benign and reactive mesothelial cells from malignant cells.

Immunohistochemical study of sex steroid hormones in primary liver cancer.

Paraffin-embedded tissue sections from 29 patients with primary liver carcinomas were retrospectively studied for the presence of estradiol and testosterone using the peroxidase-antiperoxidase (PAP) technique. Twenty-seven hepatomas and two cholangiomas were treated with antiestradiol and antitestosterone primary serum. Estradiol was detected in 17 cases and testosterone in 11 cases of hepatomas. The two cases of cholangiocarcinoma were positive for estradiol and negative for testosterone. The immunohistochemical reaction in the tumor cells was mainly cytoplasmic and in a few cases both cytoplasmic and intranuclear. The positivity of the reaction in the tumour cells was compared with that of the adjacent non-neoplastic liver tissue and bile duct cells. Our findings were also analyzed in relation to tumor differentiation and the age and sex of the patients.

Cytological evaluation of the effect of Tamoxifen in premenopausal and post-menopausal women with primary breast cancer by analysis of the karyopyknotic indices of vaginal smears.

The influence of Tamoxifen on the vaginal epithelium of 33 premenopausal and 99 post-menopausal women with primary advanced breast cancer was investigated. The karyopyknotic index (KPI) values were assessed before starting therapy and at monthly intervals during therapy with Tamoxifen. A decrease in the KPI in menstruating women and a slight but definite increase in KPI values in post-menopausal women were observed.

Presence of epidermal growth factor receptor in breast smears of cyst fluids: relationship to electrolyte ratios and pH concentration.

The purpose of this study was to evaluate and correlate different high risk factors in breast cysts to produce a more accurate prognosis. We considered the cytology of the lining epithelium (apocrine or flattened), the Na+/K+ ratio (less than 3; greater than or equal to 3), the pH (lower, equal, or higher than 7.30), and the EGFr (present or not) in an attempt to reach better prognoses and diagnoses by evaluating more than one risk factor. Our material of 40 macrocysts consisted of 23 simple cysts with flattened epithelium and 17 complex cysts with apocrine or hyperplastic epithelium. In the simple cysts, the Na+/K+ ratio was greater than or equal to 3, while in the complex cysts the Na+/K+ ratio was, in all cases but one, less than 3. The pH was not significantly lower than neutral in the complex cysts. The EGFr was detected in 5 of 23 simple cysts and in 12 of 17 complex cysts. In conclusion, reaction of EGFr in smears of cyst fluids with the low intracystic electrolyte ratios may provide an explanation of why women with apocrine metaplasia or epithelial hyperplasia may be at higher risk of breast cancer than women with cysts which are lined by flattened epithelium.

Expression of cathepsin D and pS2 in imprint smears of breast carcinoma.

The aim of this study was to add to existing information on the effects of certain tumour markers expressed by breast cancers on tumour malignancy as evidenced by size of primary and occurrence of lymph node invasion. One hundred freshly resected breast cancers were examined by immunocytochemical staining of imprint smears for Cathepsin D and pS2. Oestrogen receptor (ER) and progesterone receptor (PR) were tested for by dextrose-coated charcoal (DCC) assay and the results correlated with tumour size, histology and presence or absence of lymph node metastases at the time of surgery using chi(2) analysis. A significant positive correlation was demonstrated between Cathepsin D positivity and ER, PR and pS2 positivity. In tumours < 2 cm in diameter at surgery a positive correlation was observed between Cathepsin D positivity and the presence of lymph node metastases. The findings support the hypothesis that Cathepsin D may promote early metastasis, possibly by its proteolytic activity.

The cytologic application of carcinoembryonic antigen for the discrimination of malignant from benign serous effusions.

In an attempt to diminish false cytologic diagnosis in discriminating between benign and malignant effusions, the value of intracellular carcinoembryonic antigen (CEA) was estimated in cytologic smears of effusions using a modified immunoperoxidase technique. CEA serum level was estimated by radioimmunoassay technique. In this study we included a group of 42 patients, 23 with a malignant and 19 with a benign effusion. CEA in cells of effusions was positive and useful for confirming malignancy in 65% of malignant effusions. The percentage increased to 83% with the combination of the results of positive CEA in cells and serum. Cytology was positive for malignancy in 16 of the 23 (70%) malignant cases. CEA in cells of benign effusions was negative in 84% and cytology in 100%. It is concluded that intracellular CEA estimation, when combined with CEA estimation in serum, improves the discriminating range of cytology for differentiating malignant and benign effusions.