Proton nuclear magnetic resonance spectroscopy of serum from patients with colorectal neoplasia.

Proton nuclear magnetic resonance (NMR) spectra of serum have been recorded from patients with colorectal neoplastic polyps, before and after treatment of colorectal cancer, in patients with advanced lung cancer, and also from healthy controls. Digitally defined NMR profiles of the methyl and methylene peaks were used as input for supervised principal component modelling. An unknown sample was classified according to its residual, i.e. the difference between the spectral pattern of the unknown and control group. There was a statistically significant difference between the mean residual in the untreated colorectal cancer group and in controls (P = 0.003). The sensitivity of detecting untreated colorectal cancer was only 20%. There were no stage-dependent differences between the residuals within the untreated colorectal cancer group. After curative surgery, four patients had recurrence of malignant disease without an increase in residual prior to recurrence. Patients with advanced malignant disease (lung cancer WHO stage IIIB and IV) had a highly significant difference in mean residual from that of controls, with a sensitivity of detecting cancer of 87.5%. This increase in residual could not be explained by increase in the level of serum triglyceride. NMR spectroscopy was not a useful diagnostic tool in patients with colorectal neoplastic polyps and cancer.

Risk of cervical intraepithelial neoplasia in women with glomerulonephritis.

OBJECTIVE: To investigate the occurrence of cervical intraepithelial neoplasia in women with glomerulonephritis and its possible association with immunosuppressive treatment. DESIGN: Retrospective study of cytological or histological specimens from women presenting with glomerulonephritis and a group of case and age matched controls. SETTING: University department of pathology, Norway. PATIENTS: 81 women presenting with glomerulonephritis from 1981 to 1988, from whom gynaecological cytological or histological specimens were available. A group of 162 case and age matched controls. MAIN OUTCOME MEASURES: Age when glomerulonephritis of cervical intraepithelial neoplasia was diagnosed, type and characteristics of kidney lesion, stage of cervical intraepithelial neoplasia and presence of human papillomavirus, use of immunosuppressive treatment. RESULTS: Cervical intraepithelial neoplasia was more common in women with glomerulonephritis than in their controls (16/81 (20%) v 7/162 (4%), p less than 0.001) and was more advanced in those with glomerulonephritis than in the controls (9/81 (11%) of the study group had grade III cervical intraepithelial neoplasia compared with 1/162 (1%) of the controls). The increased occurrence of cervical lesions was independent of the use of immunosuppressive treatment, but the individual lesions tended to be more advanced when it was used (four of the seven cervical lesions in women with glomerulonephritis who had received immunosuppressive treatment were carcinoma in situ). Of the nine cervical lesions tested, seven were virus associated. CONCLUSION: Women with glomerulonephritis should have regular cervical smears, irrespective of their use of immunosuppressive treatment.

[Mollaret's meningitis]. / Mollarets meningitt.

Mollarets meningitis is a rare form of recurrent aseptic meningitis where a diagnostic feature is the characteristic cytologic picture in the cerebrospinal fluid. The article presents two cases that were clinically diagnosed as Mollarets meningitis. The cytologic picture of the cerebrospinal fluid is described and the major clinical aspects and the differential diagnoses are discussed briefly.

[Prostate-specific antigen. A new biological serum marker for prostatic adenocarcinoma]. / Prostataspesifikt antigen. En ny biologisk serummarkør ved adenokarsinom i prostata.

Prostate-specific antigen (PSA) was measured by polyclonal radioimmunoassay in 45 untreated patients with prostatic cancer and 14 patients with benign prostatic hyperplasia. Prostatic acid phosphatase (PAP) was determined in 35 patients with prostatic cancer and 14 patients with benign hyperplasia. Serum PSA was raised in 42 patients with cancer of the prostate, but only 14 of 35 patients showed increased serum levels of PAP. Half the patients with benign prostate hyperplasia had PSA greater than 4 micrograms/l and one third had PSA greater than 10 micrograms/l. PAP was slightly elevated in two patients with benign prostatic hyperplasia. Serum PSA increased with the clinical stage of prostatic cancer. However, preoperative levels of PSA were not sufficiently reliable to predict the final pathological stage for each individual patient. After radical prostatectomy for cancer confined to the prostate, serum PSA fell to an undetectable level.

[Fine needle aspiration cytology of the breast. A simple method?]. / Finnålsaspirasjonscytologi fra mamma. En enkel metode?

During the period 1981-85, 3,743 fine-needle aspiration cytologies of breast tissue from 3,188 patients were reported by the Gade Institute, Department of pathology. Subsequent histologic examination was performed in the case of 798 patients. Among 421 histologically proven carcinomas after previous fine-needle aspiration, there were no false positive and 13 false negative cytological diagnoses. The specificity was 100% and, depending on the criteria used, the sensitivity 77.9 or 96.4%. Altogether 223 doctors performed the aspirations. This high number was probably the main reason for an unacceptably high proportion of inadequate smears. In experienced hands the proportion of inadequate smears was less than 4-7% in patients with carcinomas.

Fine-needle aspiration cytology of focal liver lesions. Advantages and limitations.

Fine-needle aspiration cytology of focal liver lesions was performed 192 times in 175 patients over a 5-year period. Ultrasonic guidance was used for 153 punctures; the others were done peroperatively or on a palpable mass. A correct diagnosis of malignancy was obtained in 89/111 cases (80.2%), and of metastases (adenocarcinoma) to the liver in 71/84 (84.5%). The total of nonrepresentative aspirates was 26 (13.5%). The overall accuracy of cytologic evaluation was 87.5%, with 79.5% sensitivity and 100% specificity in malignant disease. The predictive values of positive and negative results were, respectively, 100% and 75.8%. There were no false positive tests, but 12.5% false negatives. No complications following the aspiration procedure were seen. Fine-needle aspiration biopsy is simple and safe, but the relatively high proportion of nonrepresentative aspirates is a problem. Possibly a more aggressive approach with multiple punctures may lessen this incidence and enhance the diagnostic accuracy in hepatic malignancy.

DNA ploidy and steroid receptors as predictors of disease course in patients with endometrial carcinoma.

Prognostic factors for outcome of malignant disease should be based on objective assessments whenever possible, so that the results may be reproduced. In a prospective study, tumor samples from 75 patients were subjected to flow cytometric DNA analysis. Samples were also taken from 61 patients for estradiol and progesterone receptor measurements. The course of the disease was analysed with regard to ploidy and receptor status. Receptor status was significantly correlated with ploidy, as diploid tumors were more often receptor-positive or receptor-rich (greater than or equal to 30 fmol/mg protein). Mortality and recurrence rates were highest among patients with aneuploid or receptor-poor tumors. Ploidy, receptor status, histological grade, surgical stage, and myometrial invasion were found to be of significant prognostic value. By multivariate analysis, ploidy was indicated to be the best predictor, followed by surgical stage. DNA and receptor measurements are recommended in research on endometrial carcinoma, and may become useful in routine clinical work.

Cervical lesions in patients with malignant melanoma.

Koilocytes were found in the cervical epithelium in association with cervical intra-epithelial neoplasia in 8 out of 9 cases of malignant melanoma. This suggests that the cervical lesion in them was of viral origin. In 62 women with malignant melanoma but without cervical atypia there was also an excess of koilocytosis compared with controls with neither lesion. These findings point to the possibility that human papilloma virus infection may also be involved in the development of malignant melanoma, as it has been shown to be in cervical intra-epithelial neoplasia.

Transthoracic fine-needle aspiration guided by fluoroscopy: validity and complications with 19 operators.

During a 3-year period, 19 physicians performed 271 transthoracic fine-needle aspirations (FNA) in 199 patients, using a 23-guage aspiration needle with an 18-guage guiding needle. The diagnosis was confirmed by cytological examination of the needle aspirates in 90 out of 122 patients with malignant tumors, giving a sensitivity of 74%. The specificity of the cytological diagnosis was 100%. Both cytological and histological material was available in 49 patients. The tumor typing from the FNA specimens and the biopsies was in agreement in all but 3 cases. Pneumothorax occurred in 27% of the patients, but only 3.5% required tube drainage. Small variations (p greater than 0.05) in number of diagnostic punctures and rate of complications were evident among the participating physicians and between two fluoroscopic equipments.

The distribution and prognostic implications of steroid receptors in endometrial carcinomas.

Estradiol receptors (ER) were measured in 71 and progesterone receptors (PR) in 62 primary endometrial carcinomas. ER were found in 62 (87%) and PR in 56 (90%) of the tumors. Fifty-six tumors were ER+/PR+ and 4 were ER-/PR-. The frequency of receptor positive tumors was not significantly correlated to histological grade. Highly differentiated tumors were, however, more often ER and PR rich (greater than or equal to 30 fmole/mg protein) as compared to poorly differentiated tumors. The median ER and PR values for grade I tumors were also significantly higher than for grade III tumors. No significant differences were found in the frequency of patients with ER or PR rich tumors in the different FIGO or surgical stages. The receptor status was not related to depth of myometrial infiltration. Recurrence rates and death rates were significantly higher in patients with PR poor as compared to those with PR rich tumors. This prognostic information could not be shown for ER.

Ploidy assessment of benign and malignant ovarian tumors by flow cytometry. A clinicopathologic study.

In a prospective study, 112 fresh ovarian tumor samples were collected from 83 consecutive patients. Cellular DNA content was measured by flow cytometry. All the benign (n = 24) and semimalignant (n = 6) tumors were diploid. Of 50 malignant tumors, 24 (48%) were diploid and 26 (52%) were aneuploid. Aneuploidy was more frequent in the advanced stages of the disease, in tumors of low degree of differentiation, and in older patients. The patients with aneuploid tumors had smaller primary tumors and more often ascites. The fraction of cells with S-phase DNA content was higher in the aneuploid tumors. No association was seen to the tumor type. Ploidy determination is objective and reproducible. Aneuploidy associates to most negative prognostic factors in ovarian carcinoma and may reflect the aggressiveness of the tumor. The ploidy status may be taken into consideration in the stratification of patients of comparable risk for treatment studies.

Nuclear and cell area measurements in the cytological evaluation of pleural effusions: a study of subjective assessments and morphometric measurements.

Morphometric measurements of cellular area, nuclear area and nuclear:cytoplasmatic ratio were performed on single cells in pleural effusions from 15 patients with effusion caused by bronchial, ovarian, or mammary carcinoma. The results were compared with corresponding measurements on mesothelial cells in pleural effusions from 15 patients without malignant disease. Significant differences were found between the mean values from cellular area, nuclear area, and nuclear:cytoplasmatic ratios in mesothelial cells from benign effusion versus malignant cells from effusions associated with metastatic growth. Such morphometric measurements are, however, of little value in routine diagnostic work as more than 90% of the cells in the two groups showed similar values.

Steroid receptor content in human ovarian tumors: survival of patients with ovarian carcinoma related to steroid receptor content.

Steroid receptors were measured in 31 malignant and 29 benign or semimalignant ovarian tumors in a prospective study. Estrogen receptors (ER) were found more often in highly differentiated malignant tumors (86%) than in poorly differentiated ones (23%). No such difference was found for progesterone receptor (PR). Receptor content was not related to clinical stage. The median survival of patients with PR+ or ER+/PR+ malignant tumors was 30 and 31.5 months, respectively, compared to 10 and 9 months for those with receptor negative tumors. This positive prognostic information could not be demonstrated for ER alone. Receptor content and distribution were similar in benign and semimalignant tumors. Measurement of hormone receptors in ovarian cancers can thus give valuable prognostic information.

New concept in diagnostic endometrial cytology: diagnostic criteria based on composition and architecture of large tissue fragments in smears.

Routine endometrial cytology was used instead of curettage as the first step in a morphological investigation of the endometrium in patients with postmenopausal bleeding. Premenopausal women with symptoms or signs indicative of premalignant or malignant disease were also studied using this method. Patients with alarming cytological findings were further investigated with curettage. Diagnostic criteria for endometrial cytology have not been fully established: new diagnostic criteria were used in this study, which were based on the composition and architecture of larger tissue fragments in the smears. The new criteria were especially useful for tackling diagnostic problems caused by variation in nuclear size. Two thousand six hundred and twenty five cytological investigations were conducted over three years (January 1981 to January 1984). Adequate material for diagnosis was found in 2520 specimens (96%). Diagnosis based on the cytology was negative--that is, not indicative of malignant or premalignant disease in 2378 cases (94%). Follow up studies in 1984 showed no false negative results. Adenocarcinoma of the endometrium was diagnosed in 31 cases, carcinoma or carcinoma in situ of the cervix in 11 cases, and carcinoma of the ovary in four cases, all confirmed by histological investigation. Of 20 cases reported as suspected carcinoma, 12 of these were verified. The cytological diagnosis of adenomatous hyperplasia showed a low sensibility: only ten of 50 histologically controlled cases could be verified after curettage.

Morphometric analysis of nuclei in epithelial structures from normal and neoplastic endometrium: a study using the Isaacs cell sampler and Endoscann instruments.

Morphometric analysis of nuclear area and shape in epithelial cells from cytological specimens from 35 patients with normal endometrium and from 20 patients with moderately or well differentiated endometrial adenocarcinoma was performed. The mean nuclear area in malignant cells was significantly higher than in normal epithelial cells. The range of the mean values from the normal cases, however, included 70% of the malignant values. Furthermore, individual cell groups in a normal cell population often gave values well within the malignant range. The greatest distinction between normal and malignant cases was obtained using a cut off mean value of 45 micron 2. With this as the sole criterion 17% of reports would have been false positives and 25% false negatives.

Characterization of pleural effusions by flow-cytometric DNA analysis.

Pleural effusions from 58 patients were studied by cytology and flow-cytometry. Relative cellular DNA content was measured, giving an estimate of ploidy as well as cell cycle distribution. Twenty-one patients had non-malignant diseases while the rest had malignant diseases. Pleural effusions from 13 patients contained malignant cells. In 2 cytologically equivocal cases and in one cytologically negative case aneuploid cells were demonstrated in the histograms. The cell cycle distribution of the diploid tumour cells did not differ from that of the diploid cells in benign effusions. The demonstration of an aneuploid histogram by flow cytometry favours a cancer diagnosis, and can provide valuable and decisive information in addition to cytological results.

Nuclear size and shape of epithelial cells from the endometrium: lack of value as a criterion for differentiation between normal, hyperplastic, and malignant conditions.

Nuclear area and shape of epithelial cells were measured in cytological specimens from 10 patients with cystic hyperplasia of the endometrium and four patients with adenomatous hyperplasia. Only specimens from patients with histologically confirmed widespread disease of the endometrium were accepted in the study. The mean nuclear area in cystic hyperplasia was significantly lower than in adenomatous hyperplasia. Results from previous measurements with the same method in normal and malignant conditions were compared with those from hyperplastic conditions. Both cystic and adenomatous hyperplasia differed from normal endometrium but not from malignant conditions. The scatter in values in the different conditions overlapped to such a degree as to make nuclear size of little importance as a diagnostic criterion. There were no differences in nuclear shape between normal, hyperplastic, and malignant conditions.