Correlation of pretreatment proliferative activity of breast cancer with the response to cytotoxic chemotherapy.

That most cytotoxic agents act specifically against actively proliferating cells is well-recognized. In this study, we attempted to correlate pretreatment S-phase fractions (SPF) measured on DNA histograms with regression of the tumor mass after the administration of neoadjuvant chemotherapy. Tumor cells were obtained from 60 previously untreated, premenopausal patients with no metastases and with noninflammatory disease by fine needle sampling without aspiration. We could evaluate DNA ploidy in all patients and SPF in 50 or 83% of them. Tumor responsiveness was significantly related to SPF. The 12 patients who had SPF of 10% or more showed demonstrable regression; six had complete responses. None of the other parameters tested, i.e., DNA ploidy, histopathologic grade, or hormone receptor content, correlated with response. We believe this information may prove valuable for clinicians as they make their decisions regarding patient therapy.

[Results of ultrasonographic and cytologic follow-up of 311 initially non-suspicious thyroid nodules]. / Résultats de la surveillance échographique et cytologique de 311 nodules thyroïdiens initialement non suspects.

The follow-up of initially non suspect thyroid nodules after fine needle biopsy is not completely worked out. Since 1985, we have entered upon a prospective study concerning the followup of thyroid nodules supposed to be benign after initial evaluation. What are the nature and the frequency of means to be used for their follow-up? Three hundred and eleven nodules are followed up on a mean duration of 2.44 years. The follow-up of 65 of them is 4 years or more. The follow-up of 120 others is 3 to 4 years; 197 nodules are followed up during 2 to 3 years. A physical examination, an ultrasonography completed with a fine needle biopsy or an ultrasonically guided fine needle biopsy are worked out every year. Twenty-three per cent of initial biopsies are non significant and 90% of them are ultrasonically guided biopsies. At the end of the study, the repeating biopsies reduce to 6% the non significant biopsies ratio. Four histological thyroid cancers are detected in three female patients 1 year, 2 years and 5 years after the initial evaluation. Ultrasound alterations of nodules are observed in case of very suspect biopsies. Ninety-six per cent of the followed up thyroid nodules remain not cytologically suspect. These findings allow us to propose the following guidelines for the assessment of a non suspect thyroid nodule: half-yearly or yearly physical examination, yearly or biennial ultrasonography, repeat biopsy after 2 or 3 years when clinical or ultrasound suspect modification is wanting.

[Nodular or pseudo-nodular Hashimoto thyroiditis. Value of cytologic examination]. / Thyroïdites de hashimoto à aspect nodulaire ou pseudo-nodulaire. Intérêt de l'examen cytologique.

OBJECTIVES: Nodular or pseudo-nodular aspects of Hashimoto's thyroiditis raise the problem of the association with a differentiated carcinoma or a non Hodgkin's lymphoma. METHODS: We looked for patients needing surgery in 165 cases of Hashimoto's thyroiditis. For this purpose, we used fine needle aspiration cytology. RESULTS: We found a differentiated carcinoma in 4% of cases and a non Hodgkin's lymphoma in 1% of cases. CONCLUSION: In nodular or pseudo-nodular aspects of Hashimoto's thyroiditis, fine needle aspiration cytology is helpful for the nodule diagnosis and for the selection of suspicious nodules only to be referred to surgery.

Cytological diagnosis by fine needle sampling without aspiration.

The merits of a simplified cytological method of fine needle sampling without aspiration are compared to those of the classical fine needle aspiration techniques in a series of benign and malignant mammary tumors which were subsequently proved histologically. A comparable cellular yield was obtained by both techniques. In a series of 635 benign and malignant breast tumors examined in 1981 with fine needle alone, insufficient cellular yield was recorded in 5.5% of the lesion. The same incidence (6%) was recorded with aspiration techniques in 7877 benign and malignant mammary tumors examined from 1954 to 1980. With the new technique, trauma is reduced and a better perception of the tumor and of its consistency is directly obtained.

Gastrin cell hyperplasia in rats with chronic antral stimulation.

Rats surgically prepared with the antrum transposed onto the colon were compared with suitable control rats, to investigate whether chronic antral stimulation modifies gastrin cell and other endocrine cell populations. Gastrin cell and argyrophil cell density per unit area were studied in antrum using a quantitative method after staining by immunofluorescence and Grimelius argyrophily, respectively. Both gastrin cells and argyrophil cells increased significantly in density per unit area after antrocolic transposition (P smaller than 0.001). The augmentation of gastrin cells per glandular tube (78%) was also significant (P smaller than 0.001). Electron-microscopic observations confirmed these results. On the other hand, in each group, the topographic distribution of the two categories of cells was different, and the number of gastrin cells was statistically greater than that of the argyrophil cells. Thus, it appeared evident that gastrin cells were not argyrophilic. Several hypotheses to explain the mechanism of this hyperplasia of endocrine cells are discussed. It is concluded that the increase in the gastrin cell density could be one possible explanation for the hypergastrinemia observed in the antrocolic transposition model.

Endocrine cells of the colon in Hirschsprung's and control children.

The large intestine resected from 6 Hirschsprung's patients and surgical colonic biopsies from 6 control children were examined with light and electron microscopy. The presence and the relative distribution of various endocrine cell types in both groups of mucosa were determined. In light microscope studies endocrine cell data were expressed as number of cells per unit area of mucosa using a quantitative method after argentaffin and Grimelius's argyrophilic techniques and an immunoperoxidase reaction with glucagon and somatostatin (SRIF) antisera. The results indicate that endocrine cells are apparently not involved in Hirschsprung's disease, since their number and frequency did not differ significantly between the ganglionic and aganglionic segments of Hirschsprung's patients nor between the latter and control children. Glucagon immunoreactive cells were, on the average, 5-6 times and 7-9 times more numerous that SRIF cells in the rectum and the sigmoid, respectively. Ultrastructurally, five endocrine cell types could be distinguished. The fifth type, probably a transition type, apparently disappears in adults.

Breast cancer proliferation measured on cytological samples: a study by flow cytometry of S-phase fractions and BrdU incorporation.

Cell kinetics have been shown to be an important predictor of clinical evolution of operated breast cancer. We established a method for the estimation of the proliferative activity of tumour cells obtained by fine needle sampling without aspiration (FNS), using simultaneously S-phase fractions (SPF) measured on DNA histograms and 5-bromodeoxyuridine (BrdU) labelling index (BLI) measured by flow cytometry. Biparametric BrdU/DNA flow cytometry could be performed in 122 of 189 (65%) consecutive patients. The mean BLI of the cytologically malignant FNS (118) was of 3.0 and the median of 2.2%. One hundred and forty-eight DNA histograms (78%) were suitable for SPF analysis, of which 141 presented malignant cells, showing a mean of 4.5 and a median of 3.5%, comparable to BLIs. These results were obtained from fluorescence peak area histograms with doublet discrimination and background subtraction allowing the measurements of SPFs as low as 0.4%. An excellent correlation was thus observed between BLIs and SPFs, for the 94 cases for which both results were available (r = 0.85). Infrequent discordances (9%) were noted with SPFs considerably higher than BLIs. Seven patients had three consecutive FNS of their tumour at weekly intervals before treatment. Some variability in the proportions of multiple subpopulations of tumour cells was observed on the DNA histograms. In contrast, proliferation indices (SPF or BLI) were reproducible, suggesting homogeneous growth rates. We conclude that an estimation of the proliferative activity of breast tumours at any stage of the disease is possible routinely by SPF and/or BLI analysis of FNS. At least one quantitative proliferation index could be obtained for 91% of patients.

Gastrin cell distribution in normal human stomachs and in patients with Zollinger-Ellison syndrome.

Quantitative distribution of gastrin cells was evaluated in three normal human stomachs and in four stomachs from patients with Zollinger-Ellison syndrome. Cells identified by the immunoperoxidase method were counted along the entire length of five mucosal strips parallel to the axis of the lesser curvature and sampled from the posterior to the anterior walls. The number of cells per unit area (2300 microns2) decreased from the pylorus to the borderline of the gastric body from (mean +/- SEM) 50.9 +/- 12.0 to 24.2 +/- 13.0 and from 29.6 +/- 5.6 to 10.4 +/- 2.6 for control and Zollinger-Ellison syndrome, respectively, with large interindividual variations. From factorial analysis no statistical difference was found between the two groups. It is therefore suggested that the number of gastrin cell in antral mucosa may not be a significant criteria in the diagnosis of Zollinger-Ellison syndrome.

Critical clinicopathologic analysis of 23 cases of fine-needle breast sampling initially recorded as false-positive. The 44-year experience of the Institut Curie.

BACKGROUND: Because false-positive cytologic diagnoses in breast tumors are rare, few cases have been reported, although their consequences may be highly detrimental to the patient. The authors report the Institut Curie's experience, by using a multidisciplinary approach. METHODS: Of 9334 benign breast tumors examined preoperatively for cytologic diagnosis by fine-needle sampling (FNS), the 23 (0.25%) FNS cases considered to be false-positive were retrospectively reviewed and analyzed. RESULTS: Tumors were situated close to the nipple in 7 cases and away from the nipple in 16 cases. Tumor stage was T0 for 1 case, T1 for 18 cases, and T2 for 4 cases. Radiologically, six tumors were classified as malignant, seven as indeterminate or suspicious, and nine as benign. Three of six tumors studied by flow cytometry were DNA aneuploid. Based on a multidisciplinary clinicopathologic review, 20 FNS cases were finally classified as false-positive, and the remaining 3 tumors with malignant FNS and subsequent benign histology were classified as true-positive, because local and/or metastatic progression was observed in the short term. CONCLUSIONS: The authors' review suggests two categories of false-positive cases: the first in which cytologic benign patterns are overdiagnosed, and the second in which atypical morphologic criteria were present. Nevertheless, as shown by the malignant course in three cases, patients with malignant preoperative FNS and corresponding benign histology always require close clinical follow-up. Finally, surgical overtreatment rate could be decreased if all radiologically benign tumors with positive/suspicious FNS were subject to intraoperative frozen section examination.