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.

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.

Summary 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) Proliferative activity has consistently been found to be an important biological predictor of the clinical evolution of breast cancer (Tubiana et al., 1984;Silvestrini et al., 1985;Meyer, 1986;Hery et al., 1987). Traditionally, it has been measured by autoradiography of a radiolabelled precursor (3H-thymidine) incorporated in tumour-cell DNA.With the introduction of DNA flow cytometry (FCM), fast cell-cycle distribution analysis of large numbers of cells has become available (Barlogie et al., 1982). Retrospective studies have shown that S-phase fraction (SPF), computed from DNA histograms, is also a significant prognostic factor (Hedley et al., 1987;Kallioniemi et al., 1988) and a good predictor of response to neo-adjuvant chemotherapy (Remvikos et al., 1989). Nevertheless, the possibility of establishing SPF's correctly has been questioned, either from poor quality-or complex histograms presenting multiple aneuploid peaks (Meyer et al., 1984; Kallioniemi et al., 1985 In a prospective study of feasibility, we developed complementary methods for assaying SPF and BrdU labelling index (BLI) in vitro on the same tumour samples. Indeed, the substitution of 5-bromodeoxyuridine (BrdU) to 3H-thymidine has been proposed as a more convenient method of measuring DNA synthesis, due to the instant immunofluorimetric detection (Dolbeare et al., 1983;Schutte et al., 1987). Tumour cells were obtained directly from the patients by fine needle sampling without aspiration. The inherent difficulties of each methodology are discussed in order to define the best approach for an adequate estimation of the proliferative activity of each breast cancer before treatment decision. Materials and methodsOne hundred and eighty-nine consecutive patients were subjected to fine needle sampling without aspiration, using 23 or 25 gauge needles (Zajdela et al., 1987). The cytological samples were expelled in 1 ml of incubating medium: RPMI (Gibco), 10% foetal calf serum (Calbiochem), 30 pM BrdU (Sigma). The tubes were incubated at 37°C for 15 min, then 100 yl of DMSO were added and the tubes stored at -80C.FNS were processed for DNA-FCM according to a onestep protocol. The samples were thawed and rinsed with PBS at 1,500 r.p.m., 5 min. The pellets were resuspended in 600 tl of PBS, 0.2% Tween 80 (Sigma), 50 lg m -' propidium iodide (Sigma), 250 iLg ml-Ribonuclease A (B6ehringer), and left at room temperature for 20 min.For BrdU/DNA labelling, cell-rich samples were selected and fixed in 70% ethanol. In all cases, at least 50,000 cells were kept for DNA analysis as above. The fixed samples were centrifuged, digested with 3 ml of pepsin (Sigma

Objectives: To describe cytology patterns in low-grade adenosquamous carcinomas (LGASCs) of the breast. Study Design: Low-grade adenosquamous carcinomas of the breast are a recently described rare variant of primary metaplastic carcinomas characterized by clinical indolence, slow evolution and excellent survival. To date, only 7 cases of LGASC were studied cytologically, and it was demonstrated that LGASC identification was difficult because its cellular components exhibited unspecific and nonsuspicious features. They consisted of irregularly clustered cells without prominent cytonuclear atypia, mitosis or necrosis. The presence of metaplastic cells or keratin debris was helpful in accurate tumor typing. We report here 3 additional cases of LGASC that were initially studied by fine-needle aspiration. Results: We have also encountered diagnostic difficulties and misdiagnosed tumors, since 2 cases were underdiagnosed as ‘suspicious' and only 1 was accurately diagnosed as malignancy. Conclusion: The review of our cases and the literature confirms that, despite its putative metaplastic origin, LGASC is an entity which is difficult to diagnose using classical cytological methods. Moreover, core-needle biopsy as well as frozen sections may also misdiagnose LGASC as a benign breast lesion.

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. Cancer (Cancer Cytopathol) 2001;93:132–139. © 2001 American Cancer Society.