Cellular dyscohesion in fine-needle aspiration of breast carcinoma. Prognostic indicator for axillary lymph node metastases?

The role of fine-needle aspiration (FNA) in the diagnosis of breast carcinoma is established. We evaluated whether the degree of cellular dyscohesion and the nuclear grade in FNA material of breast carcinomas are reliable prognostic predictors for ipsilateral axillary lymph node metastasis. FNA specimens from 98 women with infiltrating ductal and infiltrating lobular carcinomas were evaluated by 2 observers for degree of cellular dyscohesion and nuclear grade. Follow-up specimens from lumpectomy and/or mastectomy with axillary dissection were available for each patient. By univariate analysis, degree of cellular dyscohesion and nuclear grade were not predictive of axillary lymph node metastasis regardless of tumor size. High histologic grade, size greater than 2 cm, and patient age younger than 52 years were significant predictors of metastasis. By multivariate analysis, size greater than 2 cm and age younger than 52 years were statistically significant for lymph node metastasis. In contrast with a published study, the results of the present study fail to show cellular dyscohesion in FNA specimens as predictive of lymph node metastasis; however, the scoring method for determining the degree of cellular dyscohesion is reproducible between 2 independent observers.

Performance of liquid-based, thin-layer cervical cytology: correlation with reference diagnoses and human papillomavirus testing.

The performance of thin-layer cervical cytology with the use of ThinPrep (Cytyc Corporation, Boxborough, MA) was assessed by comparing the original independent diagnosis of ThinPrep slides and conventional smears prepared from 1780 split samples with the most abnormal diagnosis per patient on the basis of an independent pathologist's masked review and with the detection of cancer-associated types of human papillomavirus (HPV) DNA. Cases were selected on the basis of the original diagnoses to include all discordant pairs (those diagnosed as atypical squamous cells of undetermined significance or higher grade, n = 1017), all concordant abnormal pairs (n = 444), and a random 5% of concordant normal pairs (n = 319). In screening centers, thin-layer cytology detected 135 (70.3%) of 192 women diagnosed as having squamous epithelial lesions or a higher grade in the independent review, whereas locally read smears detected 91 (47.4%) of these patients (P < .001). In hospital-based cytology laboratories, thin-layer cytology detected 308 (86.3%) of 357 women diagnosed with SILs or a higher grade in the independent review, compared with 283 (79.3%) diagnosed with smears (P = .011). Cancer-associated types of HPV DNA were detected in a slightly higher proportion of women with smears diagnosed as SILs than in women with thin-layer cytology diagnosed as SILs, whereas the overall number of HPV-associated SILs diagnosed was higher with thin-layer cytology. These data suggest that the ThinPrep method detects a higher percentage of SILs as defined in a masked, independent review than do concurrently prepared smears and that diagnoses of SILs rendered with ThinPrep correlate with the detection of cancer-associated types of HPV.

Comparison of conventional Papanicolaou smears and a fluid-based, thin-layer system for cervical cancer screening.

OBJECTIVE: To compare the cytologic diagnoses and specimen adequacy of a fluid-based, thin-layer preparation and conventional Papanicolaou tests. METHODS: A total of 7360 women from six separate sites-three screening centers and three hospitals-participated in split-sample/matched-pair, double-masked clinical trials. A conventional Papanicolaou test was performed, after which residual material on the sampling device was rinsed into a fluid preservative from which a thin-layer slide (ThinPrep) was prepared using the ThinPrep 2000 automated slide processor (Cytyc Corp., Boxborough, MA). Conventional and ThinPrep slides were read independently. Cytologic diagnoses and specimen adequacy were classified using the Bethesda system. RESULTS: For the three screening centers, 65% more diagnoses of low-grade squamous intraepithelial lesions and higher were made on the ThinPrep slides (P < .001); for the three hospital centers, 6% more of these diagnoses were made with the ThinPrep method (P = .294). Comparison of specimen adequacy showed a significant increase in satisfactory specimens and a reduction in the number of "satisfactory but limited by" specimens using the ThinPrep method (P < .001). CONCLUSION: The fluid-based, ThinPrep method of sample preparation resulted in a statistically significant increase in cytologic diagnosis of cervical cancer precursors and in specimen adequacy compared with the conventional Papanicolaou testing method.

Automated screening of cervical cytology specimens.

After more than four decades of research into automation of the process of screening Papanicolaou (Pap) smears, attempts to develop commercially viable automated screening machines have increased in recent years. These developments have been made possible in part because of the improving price-to-performance ratios in computers and other electronics. Although the Pap smear has been responsible for a very significant decrease in mortality of cervical cancer over the past 40 years, concern has arisen over false-negative cases, with their effects on patients, and the associated legal liability, particularly in the United States. In addition, shortages of cytotechnologists, which have been exacerbated by new regulations limiting the number of slides that may be examined per day, have caused concern about handling the workload, which will probably increase as more individuals gain access to preventive health care. Automated screening machines can potentially allow detection of abnormal cases that are missed with conventional screening, although they may substantially increase the cost of Pap smears. The use of automated screening machines represents a change in the way cervical cytology specimens are processed, and with some machines, a significant change in the operation of the cytology laboratory. Current methods for processing and evaluating Pap smears have not changed significantly for the past four decades. This review discusses some of the principles of operation and practical aspects of automated screening machines.

Coculture of primary rat hepatocytes and nonparenchymal cells permits expression of insulin-like growth factor binding protein-3 in vitro.

In biological fluids, the insulin-like growth factors (IGFs) are associated with binding proteins (IGFBPs), which modify IGF distribution and action. Circulating IGFs are bound predominantly to IGFBP-3, of apparent hepatic origin, but regulation of IGFBP-3 has been difficult to dissect because of the lack of systems suitable for examining hepatic production of IGFBP-3 in vitro. In the present studies, IGFBP-3 expression was identified primarily in hepatic nonparenchymal cells, particularly Kupffer and sinusoidal endothelial cells. Coculture with hepatocytes enhanced the stability of nonparenchymal cells to express IGFBP-3 in vitro. IGFBP-3 in conditioned medium had apparent mol wt of 150-300 kilodaltons, suggesting formation of a ternary complex with IGFs and the acid-labile subunit. Expression and secretion of IGFBP-3 were hormonally responsive and strongly correlated (r = 0.79; P < 0.001), with 2- to 3-fold stimulation by added insulin or IGF-I (both P < 0.05), but not by added GH alone. Our findings suggest that GH may act indirectly to promote IGFBP-3 generation in vivo via increasing both the secretion of insulin and the hepatic production of IGF-I; in patients with diabetes mellitus, reduced circulating levels of IGFBP-3 despite high levels of GH may result from both insulin deficiency and inadequate hepatic production of IGF-I. Coculture of hepatic nonparenchymal and parenchymal cells should be useful for further analysis of the mechanism of IGFBP-3 regulation.

Adenomyoepithelioma of the breast: report of a case initially examined by fine-needle aspiration.

This report describes the morphologic features of an adenomyoepithelioma of the breast that was first examined by fine-needle aspiration. On retrospective review of the cytology, the stromal elements of this adenomyoepithelioma showed extensive metachromasia on Diff-Quik stain, had elongated nuclei, and on Papanicolaou stain showed elongated, pale, wispy cytoplasm. Clusters of stromal cells were usually intimately associated with epithelial elements. While the main differential consideration, cystosarcoma phylloides, can show similar features, it may be possible to distinguish the two lesions in some instances.

Breast fine needle aspiration cytology. Utility as a screening tool for clinically palpable lesions.

We examined breast fine needle aspiration cytology's role as a screening tool in addition to mammography and clinical examination for palpable breast lesions, circumventing operative biopsy of benign lesions while identifying cancer for definitive treatment and significant ductal proliferations that need histologic evaluation, such as atypical ductal hyperplasia and marked ductal hyperplasia. Five hundred thirty-three consecutive palpable breast lesions in 498 patients referred to cytopathologists were aspirated and the cytologic findings reported as follows: (1) malignant, treat as any histologic diagnosis of breast cancer (85); (2) suspicious, intraoperative or biopsy confirmation before therapy (11); (3) atypical, biopsy recommended to exclude breast cancer or significant ductal proliferation (atypical ductal hyperplasia and marked ductal hyperplasia) (45); (4) benign, excision not necessary (334); and (5) nondiagnostic, no ductal cells, and biopsy recommended if indicated clinically (58). Excision of 57/85 malignant lesions confirmed cancer in all cases. Follow-up of the remaining 28 patients showed: 17 were undergoing treatment for cancer without surgery, 8 were dead of the disease, and 3 were lost to follow-up. Biopsy of 11/11 suspicious lesions confirmed cancer. Biopsy of 27/45 atypical lesions showed: 1 carcinoma, 12 significant ductal proliferations (1 atypical ductal hyperplasia and 11 marked ductal hyperplasia) and 14 benign, nonproliferative breasts; 18 atypical lesions from 14 patients were not biopsied. Biopsy of 61/334 benign lesions showed 51 benign nonproliferative breasts, 7 missed significant ductal proliferations (6 marked ductal hyperplasia and 1 atypical ductal hyperplasia) and 3 false negatives (3 carcinomas). The three false negatives and the atypical ductal hyperplasia had a biopsy because of an abnormal mammogram. Review of material from false-negative cases showed underinterpretation of cells present on cytology slides in two cases and carcinoma missed by the aspiration needle in one case. The atypical ductal hyperplasia was in a separate, nonpalpable area in the same breast. Biopsy was avoided in 273/334 benign lesions from 249 patients: 86 had no follow-up, 160 had stable lesions, and 3 reported a change in their lesions (mean follow-up, 13 months). One of these three had a biopsy that showed a benign, nonproliferative breast. Biopsy of 11/58 nondiagnostic lesions showed 9 benign nonproliferative breasts, 1 atypical ductal hyperplasia and 1 carcinoma. No biopsy was performed on 47/58 nondiagnostic lesions from 45 patients: 1 had a repeat aspiration that was malignant, 10 had no follow-up, 33 had stable lesions, and 1 had an increase in the size of her lesion (mean follow-up, 13 months).(ABSTRACT TRUNCATED AT 400 WORDS)

Primary non-Hodgkin's lymphoma of the heart in two patients with the acquired immunodeficiency syndrome.

We report two cases of primary cardiac lymphoma that developed in patients suffering from the acquired immunodeficiency syndrome. Both cases of lymphoma were histologically aggressive as generally observed in patients with the acquired immunodeficiency syndrome. The lymphoma cells in the center of a tumor nodule obtained from one patient were monoclonal B-cells, whereas those at the periphery showed a polyclonal pattern of staining. It is postulated that this represents a monoclonal lymphoma evolving from a polyclonal B-cell lymphoproliferation analogous to those reported in some cases of lymphoma in immunosuppressed patients infected with Epstein-Barr virus. The lymphoma cells in the other case failed to stain for cytoplasmic immunoglobulins. The possible underlying basis for the increase in incidence of lymphoma in immunodeficiency and the reasons for prevalence of extranodal sites are discussed.