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Fine-needle aspiration (FNA) biopsy of a thyroid nodule was performed in 797 patients. Ninety-six patients had resection of the thyroid nodule performed subsequent to a one-time FNA biopsy. The surgical pathology of these 96 cases demonstrated a 5.8% false-negative rate and a 9.9% false-positive rate. As a consequence, we prospectively evaluated the routine practice of repeat FNA of cytologically benign thyroid nodules. Repeat FNA confirmed the original benign cytology in 183 (93%) of 196 patients. Seventeen of these 183 patients with benign FNA on both biopsies had resection of the nodule performed because of the development of suspicious clinical signs or in response to the patient's choice; 1 recurrent cyst was found to be carcinomatous. Of the 13 patients demonstrating a change in cytology on repeat FNA biopsy, 9 had a nodule that was classified as possibly malignant (suspicious); 6 of these patients underwent resection, and 1 patient was found to have a carcinomatous nodule. Four patients had nodules that were classified as probably malignant on repeat FNA biopsy; all of their nodules were resected, and three of them were found to be carcinomatous. This study demonstrates that, although one-time FNA biopsy of thyroid nodules is highly accurate, with a relatively low false-negative rate, repeat fine-needle biopsy improves on this diagnostic accuracy, thereby decreasing the risk of misdiagnosing a thyroid nodule that is malignant.

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Two hundred fifty mammographically detected nonpalpable breast lesions suspicious for malignancy in women who underwent routine screening mammography were stereotaxically localized. Fine-needle-aspiration (FNA) cytologic specimens and needle-core biopsy specimens were obtained before open biopsy in every case. Seventy-six lesions (30.4%) were malignant. Sixty-three (83%) of these 76 cancers were 1 cm long or smaller. Needle-core biopsy alone was used to diagnose conclusively 41% (n = 31) of these cancers, while FNA cytologic study alone was used to diagnose 32% (n = 24). No false-positive results occurred with either test. The same diagnosis was reached in 54% (n = 41) when the combined results of both needle tests were considered. In applying the two needle tests to 125 mammographically defined low-suspicion lesions, 85 (68%) were found to be benign by means of either one or both needle tests; there was one lobular carcinoma in situ. By applying this algorithm, 85 (34%) of 250 patients with abnormal mammograms, or one-third of all patients recommended for open biopsy, might have avoided surgery.

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Approximately three-fourths of open biopsies of the breast performed for mammographically detected suspicious lesions are shown histologically to be benign. Under the narrow conditions described herein, stereotaxic fine-needle aspiration (FNA) can identify these lesions with an accuracy of more than 90 per cent and a false-negative rate of 5 per cent. In an effort to reduce this failure rate, the mammographic appearance and stereotaxic FNA results of these lesions each were given scores on a scale of zero (benign) to five (malignant), to derive an over-all risk score prospectively applied to 264 suspicious occult lesions of the breast prior to open, biopsy. While all 264 lesions could be assigned a mammographic score, adequate tissue for assignment of a cytologic score could be obtained from 150 lesions. Of the 150 evaluable lesions, 53 were malignant and 97 were benign, historically. With a total score of two as the threshold for open biopsy, 21 of 150 (14 per cent) were proved to be benign, with no false-negative findings. If the total threshold score mandating an open biopsy was raised to four, the comparable figures were 61 of 150 (40 per cent) benign lesions and two false-negative instances of carcinoma in situ. Provided adequate tissue is aspirated for cytologic examination, we conclude that this algorithm has practical value in the management of nonpalpable lesions of the breast in that it can reliably identify a fraction of the benign lesions and spare these patients an operation.

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Classic multidrug resistance is mediated by a P-glycoprotein. Using monoclonal antibody C219 (MAb C219) in an immunohistochemical study, we found high levels of putative Golgi P-glycoprotein in normal columnar and transitional epithelium in subpopulations of patients with specific blood types. For example, Golgi staining was present in blood type A patients in 46% of normal colon samples (N = 21) and 88% of normal ureter samples (N = 17). In comparison, Golgi staining was present in blood group O patients in only 6% of normal colon samples (N = 34) and in 0% of normal ureter samples (N = 19). The association of MAb C219 Golgi staining with blood type A and lack of Golgi staining with blood type O was statistically significant in normal colon (P = .001) and normal ureter (P less than .0001). Inappropriate hyperexpression of P-glycoprotein was frequently found in colon carcinomas. Additional evidence that Golgi MAb C219 reactivity represents P-glycoprotein is presented. This includes (1) immunostaining of Golgi with two anti-P-glycoprotein MAbs, C219 and JSB-1, and (2) experiments in which Mab C219 Golgi reactivity was blocked by preincubation of MAb C219 with a specific P-glycoprotein epitope-containing peptide. The high degree of association of Golgi P-glycoprotein with blood type A may suggest a role for P-glycoprotein in processing or trafficking of specific blood group antigens.

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Many cancers do not respond to chemotherapy on primary exposure to drugs, thus manifesting intrinsic drug resistance. Other cancers that do initially respond subsequently become resistant to the same drugs and simultaneously to other drugs to which the patient has had no previous exposure. This is a form of acquired drug resistance. There is a pressing need to better understand the mechanisms of drug resistance and to use this information to develop strategies for the chemosensitization of drug-resistant tumors. A goal of the pathology laboratory is to offer chemosensitivity tests that identify intrinsic or acquired resistance of tumors to specific drugs or classes of drugs to enable the clinician to tailor therapy to the biology of cancers in individual patients. Multidrug resistance is one type of drug resistance. It can be present in either an intrinsic or acquired form. The human gene that confers human multidrug resistance, the MDR1 gene, has been cloned and classified as a member of the MDR gene family. Its encoded protein, called Mdr1, is an energy-driven membrane efflux transporter that maintains intracellular concentrations of certain chemotherapeutic drugs at nontoxic levels. Useful model systems for studying multidrug resistance have been developed in several research laboratories. Applying selection pressure by exposing cultured cancer cells to escalating doses of natural product anti-cancer drugs allows cross-resistant cell lines to be produced which share patterns of drug resistance with human cancers. A common feature of these drug-resistant lines is the expression of Mdr1. Using techniques of genetic engineering, molecular probes have been developed that can be used to measure MDR1 mRNA and MDR1 gene amplification. Mdr can be measured by immunochemistry methods. Currently, such measurements are being used to stratify patients in clinical trials designed to determine if chemosensitization by inhibition of the pump function of Mdr is a clinically useful therapeutic strategy. If successful, Mdr/MDR1 mRNA laboratory testing might significantly increase the clinical laboratory's role in cancer patient management.

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The relative increase in endometrial adenocarcinoma in women has increased the need for more objective criteria in the distinction of hyperplastic and neoplastic endometrium. The authors have used the ability of lectins to detect changes in surface glycoproteins to probe the differences among proliferative endometrium, endometrial adenomatous hyperplasia and adenocarcinomas. Paraffin-embedded sections of tissue obtained by Vakutage endometrial sampling technics were stained with each of 7 FITC lectin conjugates. Thirty-four specimens were examined (7 proliferative, 12 hyperplastic, and 15 adenocarcinomatous). Wheat germ agglutinin binding was detectable in all specimens with a distribution at the cell luminal border of glandular formations irrespective of diagnosis. However, adenocarcinoma cases showed distribution along the lumenal border and the cell periphery with loss of orientation of the lectin binding. Similar alterations and increased binding were noted for Concanavalin A. The WGA binding to sections was specifically inhibitable by oligosaccharides of N-acetyl-glucosamine. The results provide an objective criterion for detection of loss of cell orientation useful in the diagnosis of endometrial adenocarcinoma in tissue fragments.

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Clonal chromosome abnormalities were observed in 30 patients with non-Hodgkin's lymphoma; the type of lymphoma was characterized on the basis of the International Working Formulation. The 30 patients were classified into five groups according to the chromosome abnormality. There were 8 patients with t(14;18), 3 with t(8;14), 7 with a translocation to the long arm of chromosome 3 (a 3q+ chromosome), 5 with near-tetraploidy, and 7 with other abnormalities. Among the 8 patients with t(14;18), 5 had follicular small cleaved-cell lymphoma (FSC), I had follicular mixed cell lymphoma (FM), and 2 had diffuse large-cell lymphoma (DL); the diagnosis in these 2 patients was based on extranodal tissue. All 3 patients with t(8;14) had DL and B-cell markers. Except for 1 patient, all those with a 3q+ chromosome had DL; 4 of those who were tested had B-cell or pre-B-cell markers. Four of the 5 patients with near-tetraploidy had follicular mixed-cell lymphoma, and 2 of the 7 patients with other abnormalities had T-cell lymphoma. Thus, patients with a t(8;14), a 14q+ chromosome, or a 3q+ chromosome all tend to have diffuse large-cell lymphoma, usually of the non-cleaved type. On the other hand, our data suggest that patients with FSC generally have a t(14;18) whereas those with follicular and diffuse mixed small cleaved cells and large noncleaved cells have a different pattern with modal chromosome numbers in the tetraploid range. We added 17 previously reported patients to the 30 presented here and correlated the karyotype with survival. The 6 patients with near-tetraploidy had the longest median survival, 69 months, the 15 patients with t(14;18) had the next longest, 48 months. The 4 patients with t(8;14) had the shortest survival, 12 months, and the 9 with other abnormalities had the next shortest, 17 months. Intermediate survivals of 27 and 30 months were observed in patients with a 14q+ or a 3q+ chromosome, respectively. The median survival of these various categories differs and our data, thus, indicate that the karyotypic pattern of the malignant cell may be a significant independent prognostic feature influencing the survival of patients with non-Hodgkin's lymphoma.

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Circulating lymphocytes were enumerated in 28 patients with Crohn's disease and in 12 patients with other diseases by rosetting and by immunofluorescent staining using monoclonal antibodies for T-cell surface phenotypic markers [OKT3 (mature), OKT4 (helper), and OKT8 (suppressor/cytotoxic)] or polyvalent antisera for surface immunoglobulins (B cells). Total lymphocyte counts were reduced only in those with non-steroid-treated active Crohn's disease. Circulating monocyte counts, proportions of peripheral T and B cells, and percentages and absolute numbers of mature, helper, and suppressor T-cell subclasses in Crohn's disease were not significantly different than in the controls. Helper to suppressor T-cell ratios were comparable in all subjects, varying directly with numbers of helper T cells (p less than 0.05). Individual ratios of helper to suppressor T cells did not correlate with disease activity or location, the use of steroids, serum albumin, or total lymphocyte or monocyte counts. This study provides no evidence for underlying abnormalities of circulating lymphocyte subpopulations in Crohn's disease when compared to subjects with other illnesses. The characterization of lymphocyte subclasses in affected tissues is an important area of continuing investigation.

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