Effect of analytic uncertainty of conventional and point-of-care assays of activated partial thromboplastin time on clinical decisions in heparin therapy.

The authors assessed the capability of assays of activated partial thromboplastin time (aPTT) for supporting clinical decision algorithms for heparin therapies of varying complexity. Blood samples were collected prospectively in three explicit management strategies from 100 sequential patients for whom heparin dosage was adjusted for therapeutic monitoring, femoral venous sheath removal after cardiac catheterization, or heparinization after thrombolytic therapy. In two- and three-way decision algorithms, conventional and point-of-care aPTT assays agreed with heparin assays in approximately two thirds of cases, and the two aPTT assays agreed in 80% or more of all cases. In six-way decision algorithms, the two aPTT assays agreed in only about half of all cases. The authors conclude that the reliability of point-of-care aPTT assays is similar to that of conventional assays. Both techniques can support two- and three-way decision algorithms but not some more complex patient classifications.

Diagnostic accuracy in fine-needle aspiration of soft tissue and bone lesions. Influence of clinical history and experience.

Interpretation of soft tissue and bone lesions with fine-needle aspiration (FNA) is difficult. We determined whether clinical history or experience improves diagnostic accuracy of FNA interpretation of these lesions. Four cytopathologists with varying degrees of experience retrospectively reviewed 89 soft tissue and bone lesions, initially without knowledge of clinical history and subsequently with knowledge of clinical history. Each time, the pathologist rendered a precise diagnosis (histogenetic classification, e.g., angiosarcoma, lipoma) for each case and classified the lesion into one of 4 categories: benign, probably benign, probably malignant, or malignant. The proportion of correct precise diagnoses was calculated. Also, the numbers of correct and incorrect classifications of malignancy were used in standard relative operating characteristic (ROC) curve analysis. The area under the ROC curve was estimated to give an indicator of diagnostic accuracy. Knowledge of clinical history increased the proportion of correct diagnoses and the accuracy of the classification for all observers. Experienced observers more accurately classified lesions, and knowledge of clinical history particularly improved the diagnostic accuracy of less experienced observers.

Comparative clinical evaluation of biochemical and genomic tumor markers.

The clinical utilities of established biochemical tumor markers and of emerging genomic markers are compared by six formal criteria: [1] tests negative in health or benign disease, [2] produced exclusively by specific tumor cells, [3] present frequently in the targeted malignancy, [4] detectable in occult disease, [5] degree of expression reflects tumor burden and prognosis, and [6] degree of expression correlates with therapeutic result. Evaluation of eight widely accepted marker systems combining a biochemical indicator with a specific cancer, on the one hand, and five representative genomic marker-target combinations involving chromosomal translocation, gene amplification and mutation, on the other hand, produces three main conclusions: First, specified applications are sufficiently well documented for the best biochemical markers to now tailor analytical performance goals to these uses. Second, further clinical trials of genomic markers are needed to document the useful linkage of specific indicators with specific clinical problems. Third, the different profiles of marker characteristics defining the two classes of indicators suggest some mutually complementary uses.

Regional cardiac compression due to a large anaerobic bacterial empyema.

Compression of the heart outside the pericardial sac is a rare cause of hemodynamic compromise and cardiac tamponade. We report an atypical case of regional cardiac compression caused by a large loculated anaerobic bacterial empyema.

Percutaneous fine-needle aspiration of gastrointestinal wall lesions with image guidance.

The fear of complications related to transgression of the bowel wall has limited the application of fine-needle aspiration (FNA) in gastrointestinal wall masses. We have undertaken a study examining our use of image-guided FNA in this setting, and evaluated diagnostic outcome and procedural risk. Twenty patients underwent percutaneous computed topography (CT) or ultrasound (U/S)-guided FNA biopsy of gastrointestinal wall masses over a 3-yr period. Hollow-bore needles were used to aspirate 8 gastric wall masses, 5 perirectal/distal sigmoid masses, 4 colonic masses, and 3 small-bowel masses. Lesions ranged in size from 1.5-13.0 cm (mean, 3.9 cm). One to five passes were made into each lesion (mean, 2.4). Immediate assessment for adequacy by a cytopathologist was performed in all cases. Neoplastic processes were identified in 15 cases (8 primary adenocarcinomas, 2 gastrointestinal stromal tumors, 3 metastases to the bowel wall, 1 Kaposi's sarcoma, and 1 primary lymphoma). Eleven of these 15 patients had histologic confirmation (all neoplastic lesions, excepting patients with metastases or Kaposi's sarcoma). Negative diagnoses (no evidence of malignancy) were obtained in the remaining 5 patients (2 benign colonic epithelium, 1 benign lymphoid population, 1 benign stroma, and 1 acute inflammatory process). A benign clinical course was followed in 4 patients, with 1 patient lost to follow-up. No acute or chronic postprocedural complications were identified. The earlier literature as well as this current study suggest that complications of FNA in this setting are rare. Diagnostic material may be obtained in a less invasive manner than open surgical biopsy.

Sources of diagnostic error in the fine-needle aspiration diagnosis of Warthin's tumor and clues to a correct diagnosis.

Squamous metaplasia and cystic degeneration in Warthin's tumor (WT) are not uncommon. A recent case of WT misdiagnosed as metastatic squamous carcinoma with cystic change prompted us to review our experience with fine-needle aspiration (FNA) of WT, with special attention given to potential sources of diagnostic pitfalls. Aspirations from 16 cases of histologically confirmed WT were retrospectively evaluated for cellularity, cell composition, and background. The FNA review diagnosis was compared with the previous FNA and corresponding tissue findings. All tumors presented in the parotid gland. The initial cytologic diagnoses were: WT in 13 cases, oncocytoma vs. low-grade mucoepidermoid carcinoma in 1, squamous carcinoma vs. branchial cleft cyst in 1, and squamous carcinoma in 1. On review, 13 cases (81%) showed typical features associated with WT: Moderate to abundant oncocytic epithelium, lymphoid stroma, background debris, and mild squamous metaplasia. In the remaining cases, one lacked a lymphoid stroma and could not be further classified (initially called "oncocytoma vs. low-grade mucoepidermoid carcinoma"). The other 2 cases contained moderate to abundant atypical squamous cells and extensive necrotic/mucoid debris, and review diagnoses were consistent with the initial cytologic diagnoses (squamous carcinoma in one, and branchial cleft cyst vs. squamous carcinoma in the other). In our series, typical features of WT were seen in 81% of cases. Atypical features are largely present as individual metaplastic squamous cells. Diagnostic errors are caused by a lack of typical features and the presence of individual atypical squamous cells in a necrotic background mimicking carcinoma. An awareness of the morphologic variation present on cytologic preparations and correlation with clinical findings should prevent erroneous interpretation in the FNA setting.

Spindle-cell lesions of the liver: diagnosis by fine-needle aspiration biopsy.

Rarely, spindle-cell lesions in liver fine-needle aspiration biopsies (FNABs) are encountered. A retrospective review of our experience with lesions that are mesenchymal in origin or appearance was undertaken to elucidate the frequency and spectrum of these lesions. Image-guided liver FNABs performed over a 3-year period (n = 585) at our institution (1996-1998) were retrospectively evaluated. Cytologic smears, cell block preparations, and clinical follow-up of lesions with spindle-cell morphology were reviewed. Twenty-nine of 585 cases were of spindle-cell morphology (5%). Hemangiomas (n = 12, 41%) and metastatic sarcomas (n = 6, 21%) comprised the largest categories, followed by granulomatous inflammation (n = 3, 10%). Other cases included primary angiosarcoma and fibrolamellar hepatocellular carcinoma. The most frequent spindle-cell liver lesion encountered is hemangioma, followed by metastatic leiomyosarcoma and granulomatous hepatitis. Awareness of diagnostic possibilities, special attention to specimen adequacy, and use of ancillary procedures can maximize diagnostic yield.

Cytologic features of well-differentiated villoglandular adenocarcinoma of the cervix.

OBJECTIVE: To evaluate the cytologic features of villoglandular adenocarcinoma of the cervix in cervical smears. STUDY DESIGN: Eleven cervical smears from six patients with histologically proven villoglandular adenocarcinoma were reviewed. RESULTS: All smears were positive for tumor upon retrospective evaluation and revealed similar cytologic features. The tumor cells were abundant and were shed in sheets, tight clusters and tissue fragments. Papillary projections, clusters with smooth borders and flattened cells at the periphery, strips with peripheral nuclear palisading and pseudostratification, and rosettes were present. Nuclear crowding and overlapping were prominent. The nuclei were small, ovoid and hyperchromatic. The chromatin was granular and evenly distributed. Nucleoli were absent or inconspicuous. Mitoses were present. CONCLUSION: VGA may cause diagnostic difficulty because it shares some morphologic similarities with adenocarcinoma in situ, squamous cell carcinoma in situ involving endocervical glands, endometrial cells directly sampled with the Cytobrush and reactive endocervical cells. However, the above constellation of features should permit a cytologic diagnosis.

Can core needle biopsy replace fine-needle aspiration cytology in the diagnosis of palpable breast carcinoma. A comparative study of 124 women.

BACKGROUND: There appears to be a growing movement in favor of core needle biopsy (CNB) over fine-needle aspiration (FNA) cytology in detecting breast carcinoma in women. The authors compared the sensitivity and specificity of these two methods in patients who presented to The University of Texas M. D. Anderson Cancer Center for evaluation of a palpable breast mass. METHODS: One hundred and twenty-four women (mean age, 51 years; range, 28-86 years) with a clinically suspicious palpable mass (mean size, 4.4 cm; range, 1-12 cm) underwent concurrent FNA and CNB. For the FNA, an average of three needle passes were made. FNA was followed by three CNBs using the Bard Monopty needle. CNB samples were submitted for frozen section to determine adequacy, and an additional three cores were performed if the first batch was deemed inadequate. All patients ultimately had histologic confirmation of their neoplasms either by the core needle procedure or by definitive open surgical biopsy. Features of cases with discrepant diagnoses were examined in relation to tumor size and histologic type. RESULTS: Specificity of both FNA and CNB was 100%. The sensitivity in detecting a malignant neoplasm was higher for FNA than for CNB (97.5% vs. 90%, P < 0.004). CONCLUSIONS: In our experience, FNA of palpable breast lesions is a more sensitive method for the detection of carcinoma regardless of tumor type, size, or differentiation. Contrary to other reports, not only was FNA alone more sensitive than CNB alone, the addition of CNB to an already negative FNA failed to increase sensitivity in the detection of carcinoma. However, CNB did contribute to a more definitive diagnosis in some cases. The authors also found FNA to be more cost effective than CNB for palpable breast lesions when time and effort are taken into consideration. This reinforces the benefit of FNA over CNB in the detection of early stage breast carcinoma.

Fine needle aspiration biopsy of the liver.

The liver is a commonly targeted deep-seated organ in which fine-needle aspiration biopsy (FNAB) is performed. By far, the most frequently encountered lesions on FNAB of the liver are metastases; however, a wide variety of other lesions have been described and are likely to be encountered. Because of this wide variety, attention to architectural as well as cytologic features on smears and cell block preparations, ancillary techniques, and special studies are often required. In the setting of proper specimen handling and judicious use of ancillary procedures, FNAB of hepatic lesions can be an accurate diagnostic procedure.

Activation of extracellular signal-regulated kinase in human prostate cancer.

PURPOSE: To investigate the level of expression, activation state, and functional significance of extracellular signal regulated kinase (ERK) in prostate cancer. MATERIALS AND METHODS: Human prostate tissue samples (n = 22) were obtained from patients undergoing radical prostatectomy for localized adenocarcinoma of the prostate (n = 16, age range 44 to 72 years) or normal prostate specimens (n = 6, age ranges 19 to 47 years) obtained from rapid autopsy. Immunoblots, in vitro kinase assays, and immunohistochemistry were used to determine the expression and activation state of ERK in human prostate cancer. RESULTS: Immunoblot and in vitro kinase assays demonstrated a 15-fold increase in ERK activation in prostate cancer specimens compared with normal human prostate tissue; however, ERK expression levels were only 1.3-fold higher in cancer. Immunohistochemical analysis demonstrated similar expression of ERK in cancer and normal tissues; however, phosphorylated ERK demonstrated greater intensity in the cancer specimens. Experiments conducted on a prostate cancer cell line demonstrated that EGF induced activation of ERK and cellular proliferation was partially inhibited by PD98059, a chemical inhibitor of the immediate upstream signaling component responsible of activation of ERK. CONCLUSIONS: Collectively, these data demonstrate a dramatic increase in ERK activation in prostate cancer compared with normal prostate tissue and suggest that inhibitors designed to target this signal transduction cascade might have therapeutic benefit in the treatment of prostate cancer.

Induction of polyclonal prostate cancer-specific CTL using dendritic cells transfected with amplified tumor RNA.

Polyvalent cancer vaccines targeting the entire antigenic spectrum on tumor cells may represent a superior therapeutic strategy for cancer patients than vaccines solely directed against single Ags. In this study, we show that autologous dendritic cells (DC) transfected with RNA amplified from microdissected tumor cells are capable of stimulating CTL against a broad set of unidentified and critical prostate-specific Ags. Although the polyclonal CTL responses generated with amplified tumor RNA-transfected DC encompassed as a subcomponent a response against prostate-specific Ag (PSA) as well as against telomerase reverse transcriptase, the tumor-specific CTL were consistently more effective than PSA or telomerase reverse transcriptase CTL to lyse tumor targets, suggesting the superiority of the polyclonal response. Although tumor RNA-transfected DC stimulated CTL, which recognized not only tumor but also self-Ags expressed by benign prostate tissue, these cross-reactive CTL were exclusively specific for the PSA, indicating an immunodominant role of PSA in the prostate cancer-specific immune response. Our data suggest that tumor RNA-transfected DC may represent a broadly applicable, potentially clinically effective vaccine strategy for prostate cancer patients, which is not limited by tumor tissue availability for Ag preparation and may minimize the risk of clonal tumor escape.