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Study objective: To determine whether monoclonal antibody (Mab) detection of tumor-associated antigen expressed on sputum epithelial cells precedes clinical presentation of second primary lung cancer. Design Setting/Participants: Eleven oncology centers [...]

EXPRESS STOP Why the Bethesda System: The Bethesda System for cervical and vaginal diagnoses was devised to improve communication between the cytopathologist and referring physician, notably by providing descriptive diagnoses [...]

Cytologic screening for urothelial carcinoma is fraught with low sensitivity, a high indeterminate rate, and until recently, poor standardization of terminology. The Johns Hopkins Hospital John K. Frost Cytopathology Laboratory has recently developed and published a template for reporting urine cytopathology; herein, we evaluate its interobserver reproducibility.

Background and aim: Subtle changes in hypothalamic-pituitary-adrenal (HPA) axis of subjects with non-functioning adrenal adenoma may be associated with endothelial alterations. We sought to investigate endothelial function, visceral adiposity and osteoprotegerin (OPG) and interleukin-18 (IL-18) levels in subjects with non-functioning adrenal adenomas. Subjects and methods: The adenoma group included 40 subjects without clinical and subclinical findings of hypercortisolism or other adrenal gland disorders. Twenty-two body mass index-matched controls were also enroled. The patients and control subjects underwent hormonal evaluation and assessment of anthropometric and metabolic parameters. Endothelial function was assessed with flow-mediated dilatation (FMD) of the brachial artery and intima media thickness (IMT) of common carotid arteries. Visceral adipose tissue area was measured by computed tomography. Plasma OPG and serum IL-18 levels were also measured. Results: When compared with healthy controls, the adenoma group had elevated systolic blood pressure, post-dexamethasone suppression test cortisol and reduced DHEAS. Visceral adipose tissue area and IMT of common carotid arteries were comparable. In the adenoma group, FMD of the brachial artery was significantly impaired and IL-18 level was significantly elevated. Visceral adipose tissue area was independently related with FMD. Homeostasis model assessment (HOMA) was the independent factor associated with visceral adipose tissue area. Cortisol, DHEAS and visceral adipose tissue area were independently associated with HOMA. Conclusions: We achieved evidence that could be attributable to endothelial alterations in subjects with non-functioning adrenal adenomas. Impaired FMD appeared to be a consequence of subtle changes in HPA axis in terms of elevated cortisol and reduced DHEAS as these conditions were known to disturb endothelial-dependent vasodilatation.

Background: Because of the increased use of imaging interventions, more subjects have been diagnosed with adrenal incidentaloma in recent years. Aim: To evaluate the risk of mass enlargement, hormone hypersecretion and development of adrenal carcinomas during short-term followup. Subjects and methods: There were 317 subjects with incidentally discovered adrenal tumors in the registry. Forty subjects were excluded because of clinically overt hormone secretion at diagnosis and subjects with complete data were included in radiological (no.=150) and hormonal (no.=150) follow-up. Radiological evaluation was performed with computed tomography (CT) and/or magnetic resonance imaging (MRI). There were 143 subjects with adrenal adenomas and 7 subjects with other tumor types (cyst or myelolipoma). Median follow-up duration was 24 months. Results: Increase in tumor size was detected in 25 subjects (17.4%) with adenomas and 1 subject with adrenal myelolipoma (14.3%). Decrease in tumor size was found in 7 subjects (4.8%) with adrenal adenomas. One patient was diagnosed with adrenocortical carcinoma during follow-up. In subjects with non-functioning adrenal adenoma (NFA, no.=120) or subclinical Cushing syndrome (sCS) (no.=30), no subject developed clinically overt hormone hypersecretion, while 8 (6%) subjects in the NFA group developed sCS. Tumor diameter and follow-up duration were significantly higher in subjects who developed sCS. Conclusion: In conclusion, we demonstrated that, despite being infrequent, adrenal tumors may increase in size, develop overt or subclinical hormone secretion or feature malignant transformation. Therefore, radiological and hormonal follow-up should be recommended to the patients. More investigations are needed for the establishment of long-term follow-up protocols.

BACKGROUND:The objective of this study was to assess the frequency of premalignant and malignant cells in sputum from patients with lung cancer and to measure the dependence of these cells on cancer stage, histologic type, tumor size, and tumor location.METHODS:This analysis included 444 patients with lung cancer. First, all patients were asked to produce sputum spontaneously; then, they underwent sputum induction. Slide preparations of the sputa were screened for the presence of abnormal cells.RESULTS:Of all patients with lung cancer who had produced adequate specimens, 74.6 had sputum that was positive for premalignant or worse cells, whereas 48.7 had sputum that was positive for malignant cells alone. Surprisingly, the presence of premalignant or worse cells in sputum depended only moderately on disease stage 82.9 of stage IV cancers vs 65.9 of stage I cancers, tumor size 78.6 of tumors >2 cm vs 64.7 of tumors ≤2 cm, and location 83.3 of central lesions vs 68 of peripheral lesions and was found to be independent of histologic tumor type 78.4 of squamous cell carcinomas vs 71.5 of adenocarcinomas, 74.5 of small cell carcinomas, and 75 of large cell carcinomas.CONCLUSIONS:The findings of the current study suggested the important potential of sputum cytology for lung cancer detection and risk assessment across all stages, histologic types, tumor sizes, and locations. However, the high sensitivities in this study were achieved with a level of scrutiny not feasible in the laboratory routine. The diagnostic potential of sputum cytology may be exploited better through the standardization and automation of sputum preparation and analysis. Cancer Cancer Cytopathol 2009. © 2009 American Cancer Society.

Aim: Although the majority of adrenal incidentalomas (AI) are non-functioning, studies evaluating metabolic disturbances in this particular group are limited. The objective of this study is to investigate metabolic syndrome components and levels of plasma von Willebrand factor (VWF), fibrinogen, and D-dimer in subjects with non-functioning AI. Subjects and methods: Forty-five subjects without clinical and subclinical findings of hypercortisolism or other adrenal gland disorders and 37 healthy controls were enrolled. The patients and controls underwent hormonal evaluation including morning cortisol, ACTH, post-dexamethasone suppression test (DST), morning cortisol, DHEAS, and urinary free cortisol. Anthropometric and metabolic parameters and body composition were assessed and fibrinogen, D-dimer, and VWF were measured. Results: When compared with healthy controls, subjects with AI had significant elevations in several metabolic and anthropometric parameters, uric acid, post-DST cortisol, and D-dimer. When compared with body mass index-matched controls, blood pressure (p=0.004), uric acid (p=0.009), post-DST cortisol (p=0.014), and D-dimer (p=0.045) remained significantly elevated. We demonstrated weak correlations between D-dimer and other metabolic and anthropometric variables. Morning cortisol was demonstrated as an independent variable associated with homeostasis model assessment levels in subjects with AI (β=410, p=0.004). Conclusion: Individuals with clinically and hormonally inactive adrenal adenomas feature insulin resistance and a variety of metabolic disturbances. The subtle cortisol autonomy seems to be associated with insulin-resistant state. D-dimer elevation in AI group was a consequence of insulin-resistant state associated with subtle cortisol autonomy rather than a direct effect of cortisol secretion.

Aim: this study was conducted to demonstrate the plasminogen activator inhibitor-1 (PAI-1) and thrombin activatable fibrinolysis inhibitor antigen (TAFI-Ag) levels in non-alcoholic steatohepatitis (NASH). Materials and methods: Twenty-seven patients with biopsy-proven NASH and 18 healthy controls (HC) were recruited for the study. Anthropometric data, liver histology (no.=20) and laboratory parameters including PAI-1 and TAFI-Ag assessments were recorded. Results: When compared with HC, patients with NASH had higher body weight, higher waist circumference, elevated blood pressure, higher fasting plasma glucose (FPG) levels and higher homeostasis model assessment (HOMA) scores. the mean plasma PAI-1 levels of patients was found to be higher than HC (87.60 ng/ml vs30.84 ng/ml p=0.000) and mean plasma TAFI-Ag levels of patients was found to be significantly lower (8.69 μg/ml vs 12.19 μg/ml p=0.000). PAI-1 levels were correlated with systolic blood pressure, age, body weight, transaminases, waist circumference, FPG, body mass index, and HOMA score. TAFI-Ag levels were found to be negatively correlated with transaminases, waist circumference, and body weight. In multiple regression analysis, BMI was the independent variable effecting PAI-1 levels. We did not show any association between PAI-1, TAFI-Ag, disease activity score and fibrosis score. HOMA was the independent variable effecting liver fibrosis in our patients. Conclusion: In this study we demonstrated that patients with biopsy-proven NASH had higher PAI-1 and lower TAFI-Ag expression than HC. Elevated levels of PAI-1 in NASH is the consequence of insulin resistance state. Lower TAFI-Ag levels may be related to the overactivation of TAFI pathway resulting in TAFI-Ag depletion. Furthermore, liver function disturbances may impair TAFI production in NASH. We also showed that NASH patients even with slight elevations of transaminases feature marked insulin resistance and components of metabolic syndrome.

Introduction: Although the etiology of osteoporosis is different between men and women, the underlying pathophysiological mechanism is similar, namely an absolute or relative increase in bone resorption, leading to progressive bone loss. transforming growth factor (TGF)-β1 is a growth factor in human bone, which is produced by osteoblasts, and which has various effects on osteoclasts and osteoblasts. the aim of our study was to determine serum TGF-β1 levels in male patients with idiopathic osteoporosis. Methods: twenty five males with idiopathic osteoporosis and 25 age-matched controls were studied. Osteoporosis was defined by a T score of <−2.5 in the lumbar spine or at the femoral neck. We measured levels of TGF-β1, estradiol, total and bioactive testosterone. Various markers of bone remodeling were also measured. Results: TGF-β1 was significantly lower in osteoporotic patients than in controls (3.706 ng/dl, 25−75 percentiles: 2.81−5.33 vs8.659 ng/dl, 25−75 percentiles: 4.837−11.835; p=0.000). Moreover, TGF-β1 levels were positively correlated with bone mineral density (BMD) at the femoral neck (r=0.439, p=0.028), and at the lumbar spine (r=0.41, p=0.042). No correlation was found between serum estradiol, testosterone and TGF-β1 levels. Discussion: Serum TGF-β1 levels are depressed in osteoporotic men and are positively correlated with hip and spine BMD. The results of our study suggest that TGF-β1 may play a role in the pathogenesis of idiopathic male osteoporosis.

Pineal gland lesions are rare, with only a few cytologic descriptions occurring in the literature, according to the authors' knowledge. The current article describes the cytopathologic characteristics of 20 such lesions with discussion of differential diagnoses.Cytologic material was obtained either by fine‐needle aspiration biopsy (FNAB) under stearotactic radiologic guidance or by touch imprinting (TI) at the time of frozen sectioning. The 20 specimens include pineoblastoma (five specimens), pineocytoma (four specimens), astrocytoma (three specimens), germ cell tumor (three specimens), meningioma (one specimen), epidermoid cyst (three specimens), and pineal cyst (one specimen). Smears were stained with Diff‐Quik and with Papanicolaou and hematoxylin and eosin stains. In selected specimens, immunoperoxidase (IPOX) stains were performed on cell block sections using synaptophysin, neuron‐specific enolase, placental alkaline phosphatase, glial fibrillary acidic protein, leukocyte common antigen, cytokeratins, and human chorionic gonadotropin antibodies.Several cytomorphologic characteristics unique to each lesional category with occasional overlapping features were observed. The unique features included the following: small, hyperchromatic, round to oval cells with frequent rosetting (pineocytoma), with a few specimens in addition showing hypercellularity, crowding, mitoses, and necrosis (pineoblastoma); pleomorphic round cells in a fibrillary background (astrocytoma); large polygonal cells with prominent nucleoli and clear cytoplasm (germ cell tumor); spindled fibroblastic cells (meningioma); anucleate squames and mature squamous cells (epidermoid cyst); and small uniform polygonal cells (pineal cyst). When necessary, IPOX studies supported the morphologic diagnoses.FNAB and TI cytology were found to provide a rapid and reliable diagnosis of pineal lesions. This is particularly important when dealing with minute amounts of tissue material. Both techniques appeared to provide equally good cytomorphology on smears. IPOX studies played an important complementary role in difficult cases when performed on cell blocks. Cancer (Cancer Cytopathol) 2005. © 2005 American Cancer Society.

Hepatocellular carcinoma (HCC) is routinely graded histopathologically using a modified Edmondson system (ES). The cytologic grading of HCC has been used predominantly as an adjunct in differential diagnoses (i.e., to help distinguish HCC from other tumors as well as nonneoplastic lesions). However, there are unanswered questions regarding the reliability of the cytologic grading of HCC and its correlation with histologic follow‐up.A total of 106 cases of HCC were identified in the authors' cytopathology files from 1977 to the present. Of these cases, 64 had either a core needle or excisional biopsy sample that was judged to be adequate for histologic grading. From each case smears were graded independently in a blinded fashion by two cytopathologists, and tissue slides were graded by a liver pathologist. The cytopathologists' grading was then adjudicated by considering the histologic diagnosis as the “truth standard”. Finally, after the scores were calculated, a statistical analysis was performed to ascertain the accuracy of the cytopathologic grading.The sensitivity for accurate grading was found to be highest for well differentiated (WD) lesions; the specificity was found to be highest for poorly differentiated (PD) HCC for both cytopathologists. Interobserver agreement was highest for WD HCC. WD HCC displayed cohesive fragments, often associated with characteristic vascular/endothelial patterns. In addition, moderately differentiated (MD) HCC demonstrated numerous single cells and atypical naked nuclei, usually with prominent nucleoli. PD HCC displayed loose nests and three‐dimensional fragments (often gland‐like), pleomorphism, macronucleoli, and focal necrosis.In the authors' experience, the three‐tier cytologic grading of HCC was found to be only moderately accurate. The accuracy of cytologic grading was reported to be high for WD/PD HCC and low for MD HCC. The architectural criteria appear to be more useful for WD HCC, whereas marked cellular pleomorphism is specific for PD HCC. The authors propose that a two‐tier grading system may be more useful, given the recent studies of HCC recurrence. Cancer (Cancer Cytopathol) 2004. © 2004 American Cancer Society.

The authors evaluate the role of immediate cytologic evaluation (ICE) with fine-needle aspiration biopsy (FNAB) for lung lesions at highest risk for pneumothorax.

Sputum cytopathologic monitoring detects squamous cell lung cancers at an extremely early stage (x-ray negative). It holds further potential for preventing disease by detecting epithelial alterations which reflect environmental hazards. The addition of sputum cytology screening to screening by chest x-ray film does not significantly reduce mortality from all types of lung cancer, but preliminary analysis of Johns Hopkins Lung Project data suggests that mortality from squamous cell carcinoma is reduced. Quantitative automated cytopathology systems and biochemical/immunological cell markers enhance understanding of these precursors and offer great promise for increasing capacity, accuracy, and usefulness in cytopathology screening of workers. Cytological specimens collected over years of screening workers considered at risk may beimportant to eventually understanding development and prevention of major occupational diseases.

Cul-de-sac fluid from women with histologically confirmed endometriosis (n=45) or with no evidence of endometriosis (n=17) was removed during the proliferative phase of the menstrual cycle (days 8 to 12) and analyzed for prostaglandin E2(PGE2), prostaglandin F2α(PGF2α), 15-keto-13,14-dihydroprostaglandin F2α(PGFM), and thromboxane B2(TXB2). The fluid volume was recorded. Peripheral blood was also obtained to determine the concentration of PGFM.

• Two cases are reported in which pars plana vitrectomy was employed to restore vision and confirm the diagnosis of "primary" intraocular reticulum cell sarcoma. Cytologic study of material removed from the vitreous cavity confirmed the clinical diagnosis. The clinical, histologic, and cytologic features of intraocular reticulum cell sarcoma are reviewed.

Transbronchial needle aspiration of cytopathological specimens has proven useful in the diagnosis and staging of bronchogenic carcinoma, but its value in conditions requiring histologic confirmation has been hampered by the small size of the sample provided. To expand the utility of this procedure, we designed a larger (18 gauge) needle with a beveled stylet with which tissue cores for histologic study can be obtained during rigid bronchoscopy, and we have evaluated the safety and efficacy of this technique. Diagnoses of five neoplastic and three granulomatous diseases were established in eight of the ten patients with this procedure, and there were no complications. These findings suggest that transbronchial needle aspiration biopsy is relatively safe and effective, further extending the bronchoscopic approach to selected patients with mediastinal disease.

A screening project consisting of 10,362 men was designed to detect early lung cancer. Half of the subjects had sputum cytologic studies and chest radiographs, and the other half had chest radiographs. Seventy cases of bronchogenic carcinoma were detected. Eight patients had malignant cells in their sputum and normal chest radiographs, and 62 patients had radiographic evidence of bronchogenic carcinoma. After clinical assessment including bronchoscopy, percutaneous needle biopsy, mediastinoscopy, and mediastinotomy in selected cases, 48 of the patients underwent exploratory thoracotomies. Six patients had benign disease. Thirty-nine of the remaining 42 patients had tumors resected for cure, an overall resectability rate of 55%. Staging was accomplished after resection and histologic examination of the operative specimens. Five patients with Stage 0 carcinoma have survived a median of 36 months without evidence of recurrence. Twenty-six patients had Stage I disease, and 77% have survived a median of 36 months without recurrence. Four of these patients have developed second primary tumors. Of the seven patients with Stage II disease, three are alive 40 to 50 months following operation. Seventeen patients had Stage III disease, two of whom have survived. Nine patients with oat cell carcinoma were treated by irradiation and chemotherapy, and all are dead. The median survival was 8 months. The results of this study are encouraging. However, long-term follow-up is necessary to demonstrate whether early detection by sputum cytologic studies and chest radiographs and the apparently improved survival of these paitents will result in a decreased death rate from bronchogenic carcinoma. The high initial survival rates may be due simply to earlier intervention in the natural history of the disease.

In recent years we have witnessed increased reliance on 2 modalities in the management of patients with superficial transitional cell cancer of the bladder, that is intravesical chemotherapy for the control of existing and recurrent disease, and urinary cytology for the diagnosis of persistent or new neoplastic cells. This development has prompted some concern as to whether the use of chemotherapy might affect the morphological appearance of cells so as to make the interpretation of cytological specimens in this setting unreliable. We describe morphological differences between neoplastic cells and normal as well as cancer cells exposed in situ and in vitro to thiotepa. An appreciation of these differences has permitted accurate diagnosis of urinary cells in the presence or absence of cancer despite the regular use of this agent. Thus, it appears that the status of bladder cancer can be monitored successfully by an assessment of urinary cytology in the context of long-term treatment and prophylaxis with this agent.

Quality control in cytopathology involves specimen collection, preparation, screening, and final diagnosis. The measures to assure the optimal performance and to detect the malfunctions in these areas are discussed. Careful selection and application of proper procedures, proper training and continuing education of cytotechnologists and pathologists, and reasonable workload for screening cytotechnologists are important factors in quality assurance.

Ultrafine titanium dioxide, zinc oxide, and a 1:1 mixture of ZnO/TiO2 were used as 5% dispersions in sunscreen formulae. Three different carrier bases were evaluated for their accelerated stability and rheological properties with and without metal oxides based on sodium lauryl sulphate/polysorbate 80, triethanolamine stearate, and cetyl trimethyl ammonium chloride. All three bases showed thixotropic behaviour. Addition of metal oxides only affected the magnitude of viscosity not the viscoelastic behaviour. The cationic emulsion base was found to be the most stable to incorporate the microfine metal oxides, the others' viscosity values showing a significant drop in storage. The in vivo sun protection factors were determined on the cationic based emulsions in four human subjects using an UV source covering both UVA‐UVB regions. The mean sun protection factors were found to be 5.03, 4.03, and 4.8 for TiO2, ZnO, and 1:1 ZnO/TiO2 respectively for 4 mg.cm‐2 applications, the differences not being significant. Dans cette etude pour preparer les formules d'ecrans solaires fournissant la protection contre les regions UVA et UVB, on a utilise au taux de 5 pourcent du dioxyde de titane ultrafin, oxyde de zinc ultrafin et une mixture 1:1 de ZnO/TiO2. La stabilite acceleree et les proprietes rheologiques de trois emulsions de base ont ete evaluees avec ou sans les oxydes de metaux. Toutes les trois des emulsions de base ont montre un comportement thixotropique. L'addition des oxydes de metal a seulement affecte le degre de viscosite et non le comportement de viscoelastique. L'emulsion cationique de base a ete determinee comme etant le plus stable pour l'incorporation de l'oxyde de metal microfin. Les autres valeurs de viscosite ont presente une baisse significative a la temperature et a la duree de stockage. Les facteurs de protection solaire ont ete determines des emulsions utilisant le tansio actif cationique in vivo sur quatre sujets utilisant une source UV couvrant a la fois les regions UVA et UVB. En moyenne on a trouve que les facteurs de protection solaire etaient respectivement de 5.03, 4.03 et 4.8 pour TiO2, ZnO, et ZnO/TiO2.

The histopathology of Fuchs' heterochronic iridocyclitis has been infrequently documented. It is surprising for, in the opinion of some observers, the syndrome constitutes about 2% of all cases of uveitis.1 Its etiology and pathogenesis are largely unknown. It is characterized by unilateral (rarely bilateral) hypopigmentation of the iris, low-grade signs of chronic inflammation in the anterior chamber and vitreous, and, in some cases, cataract and glaucoma.2 The striking transillumination of the iris has been considered to be a secondary manifestation of atrophy and sclerosis of the stroma and of patchy depigmentation of the epithelium.In large measure, lack of interest in this syndrome has been engendered by the belief that there may be no cause-and-effect relationship between this type of heterochromia and a specific, unique form of uveal inflammation. If true, there would be no reason to consider Fuch's heterochromic iridocyclitis a distinct nosologic entity.3In the

Pleural fluids from 182 patients were studied prospectively. Although red blood cell (RBC) counts of greater than 10,000/cu mm were common with all types of effusions, an RBC count greater than 100,000/cu mm strongly suggested malignant neoplasm, pulmonary infarction, or trauma. Of 31 exudative effusions with a lymphocytic predominance, 30 were due either to tuberculosis or neoplasm. No tuberculous effusions had more than 1% mesothelial cells, while most other effusions contained at least 5% mesothelial cells. Pleural fluid cytological studies showed malignant cells in 33 of 43 patients with effusions due to tumor. More than 50% of the effusions with originally inconclusive pleural fluid cytological findings were proved to be due to neoplasm. When tumor is suspected, at least three separate pleural fluid specimens should be submitted for cytological examination.

Thirty-two consecutive patients with mediastinal lesions suggestive of bronchogenic carcinoma underwent transbronchial needle aspiration. Eighteen of 20 patients (90 percent) with proved bronchogenic carcinoma had malignant cytology specimens or tissue fragments. Of 12 patients with normal cytology specimens, six were subsequently proved to have nonneoplastic disease. Transbronchial needle aspiration appears to offer a sensitive and specific alternative to more invasive surgical techniques used in the diagnosis of malignancies with mediastinal involvement

Cancer of the uterine cervix, the sixth most common cancer among women, is still considered a significant health problem, despite declining mortality rates during recent decades. In Baltimore, the age-adjusted mortality rates for cervical cancer are significantly higher than the U.S. average, for both black and white women. Early detection of cervical cancer through screening with the Papanicolaou (Pap) test has been shown to decrease mortality by preventing development of invasive disease, and intervention programs have been developed to increase use of Pap testing. However, the evaluation of those programs is difficult, as self-reports of Pap screening may be inaccurate, and repeated inquiries about Pap tests may influence the behavior being studied. We report in this article a method to use data from cytopathology laboratories to estimate the use of Pap screening by women in a defined population. This approach can be used to evaluate changes in receipt of Pap smears and to provide feedback to intervention programs. [Am J Prev Med 1994;10:235–7]