K-ras and p16(INK4A)alterations in sputum of NSCLC patients and in heavy asymptomatic chronic smokers.

NSCLC rates among the most frequent and lethal neoplasm world-wide and a significant decrease in morbidity and mortality relies only upon effective early diagnostic strategies. We investigated K-ras mutations and p16(INK4A) hypermethylation in tumor tissue and sputum of 50 patients with NSCLC and correlated them with sputum cytology and with tumor staging, grading and location, to ascertain, in sputum, their potential diagnostic impact. The same genetic/epigenetic abnormalities and cytological features were also evaluated in sputum from 100 chronic heavy smokers. Genetic analysis identified molecular abnormalities in 64% tumors (14/50 K-ras mutations and 24/50 p16(INK4A) hypermethylation) and in 48% sputum (11/50 K-ras mutations and 16/50 p16(INK4A) hypermethylation). In tumors K-ras mutations and p16(INK4A) hypermethylation were mostly mutually exclusive, being found in the same patients in 3 cases only. Genetic abnormalities in sputum were detected only in molecular abnormal tumors. Molecular changes in sputum had rates of detection similar to cytology (42%) but the cyto-molecular combination increased the diagnostic yield up to 60%. Interestingly, the rate of detection of genetic changes in sputum of tumors at early stage (T1) was not significantly different from that of tumors at more advanced stage (T2-T4). In fact K-ras point mutations were frequently recognised in tumors at early stage while p16(INK4A) inactivation prevailed in tumors at advanced stage ( P=0.0063). As expected, diagnostic cytological findings were more frequently found in tumors at advanced stage (P=0.004). No correlation was found between tumor grading and location (central versus peripheral) and molecular changes. p16(INK4A) hypermethylation, but not K-ras mutations, was documented in sporadic cases of asymptomatic heavy smokers (4%) where it was uncoupled from cytological abnormalities. In conclusion the cyto-molecular diagnostic strategy adopted in this study was able to detect the majority of tumors but in order to be proposed as effective and early diagnostic tool, this molecular panel needs to be tested in prospective studies with adequate follow-up.

Cytology of yolk-sac tumor of the ovary in ascitic fluid. Report of a case.

The cytologic, serologic, immunocytochemical and histologic findings of a yolk-sac tumor of the ovary in which the diagnosis was suggested by the cytologic examination of ascitic fluid specimens are reported. The case emphasizes the importance of evaluating, in addition to smears, the cytologic findings of a cell block specimen (which is generally prepared from an effusion) to obtain more diagnostic clues. A preliminary cytomorphologic diagnosis of this highly malignant tumor is valuable as a guide in planning further immunocytochemical and serologic studies.

Transthoracic fine needle aspiration biopsy in pulmonary lesions. Updated results.

An investigation was carried out on 271 patients who underwent transthoracic fine needle aspiration biopsy ( FNAB ) for suspected pulmonary lesions in a four-year period; 80% of them had a malignant tumor. The histologic control of the cytologic diagnoses made on the transthoracic FNAB was possible in over 50% of the cases. The sensitivity and predictive value for positive results were, respectively, 0.890 and 0.995, whereas the typing accuracy verified in 58 cases on the surgical specimen was 0.76. The comparison of the data obtained from the most recent case material with that of early observations confirmed the high sensitivity of transthoracic FNAB in the detection and characterization of malignant lesions in the lungs. The sensitivity was almost identical for primary tumors, 0.90, and metastatic disease, 0.88. Furthermore, over the years the data showed an improvement in the results due to the experience gained, the combined use of cytology and histology and the application of histochemical methods. More sophisticated methods, such as immunocytochemistry and electron microscopy, were essential to the final diagnosis in only a few cases.

Fine needle aspiration biopsy cytology of primary and metastatic pulmonary tumors.

A total of 130 patients with clinically suspected primary or secondary malignant neoplasms of the lung underwent fine needle aspiration biopsy under fluoroscopic control. The cases included 80 primary malignant tumors of the lung, 35 metastatic deposits, 14 nonneoplastic lesions and 1 benign tumor. The cytologic diagnoses were confirmed histologically in 56 cases and clinically in 74. Among the latter, the cytologic findings were comparable to the histology of the primary tumor in 19 cases with metastatic pulmonary lesions; in five cases, the extrapulmonary primary was identified on the basis of the cytologic study of the metastatic pulmonary lesion. The diagnostic sensitivity was 0.91 because of a false-negative result in a case of bronchial carcinoid, and the diagnostic specificity was 0.95. The predictive value was 0.99 for positive results because of a false-positive diagnosis given on a chondroid hamartoma and 0.70 for negative results. The sensitivity was 0.92 for primary malignancies and 0.89 for metastases. The cytologic typing accuracy of the 32 cases with histologically confirmed primary carcinoma of the lung was 0.65. Large-cell carcinoma and adenocarcinoma were the types that were cytologically unidentifiable most frequently. No major complications caused by the procedure were recorded in the present series.

Sputum cytology for the diagnosis of carcinoma of the lung.

Of 400 consecutive patients with histologically proven carcinoma of the lung, one to six sputum samples (mean, 2.8) were examined cytologically; 60% also had histologic examination of paraffin-embedded material. The overall sensitivity of sputum cytology was 0.58. The sensitivity increased from 0.37 to 0.57 when three samples rather than one were examined; it increased by only another 0.01 when four to six samples were studied. The examination of paraffin-embedded material yielded another 0.075 increase in sensitivity. A multiparametric study, including diameter, cavitation, site and histologic type of the pulmonary tumors, showed that sputum cytology was particularly significant for neoplasms of the left upper lobe and that the sensitivity related to the histologic type was not independent of the site, diameter and cavitation. The overall cytologic typing accuracy was 0.77, with a range from 0.20 to 0.96. The majority of the diagnoses at variance with histology and the unclassified malignant epithelial tumor cells were found to be associated predominantly with carcinoma of the large-cell type and with poorly differentiated adenocarcinomas.

Cytologic diagnosis of pulmonary carcinoma on bronchoscopic brushing material.

The material obtained by brushing procedures under visual control from 370 consecutive patients with histologically confirmed primary carcinoma of the lung who underwent bronchoscopy was examined cytologically. The sputum of 276 of these patients was also investigated. The overall sensitivity of the bronchoscopically obtained cytology was 0.67; however, the values were 0.78 and 0.28, respectively, for the cases with and without visible lesions of the bronchi. Sputum examination enhanced the sensitivity to 0.79 overall and to 0.84 and 0.61, respectively, for the two groups, with a greater benefit for the group with negative bronchoscopy. The overall cytologic typing accuracy for 252 cases was 0.66, with a range of 0.19 to 0.86, depending on the histologic type. Typing failures were essentially related to adenocarcinomas and large-cell carcinomas.

[Cytological changes caused by intrauterine devices]. / Alterazioni citologiche da dispositivi intrauterini.

PIP: As part of a mass screening program, 100 cervical-endocervical smears of IUD wearers were examined and compared with the smears of 100 women in a control group. A positive relationship between the use of IUDs and the cellular changes in the glandular epithelium, both of endocervical and endometrial origin, could be demonstrated. The most striking abnormalities occurred in the cytoplasms; however, the nuclei also showed some degree of variation in size and shape, thus giving rise to problems concerning the differential diagnosis with atypias due to cervical intraepithelial neoplasia in various stages as well as to adenocarcinoma and its precursors. (author's)^ieng