Atypical epithelium of the protuberant lesions in the stomach.
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Biomedical subjects
Publications and source records attributed to S Pilotti.
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In gastric smears obtained by direct vision fiberoptic brush technique from 78 patients with carcinoma of the stomach, an attempt was made to recognize cytologically the histologic type of the tumor with reference to Lauren's classification. The cytologic diagnosis of intestinal type carcinoma was made in 36/45 positive cases on the basis of an abundant cellularity and the presence of rather large pleomorphic cohesive cells often arranged in sheets with a moderately increased N/C ratio. One case of intramucous and two of "early" invasive carcinoma revealed malignant cells which did not differ from those of the advanced cases. In these cases as well as in some of the advanced ones, atypical epithelial cells were found in addition to the malignant ones; these cells could have derived from the histologic areas of atypical hyperplasia of the gastric mucosa surrounding the carcinoma. 14/15 cases of advanced diffuse carcinoma of the stomach could be cytologically identified on the basis of a scanty cellularity and the presence of rather small, monomorphic poorly differentiated cells with a high N/C ratio. The cytologic diagnosis of the mixed-type carcinoma was made in 2/5 positive cases on the basis of the presence of an admixture of both cell types described above. In two cases of the mixed-type carcinoma, only intestinal type cells were found. In the smears of nine cases of intestinal type carcinoma, one of which was intramucous, and of one case of mixed-type carcinoma, the tumor cells could not be specified. 13/78 cases (16.7%) showed negative cytology. The overall accuracy rate was 83.3 per cent. The statistical analysis of a number of cytologic parameters indicated that morphologic differences between Type I and Type D carcinomas of the stomach do exist and that they can be evaluated for differential diagnostic purposes.
An attempt was made to diagnose cytologically non-Hodgkin's malignant lymphomas (ML) of the stomach on gastric smears in terms of the Kiel classification. This classification represents a more advanced approach for the identification of ML with regard to the cell type specificity, with some functional connotations as compared with previous classifications. The endoscopic brushing cell film studies, when compared with histology of endoscopic biopsies and/or surgical specimens, indicated a high accuracy of cell type identification. Sampling may represent problems in relation to the type of gross lesion. Specific cell types could be recognized in 20 of 25 cases of gastric involvement of ML. Six of nine cases of lymphoplasmacytoid ML revealed diagnostic cells, such as lymphoplasmacytoid cells, plasma cells, lymphocytes, and occasional immunoblasts. Six of seven cases of centrocytic ML had a large number of small cells with indented nuclei, and seven of eight centroblastic-centrocytic ML yielded a mixture of large centroblasts and small centrocytes. In addition to these 24 low-grade ML, one case of unclassifiable high-grade ML was diagnosed. Differential diagnostic problems within ML subtypes and with benign lesions, such as pseudolymphoma of the stomach, as well as malignant tumors and especially diffuse type gastric carcinoma, are taken into consideration.
A study of the diagnosis of hepatic and pancreatic malignancies by fine needle aspiration (FNA) was made, based on 221 aspirates obtained from 209 patients with histologic or clinical confirmation: 159 with hepatic and 50 with pancreatic lesions. The values of sensitivity, specificity and predictivity for positive FNA results were, respectively, 0.84, 0.96 and 1.0 for the liver and 0.76, 1.0 and 1.0 for the pancreas. The composition of the case material showed an incidence of malignant tumors of the liver and pancreas of 84% and 60%, respectively (among which the primary malignancies were 39% and 48%), while nonneoplastic lesions had incidences of 14% and 40%. However, conclusive FNA diagnoses of the histologic type of the primary and the site of origin of metastatic tumors were made in 60% of the hepatic lesions but in only 9% of the pancreatic lesions. Primary hepatocellular carcinoma was diagnosed by FNA of the liver in 95% of the cases; FNA specifically diagnosed 42% of intrahepatic bile duct carcinomas and 40% of hepatic metastases. These findings correlate with the unique cytologic features of primary hepatocellular carcinoma of intrahepatic rather nonspecific morphology of carcinoma of intrahepatic and extrahepatic origin, as well as of pancreatic ductal origin.
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An investigation of the role of fine needle aspiration in the assessment of renal masses was carried out on 132 consecutive patients, 11 of whom were children. Selection was based on the presence of a solid or mixed solid and cystic renal mass that could not be defined by radiology, either in symptomatic patients or in patients to be submitted to embolization of the renal artery and at high surgical risk. Histologic and clinical data showed 49% of the cases to have a malignant, predominantly (45%) primary disease of the kidney and the remainder to have a nonneoplastic lesion. In five cases, the primary lesion was in the adrenal gland (three neuroblastomas and two pheochromocytomas). Sensitivity, specificity and predictive values for positive results were, respectively, 0.93, 0.96 and 0.935 because of a false-positive diagnosis in a case of multilocular cystic nephroma. Furthermore, in 43 of 65 cases (66%), consisting of 33 renal cell carcinomas, 1 transitional cell carcinoma, 3 Wilm's tumors, 1 neuroblastoma, 2 pheochromocytomas and 3 metastatic lesions, the histologic type could be ascertained on the tissue yielded by the fine needle aspiration. The findings stress the usefulness of this method for the clarification of radiologically not unequivocal space-occupying lesions of the renal area, especially when, in addition to the smears, histologic sections of paraffin-embedded tissues are available. Ultrastructural and immunohistochemical studies are cost-effective mainly in pediatric patients.
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A detailed description is given of two challenging cases of pulmonary carcinoid with glandular features that were diagnosed cytologically on fine needle aspiration biopsy material. The histologic type in the first case was identified on the aspirated material obtained from the tumor at the time of its radiologic discovery; for the second case, after a prior diagnosis of adenocarcinoma, the correct diagnosis was made upon review of the material; the diagnosis was warranted by the indolent clinical course. The cytologic diagnoses were unequivocally confirmed by the histology of the surgical specimen in the first case and by an ultrastructural investigation of the second.
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.
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.
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.
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.
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Two hundred eighty-five consecutive outpatients with enlarged superficial lymph node either clinically suspicious (152) or with a previous diagnosis of a malignant tumor (133) underwent fine needle aspiration (FNA) followed by excisional biopsy. Cytologic and/or cytologic-immunophenotypic diagnoses made on direct smears were compared with subsequent histologic findings. The comparison demonstrated (1) a high rate of conclusive cytologic diagnoses in the assessment of metastatic malignancies, with an overall accuracy rate of 99.1% and a typing accuracy rate of 96.5%; (2) a high rate of conclusive diagnoses in the assessment of high grade non-Hodgkin's lymphomas and Hodgkin's disease, with the exception of the lymphocytic predominance variant of the latter; and (3) significant limitations in the assessment of low grade non-Hodgkin's lymphomas because of the high rate of false-negative diagnoses in cases with a substantial nonmalignant cell component. This was particularly evident in follicular centroblastic-centrocytic lymphomas. Immunocytochemistry appeared to be of limited value in the distinction between centroblastic-centrocytic follicular lymphomas and reactive follicular hyperplasia. The results confirmed the diagnostic value of fine needle aspiration as the first step in the workup of patients with nodal enlargement suspicious for malignancy. In the area of low grade non-Hodgkin's lymphomas, morphologic and immunocytochemical methods need to be supplemented by molecular techniques in order to achieve conclusive diagnoses.
The recent availability of the monoclonal antibody MIB-1 (which is able to detect the human nuclear cell proliferation-associated antigen Ki-67 even on formalin-fixed, paraffin-embedded sections, microwave-treated and routinely processed for immunohistochemistry) could open new avenues for validation of the clinical role of tumour cell proliferation on large, consecutive and unselected series of human tumours. However, the routine use of such a marker requires a methodological standardization as well as the comparative assessment of some technical and biological aspects. The MIB-1 index was determined in parallel samples from 50 consecutive invasive breast carcinomas processed with different fixatives for different times. The median values of MIB-1 indices following 2, 6 and 24 h of formalin fixation were similar (29.4%, 30.6% and 29.7%, respectively) and consistent with those reported in the literature; squared linear regression coefficients were 0.99. The median values of MIB-1 indices were markedly lower in Bouin-fixed, paraffin embedded, and in frozen samples (20.0% and 19.8%, respectively), with a poor correlation coefficient with the values detected following formalin fixation (R2 = 0.456). Moderate and poor correlations were observed between Ki-67 index and MIB-1 detected on frozen (rs, 0.78) or formalin-fixed, paraffin-embedded samples (rs, 0.47) and a minimal concordance was observed between TLI and MIB-1 or Ki-67 (rs, 0.25 and 0.22, respectively). Our results indicate interference of the fixative type on immunoreactivity to MIB-1 and also suggest that Ki-67 and MIB-1 reacted with different epitopes of the same antigen.
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