Polyclonal carcinoembryonic antigen staining in the cytologic differential diagnosis of primary and metastatic hepatic malignancies.

In order to assess the utility of immunocytochemical staining of bile canaliculi with a polyclonal antiserum to carcinoembryonic antigen (pCEA) in the differentiation of primary hepatocellular carcinomas from metastatic malignancies, pCEA staining was performed on fine needle aspiration specimens from hepatic lesions in 60 patients. The original cytologic diagnoses were hepatocellular carcinoma in 22 patients, metastatic neoplasm or cholangiocarcinoma in 27 patients and benign hepatocytes in 11 cases. The cytologic diagnoses of malignancy were confirmed by surgical excision, autopsy or clinical investigations in 82% of the patients. Follow-up data, supported by pCEA staining, reversed the original cytologic diagnosis in three cases. Bile canalicular pCEA staining was identified in 18 of 22 cases of hepatocellular carcinoma and in all 11 benign hepatocellular aspirates. All 27 cases of metastatic malignancy or cholangiocarcinoma were negative for canalicular pCEA staining, although 11 cases exhibited cytoplasmic staining. Interpretation of pCEA staining was not affected by the intermingling of malignant cells and benign hepatocytes. Predictive values were 100% for a positive test and 87% for a negative test. These findings indicate that staining with pCEA antiserum is a useful adjunct in the differential cytologic diagnosis of malignant hepatic lesions.     

Stereotaxic fine needle aspiration cytology of clinically occult malignant and premalignant breast lesions

Stereotaxic fine needle aspiration (FNA) cytology was used to study clinically occult (nonpalpable) breast lesions in 114 consecutive patients with mammographically suspicious findings prior to excisional biopsy. The aspirate contained insufficient material for cytologic evaluation in 15 cases (13.2%), which were histologically diagnosed as benign (7 cases), atypical hyperplasia (7 cases) or carcinoma in situ (1 case). The cytologic findings indicated a benign lesion in 77 cases (67.5%), which were histologically diagnosed as benign (71 cases) or atypical ductal hyperplasia (6 cases). The cytologic sample showed atypia in eight cases (7.0%), which were histologically diagnosed as severe atypical ductal hyperplasia (three cases), carcinoma in situ (one case) or proliferative fibrocystic disease (four cases). In the eight cases (7.0%) cytologically interpreted as probably malignant, histology confirmed six invasive carcinomas, one carcinoma in situ and one fibrocystic disease. Of six cases (4.4%) cytologically reported as malignant, five were histologically diagnosed as invasive carcinoma and one as carcinoma in situ. Overall, stereotaxic FNA cytology reported as malignant or probably malignant 14 of the 15 cases with a histologic confirmation of malignancy, for a sensitivity of 93.3%. Cytology correctly identified 78 of the 83 histologically negative cases, for a specificity of 94.0%. The 16 cases histologically diagnosed as ductal hyperplasia, which carries a high risk for subsequent malignancy, were studied in detail in an effort to define histologic and cytologic criteria for this entity. Using selected histologic criteria, 11 of these cases were graded as showing mild-to-moderate atypical hyperplasia and 5 as showing severe atypical hyperplasia. Three of the latter cases were similarly identified by an analogous cytologic grading; the other two cases had insufficient cytologic samples. The total results in this series of 114 cases support the use of stereotaxic FNA cytology in the diagnosis of these nonpalpable breast lesions, examples of which are illustrated. In particular, it may help to raise the low specificity yielded by mammography alone, which would represent a significant advance for the patient in terms of the accuracy, expediency and reduced cost of diagnosing these lesions.     

Negative predictive value of pulmonary fine needle aspiration cytology.

Percutaneous fine needle aspiration (FNA) for cytologic examination is an accepted and reliable technique for diagnosing neoplasia. It is less useful, however, in excluding that diagnosis. We performed a retrospective analysis of a consecutive series of pulmonary FNA specimens at Memorial Sloan-Kettering Cancer Center to determine the negative predictive value (NPV) of this technique in the setting of a large cancer hospital. Fifty-seven cases were studied. Six cases (10.5%) were initially diagnosed as negative but acellular and were not further analyzed, and another 6 were lost to follow-up; 24 cases (42.1%) were subsequently confirmed negative by tissue or clinical follow-up, and 21 of the cases (36.8%) were proven positive for malignancy by repeat aspiration, tissue diagnosis or clinical means. Of these 21 cases, 1 was misdiagnosed as negative, and review demonstrated malignant cells on the slide; 3 of the 21 cases should have been initially rejected as unsatisfactory, and 18 of the 21 contained material sufficient for a cytologic diagnosis but not representative of the lesion. On follow-up the false-negative cases showed primary adenocarcinoma, epidermoid carcinoma, lymphoma, metastatic breast carcinoma and metastatic sarcoma. Specific benign diagnoses were made on the initial cytologic preparation in three cases. No benign tumors were found. The NPV in our series was 53.3%, comparable to values in previous reports. The single largest factor contributing to false-negative diagnoses is sampling error, and we recommend repeat aspiration when no specific benign diagnosis is made. In addition, we suggest that the diagnoses of negative for malignant cells and insufficient for diagnosis or acellular be considered separate categories.     

Carcinoembryonic antigen in effusions. A diagnostic adjunct to cytology

A total of 189 effusion specimens (100 benign and 89 malignant) submitted for cytologic examination were assayed for carcinoembryonic antigen (CEA) by an enzyme immunoassay to determine whether the addition of CEA evaluation to cytologic study would improve the diagnostic accuracy for the detection of malignancy. The sensitivity and specificity were 78% and 90%, respectively, for a cytologic diagnosis of malignancy and 68% and 99%, respectively, for a positive CEA (greater than 5 ng/mL). CEA assay was negative in the most common epithelial malignancies of the female genital tract (15 of 17 cases), mesotheliomas (5), lymphomas (7) and alveolar-cell carcinoma of lung (1). CEA assay was positive in 55 of 89 cases of malignancy, including 14 cases with cytologically negative malignant effusions. The CEA assay sensitivity for lung carcinoma (95% for adenocarcinoma, 100% for oat-cell carcinoma and 100% for carcinosarcoma), breast carcinoma (95%), and gastrointestinal carcinoma (100%) were all over 90%. No significant difference in the levels of CEA was noted between gastrointestinal and lung adenocarcinomas. Oat-cell carcinomas and squamous-cell carcinomas had lower values. In cases of an effusion with an unknown primary, an elevated CEA in the fluid is diagnostic of metastatic carcinoma arising from the breast, lung or gastrointestinal tract.     

The Isaacs Endometrial Cell Sampler. An evaluation in 100 patients with postmenopausal bleeding

The Curity Isaacs Endometrial Cell Sampler was used to obtain cytologic material from 100 consecutive patients presenting with postmenopausal bleeding. It was followed by uterine curettage to obtain material for histology. Satisfactory endometrial aspiration smears were obtained from 92 patients, whereas curettage yielded endometrial tissue in only 48. Of 17 patients with histologic confirmation of malignancy, 7 had smears diagnosed as showing malignancy, and 7 had smears showing hyperplastic changes; 3 of the aspiration smears were judged to be unsatisfactory for cytologic evaluation. All the carcinomas were found in the hyperplastic, malignant or unsatisfactory smears. This technique is worthy of further study.     

Fine needle aspiration cytology of neoplasms metastatic to the breast

The fine needle aspiration (FNA) cytologic findings in 18 cases of metastatic neoplasms of the breast are reported. The cases were encountered in a combined series of 2,529 FNA breast biopsies, of which 666 were malignant; the metastatic neoplasms of the breast thus constituted 2.7% of all the malignant breast tumors. The series consists of 15 women and 3 men, with a mean age of 48 years (range of 11 to 73 years). Sixteen biopsies confirmed metastatic malignancy in patients with known extramammary primaries; the prebiopsy clinical diagnoses in six of the patients were benign breast lesions. In eight patients, the clinical differential diagnosis was either a benign or malignant primary breast lesion versus a metastatic malignancy. In two additional patients, the FNA biopsy identified metastatic neoplasms from unsuspected extramammary primaries. The metastatic neoplasms included three small-cell carcinomas of the lung, one squamous-cell carcinoma of the lung, two malignant melanomas, three ovarian malignancies, including a dysgerminoma, and one each of carcinoma of the fallopian tube, endometrial carcinoma, transitional-cell carcinoma of the urinary bladder, prostatic carcinoma, acute granulocytic leukemia, lymphoma, mycosis fungoides, hepatoma and neuroblastoma of the retroperitoneum. Recognition of unusual cytologic patterns raised the suspicion of, or confirmed the diagnosis of, malignancy in all cases, with no false-negative diagnoses. None of the cases were cytologically interpreted as a primary breast malignancy. Ancillary studies performed on the FNA material, including immunocytochemistry, contributed to a definitive diagnosis in three cases. FNA diagnosis of metastatic malignancy of the breast is essential in order to avoid unnecessary mastectomy and to ensure appropriate chemotherapy and/or irradiation treatment.     

Positive effusion cytology as the initial presentation of malignancy

During a period of four years (1981 to 1984), 641 ascitic, 860 pleural and 47 pericardial fluid specimens were examined cytologically. Of these, 154 ascitic samples, 174 pleural specimens and 10 pericardial effusions, obtained, respectively, from 108, 133 and 7 patients, were found to contain malignant cells. In 7 patients, ascites, and in 18 cases, pleural effusions were the first indication of cancer. None of the positive pericardial fluids was the initial presentation of malignancy. The cytologic findings and follow-up data on these 25 patients are the subject of this study. The most common type of neoplasm in these effusions was adenocarcinoma (86% of the ascitic and 78% of the pleural fluids). Most of the malignant neoplasms in ascitic fluids were derived from ovarian tumors (5 of 7) while those in pleural effusions came mainly from lung tumors (12 of 18). Mammary carcinoma, which was the most common malignant tumor found in cases of pleural effusions, did not present initially with an effusion in any of our cases. The cytologic diagnosis was confirmed in all cases by either biopsy or strong clinical evidence. The prognosis in patients who initially presented with an effusion was poor. All of the patients with an adequate follow-up died within 29 months in cases of ascites and within 19 months in cases of pleural effusions.     

False negative cytologic diagnosis of breast carcinoma.

OBJECTIVE: To study the reasons for interpretive errors in false negative diagnosis of breast carcinoma on fine needle aspiration cytology material. STUDY DESIGN: We reviewed only those histologically proved malignant cases where the cytologic material was abnormal and to some extent misinterpreted. RESULTS: There were four lobular carcinomas and one each case of in situ, infiltrating duct, medullary and tubular carcinoma. Smears of lobular carcinomas were hypocellular overall, and the cells showed minimal nuclear pleomorphism. In situ, medullary and tubular carcinoma were associated with fibrocystic changes. The presence of bipolar cells and stromal fragments was misleading in cases of infiltrating duct carcinoma. CONCLUSION: The presence of associated fibrocystic disease may be a misleading factor since it may mask a malignancy. Hypocellularity and relatively nuclear monomorphism were the most common reasons for failure to diagnose malignant breast lesions. Careful attention should be paid to extreme nuclear monomorphism and absence of naked bipolar cells. A cytologically atypical or suspicious diagnosis together with radiologic suspicion should suggest a diagnosis of malignancy.     

Detection of benign or malignant origin of ascites with combined indirect immunoperoxidase assays of carcinoembryonic antigen and lysozyme

The indirect immunoperoxidase method was used to study the presence of the intracellular carcinoembryonic antigen (CEA) and lysozyme (LZ) in alcohol-fixed cytologic smears of peritoneal fluids from 2 patients with chronic active hepatitis, 31 patients with liver cirrhosis and 7 patients with malignant liver disease. In the two patients with hepatitis, LZ was positive in both CEA was positive in one and negative in the other. Of the 31 patients with liver cirrhosis, 21 (67.5%) were LZ positive, 27 (87%) were CEA negative and only 4 (13%) were CEA positive. Of the seven patients with malignant disease, six were CEA positive and six were LZ negative. It is of interest that 23 of 24 (96%) LZ-positive results and 28 of 29 (97%) CEA-negative results corresponded to negative cytologic diagnoses for malignancy. Cytologic diagnosis of "reactive mesothelial cells" seemed to correlate better (71%) with CEA-negative and LZ-positive results. The data suggest that the investigation of CEA and LZ in the cells of peritoneal fluids appears to have promise as an adjunct to cytology in differentiating benign from malignant origins of the fluid.     

Statistical analysis of fine needle aspiration cytology of the breast. A review of 678 cases plus 4,265 cases from the literature

Between 1979 and 1984, 678 breast fine needle aspiration (FNA) cytologic specimens were received in our laboratory; tissue follow-up was available for 159 cases (23%). The diagnoses rendered in cases with subsequent tissue study were benign (41%), insufficient (10.5%), atypical and/or suspicious for carcinoma (10.5%) and malignant (38%). Using the tissue diagnosis as the standard, there were four false-negative cytologic results and one false-positive result. Considering only cases with a definitive diagnosis of benign or malignant, the sensitivity of cytologic interpretation for diagnosing malignancy on adequate material was 94% while the specificity was 98%; the overall efficiency of the test was thus 96%. The predictive values were 98% for a positive test and 94% for a negative test. Of the total number of submitted cases, a correct and definitive diagnosis was rendered 76% of the time. Calculation of similar statistics from six other series in which the FNA cytologic diagnoses were compared with the histologic diagnoses yielded data almost identical to our findings. The high degree of uniformity in the data indicates that these statistical parameters can be used as standards for evaluating the efficiency of breast FNA cytology.     

Early detection of precancerous lesions in dysplasias of the lung by rapid DNA image cytometry

Hematoxylin-and-eosin-stained cytologic smears of sputum from 28 patients with dysplastic and suspicious cell findings were subjected to DNA image cytometry after Feulgen restaining. The nuclear DNA contents were measured with a TV-based image-analysis system, the Leitz TAS plus, combined with an automatic microscope. Computation of DNA data was performed according to an algorithm for the diagnosis and grading of malignancy. Of the 19 cases that were proven to be malignant in the follow-up, either by histologic examination, sputum cytology, fine needle aspiration biopsy or autopsy, the algorithm identified 17 as malignant in a stage (dysplasia) in which cytology was not yet able to present a definite diagnosis of malignancy. Only two cases of bronchial carcinoma were not detected in the state of dysplasia by this procedure. The periods between the DNA diagnosis of malignancy in dysplasia and the morphologic evidence of cancer varied from three days up to six months. Of the 11 cases that had been classified as benign by the algorithm, 9 were confirmed as benign during the clinical follow-up. Rapid DNA image cytometry appears able to separate squamous dysplasias of the lung into precancerous and nonprecancerous lesions.     

Cytologic features of urothelial carcinoma in catheterized urine with cellular fragments

OBJECTIVE: To identify architectural and cytomorphologic differences that might help distinguish urothelial neoplasms from instrumentation artifact. STUDY DESIGN: We examined 73 cytologic smears of catheterized urine containing urothelial cell clusters between 1998 and 2004. All patients had at least 1 follow-up biopsy. Smears were reviewed for several morphologic features blindly, without knowledge of the follow-up diagnosis. RESULTS: Of the 73 smears, 39 had a benign diagnosis on follow-up biopsy, and 34 had urothelial carcinoma. Cytoplasmic collar, regular and rounded fragment borders, and fine nuclear chromatin were statistically more common in benign smears than those with urothelial carcinoma (p < 0.0001). No significant differences were identified with regard to the presence of background inflammation or nucleoli in the urine specimens. Of the 17 smears that had a cytoplasmic collar, regular fragment borders and fine nuclear chromatin, only 1 (6%) was found to have urothelial carcinoma on follow-up biopsy. All 20 smears in which all 3 features were absent were proven malignant on biopsy. CONCLUSION: Certain architectural and nuclear features can help differentiate urothelial neoplasms from instrumentation artifact in urine cytologic smears.     

Colonic cytology. A retrospective study with histopathologic correlation

Three hundred sixty cytologic specimens obtained by colonoscopic brushing from 336 patients were compared with biopsy specimens simultaneously obtained for histologic examination. Of the cytologic specimens, 160 (44%) were positive for malignant cells, 37 (10%) contained suspicious cells, 54 (15%) had atypical glandular cells, 107 were cytologically negative, and 2 were considered unsatisfactory. Eight-four percent of the patients with cytologically positive smears and 54% of those with suspicious smears had malignant neoplasms in the simultaneously obtained tissue biopsies. Of the patients with follow-up, all with cytologically positive findings and nine with suspicious findings on the initial cytologic examination and simultaneous negative tissue biopsies, were subsequently found to have carcinoma of the colon. Cytology proved to have a sensitivity of 0.73 and a specificity of 1.00 while tissue biopsy showed a sensitivity of 0.81 and a specificity of 1.00. By combining the two methods, the sensitivity increased to 0.92. It is concluded that cytologic examination of colonic brushings is a highly accurate and reliable technique for the detection of malignant neoplasms of the colon and can preempt the use of biopsy forceps.     

Value of the cytologic analysis of fine needle aspiration biopsy specimens in the diagnosis of pancreatic carcinomas

Between 1982 and 1986, 410 preoperative percutaneous fine needle aspiration (FNA) biopsies of the pancreas were performed on 316 patients clinically suspected of having a malignant pancreatic tumor. Of 58 patients with pancreatic carcinomas subsequently confirmed by histologic investigation, the FNA biopsy yielded a cytologically positive diagnosis of carcinoma in 39 cases (67.2%) and suspicious findings in another 5 cases (8.6%). In 14 cases of malignancy (24.1%), the FNA puncture failed to sample material from the tumor; hence, the cytologic evaluation yielded false-negative results. Of 21 patients with inflammatory disorders of the pancreas, cytologically suspicious cells were observed in 5 cases (23.8%); in none of those 5 cases did the histologic examination show any evidence of carcinoma. This indicates that caution should be taken not to cytologically over-diagnose cases of pancreatitis. On the whole, cytology proved to be a valuable method for the diagnosis of pancreatic carcinoma; it provided the highest rate of positive results in comparison with other modern clinical diagnostic methods. Furthermore, cytology may improve the diagnostic results even in those cases with clinically negative or merely suspicious findings. FNA punctures of the pancreas produced no serious complications in this series.     

False positive diagnosis in conventional and liquid-based cervical specimens

OBJECTIVE: To examine conventional and liquid-based cervical smears falsely diagnosed as malignant at our institution and to investigate, through cytologic-histologic correlation, factors influencing false positive diagnoses. STUDY DESIGN: Cervical cytologic diagnoses of malignancy from May 1, 1995, to April 30, 2001, were retrieved through a computer search. A retrospective review of hospital records and pathology reports was performed. Cases identified as false positives were reviewed and correlated with histologic follow-up specimens. RESULTS: A group of 68 patients with malignancy reported on cervical smears and with histologic follow-up was identified. Conventional smears numbered 32 (47%); the remaining 36 (53%) were liquid-based samples. Of the total, 7 false positive cases (10.3%) were identified in 4 conventional and 3 liquid-based preparations. Cytologic diagnosis in these cases was squamous cell carcinoma in 5 and adenocarcinoma in 2. On histologic follow-up, all 7 patients were ultimately found to have high grade squamous intraepithelial lesions (HSILs) without invasion. Review of the original slides confirmed most, or all, of the following features in all cases: major cellular pleomorphism, extensive cytoplasmic keratinization, intense nuclear pyknosis, background necrosis and severe atrophy. CONCLUSION: There was no significant difference in rates of false positive diagnoses between conventional (12.5%) and liquid-based (8.3%) samples. The chief reason for overdiagnosis in this series was the capacity of HSIL to exfoliate cells mimicking invasive malignancy, particularly when keratinized and especially in an atrophic milieu. The other cause of false positivity was superimposition of inflammation and atypical reparative change on a background of HSIL, which then suggested invasion.     

Immunohistochemical study of lysozyme, alpha 1-anti-chymotrypsin, tissue polypeptide antigen, keratin and carcinoembryonic antigen in effusion sediments

The cellular sediments of 42 malignant and 16 benign effusions (58 cases) were studied using the immunoperoxidase technique. Serial sections of formalin-fixed, paraffin-embedded residual sediments of effusions, sent for routine cytologic examination, were studied by commercially available polyclonal antisera against lysozyme, alpha 1-anti-trypsin, alpha 1-anti-chymotrypsin, tissue polypeptide antigen (TPA), a wide-spectrum anti-keratin, carcinoembryonic antigen (CEA) and, in single cases, thyroglobulin and prostate-specific antigen. A final definite diagnosis from histologic study of biopsy or autopsy specimens was known in all cases. All carcinomas, the mesotheliomas and the reactive mesothelial cells showed a positive reaction for TPA and, partly, the wide-spectrum keratin. Lysozyme could be demonstrated in the cells of the one proven malignant fibrous histiocytoma; all malignant epithelial cells were negative. Alpha 1-anti-chymotrypsin and alpha 1-anti-trypsin showed similar reactions: they were often positive in carcinoma cells of the breast, the bronchial system and the pancreas, in contrast to a mostly negative reaction in carcinomas of the stomach and ovary. CEA showed considerable differences; it was always negative in benign and malignant mesothelial proliferations but mostly positive in carcinomas of the stomach, pancreas and bronchial system. It was only positive in less than 20% of the carcinomas of the breast and always negative in the proven malignant effusions of primary carcinomas of the ovary and prostate. Studying a combination of several tumor markers is possible in serial paraffin-embedded sections and may be a valuable criterion in the cytologic diagnosis of effusions.     

DNA-cytometric diagnosis of prospective malignancy in borderline lesions of the uterine cervix

Interactive DNA cytometry was used for the diagnosis of prospective malignancy in 48 smears with borderline lesions (mild and moderate dysplasias) of the uterine cervix. In addition, 183 smears with benign squamous epithelia, 38 with carcinoma in situ and 7 with invasive squamous carcinoma were also measured. Nuclear Feulgen-DNA measurements were performed using various methods, and the resulting data were analyzed by an algorithm for a DNA-cytophotometric diagnosis of malignancy. The results were compared with the data on follow-up and subsequent histologic studies in these cases. There was no false-positive diagnosis in the 183 benign smears and only 1 false-negative diagnosis in the 76 histologically proven squamous-cell carcinomas, which yields a specificity of 100% and a sensitivity of 98.6%. The sensitivity for the detection of subsequent histologically proven malignancy in cases with cytologically mild or moderate dysplasia amounted to 97%. In 13 borderline cases, there was a mean interval of 21 months between the taking of the cytologic smear on which the DNA diagnosis of malignancy was made and the date on which the histologic confirmation of malignancy was made. In 17% of the cytologically dysplastic cases, the DNA diagnosis of malignancy was not verified by subsequent histologic investigation. These results indicate that interactive DNA cytometry is able to detect prospective malignancy in smears from borderline lesions of the uterine cervix with a high sensitivity.     

Diagnosis of metastatic tumors in cerebrospinal fluid samples using thin-layer cytology

OBJECTIVE: To evaluate the application of ThinPrep liquid-based cytology (LBC) and present our experience using LBC in the diagnosis of metastatic tumors in cerebrospinal fluid (CSF) samples. STUDY DESIGN: We examined 38 cytologic specimens of CSF, processed by ThinPrep technique. Of these, 18 presented with a previously diagnosed primary malignancy. Various immunocytochemical markers were performed. RESULTS: ThinPrep technology provided preservation of cytomorphologic features, high cellularity per slide and clear background. Analysis revealed 8 breast carcinomas, 5 lung carcinomas, 4 lymphomas, 3 adenocarcinomas of the gastrointestinal tract, 1 squamous cell carcinoma of uterine cervix and 1 urinary bladder carcinoma. Fifteen samples were negative for malignancy. CONCLUSION: CSF cytology is the only examination that verifies the presence of malignancy. Thin monolayer technology is suggested as an appropriate diagnostic method for metastatic tumors in CSF in everyday routine and seems to be a valuable tool for further management and planning of treatment.     

Role of biliary brush cytology in primary sclerosing cholangitis

OBJECTIVE: To assess the role of brush cytology in the routine evaluation of patients with primary sclerosing cholangitis (PSC). STUDY DESIGN: From January 1995 to June 2000, 64 brush cytology specimens were obtained from 21 patients who had at least one cytologic sample obtained during endoscopic retrograde cholangiography. All patients had a diagnosis of primary sclerosing cholangitis. Cases were classified as benign, atypical or malignant according to major cytologic criteria (nuclear contour and chromatin irregularities) and minor cytologic criteria (polarity, cellularity, nuclear enlargement, mitosis, increased nuclear/cytoplasmic ratio) used by us to diagnose biliary brush cytology. Follow-up was available in all cases. RESULTS: Diagnoses were benign (13), atypical (5) and malignant (3) on cytology. Follow-up of the 13 benign cases showed bile duct stones (2), gallbladder adenocarcinoma at cholecystectomy (1), ascending cholangitis (1) and clinically/cytologically by benign follow-up (9). Five of 13 benign cases had subsequent liver transplantation for liver failure, with explants showing changes of primary sclerosing cholangitis. Of the 3 malignant cases, 1 had carcinoma in situ on biopsy, with the explanted liver showing high grade dysplasia; the second patient had cholangiocarcinoma on explant; and the third had hepatocellular carcinoma on liver five needle aspiration. The 5 patients with atypical cytology were reclassified on review as reactive (3) and atypical not otherwise specified (2). Follow-up showed benign disease in 3 of 3 atypical cases reclassified as reactive; 2 of 2 reclassified as atypical not otherwise specified showed low grade dysplasia in the explant. CONCLUSION: The overall incidence of malignancy was low (3 of 21) in patients with PSC. Bile duct brushing is a sensitive method of detecting neoplasia in the setting of PSC when well-defined cytologic criteria are applied.     

Pulmonary fine needle aspiration biopsy. Assessing the negative diagnosis.

OBJECTIVE: To assess the significance of the "negative for malignancy" category when applied to pulmonary transthoracic fine needle aspiration biopsy (FNAB). STUDY DESIGN: Transthoracic lung FNABs diagnosed as "negative for malignancy" were identified from the files of Barnes-Jewish Hospital's South and North Campus over a period of five and nine years, respectively. Histologic correlation and clinical follow-up were obtained. RESULTS: Of the 1,181 lung FNABs performed during the study period, 108 cases (9%) had a negative cytologic diagnosis. Histologic correlation was available in 46 cases (43%), of which 23 cases had benign histologic findings, and 19 cases were malignant. Thirty-five of the 62 cases without histologic correlation had clinical follow-up consistent with a benign process. CONCLUSION: Based on the histologic correlation and clinical data available, the negative predictive value was 77%. Inadequate sampling was responsible for all false negative cytologic diagnoses in this series.