Diagnosis of bronchial carcinoma on sections of paraffin-embedded sputum. Sensitivity and specificity of an alternative to routine cytology.

The diagnostic accuracy of sputum cytology for the diagnosis of bronchial carcinoma using paraffin-embedded, serially sectioned and hematoxylin and eosin-stained specimens was tested in 4,297 sputum samples from 1,889 patients, 219 of whom had bronchial carcinoma. The diagnostic sensitivity depended mainly on the number of investigated samples and was 85.4% with three sufficient sputa. The sensitivity was not influenced by the histologic types, location or TNM stage of the tumor. The specificity of the method was 99.5%. In three cases localization of sputum cytologically diagnosed bronchial carcinomas was not possible immediately (occult carcinomas, pTx); in two of these cases the bronchial carcinomas were located during follow-up. The third patient died without verification of the cytologic diagnosis. According to our results, sputum cytology on serial sections is a valuable instrument for mass screening of high-risk groups for the early detection of bronchial carcinoma. Lower sensitivities of sputum cytology in mass screening programs for the early diagnosis of lung cancer are discussed critically.     

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.     

Contribution of exfoliative cytology to the diagnosis of laryngeal lesions

OBJECTIVE: To estimate the diagnostic accuracy and reliability of exfoliative laryngeal cytology. STUDY DESIGN: Over three years (1996-1999) cytologic smears were obtained from clinically suspicious laryngeal lesions during laryngoscopy in a total of 31 selected patients (28 males and 3 females with an age range from 28-90 years). The cytologic diagnoses were analyzed and correlated with the histologic and final clinical diagnoses in 17 and 14 cases, respectively. Cytologic identification of the exact histologic type of the lesion was evaluated in 17 patients from whom both cytologic smears and biopsy material were obtained. RESULTS: The overall specificity was 100%, with no false positive diagnoses. The overall sensitivity was 93.3%, with one false negative cytologic diagnosis, in a case of non-Hodgkin's lymphoma. Cytohistologic correlation showed complete agreement between cytologic and histologic diagnoses in five of six benign lesions, in four cases of dysplasia and in six cases of squamous cell carcinoma. The overall diagnostic accuracy of cytology was 96.7% CONCLUSION: Exfoliative cytology by the smear technique is a reliable and accurate method in clinically suspected laryngeal lesions. Moreover, exfoliative cytology may be applied as the only alternative diagnostic method, especially in elderly patients with coexistent cardiorespiratory problems, when biopsy is not advisable or indicated.     

Cytomorphology of the variants of small-cell carcinoma of the lung

Cytologic classification of subtypes of small-cell carcinoma of the lung (SCCL) was retrospectively performed on respiratory material of 90 cases of lung carcinoma cytologically diagnosed as SCCL. Additionally, the cytologic material was reexamined for the presence of variants of SCCL in 68 cases of lung carcinoma whose types had not been conclusively defined by cytology. The type of lung cytology specimens reviewed were sputa, bronchial washings and brushings and fine needle aspirations. The study included review of pretreatment tumor histology, when present, and examination of the ultrastructure of the tumor in selected cases whose type had not been well defined by histology. Subtype recognition depended on the adequacy of the specimens rather than on the type of cytologic material examined. The cytologic subtyping was generally in agreement with the histologic subtyping of the tumor, except for cases in which SCCL was combined with other types of lung carcinoma, where certain discrepancies were noted.     

Immunocytochemical and ultrastructural diagnosis of a rare mixed apocrine-medullary carcinoma of the breast in a fine needle aspirate

A rare mixed apocrine-medullary mammary carcinoma in a 57-year-old woman was preoperatively diagnosed by fine needle aspiration cytology. The aspirate was characterized by carcinoma cells with an apocrine differentiation and significant cellular atypia admixed with many lymphocytes and plasma cells. These findings were confirmed by histologic examination of the breast tumor and its metastasis in lymph nodes. Electron microscopy (EM) and immunoperoxidase staining for cytokeratin, S-100 protein, epithelial membrane antigen and carcinoembryonic antigen were done on samples of the aspirated material. Although immunostaining was of little help in this case, the EM findings did show many carcinomatous cells of apocrine type in the tumor.     

Efficacy and pattern of use of sputum cytology as a diagnostic test

Sputum cytology is regarded by many clinicians as a noninvasive, cheap and simple test for the diagnosis of bronchogenic carcinoma. Since the introduction of fibre-optic bronchoscopy and more easily obtained bronchial biopsies reliance on sputum cytology has diminished. However, in Edinburgh it was perceived that sputum samples were still being sent as well as, rather than instead of, bronchoscopic specimens. This retrospective study was undertaken to determine whether or not cytological examination of sputum is an efficient and sensitive test in the investigation of patients with suspected bronchogenic carcinoma. It demonstrated that the Lothian University Hospitals NHS Trust Pathology Directorate receives many sputa from departments not specializing in respiratory disease when there is no indication for the test. In addition, we have shown that the absolute sensitivity of the test is only 5% and that when there is a strong clinical suspicion of bronchogenic carcinoma the results of sputum cytology do not play a significant role in the management of the patient. We recommend that sputum cytology is restricted to those patients under the care of Respiratory Units in whom bronchoscopy is inappropriate or unsuccessful.     

Cytologic diagnosis of lung tumors from bronchial brushings of Chinese patients in Hong Kong

In 1,156 single or multiple specimens obtained from fiberoptic bronchoscopy on 1,016 Chinese patients in Hong Kong, a positive diagnosis of malignancy was made on cytologic examination in 288 and a histologic type assigned. On histologic examination of tissue, malignant tumors were diagnosed in 284 cases. The total positive yield by cytology was 88%, and the overall cytologic accuracy in correlation with histology was 73%. Comparing cases typed by cytology and by histology, the diagnostic accuracy of cytology was 83% in squamous-cell carcinoma, 81% in small-cell carcinoma, 69% in adenocarcinoma and 46% in large-cell carcinoma. The detection rate of nonbronchogenic tumors was 50%. Bronchogenic tumors showed a low male:female ratio, 1.96:1, whereas 80% of squamous-cell carcinomas and 45% of adenocarcinomas occurred in males. All seven cases of bronchogenic carcinoma in patients under 40 years of age occurred in males.     

Relationship between patient characteristics and the sputum cytologic diagnosis of lung cancer

In 421 patients with a malignant lung process, from whom samples of sputum of satisfactory quality were received, patient characteristics relevant to the cytologic diagnosis of malignancy were investigated. In patients with primary lung cancer, the presence of blood in the sputum was highly significant from the point of view of its association with a correct positive cytologic diagnosis on sputum. The same relationship was noted in patients with metastatic lung cancer. In patients producing bloody sputum, the examination of at least three sputum samples gave a proportion of correct positive diagnoses of 0.88 in primary lung cancer patients and of 0.77 in patients with metastatic lung disease. Furthermore, a high sensitivity of the sputum cytology diagnosis of malignancy was found in primary lung cancer patients with low forced expiratory volume values (less than 50% of the vital capacity), with large tumors (greater than 24 mm in diameter) and with squamous-cell cancers. A central location of the tumor correlated with significantly better cytodiagnostic results in patients with both primary and metastatic cancers.     

Factors significant in the diagnostic accuracy of lung cytology in bronchial washing and sputum samples. II. Sputum samples

Some factors influencing the detection of malignant cells in sputum samples were evaluated in 449 consecutive cases of primary lung carcinoma seen between 1959 and 1974. Diagnostic accuracy increased during the years under study; the reasons are discussed. The overall accuracy was 82.8%. Detection of malignant cells was 85% for small-cell carcinoma, squamous-cell carcinoma and large-cell carcinoma, 75% for adenocarcinoma, bronchioloalveolar carcinoma and adenosquamous carcinoma and 64% for the uncommon tumors. Accuracy was 87% for central tumors and 42% for peripheral lesions. Tumors less than 2 cm in diameter yielded only 39% accuracy as compared to 90% for larger tumors. The specificity of diagnosis of cell type in those specimens with malignant cells was 95% for small-cell carcinoma and squamous-cell carcinoma, more than 80% for adenocarcinoma and large-cell carcinoma, 65% for bronchioloalveolar-cell carcinoma and adenosquamous carcinoma and less than 30% for the uncommon tumors. Diagnostic accuracy was optimal in those cases with three or more sputum samples: 83% for those with three samples and 90% for those with five or more samples per case. The use of both sputum and bronchial specimens was complementary and increased the accuracy further. Reasons for unsatisfactory specimens included no deep cough, limited cellular material, excessive blood or leukocytes and drying artifacts; the first two were the most common causes.     

Apoptosis in breast cancer

OBJECTIVE: To evaluate apoptotic rates on fine needle aspiration (FNA) samples of infiltrating duct carcinoma of the breast and to determine whether cytologic grading improved with consideration of the apoptotic rate in comparison with histologic grading. STUDY DESIGN: We studied 35 women who underwent mastectomy following an FNA diagnosis of infiltrating ductal carcinoma. Concordance between cytologic and histologic grades was calculated. Next, cytologic grades were considered with the apoptotic rates and compared with the histologic grades. RESULTS: An overall concordance of 82.9% was noted between the cytologic and histologic grading systems, with maximum concordance in grade 1 and minimum in grade 3 breast cancers. A highly significant difference in the apoptotic rates, as calculated on cytology, existed between the three histologic grades, indicating a significant increase in apoptosis with rising histologic grade. Applying multiple regression analysis, a significant improvement of cytologic grade with consideration of the apoptotic rate was observed. CONCLUSION: Employing histologic grade as the yardstick, cytology was less sensitive for the purpose of grading breast ductal carcinoma. However, by considering the apoptotic rates, the sensitivity of cytologic grading significantly rose in relation to histologic grade. Larger studies are required to determine whether apoptosis can be incorporated into the existing cytologic grading systems to increase their sensitivity.     

Bronchial brushing during fiberoptic bronchoscopy for the cytodiagnosis of lung cancer: comparison with sputum and bronchial washings.

In a study of 50 cases of bronchogenic carcinoma in which brushings and washings during fiberoptic bronchoscopy, as well as sputum cytopathologic examinations were performed in the same patients, accuracy rates were respectively: 76 per cent, 76 per cent and 56 per cent. The main cytologic differences setting brush apart from wash and sputum specimens referred to the arrangement of tumor cells as well as the distribution of chromatin within their nuclei. These differences appeared related to cell degeneration which was minimal in brush materials and maximum in sputum specimens. Only six cases were assigned a different cell type of bronchogenic carcinoma when brush cytopathologic diagnoses were compared with results obtained by biopsy or lobectomy specimens. Our findings are consistent with the view that the brush technique is very accurate for the cytodiagnosis of lung cancer and becomes also rather specific once cytologic characteristics of the fresher samples obtained become familiar to the cytopathologist. Non-observance of the special characteristics of these better preserved cellular samples is the major pitfall as to diagnosing, cell typing and judging degree of differentiation of bronchogenic carcinoma in brush cytology specimens.     

Warty (condylomatous) carcinoma of the cervix. A review of 3 cases with emphasis on thin-layer cytology and molecular analysis for HPV

OBJECTIVE: To describe the thin-layer cytology (if available) and histologic findings of warty (condylomatous) carcinoma of the cervix, with molecular analysis for HPV screening. STUDY DESIGN: The authors reviewed the clinical features, thin-layer cytology (if available) and histologic findings of all cases of warty carcinoma of the cervix encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the 4-year period January 1998-April 2002. Molecular techniques for HPV screening using polymerase chain reaction were carried out on thin-layer cytology specimens or paraffin-embedded tumor tissue. RESULTS: Three cases of warty carcinoma of the cervix were encountered during the study period. Thin-layer preparations (Autocyte, TriPath Imaging, Burlington, North Carolina, U.S.A.) were available for 2 of them, and both were of moderate cellularity. There were small, cohesive clusters and syncytial sheets of tumor cells with vague papillary configurations. Dispersed squamous carcinoma cells and necrotic tumor debris (diathesis) were focally present in the background. The tumor cells were polygonal to elongated and contained oval nuclei, coarse chromatin and sometimes distinct nucleoli. Dyskeratotic tumor cells with bizarre shapes were also noted. Characteristically, there were also many koilocytes demonstrating extreme nuclear atypia and increased nuclear/cytoplasm ratio. These koilocytic cells possessed pleomorphic nuclei, distinct nucleoli and perinuclear cytoplasmic halos. Histologic examination of the tumor biopsies showed classic features of warty carcinoma, with papillary architecture, obvious koilocytic cytopathic change and focal stromal invasion. Molecular analysis confirmed the presence of HPV DNA in all the samples. CONCLUSION: Although koilocytes are rarely found in cervical cytology specimens of conventional squamous cell carcinoma, they are characteristically observed in warty carcinoma. A correct cytologic diagnosis is possible if one pays attention to the extreme koilocytic atypia, focal papillary configurations and otherwise classic features of squamous cell carcinoma. Abundance of koilocytes does not necessarily rule out invasive malignancy.     

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.     

Fine needle aspiration biopsy versus sputum and bronchial material in the diagnosis of lung cancer. A comparative study of 168 patients

A group of 168 consecutive lung cancer patients in whom a definitive diagnosis of primary lung cancer was established either in a conventional cytologic specimen of sputum or bronchial material or in a specimen obtained by fine needle aspiration (FNA) biopsy was reviewed to compare the relative accuracies between the modalities of sputum and bronchial material on one hand versus FNA cytology on the other in the diagnosis of lung cancer. The patients included in the study were selected from a total of 1,093 patients who had been diagnosed and treated for lung cancer at Duke University Medical Center over the five-year period of January 1, 1980, through December 31, 1984. In 325 (29.8%) of the 1,093 patients, a definitive cancer diagnosis was established from histopathologic study alone, without any cytologic diagnoses. In 420 patients (38.4%), both histologic and cytologic material had been interpreted as being conclusively diagnostic for lung cancer. In 348 patients (31.8%), a cytologic diagnosis of lung cancer was made without a histologic confirmation. Thus, in a total of 768 (70.3%) of the 1,093 cases, a definitive cytologic diagnosis of cancer had been made. Of these 768 patients, 168 had been evaluated by both conventional respiratory cytologic methods (examination of sputum and bronchial material) and with FNA biopsy cytology. In 9 patients (5.4%), only conventional respiratory cytologic specimens were conclusively diagnostic for cancer. In 122 patients (72.6%), only the FNA biopsy specimen was diagnostic. In 37 patients (22.0%), both conventional respiratory specimens and FNA specimens yielded a definitive lung cancer diagnosis. The FNA specimen was the only positive cytologic specimen in 90.2% of large cell undifferentiated carcinomas, 79.5% of adenocarcinomas, 66.7% of small cell undifferentiated carcinomas and 58.2% of squamous cell carcinomas. In 26.5% of the patients, a diagnosis of cancer could have been established on conventional cytologic specimens, without the necessity of proceeding to percutaneous FNA biopsy. From this study, it is concluded that the techniques of conventional respiratory cytology and FNA biopsy cytology are complementary in the diagnosis of lung cancer. While the percentage of lung cancers diagnosed by FNA biopsy cytology alone is much greater than that obtained by conventional respiratory cytology alone, more than one-fourth of these cancers could be detected by the less invasive techniques of sputum collection and bronchoscopy.     

Salivary duct carcinoma of the parotid gland: report of a rare case with a comparative study of aspiration cytology and histomorphology

BACKGROUND: Salivary duct carcinomas affecting primarily the parotid gland are extremely rare (0.2-2% of all salivary gland tumors). These carcinomas are considered to be of high grade malignancy, with mortality in up to 70% of cases. They usually affect elderly males and less often young adults. Despite the fact that the histomorphologic characteristics of this tumor are always necessary for its classification, several authors have reported that the cytopathologic approach, using fine needle aspiration (FNA) cytology, can establish the final diagnosis. The aim of this paper is to present a rare case of salivary duct carcinoma of the parotid gland with no typical microscopic findings that was diagnosed by FNA cytology through a combination of techniques on biopsy material. CASE: A 56-year-old male presented with a right parotid mass measuring 6 cm in diameter. The mass appeared to expand subcutaneously and infiltrate the skin of the neck region. Biopsy material from both the mass and skin was obtained using FNA and processed with conventional, cell block and liquid-based cytology techniques. A core biopsy was also performed on the mass for histologic evaluation. CONCLUSION: The findings were consistent with a salivary duct carcinoma of the parotid gland and were confirmed by the histologic report. FNA cytology combined with such techniques as liquid-based cytology provides the potential for the final diagnosis. Liquid-based cytology can improve the cellular morphology of the material and allows immunocytochemistry and other diagnostic techniques. The application of such techniques is significantly restricted by conventional processing; thus, combining liquid-based cytology with other techniques expands the boundaries of cytology as a diagnostic test.     

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.     

Cytology and immunocytochemistry of bronchioloalveolar carcinoma

A study of the value of cytologic examination in the diagnosis of bronchioloalveolar carcinoma showed that fine needle aspiration (FNA) cytology is a definitive means of making the diagnosis of bronchioloalveolar carcinoma. In experienced hands, FNA cytology approached a diagnostic accuracy of 100%. With exfoliative cytology, technically adequate sputum samples offered an 82% diagnostic yield; sputum cytology should thus be considered as an adjunct method in establishing the diagnosis. Several cytologic features that strongly suggest the diagnosis of bronchioloalveolar carcinoma and help to differentiate it from adenocarcinomas of other body sites are outlined. It is also concluded that immunocytochemical stains have limited value in differentiating bronchioloalveolar carcinoma and other types of clear cell malignant neoplasms, including mesothelioma, unless a panel of antibodies is used, and are of no value in ascertaining whether the cells are benign or malignant.     

Cytologic evaluation of prognostic markers in breast carcinoma

To type breast carcinomaon on fine needle aspiration cytology (FNAC) material and correlate the results with histologic typing, to grade breast carcinoma on FNAC material and correlate the findings with Bloom-Richardson histologic grading, and to determine the estrogen receptor (ER) status in cases of breast carcinoma by immunocytochemical (ICC) staining of FNA cytologic material and correlate the findings with ER status, as determined by immunohistochemical (IHC) staining of tissue sections. STUDY DESIGN: Seventy-seven cases of breast carcinoma diagnosed on FNAC formed the basis of this study. Typing was done in all cases on the basis of cytologic features and grading in 62. (Fifteen cases were special types of breast carcinoma). In all cases, ER status was determined by immunostaining of cytologic smears. Results of tumor typing, grading and ER status on cytologic material were compared with the results of histologic typing, grading and immunostaining of histologic material obtained from mastectomy or wide excision specimens. RESULTS: Tumor typing was accurate in 73 of 77 cases (94.8%). Fifteen of 18 cases that were cytologically grade 3 were confirmed on histology, while 3 proved to be grade 2. Of 40 cytologic grade 2 cases, 26 were confirmed on histology, while 14 cases were grade 3. Three of 4 cytologically grade 1 cases were confirmed on histology while 1 was grade 2. The overall accuracy for cytologic grading was 71% (44 of 62 cases). Thirty-seven of 40 ER-positive cases (92.5%) were labeled ER positive on ICC. One case was ER negative on cytology, while in 2 cases the cellularity of the cytologic smear was insufficient to assess ER expression. Thirty-seven cases were negativefor ER on IHC. Nine of these showed ER positivity on ICC, 26 were negative, and 2 had cellularity that was inadequate for assessment of ER. Sensitivity and specificity rates for ER detection on ICC were 97.4% and 74.3%, respectively. CONCLUSION: Tumor typing, grading and evaluation of ER status on FNA C material in breast carcinomas are simple, quick and moderately reliable techniques that compare and correlate favorably with histologic typing, grading and ER status on IHC.     

Sputum cytology for the diagnosis of lung cancer. Comparison of smear and modified cell block methods

OBJECTIVE: To compare the sputum smear cytology and cell block methods for specimen adequacy, cytology quality and diagnostic accuracy in the diagnosis of lung cancer. STUDY DESIGN: We assessed 2,524 sputum specimens from 768 patients. The specimens were prepared as smears and cell blocks for cytopathologic examination between March 1, 1992, and December 31, 1998. The smear and cell block slides were evaluated both separately and together, and the results were compared with radiologic and histopathologic diagnoses. RESULTS: The sensitivity of the smear method was 69.4% and specificity was 99.5%. The sensitivity of the cell block method was 84.4% and specificity, 100%. The sensitivity of the smear and cell block together was 87.6% and specificity, 99.5%. CONCLUSION: The cell block method increases the sensitivity and specificity of sputum cytology, and when smear and cell block slides are evaluated together, sensitivity reaches its highest value. Therefore, application of smear and cell block methods together seems most useful in the diagnosis of lung cancer.