Ten years of respiratory cytopathology at Duke University Medical Center. II. The cytopathologic diagnosis of lung cancer during the years 1970 to 1974, with a comparison between cytopathology and histopathology in the typing of lung cancer

In 1975 Duke University Medical Center, a retrospective and prospective survey of respiratory cytopathologic specimens was undertaken for the ten-year period 1970 to 1979. The purpose of this study was to document the role of cytopathology in the diagnosis of lung cancer at this institution. This paper presents the results of the cytopathologic and histopathologic typing of cases of lung cancer seen at Duke University Medical Center from 1970 to 1974. During this period, 9,892 cytologic specimens from the lower respiratory tract were processed. Cytopathologic diagnoses of cancer with tissue confirmation were made on 483 specimens from 232 patients. Because original cytologic diagnoses, but not histopathologic diagnoses, had been made in conformity with a modified WHO classification of lung neoplasms, all histopathologic material was reviewed and reclassified when necessary. This was carried out by one of the authors (E.H.B.) as a blind review without benefit of knowledge of either preexisting cytopathologic or histopathologic diagnoses. Twenty-six patients were excluded from the current study because of lack of satisfactory histologic material. In 94 patients classified by histopathology as having squamous cell carcinoma, 76.4% of the positive cytologic specimens were also called squamous cell carcinoma; 18.6% were interpreted as large cell undifferentiated carcinoma. In 39 patients classified by tissue as having large cell undifferentiated carcinoma, the cytology agreed in 42.4% of the positive specimens. For the 29 patients thought histologically to have small cell undifferentiated carcinoma, the same diagnosis was rendered in 95.5% of the cytologically positive specimens from these patients. For the adenocarcinoma group of 43 patients, a cytopathologic diagnosis of adenocarcinoma was made in 67.8% of the positive specimens.     

Fine needle aspiration cytology of the thyroid: a cytohistologic study with evaluation of discordant cases

OBJECTIVE: To analyze the diagnostic efficacy of fine needle aspiration cytology (FNAC) in the initial evaluation of thyroid nodules, with special emphasis on discrepant cytologic diagnoses. STUDY DESIGN: A total of 192 thyroid fine needle aspirates with subsequent histopathologic follow-up were analyzed. The cytologic diagnoses were divided into 4 categories: positive for malignancy, negative for malignancy, indeterminate for diagnosis and nondiagnostic. The detailed cytologic features were studied along with histopathology sections in all these cases by 2 observers (S.J. and P.D) independently. RESULTS: Cytohistologic correlation was seen in 78.1% of cases and discordance in 21.9%. Indeterminate diagnoses accounted for 15.1% of cases. The majority of these were "follicular neoplasms." The overall sensitivity was 84.44% and specificity 99.11 %. A false positive diagnosis was made in 1 case (0.5%), proven a follicular adenoma on histopathologic examination. A false negative diagnosis was seen in 3.6% of cases. These were cases of papillary microcarcinoma. CONCLUSION: FNAC is a safe, sensitive and specific technique in the initial evaluation of thyroid nodules. A correct cytologic diagnosis can be achieved in a majority of cases, thus obviating the need for a second surgical intervention. A careful and diligent search for various cytologic features and accurate sampling can help in reducing the number of indeterminate, false positive and false negative diagnoses.     

Fine needle aspiration cytology of primary lymphoid lesions of the orbit: report of four cases

BACKGROUND: The role offine needle aspiration cytology (FNAC) in diagnosis and differentiation of primary orbital lymphoid lesions is debatable, and little literature exists on cytodiagnosis of orbital lymphoid lesions. CASES: Four patients with orbital lesions underwent routine FNAC. In 3 cases, histopathologic examination was performed with immunohistochemistry (IHC). Cytologic features and diag- noses were correlated with histopathologic diagnoses. Two were cytologically diagnosed with low-grade non-Hodgkin lymphoma (NHL) and 2 with pseudolymphoma and inflammatory pseudotumor, respectively. Of the 2 cases of histologically diagnosed NHL, 1 had concordant diagnosis and the other had a jalse negative diagnosis of pseudolymphoma; both showed significant increase in mast cells, with neoplastie lymphoid cells exhibiting a higher N:C ratio and coarser chromatin texture. The case cytologically interpreted as suspicious for NHL was identified as a psetedolymphoma on histology (false positive). The case of inflammatory pseudotumor, in which hiopiy was not peiformned, responded well to corticosteroids, strengthening the cytologic diagnosis. CONCLUSION: FNAC diagnosis and differentiation of benign vs. malignant primacy orbital lymphoid lesions is often difficult. Careful cytologic interpretation with respect to certain subtle cytologic details is needed in minimizing false positive or false negative diagnoses. In difficult situations, IHC using suitable immunomarkers proves highly useful.     

Rapid detection of rectal cancer by gloved digital-scrape cytology

To evaluate the use of cytology for the rapid detection of rectal cancer, 39 suspected cases of carcinoma of the rectum and anal canal and 7 age- and sex-matched control cases were studied by the gloved digital-scrape method. The cytologic findings were then correlated with the histopathologic diagnoses. Of 30 evaluable cases with follow-up, a correct cytologic diagnosis was made in 28 cases (93.4%), with 1 false-negative diagnosis (3.3%) and 1 false-positive diagnosis (3.3%). Gloved digital-scrape cytology is very simple, quick and inexpensive and can be carried out an out-patient basis without any complications.     

Epithelial atypia in gynecomastia induced by chemotherapeutic drugs. A possible pitfall in fine needle aspiration biopsy.

The clinical, cytopathologic and histopathologic features of a case of gynecomastia induced by chemotherapeutic drugs are described. Fine needle aspiration (FNA) smears showed epithelial atypia, and an erroneous cytologic diagnosis of carcinoma was made. Histopathologic study showed gynecomastia with epitheliosis, papillomatosis and atypical ductal hyperplasia. Review of the FNA smears showed the findings to be more typical of a reparative or regenerative process; these findings had been cytologically overinterpreted, partly due to the lack of adequate clinical information submitted with the aspirate. The possible causes of gynecomastia, the induction of epithelial atypia by cytotoxic chemotherapy and the cytologic features whose recognition may prevent false-positive diagnoses in such cases are discussed.     

The diagnostic reliability of cytologic typing in primary lung cancer with a review of the literature

To evaluate the growing tendency in recent years to attribute more diagnostic reliability to cytologic methods, we investigated the accuracy of cytologic typing in specimens obtained from bronchopulmonary material by five different clinical sampling methods, comparing the cytologic diagnoses with the known histologic diagnoses. The study consisted of 232 cytologic specimens from 157 cases of primary lung cancer. Of the 232 specimens, 173 (75%) were correctly typed and 59 (25%) incorrectly typed with respect to the appropriate histologic diagnoses. When all sampling methods were considered together, the study demonstrated that well-differentiated epidermoid carcinoma and "oat cell" and spindle-polygonal anaplastic carcinomas yielded high cytologic typing accuracies. In poorly differentiated tumors, bronchioloalveolar cell carcinoma and bronchogenic adenocarcinoma, the correct cytologic typing was much lower. The different tumor types and their degrees of differentiation seem to be the decisive factors in cytologic typing accuracy. The findings of this study were compared with those of others and were found to be consistent with the results of even larger series of cases. For some types the typing accuracy was higher than that reported in other series, whereas for other types, e.g., adenocarcinomas, it was lower.     

Quality assurance in pathology. Cytologic and histologic correlation.

In this study we used a computerized program to compare the cytologic and histologic diagnoses made in a three-year period with the aim of evaluating the data obtained as an index of the diagnostic accuracy of cytology in a pathology quality assurance program. Concordance between the cytologic and histologic diagnoses was observed in 83.2% of the cases. In 1.2% the cytologic diagnosis was suspected malignancy, and 78.4% of these cases were positive for tumor at histologic examination. Analysis of the data must be performed in accordance with the anatomic site involved, and discordance must be investigated by a pathologist, especially in view of the different modalities of cytologic and histologic sampling. Analytic data on the breast, bladder and lung are presented.     

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.     

Transthoracic fine needle aspiration and core biopsy of pulmonary lesions. A study of 296 patients

OBJECTIVE: To retrospectively investigate and compare the usefulness of transthoracic fine needle aspiration (FNA), core biopsy and a combination of the two in the diagnosis of pulmonary lesions. STUDY DESIGN: Two hundred ninety-six patients who had undergone FNA, core biopsy or both for lung lesions were divided into malignant and benign groups according to the final diagnoses, which were based on the cytologic and histopathologic findings combined with clinical features. In each group, the diagnostic usefulness of FNA, core biopsy and a combination of the two were evaluated by comparing the results of each with the final diagnoses. RESULTS: In the malignant group, FNA was diagnostically helpful in 188 of 205 patients (91.7%) and core biopsy in 158 of 180 patients (87.8%). The combination of the two methods improved the result to 172 of 178 patients (96.6%). The sensitivities were 94.6%, 88.3% and 97.2%, respectively, for each result. In the benign group, 71.1% (64/90), 70.1% (47/67) and 74.2% (49/66) of cases received specific or nonspecific diagnoses by FNA, core biopsy and their combination, respectively. The rates of specific diagnoses were 20.1%, 21.0% and 31.8%, respectively. CONCLUSION: The combination of FNA and core biopsy markedly improved the diagnostic yields in the malignant group and, to a lesser degree, also in the benign group.     

Value of fine needle aspiration cytology in the initial diagnosis of Hodgkin's disease. Analysis of 188 cases with an emphasis on diagnostic pitfalls

OBJECTIVE: To evaluate the diagnostic accuracy and pitfalls of fine needle aspiration (FNA) cytology in the initial evaluation of Hodgkin's disease (HD) and to assess the influence of the pathologist's experience by comparing the results during two periods. STUDY DESIGN: A total of 170 cytodiagnoses of HD were reviewed and compared with those on the final histopathologic report. Thirty-three cases of HD with a previous, different cytologic diagnosis were also selected. In all the cases under study, FNA was performed as part of the initial diagnostic approach. From a practical perspective, diagnostic errors were divided into major or minor according to the consequences on patient management. RESULTS: Fifteen cytologic diagnoses of HD were followed by a different histologic diagnosis after lymph node biopsy. In 33 cases of HD an erroneous cytologic diagnosis was given prior to biopsy. The sensitivity of the series was 82.4% (86.1% excluding nonrepresentative cases). The positive predictive value reached 91.2%. Sensitivity varied from 79.3% in the first period (1982-1990) to 84.9% in the second (1991-1999) (83.3% and 88.2%, respectively, excluding nonrepresentative cases). Similarly, the positive predictive value increased from 89% to 92.8%. Diagnostic errors with important consequences for patient management diminished from 14 in the first period to 5 in the second. CONCLUSION: Cytology offers a rapid and accurate approach not only for the diagnosis of recurrent HD but also for its initial recognition. These results increase the capacity of FNA as a first-level diagnostic technique in the screening of lymphadenopathies.     

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.     

Significance of cytologic criteria in distinguishing small cell from non-small cell carcinoma of the lung

OBJECTIVE: To study the significance of cytologic features in distinguishing small cell carcinoma (SCC) from non-small cell carcinoma (NSCC). STUDY DESIGN: Prospective study of 76 patients with lung carcinoma. Percutaneous fine needle aspiration and bronchial washings stained with Papanicolaou and May-Grünwald-Giemsa stain were used for categorization of tumors according to the World Health Organization classification. Each tumor was also scored for the presence or absence of standard cytologic criteria used in the diagnosis of SCC. Data were analyzed for sensitivity, specificity and significance using the chi 2 and Fisher exact tests. Undifferentiated and unclassified tumors were examined immunocytochemically for the presence of neuron-specific enolase, epithelial membrane antigen and leukocyte common antigen. Cytologic diagnoses were compared with histopathologic diagnoses. RESULTS: Seventy-six lesions classified on cytomorphology consisted of SCC (15), NSCC (50), non-Hodgkin's lymphoma (1), carcinoid (1) and undifferentiated or poorly differentiated carcinomas (9), 2 of which showed nuclear molding and salt-and-pepper chromatin. Immunocytochemistry and biopsy confirmed the diagnosis of SCC in those two patients. CONCLUSION: Nuclear molding, cell size and scant, basophilic cytoplasm were highly sensitive and specific by univariate analysis for distinguishing SCC from NSCC. Other features, such as salt-and-pepper chromatin, crush artifact and apoptotic bodies, also had significantly high specificity; however, their low sensitivity precluded their usefulness in separating SCC from NSCC. Thus, morphologic evaluation plays a major role, while immunocytochemistry can make a limited contribution in differentiating SCC from NSCC.     

Reliability of cytologic typing of lung cancer.

In a prospective study of 111 cases of lung cancer, cytopathologic diagnoses were compared with histologic diagnoses. In 77.5 per cent of the cases, histopathologic diagnoses were in concurrence with cytopathologic diagnoses. The discrepancies occurred mainly in poorly differentiated adeno and epidermoid carcinoma. Well differentiated adeno and epidermoid carcinoma were cell typed with 100 per cent accuracy and small cell carcinoma with 90 per cent accuracy.     

Inflammatory atypia and the false-negative smear in cervical intraepithelial neoplasia

The effectiveness of cervical cytologic screening is compromised by the increasingly recognized prevalence of false-negative smears. Our previous studies suggested that some false-negative cytologies can be accounted for by smears showing cervical intraepithelial neoplasia (CIN) reported as inflammatory atypia; we found that at least 4% of 5,752 consecutive smears had been underreported in this manner. In the present study, that data was reanalyzed to derive 95% confidence limits for the number of CIN smears reported as inflammatory atypia. Using several differing estimates of cytologic screening sensitivity, it is speculated that, under certain testable assumptions, colposcopy of patients with cytologic diagnoses of inflammatory atypia may be one cost-effective approach to finding CIN cases missed by screening. If confirmed, these findings imply that laboratory quality assurance efforts, traditionally directed to the most serious cytologic diagnoses, should also focus in part on nondysplastic atypia.     

Nonaspiration-needle smear preparations of pulmonary lesions. A comparison of cytology and histology

Material for cytologic smears was obtained from pulmonary lesions in 146 patients at the Ohio State University between 1979 and 1984 using Rotex or Lee screw needles. Corresponding histologic specimens were available for comparison in 77 of these cases. Diagnoses of malignant neoplasms made by cytologic evaluation (55 cases) were confirmed by the corresponding histologic specimens in 93% of those cases. Possible explanations for the cytologic false-positive diagnoses of malignancy are presented. Correlations between the cytologic and histologic diagnoses of the morphologic type of tumor were 100% for adenocarcinoma, 75% for squamous-cell carcinoma and 20% for large-cell undifferentiated carcinoma. The correlation was 100% for small-cell carcinoma when the histology specimen represented the tumor. Nonneoplastic benign lesions diagnosed cytologically had corresponding benign histologic diagnoses in 94% of the cases. These results compare favorably with those reported for other fine needle aspiration studies of pulmonary lesions. The advantages of using Rotex needles as compared to fine needle aspiration are discussed.     

Comparing the accuracy of ThinPrep Pap tests and conventional Papanicolaou smears on the basis of the histologic diagnosis: a clinical study of women with cervical abnormalities

OBJECTIVE: To confirm that the ThinPrep Pap test (TP) is as effective as or more effective than the conventional Papanicolaou smear (CS) in detecting epithelial cell abnormalities in a population with cervical abnormalities. STUDY DESIGN: In a blinded, split-sample, matched-pair study, a CS was prepared using a cytobrush, and then TP slides were prepared from the remainder of the sample. All slides were evaluated as defined and classified by the Bethesda System. The results of the two cytologic tests were compared in 483 women relative to the histologic diagnoses of subsequent colposcopically directed cervical biopsies in 158 cases. RESULTS: The cytologic diagnoses from the two methods agreed exactly in 91.4% of cases. The comparison between the two cytologic diagnoses with reference to the histologic diagnosis of subsequent colposcopically directed cervical biopsies showed that TP was significantly more specific for diagnosing lesions than was CS. The sensitivity of the two methods was equivalent. CONCLUSION: In a population with cervical abnormalities, TP is more specific than and as effective as CS in detecting cervical epithelial cell abnormalities. TP improved the specificity of disease detection by reducing the atypical squamous cells of undetermined significance category and/or false positive cases.     

Cytologic detection of hepatic metastases

Cytologic preparations and histologic specimens from 404 liver biopsies were reviewed. The cytologic specimens were prepared from the saline rinsings of the Klatskin biopsy needle. Malignant neoplasms were detected by both methods in 50 cases. In seven cases, neoplasms were diagnosed by cytologic techniques alone; in nine cases neoplasms were present in the biopsy only. No false-positive cytologic diagnoses of malignancy occurred. The results of this study show that cytologic examination of the rinsings of the biopsy needle is a sensitive and highly specific adjunct to biopsy in the detection of hepatic metastases.     

Comparison of suspicious and positive colposcopic, cytologic and histologic findings in the uterine cervix

One hundred thirty-five cases of suspicious or positive colposcopic or cytologic findings were histologically analyzed. In cases of colposcopically detectable atypical changes or suspicious findings as well as of cytologic dysplasias or carcinomas, the histologic diagnoses were almost the same. The results demonstrated that colposcopy and cytology with a quick staining method are of value. Biopsy can quickly follow in cases of suspicious findings.     

Fine needle aspiration biopsy in the evaluation of lymphoreticular tumors of the thorax

The role of fine needle aspiration (FNA) biopsy in the evaluation of lymphoreticular disorders involving the lung and mediastinum was evaluated in a study of 16 cases from the authors' institutions. The cytologic material from these cases was reviewed, and the original cytologic interpretations were compared to the tissue diagnoses, with the overall accuracy of the cytologic interpretation evaluated. There were no false-positive diagnoses of malignancy in this series. A definite diagnosis of malignant lymphoma was most readily made in those cases in which the lymphoma was of the large-cell type. Small-cell and mixed large-cell and small-cell lymphoid proliferations were less able to be definitively interpreted, with pseudolymphoma presenting particular difficulty. The results support the conclusion that FNA biopsy can be useful in evaluating these lesions but also emphasize the fact that accurate diagnosis requires correlation of cytologic, clinical and laboratory data.     

Fine needle aspiration cytology of cat scratch disease

The cytologic features of cat scratch disease diagnosed by fine needle aspiration cytology of a right inguinal lymph node in a 23-year-old woman are reported. Characteristic granulomas, with peripherally palisading epithelioid histiocytes and centrally located neutrophils, and an associated polymorphic cell population were observed. The cytologic pattern closely parallels the expected histopathologic findings and therefore can suggest the diagnosis in unsuspected cases or can confirm the clinical impression. The cytologic differential diagnosis and a discussion of other granulomatous lymphadenitis are presented.