Effectiveness of smear technique in detection of pulmonary and gastric cancer

In the initial use of cytologic examination of smears to detect pulmonary and gastric cancer at the Los Angeles County Hospital during the period April 1949 to June 1950, 350 patients with suspicion of pulmonary disease and 128 with gastric problems were studied. In the pulmonary group, 80 per cent of 51 malignant lesions were diagnosed by the smear technique. Sixty per cent of 15 neoplasms in the stomach were diagnosed by the method. The results are analyzed in terms of sensitivity, accuracy, reliability and "yield" for the method. Cytological criteria of the presence of malignant disease are given and illustrated by photomicrographs. The method is one of potentially great value as an aid to diagnosis. Use of it in examination of selected categories of patients seems warranted.     

CANCER OF THE LUNG IN TUBERCULOUS PATIENTS

Of all tuberculous patients over 45 years of age admitted to Olive View Sanatorium in the five-year period ended July, 1958, 1.4 per cent had cancer of the lung. This is a much higher incidence than in a comparable segment of the general population.Careful examination of serial roentgenographic studies in all cases of suspected pulmonary lesions was found to increase diagnostic acuity. Scalene node biopsy, cytologic study and bronchoscopy were of less help. Diagnostic thoracotomy was the single most useful procedure for diagnosis.As to operability, the results in patients with both cancer and tuberculosis compared very well with those in patients who had only cancer. Patients who have inactive pulmonary tuberculosis and cancer have much poorer results than patients with active tuberculosis and cancer. There are difficulties in accurately diagnosing cancer in the presence of tuberculosis; and there are special problems in patients with inactive tuberculosis and cancer.     

The Papanicolaou-Traut method of cancer diagnosis; its use as a routine pathologic laboratory procedure

In a series of 450 examinations by the smear technique in the pathologic laboratory of a small private hospital, the total diagnostic error on all smears was 6.6 per cent. The error on vaginal smears was 4.7 per cent. These figures include false positives, false negatives, and all those smears classified as suspicious even though positive or negative diagnoses were made on subsequent examinations. The Papanicolaou-Traut method of cancer diagnosis can easily be made one of the routine pathologic procedures in the small hospital laboratory. Technicians with little previous cytologic experience can be trained to screen vaginal and other smears accurately after a short training period. This cytologic method is proving to be of value in the early detection of some neoplasms, and if its application is to be extended, the practicing pathologist should add the test to his diagnostic routine.     

THE PAPANICOLAOU-TRAUT METHOD OF CANCER DIAGNOSIS,Its Use as a Routine Pathologic Laboratory Procedure

In a series of 450 examinations by the smear technique in the pathologic laboratory of a small private hospital, the total diagnostic error on all smears was 6.6 per cent. The error on vaginal smears was 4.7 per cent. These figures include false positives, false negatives, and all those smears classified as suspicious even though positive or negative diagnoses were made on subsequent examinations.The Papanicolaou-Traut method of cancer diagnosis can easily be made one of the routine pathologic procedures in the small hospital laboratory. Technicians with little previous cytologic experience can be trained to screen vaginal and other smears accurately after a short training period. This cytologic method is proving to be of value in the early detection of some neoplasms, and if its application is to be extended, the practicing pathologist should add the test to his diagnostic routine.     

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.     

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.     

Earlier Diagnosis of Cervical Cancer—An Analysis of Reports to the California Tumor Registry from 1942 to 1963

The mortality rate for cervical cancer in California declined during the period 1950-64. Indirect evidence shows that the incidence is also declining, but it is difficult to assess this decline because of the effect of the increasing use of cytologic examination on incidence rates for cervical cancer.Cervical cancer, in the 57 hospitals reporting to the California Tumor Registry, is being diagnosed at an earlier stage than in previous years. The proportion of cases diagnosed with the lesion still in the in situ stage rose from zero in 1942 to 56 per cent in 1963, and invasive cervical cancer, as a proportion of all invasive cancer in women, decreased from 15 per cent to 9 per cent. There is wide variation among hospitals in the proportion of cervical cancer cases that are in situ at time of diagnosis.     

Gastrin--a normal and pathologic regulator of gastric function.

Fine needle aspiration biopsy (FNAB) is an underused diagnostic procedure in children, particularly in the evaluation of superficial masses. A total of 54 FNABs of superficial masses were performed in children aged 1 month to 15 years. Adequate material for diagnosis was obtained in 50 attempts. The cytologic diagnosis increased clinical understanding and provided a guide for treatment in 46 of the 50 cases. The cytologic diagnosis was confirmed in 15 of 19 patients who underwent an operation. Surgical intervention was obviated in 31 patients. There was one false-positive diagnosis of cancer. We describe the role of FNAB in children and its technique, accuracy, and diagnostic problems.     

VAGINAL SMEARS—A Plea for More Critical Evaluation

To determine whether a conscious effort to reduce the incidence of equivocal (Class III) vaginal cytologic smear readings might have demonstrable clinical value, we have compared a previous study of our predictive efforts with a recent experience in screening a similar number of patients.It was possible to achieve an appreciable reduction in the incidence of Class III smears—from 2.4 per cent to 0.6 per cent. There was a modest increase in the reliability of the Class III smear as an indicator of cancer and a very notable increase in the reliability of the Class IV and V interpretations. While only 66 per cent of the earlier group with Class IV and V smears were shown to have cancer, 86 per cent of the present series with IV and V readings had malignant disease (97 per cent of the Class V group).The ultimate yield of malignancies was similar in the two series, but theoretically the overloading of Classes III, IV and V with women who do not actually have cancer necessarily leads to large numbers of diagnostic surgical procedures that might be avoided. Class III should be used to denote merely a temporary state of inconclusiveness rather than a real suspicion of cancer. With proper collaboration between physician and cytologist, most of the initially confusing situations can be either upgraded or downgraded to the proper rating, and eventually the bulk of patients standing to profit from conization will fall into Classes IV or V.     

Cytology of prostatic carcinoma. Quantification and validation of diagnostic criteria

The validity of diagnostic criteria for the cytologic differentiation between benign and malignant cases and between normal (hyperplastic) and inflammation-activated (prostatitis) prostatic cells was tested by means of semiautomated image analysis and cytophotometry. The following criteria were found to have significant differences between benign and malignant prostatic cells: nucleoli (number, size and size variability), regularity of nuclear arrangement, anisonucleosis, nuclear size, nuclear polymorphism and dissociation of cells. The following criteria were found to be invalid for the detection of prostatic cancer cells: nuclear-cytoplasmic ratio, hyperchromasia and anisochromasia. the cytologic diagnosis of prostatic cancer was achieved by observing a variable constellation of at least three of six pathognomically altered diagnostic criteria. No fixed pattern of diagnostic criteria was found either for prostatic cancer cells in general or for the different malignancy grades.     

Perforated gastric and duodenal ulcers; an analysis of 73 cases

In 73 cases of perforated gastroduodenal ulcers in which operation was done at St. Joseph's Hospital, San Francisco, during the ten-year period July 1939 to July 1949, the death rate was 13.7 per cent. In all but three of the cases, simple closure of the perforation was carried out. In 46 cases there were postoperative complications. Of this number, peritonitis and its sequelae comprised 35 per cent and pulmonary complications, 37 per cent. The mortality rate in the group in which these complications occurred was 35 per cent.     

Cytologic evaluation of bronchoalveolar lavage specimens in immunosuppressed patients with suspected opportunistic infections

The role of bronchoalveolar lavage cytology in the diagnostic evaluation of immunosuppressed patients with suspected opportunistic pulmonary infections was evaluated by comparing two groups of patients who underwent fiberoptic bronchoscopy. Bronchoalveolar lavage specimens were compared with other available diagnostic techniques, including bronchial washings, bronchial brushings, transbronchial lung biopsies and open lung biopsy. Prior to the initiation of a protocol for bronchoalveolar lavage, a specific etiology for the pulmonary infiltrate using the above combined modalities was identified in 23 of 47 cases, for an overall diagnostic rate of 49%. The combined bronchial washings and brushings (cytologic procedures) identified a specific etiology in 9 of 47 (19%) of the cases. There were ten cases in which a cytologically identifiable organism (Pneumocystis, virus or fungus) was not present in the bronchial washings and brushings and one missed case of malignancy, for a false-negative rate of 23%. With the addition of the lavage technique and better sampling of the distal airways, a specific etiology for the pulmonary infiltrate was identified in 32 of 48 (67%) of the cases. This is comparable to the values of 40% to 65% cited in the literature for diagnosis of infectious disease by open lung biopsy. The lavage cytologic procedure identified a specific etiology in 22 of 48 (46%) of the cases, and the false-negative rate was reduced to 6%. With the excellent sampling of the bronchoalveolar lavage and the improved cytology results, the need for transbronchial or open lung biopsy has been eliminated in immunosuppressed patients with suspected opportunistic pulmonary infections. This allows these patients to be studied on an outpatient basis.     

Pulmonary Hodgkin's disease. Diagnosis by fine needle aspiration

The cytologic manifestations of pulmonary Hodgkin's disease in transthoracic fine needle aspirates from 13 patients with pulmonary radiologic abnormalities and a previous diagnosis of Hodgkin's disease are described. Classic Reed-Sternberg cells and lacunar cells were present in most cases. The so-called "mononuclear" Reed-Sternberg cells were identified in all cases. A cellular background consisting of variable numbers of histiocytes, eosinophilic and neutrophilic leukocytes and lymphocytes was frequently present. Such a background should stimulate a search for cells diagnostic of Hodgkin's disease. We conclude that the cytologic features of Hodgkin's disease are not only characteristic, but are also diagnostic, in patients with a prior history of Hodgkin's disease in whom pulmonary recurrence is suspected.     

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.     

Needle biopsy of the liver; general considerations

Needle biopsy of the liver provides concrete diagnostic information that cannot be as readily obtained in any other way. This report reviews 401 liver biopsies in 312 patients. THE MAJOR INDICATIONS FOR USE OF THIS PROCEDURE ARE: To determine the cause of an obscure liver enlargement; to establish the cause of jaundice; to distinguish between malignant disease and cirrhosis of the liver; to determine when hepatitis has subsided; and to evaluate the results of treatment. At times, systemic disease that has not been recognized by other means may be diagnosed by this technique. There is risk in performing this test, and the 0.25 per cent mortality in this series compares favorably with that reported from other clinics. Where the diagnosis by biopsy could be compared with observations at operation or autopsy, the correct diagnosis was made by biopsy in 85 per cent of cases. Greater accuracy was obtained by two or more biopsic examinations in one case then by single biopsy. In several cases in which surgical operation was considered, biopsic information made it unnecessary, and vice versa.     

Cytopathology of the esophagus. An overview of esophageal cytopathology in China

Carcinoma of the esophagus is the most common malignancy in many parts of China. In an attempt to control it by early diagnosis, the balloon sampling technique was developed approximately 20 years ago. This technique is now widely used in China and is accepted as a diagnostic method by WHO. Up to 1979, more than 500,000 people were examined in China. It is routinely used for differentiation between benign and malignant lesions in the esophagus, with an accuracy in the range of 90%. In mass surveys, 73.8% of the cancers detected have been carcinoma in situ and minimally invasive carcinomas. Dysplasias have been shown to progress to invasion by cytologic studies. The utilization of this technique has made possible epidemiologic studies and, thereby, coordination of etiologic research in esophageal cancer. Detection rates of early esophageal cancer by cytologic studies are more accurate than are those with either endoscopic or radiologic methods. The instruments and technique for balloon sampling of esophageal lesions are described, as are the cellular cytomorphology and the diagnostic cytologic criteria applicable to the samples obtained.     

Cytologic examination of post prostatic massage specimens as an aid in diagnosis of carcinoma of the prostate.

The results of cytologic examination fo post-massage prostatic secretion from symptomatic and asymptomatic subjects were evaluated by comparison with available tissue diagnosis. Specimens studied consisted of post-prostatic massage secretion and urine. The latter specimen gave much superior results. Although possibility of the cytologic diagnosis in prostatic carcinoma cases was limited, it proved to be reliable. Presently available short follow-up data indicate that this technique may play a role only as a diagnostic aid, however, its real value in prostatic cancer detection, could be only evaluated by long term follow-up of the "high risk" group.     

NEEDLE BIOPSY OF THE LIVER—General Considerations

Needle biopsy of the liver provides concrete diagnostic information that cannot be as readily obtained in any other way. This report reviews 401 liver biopsies in 312 patients.The major indications for use of this procedure are: To determine the cause of an obscure liver enlargement; to establish the cause of jaundice; to distinguish between malignant disease and cirrhosis of the liver; to determine when hepatitis has subsided; and to evaluate the results of treatment. At times, systemic disease that has not been recognized by other means may be diagnosed by this technique. There is risk in performing this test, and the 0.25 per cent mortality in this series compares favorably with that reported from other clinics. Where the diagnosis by biopsy could be compared with observations at operation or autopsy, the correct diagnosis was made by biopsy in 85 per cent of cases. Greater accuracy was obtained by two or more biopsic examinations in one case then by single biopsy.In several cases in which surgical operation was considered, biopsic information made it unnecessary, and vice versa.     

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.     

Morphometric differences between cytologically benign and malignant serous effusions

The morphometric differences between benign and malignant serous effusions, as diagnosed by standard cytologic criteria in 95 unselected cases (50 benign and 45 malignant), were studied using the IBAS semi-automated image analysis system, which calculates various parameters from tracings of cellular and nuclear outlines. Fourteen cases were also stained for cytokeratin proteins (with the CAM 5.2 antibody) by the immunoperoxidase technique and reanalyzed for positive cells. Significant differences were found for mean values between cytologically benign and malignant cases for cellular and nuclear areas, perimeters and maximum diameters, but not for two form factors. Some differences were enhanced in the CAM 5.2-stained cases. Real morphometric differences in samples of cells from benign and malignant cases are the basis of cytologic diagnosis. Fully automated diagnostic systems could operate on arbitrary threshold values, but there is considerable overlap in specimen means for all parameters between benign and malignant cases.