Comparison of cytohistologic techniques in diagnosis of gastroesophageal malignancy

OBJECTIVE: To evaluate the diagnostic performance of various endoscopic cytologic techniques, namely, brushing cytology, touch smear cytology and crush cytology, and comparison with concurrent biopsy results in diagnosis of gastroesophageal malignancy. STUDY DESIGN: This prospective study was conducted on 100 patients, with 78 clinically suspected cases of esophageal malignancy and 22 cases of gastric malignancy. RESULTS: The diagnostic accuracy of touch smear in esophageal malignancy was significantly higher (94.12%) than brushing and crush smears (89.71% each), and endoscopic biopsy had the diagnostic accuracy of 88.24%. The diagnostic accuracy of combined brushing and biopsy was 100%; it was 97.06% for touch smears combined with biopsy. In comparison, the diagnostic accuracy in gastric malignancy was 75% for brushing alone, which was significantly lower than touch smear (87.5%) and endoscopic biopsy (87.5%). The diagnostic yield for crush smear was 81.25%. A combination of touch smears and biopsy had a diagnostic yield of 100%; it was 93.75% for combined brushings and biopsy. CONCLUSION: A combination of cytohistologic techniques resulted in a statistically significant increase in the diagnostic yield of gastroesophageal malignancies and thus cytologic techniques may act as adjunct to biopsy histology to increase the diagnostic efficiency.     

Diagnosis and typing of lung carcinomas by cytopathologic methods. A review of 108 cases

A correlative review was made of the type of cytology specimens (sputum, bronchial washing and bronchial brushing) together with the corresponding histopathologic specimens of 108 patients. One hundred patients had primary pulmonary carcinomas diagnosed histopathologically (84) or clinically (16); 5 had carcinomas metastatic to the lungs and 3 had apparently false-positive cytologic results for lung cancer. The correlative review was used to determine the diagnostic reliability of pulmonary cytopathologic techniques in the detection and classification of lung carcinomas (i.e., the sensitivity and accuracy). The overall sensitivities of sputum, bronchial washing and bronchial brushing cytology were 60%, 66% and 77%, respectively (p less than 0.05). Bronchial brushing had a higher sensitivity (80%) for peripheral and metastatic lesions than did sputum (37%) or bronchial washing (60%). The overall accuracies of sputum, bronchial washing and bronchial brushing cytology were 79%, 75% and 76%, respectively, which is not statistically different. Regardless of the sampling methods, cytologic typing of squamous-cell and small-cell carcinomas was highly accurate but was less satisfactory for the other types of lung carcinomas. In the 16 cases in which endoscopic biopsies were either not attempted or gave negative results, one or more pulmonary cytologic specimens showed malignant cells. It is concluded that: (1) pulmonary cytopathologic techniques have excellent sensitivity and accuracy in the diagnosis of lung carcinomas; (2) they may establish the diagnosis of pulmonary carcinomas when endoscopic biopsies give negative results; and (3) they are particularly helpful in cases in which endoscopic biopsies suffer from a low yield (peripheral lesions) or create a considerable danger to the patients (iatrogenic hemorrhage).     

The role of brushing cytology in the diagnosis of gastric malignancy

The results of endoscopic biopsy and brushing cytology in 234 consecutive patients with established histologic diagnoses of discrete gastric lesions were analyzed. A histopathologic diagnosis of malignancy, established by independent means, was made in 74 patients. Brushing cytology was positive for malignancy in 63, a diagnostic sensitivity of 85%. Endoscopic biopsy was positive in 64, a diagnostic sensitivity of 86%. The sensitivity for combined cytology and biopsy was 91%, which was not significantly greater than for biopsy alone (P = .6). Cytology yielded false-positive results in 5 of 160 patients (3.1%) with confirmed benign disease. There were no false-positive biopsy reports. Although both brushing cytology and biopsy have high diagnostic sensitivities, based on the findings of this study, the routine addition of cytology to biopsy in the endoscopic evaluation of gastric lesions is not recommended. Cytology could be reserved for situations in which difficulty is encountered in obtaining adequate tissue for histologic examination and for cases with a high suspicion of malignancy that have yielded negative biopsies.     

Endoscopic fine needle aspiration biopsy

A catheter assembly that can be passed through the biopsy channel of a standard fiberoptic gastroduodenoscope was devised to permit fine needle aspiration biopsy of gastrointestinal neoplasms under direct vision of the endoscope. This technique for endoscopic aspiration biopsy was performed in ten consecutive patients with esophageal and gastric carcinomas, along with the conventional endoscopic brushing and biopsy. Endoscopic aspiration biopsy gave a positive diagnosis in all ten cases while the other two techniques gave inconclusive results in one patient with an ulcerative growth. We feel that endoscopic aspiration biopsy can be used to obtain representative samples from gastrointestinal neoplasms, and it may add to the diagnostic accuracy of endoscopic biopsy and brushing cytology.     

Brushing cytology of the upper gastrointestinal tract. Obsolete or not?

The merit of brushing cytology of the upper gastrointestinal tract has been questioned since it appears to duplicate biopsy. To determine its value, the reports on all endoscopic biopsy and cytology specimens from a one-year period were reviewed. The 683 procedures included 481 in which only a histologic biopsy sample was obtained, 47 in which only a cytologic brushing sample was obtained and 155 in which both types of samples were obtained ("combined specimens"). Among the 155 combined specimens, 4 of the confirmed malignancies were detected by histology only while 2 were detected by cytology only. A diagnosis of suspicious or positive for malignancy was made for 20% of the combined specimens as compared to less than 5% of the biopsy-only or brushing-only specimens. While 15% of the specimens that included a brushing sample (either alone or with biopsy) showed fungal infections, only 1.2% of the biopsy-only specimens did. It appears that the clinicians at this hospital tend to use brushing in combination with biopsy when either a malignancy or a fungal infection is suspected. Other empiric advantages of endoscopic brushing cytology include its rapid turn-around time, minimal invasiveness and good recognition of lymphoid cells. The selective use of brushing cytology should increase the probability of detecting malignancies and fungal infections without any increased risk or discomfort to the patients.     

Cytodiagnosis of gastric ulcer penetration of the liver by examination of endoscopic brushings

The penetration of a gastric peptic ulcer into the liver was initially diagnosed by the cytologic examination of endoscopic brushings and later confirmed by an endoscopic biopsy of the stomach. One of the smears of the gastric brushing contained sparse groups of liver cells with mild atypia. The endoscopic biopsy specimen included liver parenchyma with signs of peptic hepatitis. The differential diagnostic considerations for a gastric brushing containing hepatoid cells are discussed.     

Endoscopic brushing cytology and biopsy in the diagnosis of upper gastrointestinal tract lesions. A study of 350 cases

Direct-vision endoscopic examination conducted on 4,000 patients for persistent upper gastrointestinal (GI) complaints over a period of five years revealed 350 visible lesions that were subjected to brushing cytology and biopsy. Cytologic examination of brushing smears from all 350 cases showed malignant cells in 67 (19.14%), cells suggesting benign polypoid neoplasms in 4 (1.14%), ulcerative and reparative features with attendant atypias in 186 (53.14%), inflammatory findings in 91 (26%) and false-negative findings in 2 cases (0.57%). Only 259 (74%) of the visible lesions were also subjected to endoscopic biopsy. Of the 67 patients with positive cytology, 52 were judged positive on the biopsy specimen; the 2 false-negative cytologic reports were confirmed as positive by biopsy. In four patients with gastric ulcers, malignant cells were seen along with gastric repair cells. This study indicates that brushing cytology is very useful in detecting benign ulcerative lesions with their atypias, a feature that could be useful in monitoring and controlling lesions in high-risk groups of patients, such as in India. In this study, endoscopic brushing cytology gave a better diagnostic yield than did endoscopic tissue biopsy. However, the two techniques are complementary for the diagnosis of upper GI malignancies.     

Diagnostic sensitivity and specificity of pulmonary cytology: comparison of techniques used in conjunction with flexible fiber optic bronchoscopy

We examined the accuracy of pulmonary cytology in 224 consecutive patients being evaluated for lung cancer. The diagnostic yeild of specimens obtained by various methods, including flexible fiber optic bronchoscopy (FFB), was compared. Among 69 patients with lung cancer, a cytologic diagnosis was made in 87%, including 73% with peripheral tumors. Prebronchoscopy sputa were positive in 50%, bronchial washings in 63%, postbronchoscopy sputa in 82% and bronchial brushings in 59% of the patients. In only one patient was the bronchial brush specimen the only positive cytologic specimen. Normal FFB and small cell undifferentiated cancer were found with increased frequency (P less than 0.05) among the nine patients (13%) with false-negative cytology. Among 155 patients with nonmalignant lung disease, 16 (10%) had false-positive specimens; this finding was significantly related (P less than 0.05) to necrotizing pneumonia in 13 of the 16 patients (81%). The overall diagnostic accuracy of cytology showed 87% sensitivity and 90% specificity, and the predictive value of a positive specimen was 79%. In the absence of necrotizing pneumonia these values exceeded 95%.     

Bronchial submucosal needle aspiration performed through the fiberoptic bronchoscope

Retrospective review of 251 bronchial submucosal needle aspirations obtained from 171 patients with unsuspected pulmonary malignancy showed that adequate cytologic material was obtained in 87.6% of the aspirations. Eighty-one patients were found to have primary bronchogenic carcinomas (with a visible endobronchial tumor in 39), and 21 had secondary pulmonary metastases. The overall diagnostic accuracy of bronchial submucosal aspiration was 81%, with only four definite false-negative and no false-positive results. The diagnostic accuracy was 82% for bronchial brushing, 71% for forceps biopsy, 67% for postbronchoscopy sputum cytology and 46% for bronchial washing. The major advantage of the submucosal aspiration technique was in evaluating mural mucosal lesions, especially those covered with intact mucosa, that were not readily accessible to forceps biopsy or successful brush sampling. Negative results from a needle aspiration must be interpreted with caution because of the small area a single sample represents. Multiple sequential submucosal aspirations may be helpful in assessing the resectability of bronchial neoplasms. No complications have been encountered with this technique.     

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.     

Conventional respiratory cytology versus fine needle aspiration cytology in the diagnosis of lung cancer

The results of 184 fine needle aspiration (FNA) cytologic examinations were compared with the findings of "conventional" respiratory cytology (on sputums, bronchial brushings and bronchial washings) and histology (on biopsy and autopsy samples) and with the medical records. Positive cytologic results were obtained in 6 (10%) of 60 sputums, 17 (21%) of 80 brushings, 16 (19%) of 84 washings and 82 (44%) of 184 aspirates. These positive results were confirmed by biopsy for 6 of 6 sputums, 16 of 17 brushings and 15 of 16 washings. Among the 82 patients with a positive FNA cytology, malignancy was confirmed by lung biopsy in 39 and by autopsy in 2; the cytologic diagnosis was supported by clinical and radiographic findings in all but 1 of the remaining 41 patients. Using transbronchial lung biopsy, autopsy and medical records as final standards, the positive predictive values were 100% for sputum, 94.1% for brushings, 93.0% for washings and 98.6% for FNA samples. The high positive predictive values of FNA and the other cytologic procedures indicate that these diagnostic modalities provide simple, rapid and reliable methods for the diagnosis of lung cancer.     

Cervicovaginal cytology in uterine adenocarcinoma and adenosquamous carcinoma. Comparison of cytologic and histologic findings

To investigate the diagnostic accuracy and to characterize the findings in false-negative cases, the results of cervicovaginal cytology in 56 adenocarcinomas and 25 adenosquamous carcinomas (42 cervical, 36 endometrial, 2 metastatic and 1 arising synchronously from both cervix and endometrium) were reviewed, including review of the actual slides in 56 cases. Overall, 80% of the initial cytologic diagnoses resulted in diagnostic curettage (i.e., cytology was effectively positive); 84% of the postreview diagnosis were effectively positive. Nine cytology slides showed no malignant cells; eight of these negative smears showed repair, five were atrophic, two showed a high estrogen effect and one had enlarged atypical bare nuclei. These false-negative diagnoses were associated with an endometrial primary site (P less than .01), endometrioid histology (P less than .005), low-grade or intermediate-grade histology (P less than .005), small size of tumor (P less than .05) and absence of cervical involvement (P less than .005) in those cases in which a hysterectomy was performed. False-negative diagnoses were not associated with an absence of endocervical cells or with scanty cellularity. Of 39 cervical and 28 endometrial carcinomas with a positive cytologic diagnosis (initially or after review of the available slides), cytology correctly identified the primary site in 18% and 54% of the cases, respectively. Cytology incorrectly classified the anatomic site of four cervical and three endometrial carcinomas and considered one case arising in both the endometrium and cervix to be endometrial. Routine cervicovaginal cytology does have a role in screening for uterine glandular carcinoma; to maximize its diagnostic sensitivity, we suggest using a recommendation for curettage in the report of positive cases so that all of the varied cytologic diagnoses associated with glandular carcinomas will receive a uniform clinical response. In those cases with preserved cancer cells, a correlation can be made with the histologic type of the carcinoma, rather than with the anatomic site.     

Prospective study of combined use of bronchial aspirates and biopsy specimens in diagnosis and typing of centrally located lung tumours.

OBJECTIVE--To determine the diagnostic accuracy of examining bronchial secretions in pulmonary cytopathology and whether cytology and histopathology can complement each other in routine practice among lung specialists. DESIGN--A prospective study comparing 1225 cytological and biopsy results, conducted during 1987-93. Tumours were confirmed by histopathology, imaging techniques, or clinical outcome and imaging techniques combined. SETTING--11 lung or internal medicine units, France. SUBJECTS--1128 patients (874 men; 254 women) aged 65.3 (SD 13.7) years who underwent fibreoptic bronchoscopy for various pulmonary symptoms. RESULTS--Exact concordance between cytological and biopsy results was obtained in 1036/1187 (87.3%) satisfactory specimens. In all 574 lung tumours were diagnosed. One case (0.08%) was a false positive cytological diagnosis in a patient with tuberculosis. Patients with lung cancer were more likely to have positive cytological results than positive biopsy results (P < 0.001). Agreement in tumour typing was observed in 375/424 (88.4%) cases, when non-small cell carcinomas, small cell carcinomas and undifferentiated carcinomas were separated. In the 11 patients with squamous cell carcinomas in situ, eight (72.7%) of the carcinomas were diagnosed cytologically as squamous cell. Unsatisfactory material was obtained in only 20 (1.6%) and 19 (1.6%) cases by cytology and biopsy respectively. Examinations had to be repeated in 86 (7.6%) patients. CONCLUSIONS--Examination of bronchial secretions complements histopathology in both diagnosing and typing lung tumours and could be performed more systematically in patients undergoing fibreoptic bronchoscopy.     

Endoscopic suction cytology in upper gastrointestinal tract malignancy

In 50 cases of radiographically suspected malignancies of the upper gastrointestinal (GI) tract, the lesions were sampled by suctioning following brushing and forceps biopsy. The cytologic smears prepared from the suctioned material were positive for malignancy in 48 cases (96%), as were the biopsy specimens; the cytologic smears from the brushings were positive in 92% of the cases. All 50 cases were diagnosed as malignant by one or more of the techniques. Suction cytology detected the ulcerated and stenotic growths that biopsy failed to diagnose in two cases. Endoscopic suction cytology, which is a simple and rapid procedure, seems able to assist in diagnosing lesions of the upper GI tract.     

The recognition of Pneumocystis carinii in routine Papanicolaou-stained smears

Using definite criteria it is possible to accurately evaluate routine Papanicolaou-stained cytologic smears for the presence or absence of Pneumocystis carinii. Strict attention must be paid to the cellular environment and the background material intimately associated with the cells. In 133 cytology specimens evaluated from proximal and deep bronchial washings and brushings, 71 were considered positive for P. carinii and 62 were called negative. Ten of the latter were either unsatisfactory or equivocal. The 71 positives correlated in every instance with parallel Grocott methenamine silver-stained transbronchial biopsies or brushings. Fifty-one of the 52 satisfactory cytologic negatives also correlated with the biopsy and brushing findings. There was a single false negative. This high degree of correlation indicates that the Papanicolaou-stained specimen can be a valuable tool in the early diagnosis of pneumocystosis.     

Diagnostic accuracy of liquid‐based endometrial cytology in the evaluation of endometrial pathology in postmenopausal women

C. Remondi, F. Sesti, E. Bonanno, A. Pietropolli and E. Piccione
Diagnostic accuracy of liquid‐based endometrial cytology cytology in the evaluation of endometrial pathology in postmenopausal women Objective: The aim of this study was to compare liquid‐based endometrial cytology with hysteroscopy and endometrial biopsy regarding its diagnostic accuracy in a series of postmenopausal women with abnormal uterine bleeding (AUB) or asymptomatic women with thickened endometrium assessed by transvaginal ultrasound as a screening procedure. Methods: Inclusion criteria were: menopausal status; the presence of AUB and/or thickened endometrium assessed by ultrasound (cut‐off 4 mm); a normal Papanicolaou (Pap) smear; and no adnexal pathology at ultrasound. Exclusion criteria were: previous endometrial pathology; and previous operative hysteroscopy. Of 768 postmenopausal women referred to our general gynaecology clinics, 121 fulfilled the inclusion criteria and were recruited to the trial. Twenty‐one refused to participate. Cytological sampling was carried out by brushing the uterine cavity using the Endoflower device with no cervical dilation and the vial was processed using a ThinPrep® 2000 automated slide processor. The slides were stained using a Pap method. Results: In 98 cases with histological biopsies, endometrial cytology detected five cases of endometrial carcinoma, 10 of atypical hyperplasia and 47 of non‐atypical hyperplasia; 36 cases were negative. In two cases cytology was inadequate because of uterine cervical stenosis. Taking atypical hyperplasia or worse as a positive test and outcome, the diagnostic accuracy of the endometrial cytology was 93.5%, with a sensitivity of 92% and specificity of 95%, a positive predictive value of 73% and a negative predictive value of 99%. All the carcinomas were detected by cytology. Only 42% of women with a positive diagnosis were symptomatic. The cytological sampling was well tolerated by all patients. No complication was registered. Conclusions: Liquid‐based endometrial cytology can be considered an useful diagnostic method in the detection of endometrial pathology as a first‐line approach, particularly if associated with transvaginal ultrasound.     

Cytologic diagnosis of Campylobacter pylori-associated gastritis

Forty-nine paired gastric brushings and biopsy specimens were reviewed to determine the cytologic presentation of Campylobacter pylori-associated gastritis. The bacterium was identified in ten routinely prepared cytologic specimens, seven of which were positive for C pylori by biopsy. C pylori could be readily distinguished from other bacteria and was accompanied by inflammation and reparative atypia of gastric epithelial cells. Gastric brushing cytology is an effective method of diagnosing C pylori-associated gastritis.     

Reporting the presence of significant epithelial atypia in pancreaticobiliary brush cytology specimens lacking evidence of obvious carcinoma: impact on performance measures

OBJECTIVE: To assess the clinical impact of recognizing and reporting the presence of significant atypia in brush cytology specimens from the biliary and pancreatic ducts lacking obvious features of carcinoma. STUDY DESIGN: Analysis of 120 pancreaticobiliary brushings from 99 patients over a 4-year period. There were 114 bile duct and 6 pancreatic duct specimens obtained via endoscopic retrograde cholangiopancreatography at a tertiary care center. RESULTS: Overall sensitivity, specificity, accuracy, and positive and negative predictive values for carcinoma were 47%, 99%, 79%, 95% and 76%, respectively. When the presence of "significant epithelial abnormalities," cancer or cellular atypia less than carcinoma, was reported, the overall sensitivity, specificity, accuracy, and positive and negative predictive values were 62%, 93%, 82%, 85% and 80%, respectively. CONCLUSION: Recognizing and reporting the presence of significant epithelial abnormalities in pancreaticobiliary specimens lacking obvious features of malignancy in brush cytology specimens led to a modest improvement in sensitivity for "significant epithelial abnormalities" and cancer, along with a slight decrease in specificity and positive predictive value and slightly increased accuracy and negative predictive value. Maintaining high specificity is essential to avoiding false positive diagnoses on pancreaticobiliary brush cytology.     

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.