Diagnosis of metastatic malignant melanoma by fine needle aspiration biopsy: a clinical and pathologic correlation of 298 cases.

Fine needle aspiration biopsies (FNABs) from 298 lesions in patients with suspected metastatic melanoma were studied. The results were correlated either with histopathologic diagnoses on resected lesions or with prolonged clinical follow-up. Of 165 malignant aspirates, 160 were confirmed either by surgical resection (65 cases) or by an appropriate clinical course (95 cases). Of the 107 benign lesions with adequate follow-up, 73 were confirmed as benign. There were 25 false negatives: 19 were inadequate samples, and 6 were presumed failures of needle localization. No interpretative errors were identified. Although 3 cases of FNAB-diagnosed malignant melanoma could not be confirmed by surgical biopsy, the cytologic findings were typical of malignant melanoma. Clinical follow-up, however, suggested that the cytologic diagnosis was in error. One case of a second unrelated malignancy (an adenocarcinoma of the lung) was correctly diagnosed with the use of FNAB. Because of its high degree of accuracy, FNAB has proved useful in the differential diagnosis of subcutaneous nodules, enlarged lymph nodes, and lung nodules.

Tumor-associated glycoprotein (TAG-72) in ovarian carcinomas defined by monoclonal antibody B72.3.

Murine IgG1 monoclonal antibody (MoAb) B72.3, reactive with a high molecular weight glycoprotein complex [designated tumor-associated glycoprotein-72 (TAG-72)] was shown, with the use of the avidin-biotin-complex-immunoperoxidase technique and surgically resected tissues, to be reactive with a variety of histologic tumor types. TAG-72 is expressed in at least 5% (and up to 100%) of the malignant epithelial cells in 77% (n = 52) of human primary cancers and 71% (n = 31) of metastatic ovarian cancers of the common "epithelia" histologic category. Of these, several histologic types, including serous and mucinous cystadenocarcinomas, undifferentiated carcinomas, and less common types of ovarian carcinoma, were all shown to express TAG-72. In contrast, normal ovarian tissues and 26 of 27 benign ovarian tumors of various histologic types failed to express similar levels of TAG-72. Of interest is the 1 benign tumor that demonstrated unusual glandular complexity, as well as 3 tumors designated as borderline malignancy, that contained elevated TAG-72 expression. MoAb B72.3 also was used successfully to detect ovarian carcinoma cells in 28 cytologic preparations of human serous effusions and peritoneal washings. The reactivity of MoAb B72.3 was shown to be distinct from that of MoAb OC125 and an anti-CEA MoAb B1.1. The potential applications of MoAb B72.3 in the study of human ovarian cancer cell populations, as well as in several aspects of the management of human ovarian cancer, are discussed.

Selective interferon-induced enhancement of tumor-associated antigens on a spectrum of freshly isolated human adenocarcinoma cells.

Freshly isolated cells from patients with pleural or peritoneal effusions cytologically diagnosed as adenocarcinoma (n = 43), malignant nonepithelial neoplasms (n = 10), and benign (n = 8) were analyzed for expression of constitutive levels of the tumor antigens TAG-72 [recognized by monoclonal antibody (MAb) B72.3] and carcinoembryonic antigen (CEA) (recognized by MAb COL-4) as well as the class I and class II major histocompatibility (MHC) antigens, and the ability of human interferons (Hu-IFNs) to enhance cell surface expression of those antigens as measured by MAb binding. Both type I and type II IFNs enhanced the expression of TAG-72 and CEA and altered the level of expression of the MHC antigens. Comparative studies of three different Hu-IFNs (IFN-alpha A, IFN-beta ser, and IFN-gamma) revealed that IFN-gamma was the most potent in augmenting either B72.3 or COL-4 binding. Unlike the IFN-gamma -mediated induction of the class II human leukocyte antigens, the change in tumor antigen expression consisted of enhanced constitutive antigen expression; de novo induction of either TAG-72 or CEA could not be achieved by either type I or type II IFN. Of 43 effusions isolated from different adenocarcinoma patients, 42 (97.7%) expressed either CEA or TAG-72, and treatment with Hu-IFN increased the level of expression of either antigen in 36 of 42 samples (85.7%). These studies demonstrate the augmentation of tumor-associated antigens on human carcinoma cells isolated from serous effusions by Hu-IFNs which may be used to enhance the targeting of conjugated MAbs to human carcinoma lesions.

Distribution of oncofetal antigen tumor-associated glycoprotein-72 defined by monoclonal antibody B72.3.

Murine monoclonal antibody B72.3, prepared against a membrane-enriched extract of human metastatic carcinoma, was reacted with a spectrum of adult and fetal human tissues using avidin-biotin-complex immunohistochemical techniques to evaluate the expression of the reactive tumor associated glycoprotein (TAG)-72 antigen. TAG-72 was shown to be expressed in several epithelial-derived cancers including 94% of colonic adenocarcinomas, 84% of invasive ductal carcinomas of the breast, 96% of non-small cell lung carcinomas, 100% of common epithelial ovarian carcinomas, as well as the majority of pancreatic, gastric, and esophageal cancers evaluated. TAG-72 expression was not observed, however, in tumors of neural, hematopoietic, or sarcomatous derivation, suggesting that the TAG-72 antigen is "pancarcinoma" in nature. Appreciable monoclonal antibody B72.3 reactivity was generally not observed in adult normal tissues, with limited reactivity noted in a few benign lesions of the breast and colon. TAG-72 antigen expression was detected, however, in fetal colon, stomach, and esophagus, thus defining TAG-72 as an oncofetal antigen. TAG-72 has previously been shown to be distinct from carcinoembryonic antigen and other tumor associated antigens. The pancarcinoma distribution and lack of significant reactivity with normal adult tissues of monoclonal antibody B72.3 suggest its potential diagnostic and therapeutic utility for human carcinomas.

Phenotypic characterization of lung cancers in fine needle aspiration biopsies using monoclonal antibody B72.3.

Monoclonal antibody B72.3, reactive with a high-molecular-weight glycoprotein tumor-associated antigen (designated TAG-72), has been previously shown to be reactive with formalin-fixed paraffin-embedded tissue sections of adenocarcinomas of the ovary, colon, and breast and not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct to diagnose carcinoma in cell block and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. In this study, fine needle aspiration biopsies of 127 lung cancers (93 primary and 34 metastatic tumors) as well as 18 benign lung lesions were analyzed with monoclonal antibody B72.3 using avidin-biotin-peroxidase techniques. Monoclonal antibody B72.3 showed reactivity with 100% of the 27 lung adenocarcinomas and adenosquamous carcinomas, with greater than or equal to 10% of tumor cells showing reactivity in 22 of 27. A lesser percentage of squamous cell carcinomas (24 of 31) and large cell carcinomas (7 of 13) were immunoreactive, and of these several were weakly reactive with less than or equal to 1% tumor cells reacting. In contrast, monoclonal antibody B72.3 failed to react with any of the 21 small cell carcinomas or one carcinoid tumor evaluated. In 35 patients tumor-bearing tissue was resected, and formalin-fixed tissue sections were also evaluated. The staining pattern and percentage of tumor cells positive in the aspiration biopsies were, in most cases, highly predictive of the reactivity observed in corresponding resected tumor. Metastatic adenocarcinomas to lung from various body sites were also immunoreactive with monoclonal antibody B72.3; however, a variety of other tumor types (including 13 melanomas) failed to stain. Staining by monoclonal antibody B72.3 was not noted in any of the 18 benign lesions aspirated, with the exception of occasional fine stippling in the cytoplasm of bronchial epithelial cells. Hence, monoclonal antibody B72.3 and fine needle aspiration biopsy techniques may be of potential use in the differential diagnosis and antigenic phenotyping of a spectrum of lung neoplasms prior to surgical resection.

Use of a monoclonal antibody (B72.3) as an immunocytochemical adjunct to diagnosis of adenocarcinoma in human effusions.

A monoclonal antibody (MAb), designated B72.3, has been generated using membrane-enriched fractions of a metastatic human breast carcinoma as the immunogen. Previous studies have demonstrated that the reactive antigen, a novel Mr 220,000 to 400,000 glycoprotein complex, can be detected in formalin-fixed, paraffin-embedded tissue sections of human breast and colon carcinomas, and not in a variety of normal adult human tissues. In this preliminary study, we report that MAb B72.3 may be used as an adjunct for diagnosis of adenocarcinoma in cytological preparations of human effusions. Using the avidin-biotin complex method of immunoperoxidase staining and formalin-fixed, paraffin-embedded cell suspensions, MAb B72.3 detected adenocarcinoma cells in effusions from all of 21 patients with adenocarcinoma of the breast. No reactivity was demonstrated in any cell type in benign effusions from 24 patients without cancer, or 13 patients with prior or extant cancer in other body sites; moreover, B72.3 showed no reactivity to leukemic or lymphomatous effusions, or apparent mesothelial cells from malignant effusions. MAb B72.3 also detected adenocarcinoma cells in cytological effusion specimens from 12 of 12 patients with adenocarcinoma of the lung and 16 of 16 patients with adenocarcinoma of the ovary. Thus, these data suggest that the immunocytochemical application of MAb B72.3 should now be considered as an adjunct in the discrimination of adenocarcinoma cells from reactive mesothelial cells in the cytological diagnosis of malignant effusions.

Adjunct to the diagnostic distinction between adenocarcinomas of the ovary and the colon utilizing a monoclonal antibody (COL-4) with restricted carcinoembryonic antigen reactivity.

Malignant ovarian tumors may represent either primary ovarian cancers or metastatic lesions (from patients with demonstrated primary cancers at other body sites) whose distinction may be difficult using clinical, surgical, and pathological criteria. Monoclonal antibody (MAb) COL-4, reactive with carcinoembryonic antigen, has previously been shown to react preferentially with adenocarcinomas of the colon versus a variety of normal tissues. We report here that MAb COL-4 is strongly reactive with primary colonic carcinomas (N = 50), as well as regional (N = 42), and distant (N = 20) metastases of colonic adenocarcinoma. In contrast, MAb COL-4 demonstrated little to no reactivity with primary (N = 53) and metastatic carcinomas of the ovary (N = 23) including serous, mucinous, and poorly differentiated adenocarcinomas using immunohistochemical techniques. This differential reactivity was statistically significant (P less than 0.001), suggesting the potential clinical utility of MAb COL-4 in the differentiation of ovarian from colonic adenocarcinoma. Solid-phase quantitative radioimmunoassays and Western blotting techniques confirmed these results. Data are also presented that the carcinoembryonic antigen molecules or epitopes recognized by a more classical broadly reactive anti-carcinoembryonic antigen MAb are distinct from those recognized by MAb COL-4. Other carcinomas which also metastasize to the ovary and may be confused clinically with a primary ovarian tumor such as adenocarcinomas of the stomach and breast were also evaluated for reactivity with MAb COL-4. COL-4 was also reactive with all gastric carcinomas evaluated, but failed to react with breast carcinomas. Hence, COL-4 can now be utilized as an immunohistochemical adjunct for the differentiation of ovarian from gastrointestinal adenocarcinoma which can be difficult to distinguish by clinical, surgical, and histological parameters.

Establishment of a CSF bank.

A bank of well-characterized CSF has been established by collecting and storing (-70 degrees C) CSF samples remaining after completion of routine clinical studies. Over 1,700 individual patient samples were collected during a 12-month period. A database derived largely from information down-loaded from existing hospital-based systems includes the results of individual CSF laboratory studies, in addition to the patient age, primary diagnoses, and details of any malignancy. CSF control material is used to verify storage conditions. The CSF bank supplies investigators with CSF handled in a standardized manner for more precise investigation of CNS disease.

Fine-needle aspiration biopsy of the mediastinum.

Fine-needle aspiration is a useful technique to identify neoplasms of many sites, such as breast, thyroid, and lung. Thirty-two mediastinum aspirates from 29 patients were reviewed. Five aspirates yielded insufficient material. Five aspirates were of benign lesions. Four aspirates were suggestive of but not diagnostic of malignancy. Eighteen aspirates contained malignant cells; in 13 of these, a definite cell type was identified, which usually was metastatic lung carcinoma; in five instances, the cell type could not be unequivocally identified. Complications were minimal, two instances of pneumothorax (6.3 percent) and two of hemoptysis (6.3 percent). No deaths or hemorrhage occurred. In 16 of the 29 patients (55 percent), thoracotomy was avoided because of fine-needle aspiration biopsy. It is concluded that fine-needle aspiration biopsy of the mediastinum is a safe, useful diagnostic tool. This procedure may obviate the need for thoracotomy in persons with inoperable cancer, thus lowering medical costs and length of hospital stay.

Use of a monoclonal antibody (B72.3) as a novel immunohistochemical adjunct for the diagnosis of carcinomas in fine needle aspiration biopsy specimens.

Monoclonal antibody B72.3 has been shown to be reactive with a high-molecular-weight glycoprotein complex termed TAG(tumor-associated glycoprotein)-72. By the avidin-biotin immunoperoxidase method, fine needle aspirates and corresponding surgically excised tumor tissues from both malignant and benign tissues were analyzed for TAG-72 expression. Staining (range, 1 to 100 per cent of tumor cells) with monoclonal antibody B72.3 was observed in needle aspirates from 18 of 18 adenocarcinomas and adenosquamous carcinomas of the lung, 17 of 21 adenocarcinomas of the breast, and six of six adenocarcinomas of the colon, as well as adenocarcinomas from other body sites. In contrast, small cell carcinomas of the lung, malignant melanomas, lymphomas, and sarcomas did not stain with the antibody. Benign lesions from the breast, lung, pancreas, parotid, and thyroid also failed to stain. In 66 patients, tumor-bearing tissue had also been resected and was available for comparative examination with monoclonal antibody B72.3. In 62 of these 66 patients, the staining patterns in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tissues. From these studies it is concluded that monoclonal antibody B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells but not in benign cells and is most selectively expressed in adenocarcinomas. This monoclonal antibody may be used as a novel adjunct for the diagnosis of carcinoma in fine needle aspiration biopsy specimens.

Detection of tumor cells in the bone marrow of stage IV breast cancer patients receiving high-dose chemotherapy: the role of induction chemotherapy.

High-dose chemotherapy and hematopoietic support can produce long-term, disease-free remissions in selected patients with metastatic breast cancer. Occult bone marrow involvement may contribute to late relapse. We used five anti-breast cancer monoclonal antibodies and flow cytometry with cytological analysis of sorted immunostained cells to detect tumor cells in the bone marrow in two cohorts of patients. The first (Upfront) cohort was treated with a single course of high-dose chemotherapy and autologous bone marrow support (ABMS) without induction chemotherapy. The second (AFM) cohort received induction chemotherapy with doxorubicin, 5-fluorouracil and methotrexate prior to high-dose chemotherapy and ABMS. Of the 15 Upfront patients, seven (47%) had immunostained cells in the harvested bone marrow by flow cytometry and 8/15 (53%) had positive cytologies. Of the 49 AFM patients studied, nine (18%) had immunostained cells in the bone marrow, and only 1/49 (2%) had positive cytologies. Induction chemotherapy significantly decreased bone marrow contamination as detected by flow cytometry and cytology in patients with breast cancer. The detection of immunostained cells in the bone marrow did not predict for relapse or overall survival.

Prospective correlation of cervicovaginal cytologic and histologic specimens.

An effective, prospective, computer-guided method of correlation is reported. The mechanism for identification of cases, comparison of diagnoses, and reconciliation of discrepancies are explained. The results are similar to prior, retrospective, correlation studies. The benefits specific to this unique prospective approach include optimal capture of cases for correlation, minimization of errors before diagnoses are released to clinicians and patients, and internal standardization of diagnostic criteria. Three thousand four hundred and four consecutive paired cervicovaginal cytologies and biopsies were accessioned at the Pathology Department of Duke University Medical Center over a 43-month period. Of these, 481 paired cases (14%) had discordant diagnoses, defined as differing more than one degree of dysplasia or as dysplasia or carcinoma identified by only one modality. Additional evaluation reconciled the diagnostic differences in 35 cases. Eighteen initial diagnostic differences arose from cytologic screening errors, 16 from interpretive errors by staff pathologists, and one from superficial initial histologic sections. The remaining 446 discordances were attributed to sampling differences. The cytologic smear contained the diagnostic lesion in 40% of the cases and the biopsy the remainder, emphasizing the utility of pairing these sampling techniques in patients at risk for dysplasia.

Detection of breast carcinoma cells in human bone marrow using fluorescence-activated cell sorting and conventional cytology.

Flow cytometry has been compared with conventional cytology as a method for detecting breast carcinoma cells in human bone marrow. Breast cancer cells from patient effusion fluids or from established cell lines were mixed with normal human bone marrow at dilutions ranging from 1:10 to 1:100,000. Cells were labeled with five directly fluoresceinated murine monoclonal antibodies reactive against epithelial cell surface determinants of 42, 55, 72, 200, and more than 200 kD. Fluorescence of tumor cells within the mixtures was then analyzed with the use of a fluorescence-activated cell sorter. In multiple experiments, one tumor cell in 10,000 nucleated marrow cells could be detected by flow cytometry. In addition, a linear correlation was observed over approximately 3 logs between the number of tumor cells added and the number of tumor cells detected. In a double-blind study comparing flow cytometry and cytology, flow cytometric analysis detected one tumor cell among 10,000 marrow precursors in 14 of 15 instances, whereas standard cytologic methods detected similar tumor contamination in 9 of 15 instances. Neither technique used individually could detect one tumor cell in 100,000 bone marrow cells. Used in combination, however, flow cytometry and cytology could detect one breast cancer cell among 100,000 normal marrow progenitors.

Cytopathology and the management of early invasive cancer of the uterine cervix.

This study was designed to review the effectiveness of cytopathology as it entered into the evaluation of patients with possible microinvasive or early occult carcinoma of the uterine cervix. During the 7-year period of 1971 to 1977, 39 consecutive patients were found for whom either a cytopathologic diagnosis of early invasive carcinoma had been made or suggested, or a histopathologic diagnosis of early invasive carcinoma had been made. After review, 35 patients had an ample number of cytopathologic and histopathologic materials and clinical records to be included in the study. The results of these studies have shown that when cytopathology on review predicted a lesion more severe than carcinoma in situ, it was confirmed by histopathology in more than 78% of patients (22 of 28 cases). In those patients shown by histopathology to have microinvasive or occult invasive carcinoma, the cytopathology reflected it in 87% of patients (27 of 31 cases). In the cases of histologically proved microinvasive carcinoma, the corresponding genital smears either diagnosed or suggested invasive carcinoma in 81% of cases and carcinoma in situ in 19%. From these studies it has been concluded that diagnostic cytopathology is potentially a highly reliable tool when used in conjunction with other modern diagnostic modalities to aid the decision-making in cases of probable early cancer of the uterine cervix.

Vaginal administration of low-dose conjugated estrogens: systemic absorption and effects on the endometrium.

OBJECTIVE: To test the hypothesis tha a very-low-dose regimen of vaginal estrogen would provide effective relief from atrophic vaginitis without endometrial proliferation. METHODS: Twenty postmenopausal women with symptoms, signs, and cytologic evidence of atrophic vaginitis were enrolled. Each subject was treated with 0.3 mg of conjugated estrogens, administered vaginally 3 nights per week for 6 months. We examined the following outcomes: symptoms, vaginal cellular (cytologic) maturity, endometrial histology, sonographic evaluation of endometrial thickness, Doppler measures of uterine artery blood flow, and serum levels of estrone and estradiol. Pre- and post-treatment data were compared for each subject. RESULTS: Satisfactory relief of symptoms occurred in 19 of 20 cases. Vaginal cellular maturation improved significantly with therapy (P < .01). There were no significant changes in endometrial thickness, uterine artery blood flow, or serum estrogen levels. Endometrial proliferation was observed in one case. CONCLUSIONS: Relief from atrophic vaginitis can be achieved with 0.3 mg of conjugated estrogens administered vaginally three times per week. Endometrial proliferation may occur at this low dose, albeit rarely.

Fine-needle aspiration in gynecology: evaluation of extrapelvic lesions in patients with gynecologic malignancy.

Fine-needle aspiration for suspicious extrapelvic lesions is documented in 82 specimens from patients with known pelvic malignancy. Specimens were obtained from lung (39%), supraclavicular lymph nodes (24%), paraaortic lymph nodes (11%), liver (7%), and other sites. Three of 32 (9.4%) patients with transthoracic aspirates experienced pneumothoraces requiring chest tube placement, and three others had smaller pneumothoraces that resolved spontaneously. Fifty-nine (72%) specimens were positive for malignancy. There were no known false positives. Of six negative aspirates that had follow-up histology, there were two false negatives. When the subsequent course was used as an indication of accuracy, specificity was 100%, and sensitivity was 91%. Fifty-eight (71%) patients had therapeutic alterations as a direct result of aspiration diagnosis. Thirty-nine major operative procedures and 28 open biopsies were spared. Fine-needle aspiration is a reliable and cost-effective diagnostic method that should become an increasingly routine component of the diagnostic armamentarium and may have broader roles defined through continuing study.

The application of monoclonal antibodies in the cytologic evaluation of tumors.

The focus of this review has been the application of MAbs as adjuncts in the interpretation of cytology specimens. It is evident that most if not all of the MAbs studied thus far are neither completely tumor-specific nor -sensitive; however, when used to address a directed clinical question, they may be "operationally specific." More important, there continues to be no current substitute for the understanding and practice of sound diagnostic cytopathologic principles. Ultimately, the application of MAbs resides in the importance of tumor-associated antigen expression and phenotyping of tumors with therapeutic and prognostic implications.

Cytologic diagnosis of lung cancer. Principles and problems.

This diagnostic seminar discusses the current status of the principles and problems of cytology as it is applied to the diagnosis of lung cancer. This discussion is divided into four major parts. Part I presents a discussion of cytopreparatory techniques and cytology of the lung in the absence of cancer. The cytology of benign proliferations which may mimic cancer is emphasized. The role of cytology in the diagnosis of pulmonary infectious organisms is noted. Part II discusses lung cancer as manifested in specimens of sputum, bronchial washings, and bronchial brushings. Part III presents some data on the validity of cytology with respect to role of specimen number and type in lung cancer diagnosis and cell typing in lung cancer. The continued usefulness and importance of multiple specimens of sputum for lung cancer diagnosis are documented. Part IV presents a brief synopsis of fine needle aspiration biopsy of lung cancer.

Diagnostic value of conidia associated with pulmonary oxalosis: evidence of an Aspergillus niger infection.

Bronchoalveolar lavage (BAL) material is commonly received in cytopathology for the exclusion of microorganisms. When crystalline material suggestive of calcium oxalate is present in the specimen, a search for fungal elements should be undertaken. Aspergillus niger is the hyaline mold associated with the presence of oxalate crystals. Commonly fragments of hyphae and occasionally entire conidiophores may be present in BAL specimens from patients with aspergillosis. We report a case of a patient with saprophytic colonization of a bullous/cavitary lesion. The BAL consisted of abundant acute inflammation, crystalline material suggestive of oxalate, and darkly pigmented conidia. Although an extensive search was undertaken, hyphal fragments could not be found. The suspicion of an A. niger infection was confirmed by culture. We believe that even in the absence of hyphal fragments, darkly pigmented, occasionally rough-walled conidia are sufficient evidence to be highly suspicious of an A. niger infection in patients with pulmonary oxalosis.

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.