Bull's eye (target) inclusions in neoplastic cells in malignant serous effusions. A study of 289 cases

OBJECTIVE: To study the prevalence and significance of bull's eye (target) inclusions in neoplastic cells in malignant serous effusions. STUDY DESIGN: We reviewed malignant pleural, peritoneal and pericardial effusions from 289 patients who had proven cancer at known primary sites. The ages of the patients ranged from 5 to 72 years; 166 were male and 123 female. RESULTS: Bull's eye inclusions are an uncommon finding and appeared in only 13 cases of metastatic adenocarcinoma of the breast, stomach, colon, lung, ovary, pancreas and urinary bladder. They were positively stained with periodic acid-Schiff stain with diastase. The inclusions were not seen in cells of nonadenocarcinomatous neoplasms, such as squamous cell carcinoma, oat cell (small cell) carcinoma, neuroblastoma, lymphoma and germ cell tumors. CONCLUSION: Bull's eye inclusions are found in about 5% of malignant serous effusions containing cells of metastatic adenocarcinoma. The primary site of an adenocarcinoma cannot be deduced on the basis of the presence of inclusions.     

Positive effusion cytology as the initial presentation of malignancy

During a period of four years (1981 to 1984), 641 ascitic, 860 pleural and 47 pericardial fluid specimens were examined cytologically. Of these, 154 ascitic samples, 174 pleural specimens and 10 pericardial effusions, obtained, respectively, from 108, 133 and 7 patients, were found to contain malignant cells. In 7 patients, ascites, and in 18 cases, pleural effusions were the first indication of cancer. None of the positive pericardial fluids was the initial presentation of malignancy. The cytologic findings and follow-up data on these 25 patients are the subject of this study. The most common type of neoplasm in these effusions was adenocarcinoma (86% of the ascitic and 78% of the pleural fluids). Most of the malignant neoplasms in ascitic fluids were derived from ovarian tumors (5 of 7) while those in pleural effusions came mainly from lung tumors (12 of 18). Mammary carcinoma, which was the most common malignant tumor found in cases of pleural effusions, did not present initially with an effusion in any of our cases. The cytologic diagnosis was confirmed in all cases by either biopsy or strong clinical evidence. The prognosis in patients who initially presented with an effusion was poor. All of the patients with an adequate follow-up died within 29 months in cases of ascites and within 19 months in cases of pleural effusions.     

Immunohistochemical study of lysozyme, alpha 1-anti-chymotrypsin, tissue polypeptide antigen, keratin and carcinoembryonic antigen in effusion sediments

The cellular sediments of 42 malignant and 16 benign effusions (58 cases) were studied using the immunoperoxidase technique. Serial sections of formalin-fixed, paraffin-embedded residual sediments of effusions, sent for routine cytologic examination, were studied by commercially available polyclonal antisera against lysozyme, alpha 1-anti-trypsin, alpha 1-anti-chymotrypsin, tissue polypeptide antigen (TPA), a wide-spectrum anti-keratin, carcinoembryonic antigen (CEA) and, in single cases, thyroglobulin and prostate-specific antigen. A final definite diagnosis from histologic study of biopsy or autopsy specimens was known in all cases. All carcinomas, the mesotheliomas and the reactive mesothelial cells showed a positive reaction for TPA and, partly, the wide-spectrum keratin. Lysozyme could be demonstrated in the cells of the one proven malignant fibrous histiocytoma; all malignant epithelial cells were negative. Alpha 1-anti-chymotrypsin and alpha 1-anti-trypsin showed similar reactions: they were often positive in carcinoma cells of the breast, the bronchial system and the pancreas, in contrast to a mostly negative reaction in carcinomas of the stomach and ovary. CEA showed considerable differences; it was always negative in benign and malignant mesothelial proliferations but mostly positive in carcinomas of the stomach, pancreas and bronchial system. It was only positive in less than 20% of the carcinomas of the breast and always negative in the proven malignant effusions of primary carcinomas of the ovary and prostate. Studying a combination of several tumor markers is possible in serial paraffin-embedded sections and may be a valuable criterion in the cytologic diagnosis of effusions.     

The interval between the diagnosis of malignancy and the development of effusions, with reference to the role of cytologic diagnosis

An analysis was made of the time lapse between the diagnosis of malignancy and the development of an effusion in relation to the sex and age of the patients and the site of the primary malignancy. The total number of patients studied was 254; of these, 171 patients had a pleural and 83 patients a peritoneal effusion. In the total group, sex distribution was two men to three women: about equal in the pleural effusion group and about two men to nine women in the ascites group, with the latter ratio reflecting the large number of primary malignant processes in the breast and ovaries. The average age at the time of the effusion, whether it was located in the pleural or in the peritoneal cavity, was about 55 years. This figure was roughly 60 years for men and 51 years for women. The nine-year average age difference between sexes can be explained by the size of the four largest groups of different primary malignant localizations and their sex distribution. The interval between the discovery of the primary malignancy and the first fluid sample was longer for patients with a pleural effusion (average of 77.0 weeks) than for patients with ascites (average of 54.5 weeks). The longest interval was seen in the breast carcinoma group, with the shortest interval in lung carcinoma patients. The interval was significantly longer for women, being 111.9 weeks for pleural effusions and 57.9 weeks for ascites (average for both sites of 88.7 weeks). In 30.7% of the patients, the primary malignancy was discovered at the same time or later than the effusion; in patients with lung cancer, a strikingly higher percentage of 53.0% was found. In this respect, the cytologic diagnosis of effusions is of great importance not only for the detection and proper identification of a malignant process but also as an indicator of the life expectancy of a patient.     

Peritoneal washing cytology. Uses and diagnostic criteria in gynecologic neoplasms

Review of a 20-month experience with 241 peritoneal washes performed on 191 patients showed that the use of these specimens has expanded greatly. Of the 19 patients with neoplastic cells in their peritoneal washing cytology specimens, 12 had primary ovarian neoplasms, 4 had primary uterine cervical neoplasms, 2 had primary endometrial neoplasms, and 1 had mammary carcinoma metastatic to the ovary. Gynecologic oncologists at this institution are now routinely obtaining peritoneal washing cytology specimens whenever there is intraabdominal surgery on patients known to have or suspected of having a pelvic neoplasm. The following criteria were found to be essential to the accurate evaluation of these specimens: (1) cells considered to be malignant should be present both singly and in groups and should be malignant by the usual cytologic criteria, (2) the patients must have or be known to have had a neoplasm whose cells are similar to those in the washing specimen, and (3) the cells considered to be neoplastic must be different from and not confused with reactive mesothelial cells. The last criterion is important because the peritoneal lavage traumatically removes mesothelium, which can appear atypical. These criteria make the cytologic interpretation of most peritoneal washing specimens straightforward; interesting diagnostic problems occur, however, including the evaluation of neoplasms of borderline malignancy, those "spilled" during surgery and second neoplasms found by peritoneal washing cytology.     

Exfoliative cytology of nonlymphoreticular neoplasms in children

During the last 11 years, 144 nonlymphoreticular neoplasms were diagnosed in exfoliative cytology specimens obtained from patients younger than 17 years of age. Neuroblastoma was the single most common neoplasm (30 cases). Other categories of malignant neoplasms were primary bone tumors (30 cases), soft-tissue sarcomas (25 cases), brain tumors (25 cases) and epithelial neoplasms (7 cases). Of the 780 cytologic specimens, 335 were positive for malignant cells. Serous effusions provided most of the positive specimens from patients with neuroblastoma, germ-cell tumors and bone sarcomas. Exfoliated cells of metastatic embryonal rhabdomyosarcoma and primary brain tumors were detected most often in cerebrospinal fluid specimens. A most unusual presentation of an immature teratoma of the ovary is described in some detail. Despite the rarity of pediatric neoplasms, certain specific or suggestive cytologic features were recognized, including rosette formation of neuroblasts, nuclear notching of myoblasts, pleomorphism of osteoblasts and fibrillar processes of glial elements.     

Immunochemical demonstration of keratin and vimentin in cytologic aspirates

Antibodies to intermediate filament proteins were used to characterize tumor cells present in peritoneal and pleural effusions and in thin needle aspirates from palpable lymph nodes. Metastatic adenocarcinoma cells (breast, ovary, endometrium, cervix, colon and stomach) as well as squamous-cell carcinomas and mesotheliomas stained specifically with antibodies to keratin while mesenchymally derived tumor cells (lymphomas, melanoma, fibrosarcoma and neurofibrosarcoma) were positive only for vimentin. Especially in cases of lymph node aspirates, keratin staining in cells was a direct indication of metastatic carcinoma. Antibodies to these different components of the cytoskeleton can thus be used in cytopathologic diagnosis when a definitive diagnosis cannot be made on the basis of conventional cytologic features.     

DNA analysis of malignant effusions. Comparison with cytologic diagnosis and carcinoembryonic antigen content.

Twenty-three consecutive malignant effusions from 19 patients submitted for cytologic examination were analyzed for carcinoembryonic antigen (CEA) content and for DNA analysis by flow cytometry. The study was undertaken to determine if the addition of DNA analysis would improve the sensitivity of cytologic diagnosis and CEA assay. CEA examination was performed on Papanicolaou-stained smears and hematoxylin-and-eosin-stained cell blocks. Final diagnoses were correlated with histologic examination (four patients), clinical and radiologic studies, and follow-up. The malignant effusions in 19 patients were secondary to carcinoma of the breast (5), lung (5), ovary (1), endometrium (1), mucinous carcinoma of the colon (1), unknown primary (1), extraovarian papillary carcinoma (1), mesothelioma (2) and large cell lymphoma (2). The sensitivity of cytologic diagnosis was 100% and specificity 100%. DNA aneuploidy, defined as the presence of two separate peaks in the histogram, was present in 7 of 23 fluids (sensitivity, 30%). Four fluids had insufficient cells for analysis, and one histogram showed debris (following chemotherapy). DNA aneuploidy was detected in effusions secondary to carcinoma of the breast (4), lung (1) and lymphoma (2). Using 5 ng/mL as the cutoff, the sensitivity of CEA was 68%. DNA analysis of cells in malignant effusions is less sensitive than cytologic diagnosis, and CEA assay and is not recommended for routine use in the diagnosis of malignant effusions.     

Applications of monoclonal antibodies in clinical cytology as exemplified by studies with monoclonal antibody B72.3. The George N. Papanicolaou award lecture

The monoclonal antibody (MAb) 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, but not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct for the diagnosis of carcinoma in cell blocks and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. Using the avidin-biotin complex (ABC) method of immunoperoxidase staining and formalin-fixed, paraffin-embedded cell suspensions, MAb B72.3 detected tumor 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 41 patients. In contrast, MAb B72.3 showed no reactivity to leukemic or lymphomatous effusions, or to mesothelial cells from malignant effusions. MAb B72.3 also detected adenocarcinoma cells in effusion specimens from 12 of 12 patients with adenocarcinoma of the lung and 16 of 16 patients with adenocarcinoma of the ovary. MAb B72.3 has recently been used with fine needle aspiration (FNA) biopsy specimens and the corresponding surgically excised tumors to determine cellular reactivity. Using the ABC immunoperoxidase method, fine needle aspirates and corresponding surgically excised tumors were analyzed for TAG-72 expression. Positive staining with MAb B72.3 was observed in needle aspirates of 27 of 27 adenocarcinomas and adenosquamous carcinomas of the lung, 17 of 21 adenocarcinomas of the breast, 6 of 6 adenocarcinomas of the colon and in carcinomas from other body sites. In contrast, 21 small-cell carcinomas of the lung, 13 malignant melanomas, 2 lymphomas and 2 sarcomas did not stain with the antibody. Benign lesions from the breast, lung, pancreas, parotid and thyroid also showed no staining. In many patients, tumor-bearing tissue had also been resected and was available for comparative examination with MAb B72.3. In more than 90% of these patients, the staining patterns of the tumor cells in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tumors. From these studies, it is concluded that MAb B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells versus benign cells, that is most selectively expressed in carcinomas and that may be used as a novel adjunct for the diagnosis of neoplasms in effusions and in fine needle aspiration biopsies.     

Cytoskeletal proteins as tissue-specific markers in cytopathology

Antibodies to intermediate filament proteins react in a tissue-specific manner and can be used to characterize tumor cells present in thin-needle aspirates from solid tumors, from palpable lymph nodes and cells present in samples from peritoneal and pleural effusions. From our studies so far the following conclusions can be drawn: Polyclonal antisera to cytokeratins can identify carcinoma metastases in thin-needle aspirates from palpable lymph nodes and distinguish them from malignant lymphomas and nonmalignant lesions such as chronic lymphadenitis, which show only vimentin-positive cells. Monoclonal antibodies to specific cytokeratin polypeptides are able to distinguish between different types of epithelial tumor metastases, i.e. metastases from adenocarcinomas and metastases from squamous cell carcinomas. Cells present in peritoneal and pleural effusions can be partly characterized using intermediate filament antisera. We have found that metastatic adenocarcinoma cells from breast, ovary, endometrium, cervix, colon and stomach, as well as squamous cell carcinomas and malignant mesothelioma stain specifically with antibodies to cytokeratin while mesenchymally derived tumors such as malignant lymphomas, malignant melanomas, and fibrosarcomas, are positive for vimentin only. Metastatic tumor cells of epithelial origin present in aspirates from human serous body cavity fluids may coexpress vimentin next to their original cytokeratin intermediate filaments. Benign mesothelial cells present in body cavity fluids frequently coexpress cytokeratins and vimentin. Tumor cells present in thin-needle aspirates from solid tumors such as pleomorphic adenomas of the parotid gland can be identified as such because of their typical patterns of intermediate filament (co-)expression.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fine needle aspiration cytology of neoplasms metastatic to the breast

The fine needle aspiration (FNA) cytologic findings in 18 cases of metastatic neoplasms of the breast are reported. The cases were encountered in a combined series of 2,529 FNA breast biopsies, of which 666 were malignant; the metastatic neoplasms of the breast thus constituted 2.7% of all the malignant breast tumors. The series consists of 15 women and 3 men, with a mean age of 48 years (range of 11 to 73 years). Sixteen biopsies confirmed metastatic malignancy in patients with known extramammary primaries; the prebiopsy clinical diagnoses in six of the patients were benign breast lesions. In eight patients, the clinical differential diagnosis was either a benign or malignant primary breast lesion versus a metastatic malignancy. In two additional patients, the FNA biopsy identified metastatic neoplasms from unsuspected extramammary primaries. The metastatic neoplasms included three small-cell carcinomas of the lung, one squamous-cell carcinoma of the lung, two malignant melanomas, three ovarian malignancies, including a dysgerminoma, and one each of carcinoma of the fallopian tube, endometrial carcinoma, transitional-cell carcinoma of the urinary bladder, prostatic carcinoma, acute granulocytic leukemia, lymphoma, mycosis fungoides, hepatoma and neuroblastoma of the retroperitoneum. Recognition of unusual cytologic patterns raised the suspicion of, or confirmed the diagnosis of, malignancy in all cases, with no false-negative diagnoses. None of the cases were cytologically interpreted as a primary breast malignancy. Ancillary studies performed on the FNA material, including immunocytochemistry, contributed to a definitive diagnosis in three cases. FNA diagnosis of metastatic malignancy of the breast is essential in order to avoid unnecessary mastectomy and to ensure appropriate chemotherapy and/or irradiation treatment.     

MN/CA9: a potential gene marker for detection of malignant cells in effusions.

Many cancers cause malignant effusions. The presence of malignant cells in effusions has implications in diagnosis, tumour staging and prognosis. The detection of malignant cells currently presents a challenge for cytopathologists. New adjunctive methods are needed. Although the effusions provide excellent materials for molecular assay, the available molecular markers are extremely limited, which hinders its clinical application. MN/CA9 has proved to be a valuable marker in many cancers such as lung, breast, colon, kidney, etc. The present study was to evaluate MN/CA9 as a new molecular marker for the detection of cancer cells in pleural effusions. Seventy-one pleural effusions including 59 malignant effusions from patients with cancer, and 12 patients with benign diseases as a control, were subjected to RT-PCR for detection of MN/CA9 gene expression. MN/CA9 gene expression was detected in 53/59 (89.8%) pleural effusions from cancer patients (15/16 for breast cancers, 10/11 for lung cancers, 4/4 for ovary cancers, 2/3 for colon-rectal cancers, 5/6 for cancers of unknown site, 7/8 for mesothelioma and 10/11 for other cancers). Furthermore, MN/CA9 was positive in 13/18 (72.2%) of cytologically negative effusions of cancer patients. MN/CA9 was detected in only 1/12 (8.3%) effusions from the control patients (p < 0.01). The sensitivity and specificity of MN/CA9 gene expression were, respectively, 89.8% and 91.7%. Our preliminary results suggest that MN/CA9 could be a potential marker for the detection of malignant cells in effusions. A large-scale study is needed to confirm these results.     

MN/CA9: a potential gene marker for detection of malignant cells in effusions

Many cancers cause malignant effusions. The presence of malignant cells in effusions has implications in diagnosis, tumour staging and prognosis. The detection of malignant cells currently presents a challenge for cytopathologists. New adjunctive methods are needed. Although the effusions provide excellent materials for molecular assay, the available molecular markers are extremely limited, which hinders its clinical application. MN/CA9 has proved to be a valuable marker in many cancers such as lung, breast, colon, kidney, etc. The present study was to evaluate MN/CA9 as a new molecular marker for the detection of cancer cells in pleural effusions. Seventy-one pleural effusions including 59 malignant effusions from patients with cancer, and 12 patients with benign diseases as a control, were subjected to RT-PCR for detection of MN/CA9 gene expression. MN/CA9 gene expression was detected in 53/59 (89.8%) pleural effusions from cancer patients (15/16 for breast cancers, 10/11 for lung cancers, 4/4 for ovary cancers, 2/3 for colon–rectal cancers, 5/6 for cancers of unknown site, 7/8 for mesothelioma and 10/11 for other cancers). Furthermore, MN/CA9 was positive in 13/18 (72.2%) of cytologically negative effusions of cancer patients. MN/CA9 was detected in only 1/12 (8.3%) effusions from the control patients (p<0.01). The sensitivity and specificity of MN/CA9 gene expression were, respectively, 89.8% and 91.7%. Our preliminary results suggest that MN/CA9 could be a potential marker for the detection of malignant cells in effusions. A large-scale study is needed to confirm these results.     

The ultrastructure of metastatic adenocarcinoma in serous fluids. An aid in identification of the primary site of the neoplasm

Identification of the primary sites of metastatic adenocarcinomas is a diagnostic problem, particularly in cases of occult primary neoplasms. We studied the ultrastructural morphology of 16 metastatic adenocarcinomas that presented as effusions to establish organ-specific features that would characterize adenocarcinomas from various sites. The nine cases in which the site of the primary carcinoma was known included seven derived from the breast, one from the ovary and one from the colon. The primary site was unknown in seven cases at the time of presentation. After investigations, the primary site became known in five cases (lung, colon and appendix, one case each, and the ovary in two cases). Ultrastructurally diagnostic features could be detected in gastrointestinal, ovarian, bronchioloalveolar-cell and breast carcinomas. In gastrointestinal carcinomas, the presence of short microvilli with long rootlets was specific for the group. The lamellar inclusions of type II pneumocytes were diagnostic of bronchioloalveolar-cell carcinoma. The microvilli in ovarian carcinomas were long, slender and bushy, as in mesotheliomas; however, the cells lacked the perinuclear condensation of tonofilaments seen in the latter. Breast carcinomas were associated with numerous intracytoplasmic lumina, electron-dense granules and aggregates of small vesicular bodies. We conclude that ultrastructural examination of adenocarcinomas in serious fluids can help to identify the primary site of certain neoplasms or at least shorten the list of possibilities. This may reduce costs and minimize the discomfort patients have to undergo by curtailing extensive invasive investigations in search of unknown primary neoplasms.     

The positive pleural effusion. A retrospective study of cytopathologic diagnoses with autopsy confirmation.

We performed an investigation focusing on the distribution of tumor types responsible for positive pleural effusions in 143 patients who died of malignancy and underwent autopsy. The principal malignant tumors were lung carcinoma (41 cases, 51.2%) and pleural mesothelioma (23 cases, 28.7%) in males and breast carcinoma (24 cases, 38.2%) and lung carcinoma (13 cases, 20.6%) in females. Histologically, most of the cases belonged to the adenocarcinoma category. The first morphologic diagnosis was a cytologic one in 86 cases (60.1%), especially regarding lung cancer. In breast cancer a positive pleural effusion always preceded recurrent disease with a rapidly progressive course, even a long time after the initial surgery. The results of this study, based on both cytomorphologic features and postmortem data on the tumor sites, may be a useful working framework for the cytologist dealing with a positive pleural effusion.     

Ovarian carcinoma and serous effusions. Changing views regarding tumor progression and review of current literature.

Carcinoma of the ovary is the leading cause of death from gynecological cancer in western countries. Ovarian carcinoma is commonly associated with the accumulation of fluid containing malignant cells in the peritoneal, and not infrequently in the pleural cavity. The differentiation of these cells from reactive mesothelial cells is at times difficult. In addition, tumor progression in ovarian carcinoma and the biological characteristics of carcinoma cells in effusions compared to their counterparts in solid tumors are poorly understood. This review details the current knowledge regarding diagnostic and biologic aspects of effusion cytology, with emphasis on ovarian carcinoma. Results from our first studies of effusions are subsequently presented. These attempt to address several issues. First, to improve the diagnostic ability to detect cancer cells in effusions using antibodies designed for the differentiation of epithelial cells from mesothelial cells. Secondly, to study genotypic and phenotypic differences between ovarian carcinoma cells in effusions, solid primary tumors and metastatic lesions, as well as to compare malignant cells in peritoneal and pleural effusions. These studies of carbohydrate antigens, E-cadherin complex and matrix metalloproteinases (MMP) attempted to evaluate whether ovarian carcinoma cells in effusions possess true metastatic properties, or are similar to the cells in primary tumors, thereby merely representing the result of a shedding process. Finally, the prognostic role of these molecules was studied in solid tumors from a patient cohort consisting of long- and short-term survivors, followed for up to 20 years. Figure 1 on http://www.esacp.org/acp/2001/23-3,4/davidson.htm.     

Preoperative aspiration cytology of breast tumors

During a ten-year period, 1,942 aspirations of 1,906 mammary tumors in 1,874 patients were performed before excisional biopsy or mastectomy. The cytology findings were categorized as positive (1,107 cases), suspicious (152 cases), atypical (183 cases), benign (166 cases) and unsatisfactory (298 cases). All cytologically positive cases with follow-up were confirmed histologically or by clinical observation. Follow-up showed that 96% of the cases in the suspicious category, 86% of the cases in the atypical category, 51% of the cases in the benign category and 72% of the cases in the unsatisfactory category had malignant neoplasms. Aspiration cytology diagnosed 1,031 of 1,539 primary malignant mammary neoplasms (67%) and 19 of 28 neoplasms (68%) metastatic to the breast; if unsatisfactory cases are excluded, these figures become 1,031 of 1,365 cases (75%) and 19 of 25 (76%), respectively. If those cases reported as suspicious are included with the positive cases and those reported as atypical are included with the negative cases, aspiration cytology would have a sensitivity of 84% for the presence of carcinoma, a specificity of 97% for the absence of carcinoma, a predictive value of 99% for a positive diagnosis and a predictive value of 56% for a negative diagnosis; the diagnostic efficiency would be 86%. Our findings reaffirmed that the cytologic diagnosis of mammary carcinomas is reliable but that negative or inconclusive cytologic findings should not be regarded as a definitive diagnosis if there is clinical suspicion of a malignant neoplasm.     

Carcinoembryonic antigen in effusions. A diagnostic adjunct to cytology

A total of 189 effusion specimens (100 benign and 89 malignant) submitted for cytologic examination were assayed for carcinoembryonic antigen (CEA) by an enzyme immunoassay to determine whether the addition of CEA evaluation to cytologic study would improve the diagnostic accuracy for the detection of malignancy. The sensitivity and specificity were 78% and 90%, respectively, for a cytologic diagnosis of malignancy and 68% and 99%, respectively, for a positive CEA (greater than 5 ng/mL). CEA assay was negative in the most common epithelial malignancies of the female genital tract (15 of 17 cases), mesotheliomas (5), lymphomas (7) and alveolar-cell carcinoma of lung (1). CEA assay was positive in 55 of 89 cases of malignancy, including 14 cases with cytologically negative malignant effusions. The CEA assay sensitivity for lung carcinoma (95% for adenocarcinoma, 100% for oat-cell carcinoma and 100% for carcinosarcoma), breast carcinoma (95%), and gastrointestinal carcinoma (100%) were all over 90%. No significant difference in the levels of CEA was noted between gastrointestinal and lung adenocarcinomas. Oat-cell carcinomas and squamous-cell carcinomas had lower values. In cases of an effusion with an unknown primary, an elevated CEA in the fluid is diagnostic of metastatic carcinoma arising from the breast, lung or gastrointestinal tract.     

Cytologic presentation of malignant mesothelioma in pleural effusions

1,601 pleural effusions were found to be malignant between 1976 and 1987. Among these were 26 (1.6% of the malignant effusions) mesothelioma. Only 2 cases showed pronounced cytologic features that made a definite diagnosis possible on cytologic criteria alone. In 20 cases diagnosis of mesothelioma was strongly suggested by the patient's history and cytology of the effusion was compatible with mesothelioma. In the other 4 cases special examinations (histo- and immunohistochemistry, electron microscopy) led to the final diagnosis. The cytologic features of mesothelioma and other examination techniques, needed to resolve the differential diagnosis of mesothelioma versus other neoplasm in pleural effusions, are discussed.     

Expression of a melanoma-tumor-associated antigen as demonstrated by a monoclonal antibody (D6.1) in cytopathologic preparations of human tumor cells from effusions and needle aspirates

Immunocytopathologic studies were performed on 79 fine needle aspiration biopsies (FNABs) and effusions from 13 melanomas and 57 other human neoplasms with the monoclonal antibody (MAb) D6.1 raised against a partially purified melanoma-tumor-associated antigen (MTAA). The purposes of these studies were (1) to evaluate the ability of MAb 6.1 to react with melanoma cells in cytopathologic preparations and (2) to define the spectrum of reactivity of MAb D6.1 in cytopathologic preparations of non-melanomas. Cytocentrifuge preparations of the cytopathologic specimens were permitted to react with the primary antibody and were then stained by the avidin-biotin-immunoperoxidase method. Thirteen of 13 FNABs of malignant melanomas exhibited staining reactivity with MAb D6.1. Among the nonmelanoma tumors tested, staining reactivity was observed in 30 of 57 specimens. Among specific neoplasms, staining was present in 5 of 11 adenocarcinomas of the breast, 2 of 7 ovarian adenocarcinomas and 5 of 6 metastatic adenocarcinomas from the colon. Among 17 lung cancers examined, staining was noted in 4 of 7 adenocarcinomas, 3 of 4 large-cell undifferentiated carcinomas and 2 of 3 poorly differentiated squamous-cell carcinomas. Two small-cell undifferentiated carcinomas and one carcinoid failed to stain. Three of three adenocarcinomas of the pancreas showed staining. Among the remaining neoplasms examined, one specimen each of carcinoma of the prostate and the cervix and one carcinoma of undetermined primary exhibited staining. Two malignant lymphomas did not stain. Staining of mesothelial cells was observed in three of nine benign effusions.(ABSTRACT TRUNCATED AT 250 WORDS)