Cytology of peritoneal washings in gynecologic patients. Diagnostic criteria and pitfalls

A total of 226 peritoneal washing specimens obtained from gynecologic patients over a three-year period was reviewed. The diagnostic problems encountered were: differentiating reactive mesothelium from low-grade malignancies; distinguishing between benign ovarian tumors, ovarian tumors of borderline malignancy and low-grade ovarian malignancies; and potential false-positive diagnoses in endometriosis. Low-grade malignancies could be distinguished from reactive mesothelium by evaluating subtle cytologic criteria and by comparing the cells to those of the tumor on histologic section. The differentiation of low-grade epithelial malignancies from benign epithelial lesions caused difficulties that could only be resolved by evaluating the histologic material. Positive peritoneal washings increased the stage in 8 of 110 patients undergoing initial surgery for gynecologic malignancy. Two of 76 patients undergoing a second-look laparotomy had positive washings without histologic evidence of tumor. These ten patients did less well than did those with similar histology but negative washing cytology, despite receiving additional therapy because of the cytologic findings.     

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.     

Complementation of expression of carcinoembryonic antigen and tumor associated glycoprotein-72 (TAG-72) in human colon adenocarcinomas.

Enzyme-labeled monoclonal antibodies (MAbs) were used in an immunohistochemical, dual-staining study of 10 colon adenocarcinomas. MAbs B72.3 and COL-4, reactive with the high molecular weight tumor-associated glycoprotein-72 (TAG-72) antigen and carcinoembryonic antigen (CEA), respectively, were labeled with horseradish peroxidase or alkaline phosphatase. Dual staining using the two MAbs on a single tissue section (formalin-fixed, paraffin-embedded) showed that greater numbers of carcinoma cells could be detected by using the combination of the two MAbs than could be detected by use of either MAb alone. In many tumors, some carcinoma cells reacted with MAb B72.3, some reacted with MAb COL-4, and some cells reacted with both MAbs. Only 1 of 10 carcinomas showed greater than 75% reactive cells when stained with each MAb individually. In 9 of 10 cases, however, greater than 75% of cells reacted when the combination of MAbs was used. Cell surface and cytoplasmic patterns of reactivity were observed with both MAbs while some pools of extracellular mucin were composed of both TAG-72 and CEA. This study supports the rationale for the use of a combination of anti-TAG-72 and anti-CEA MAbs for in vitro immunologic detection and potential in vivo immunodiagnostic and immunotherapeutic applications for these MAbs in colon adenocarcinoma patients.     

In vivo and in vitro clinical applications of monoclonal antibodies against TAG-72

Monoclonal antibodies against a tumor-associated antigen (TAG-72) with mucin-like properties have been generated. MAb B72.3 was used to identify and help characterize this antigen. B72.3 has been successfully used for the localization of tumor metastases in situ after i.v. administration. MAb B72.3 has also been used in conjunction with CC49, another anti-TAG-72 MAb, to measure TAG-72 levels in sera and effusions. TAG-72 can be found in the fluids of patients with adenocarcinomas from many different sites. This CA 72-4 double determinant radioimmunoassay in conjunction with assays for carcinoembryonic antigen can identify patients with malignancies with greater sensitivity than either assay alone.     

The use of monoclonal antibody B72.3 in the management of gynecologic malignancies

Monoclonal antibodies are currently used in the diagnosis of gynecologic malignancies by way of immunohistochemical assays, serum assays, and in situ radiolocalization of carcinoma lesions. Among them is MAb B72.3, generated against a human tumor-associated antigen (TAG-72). Using immunohistochemical techniques, MAb B72.3 has shown reactivity with 100 percent of common epithelial ovarian carcinomas and endometrial carcinomas and non-reactivity with normal adult tissues, with the exception of normal secretory endometrium. B72.3 appears to be a valuable immunocytologic adjunct, with greater than 90 percent of effusions and fine-needle aspiration biopsies from gynecologic carcinomas showing reactivity. Using a serum assay developed to detect the presence of the TAG-72 antigen, 48 percent of patients with ovarian carcinoma demonstrated TAG-72-positive sera versus 1 percent of control sera. 131I-labeled MAb B72.3 IgG and gamma scanning have been used for the in situ detection of metastatic carcinoma. Twelve of 15 patients with ovarian carcinoma showed positive gamma scans, and approximately 80 percent of the lesions demonstrated specific localization of the antibody. These studies indicate the potential utility of MAb B72.3 in the diagnosis of gynecologic carcinoma.     

Cytohistologic correlation of peritoneal washing cytology in gynecologic disease

The peritoneal washings and cul de sac aspirates from 204 patients undergoing 217 procedures for the evaluation of gynecologic disease were examined retrospectively and correlated with the histologic diagnoses. Of the 73 washings from patients with histologically benign genital disease, cytology diagnosed 64 (87.7%) as negative, 6 (8.2%) as inconclusive and 3 as malignant. One malignant washing was a true positive from a nongenital primary. False positives thus occurred in 2.7% of the benign cases on blind review. Of 144 cytologic examinations of washings from patients with histologically confirmed malignant disease of the female genital tract, 38 (26.4%) were considered positive after cytohistologic correlation. Four malignant cases (2.1%) were undercalled on blind review while 3 (2.0%) were considered overcalls. Eleven of 47 cases (23.4%) with biopsy-proven peritoneal disease had negative cytology after histologic correlation. Recurring problems in interpreting peritoneal washings included: (1) the differential diagnosis of the spectrum encompassed by reactive mesothelium, endosalpingiosis, borderline serous tumors and well-differentiated serous cystadenocarcinoma; (2) morphologic similarities between some tumor cells and mesothelial cells associated with treatment effects; and (3) a paucity of malignant cells in some washings, resulting in false-negative interpretations. Ineffective cytopreparation, particularly of bloody specimens, hampered interpretation of some specimens. Correlation with previous histology and cytology enhanced the accuracy of peritoneal washing cytology in this study.     

Peritoneal washings in ovarian tumors. Potential sources of error in cytologic diagnosis

Peritoneal washings were performed on 48 patients with suspected or known ovarian carcinoma. The procedure was part of the initial surgical staging in 27 patients with presumed stage I and II ovarian cancer and was performed during second-look operations in 21 other cases with proven ovarian malignancy. This paper presents the microscopic features of the washings, with particular emphasis on the cytologic differentiation between benign and malignant findings outside of the ovary. Thirty-four cases showed benign or reactive mesothelial cells and no evidence of peritoneal disease. The washings of six patient showed malignant cells, which were confirmed histologically. Notable atypia that mimicked ovarian carcinoma was found in eight patients who had benign or borderline lesions. These findings included papillary and glandlike epithelial structures, with varying degrees of cellular atypia and psammoma bodies. The histologic counterparts of these atypicalities were Müllerian inclusions, mesothelial proliferations and borderline serous tumors. The differential diagnosis between these entities is essential because false-positive cytologic diagnoses may alter postoperative treatment in some patients.     

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.     

Diagnostic value of CA 15-3 antibody in detecting metastatic adenocarcinoma

OBJECTIVE: To determine the diagnostic value of CA 15-3 in detecting metastatic adenocarcinoma in body fluids using PreservCyt solution (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) as collection fluid. STUDY DESIGN: Cytospin slides prepared from 72 cases with unequivocally benign or malignant diagnosis were studied. Of the cases studied, 34 were breast carcinomas, and 17 were benign pleural effusions. Slides were stained for CA 15-3 by using the avidin-biotin complex method. Cases were evaluated for the presence of membranous or cytoplasmic staining. The percentage of cells exhibiting strong staining was estimated for both breast carcinoma and all adenocarcinomas as a group. These results were compared with CA 15-3 staining exhibited by benign mesothelium. RESULTS: Ninety-one percent of the breast cancer cases studied showed a positive reaction with CA 15-3, while 6% of the benign mesothelium cases were positive (p < 0.01). The sensitivity of CA 15-3 was 91 % for breast carcinoma and 80% for all adenocarcinomas. Specificity was 94% for breast carcinoma and for all adenocarcinoma. CONCLUSION: CA 15-3 is a sensitive and specific marker for diagnosing adenocarcinoma in cytologic specimens using PreservCyt solution as collection fluid.     

Role of biliary brush cytology in primary sclerosing cholangitis

OBJECTIVE: To assess the role of brush cytology in the routine evaluation of patients with primary sclerosing cholangitis (PSC). STUDY DESIGN: From January 1995 to June 2000, 64 brush cytology specimens were obtained from 21 patients who had at least one cytologic sample obtained during endoscopic retrograde cholangiography. All patients had a diagnosis of primary sclerosing cholangitis. Cases were classified as benign, atypical or malignant according to major cytologic criteria (nuclear contour and chromatin irregularities) and minor cytologic criteria (polarity, cellularity, nuclear enlargement, mitosis, increased nuclear/cytoplasmic ratio) used by us to diagnose biliary brush cytology. Follow-up was available in all cases. RESULTS: Diagnoses were benign (13), atypical (5) and malignant (3) on cytology. Follow-up of the 13 benign cases showed bile duct stones (2), gallbladder adenocarcinoma at cholecystectomy (1), ascending cholangitis (1) and clinically/cytologically by benign follow-up (9). Five of 13 benign cases had subsequent liver transplantation for liver failure, with explants showing changes of primary sclerosing cholangitis. Of the 3 malignant cases, 1 had carcinoma in situ on biopsy, with the explanted liver showing high grade dysplasia; the second patient had cholangiocarcinoma on explant; and the third had hepatocellular carcinoma on liver five needle aspiration. The 5 patients with atypical cytology were reclassified on review as reactive (3) and atypical not otherwise specified (2). Follow-up showed benign disease in 3 of 3 atypical cases reclassified as reactive; 2 of 2 reclassified as atypical not otherwise specified showed low grade dysplasia in the explant. CONCLUSION: The overall incidence of malignancy was low (3 of 21) in patients with PSC. Bile duct brushing is a sensitive method of detecting neoplasia in the setting of PSC when well-defined cytologic criteria are applied.     

Immunocytochemical characterization of large-cell carcinomas of the lung. Role, limitations and technical considerations.

To clarify the use of cytologic preparations, particularly those previously stained by the Papanicolaou method, for the immunocytochemical evaluation of large-cell carcinomas (LCCs), 37 cytologic preparations from cases diagnosed as LCC were examined using a battery of immunocytochemical stains for keratin, chromogranin, common leukocyte antigen (CLA) and B72.3. Thirty-two specimens were from the thoracopulmonary region (12 fine needle aspirates of the lung, 7 bronchial brushings, 5 bronchial washings, 2 sputa and 6 pleural fluids); the remaining specimens were fine needle aspirates of 3 lymph nodes, 1 vertebral body and 1 liver. Of the specimens analyzed, 30 of 37 were positive for keratin and 7 of 35 were positive for B72.3 (6 were positive for both). Only 1 of 37 was positive for CLA while none of 37 was positive for chromogranin. Six specimens showed no reaction with either keratin, B72.3 or chromogranin. These results confirm that the majority of LCCs consist of epithelial cells of either a squamous or an adenocarcinomatous type. They also show that immunocytochemistry is a useful diagnostic adjunct that can be applied to cytologic preparations previously stained by the Papanicolaou method; this is important since immunostaining is often considered after undifferentiated malignant cells are encountered in a previously stained preparation. However, a thorough understanding of some technical limitations is critical in the evaluation of the results of this technique when it is applied to cytologic specimens.     

Diagnostic utility of GLUT-1 expression in the cytologic evaluation of serous fluids

OBJECTIVE: To evaluate the extent to which adenocarcinomas in body cavity fluids express GLUT-1 in comparison to currently available markers for adenocarcinomas. STUDY DESIGN: Archival paraffin-embedded cell blocks of serous fluids from 25 cases of benign effusions containing reactive mesothelial cells and 39 cases of malignant effusions with metastatic adenocarcinoma (11 ovarian, 11 pulmonary, 9 gastrointestinal and 8 breast) were retrieved from the surgical pathology files. All cases were stained with antibodies for GLUT-1, Ber-Ep4, B72.3 and CEA. Positive staining was defined as distinct linear membrane staining for GLUT-1 and Ber-EP4, cytoplasmic staining for CEA, and cytoplasmic or membrane staining for B72.3. Strong staining in at least 10% of the tumor cells was required in order to consider the case positive for the particular marker. RESULTS: GLUT-1 was expressed in 72% (28 of 39) of cases of malignant effusions: 100% (11 of 11) from the ovary, 91% (10 of 11) from the lung, 67% (6 of 9) from the gastrointestinal tract and 12% (1 of 8) from the breast. None (0 of 25) of the benign effusions expressed GLUT-1. Malignant effusions expressed CEA in 74% (29 of 39), Ber-Ep4 in 85% (33 of 39), and B72.3 in 62% (24 of 39). Benign effusions expressed CEA in 3 cases and B72.3 in 2 cases. CONCLUSION: GLUT-1 is a useful marker that can be applied to cytologic specimens. It can be used as a reliable component of an antibody panel to distinguish reactive mesothelial cells from metastatic adenocarcinoma in particular adenocarcinomas of body cavity effusions, in particular adenocarcinomas of ovarian and pulmonary origin.     

Identification of carcinoma cells in ascitic and pleural fluid. Comparison of four panepithelial antigens with carcinoembryonic antigen.

The cell membrane antigens epithelial membrane antigen (EMA), epithelial glycoprotein 34, (egp34), BW-495 and tumor-associated antigen 72 (TAG-72) are present in most benign and malignant epithelial cells and can be demonstrated with the help of monoclonal antibodies. In a study on the identification of carcinoma cells in samples of ascitic and pleural fluid involving 170 patients, we compared the value of immunocytochemical labeling of these antigens with that of immunocytochemical demonstration of carcinoembryonic antigen (CEA). Antibodies to EMA and egp34 occasionally also reacted with reactively proliferating mesothelial cells in benign conditions and thus appear to be inappropriate for diagnostic use. Cells positive for BW-495, TAG-72 and CEA, however, have never been found in benign conditions; the specificity of these antigens thus permits their use in diagnosis. Antigen-expressing cells were found in 85% (BW-495), 62% (TAG-72) and 60% (CEA) of cytologically positive samples from carcinoma patients. Similarly, positive reactions for BW-495, TAG-72 and CEA were observed in, respectively, 36%, 29% and 34% of cytologically negative or suspicious samples. BW-495 thus appears to be a suitable marker for the demonstration of carcinoma cells in samples of pleural and ascitic fluid and to have a higher degree of sensitivity than does either TAG-72 or CEA.     

Morphologic and immunocytochemical studies of bronchioloalveolar carcinoma at Duke University Medical Center, 1968-1986

Between 1968 and 1986, the tumor registries at Duke University Medical Center and Durham VA Medical Center accumulated a total of 193 patients with a diagnosis of bronchioloalveolar carcinoma (BAC). All available histologic sections of primary lung tumors and all available respiratory and pleural cytologic material were reviewed for 135 cases having an initial histologic diagnosis of BAC and no history of a primary nonpulmonary adenocarcinoma. Thirty-nine cases showed a pure BAC pattern in histologic sections; 76 showed a dominant BAC pattern with focal areas of fibrosis and acinar differentiation; 16 were carcinomas with a focal BAC pattern; and 4 were adenocarcinomas lacking a BAC pattern. Of the 115 cases with at least a dominant BAC pattern, 51 showed predominantly mucinous differentiation while 64 showed predominantly nonmucinous differentiation. Adequate cytologic material was available for review from 111 patients. For cases having at least a dominant BAC pattern, tumor cells were present in 77 of 172 adequate sputums (44.8%), 36 of 133 bronchoscopy specimens (27.1%), 15 of 18 needle aspirates (83.3%) and 14 of 15 pleural fluids (93.3%). Of all patients in this group, 60.2% had at least one specimen positive for malignancy. No cytologic features clearly distinguished adenocarcinomas having only focal bronchioloalveolar differentiation from those with a pure or dominant BAC pattern. A significant degree of overlap was observed in the cytologic features of mucinous and nonmucinous tumors. Histologic sections from 19 mucinous and 16 nonmucinous tumors were stained with monoclonal antibody B72.3: all showed some staining, with no significant difference in degree of staining between the two groups. This suggests that expression of the tumor-associated glycoprotein TAG-72 is independent of mucinous differentiation.     

Atypical glandular cells of undetermined significance favor endometrial origin. Criteria for separating low grade endometrial adenocarcinoma from benign endometrial lesions

OBJECTIVE: To evaluate cytologic criteria for separating atypical glandular cells of undetermined significance favor endometrial origin (AGUS-EM), on Papanicolaou-stained (Pap) smears into favor benign and favor malignant categories. STUDY DESIGN: All patients who had a Pap smear diagnosis of AGUS-EM, not further qualified, followed by tissue follow-up were identified from the surgical pathology and cytopathology files from January 1992 through December 1996. The Pap smears were scored blindly for the presence or absence of 40 cytologic criteria, and univariate analysis was performed to determine which criteria were most indicative of malignancy by tissue follow-up. RESULTS: The presence of an atrophic smear, nuclear size greater than twice that of an intermediate cell nucleus and absence of clusters with irregular borders were highly indicative of adenocarcinoma, although other criteria were also helpful in identifying malignancy. CONCLUSION: There are no combinations of cytologic criteria that definitely separate AGUS-EM cases into those with benign or malignant findings on follow-up. However, some isolated criteria were useful in the differential diagnosis in a [table: see text] significant number of cases.     

Stereotaxic fine needle aspiration cytology of clinically occult malignant and premalignant breast lesions

Stereotaxic fine needle aspiration (FNA) cytology was used to study clinically occult (nonpalpable) breast lesions in 114 consecutive patients with mammographically suspicious findings prior to excisional biopsy. The aspirate contained insufficient material for cytologic evaluation in 15 cases (13.2%), which were histologically diagnosed as benign (7 cases), atypical hyperplasia (7 cases) or carcinoma in situ (1 case). The cytologic findings indicated a benign lesion in 77 cases (67.5%), which were histologically diagnosed as benign (71 cases) or atypical ductal hyperplasia (6 cases). The cytologic sample showed atypia in eight cases (7.0%), which were histologically diagnosed as severe atypical ductal hyperplasia (three cases), carcinoma in situ (one case) or proliferative fibrocystic disease (four cases). In the eight cases (7.0%) cytologically interpreted as probably malignant, histology confirmed six invasive carcinomas, one carcinoma in situ and one fibrocystic disease. Of six cases (4.4%) cytologically reported as malignant, five were histologically diagnosed as invasive carcinoma and one as carcinoma in situ. Overall, stereotaxic FNA cytology reported as malignant or probably malignant 14 of the 15 cases with a histologic confirmation of malignancy, for a sensitivity of 93.3%. Cytology correctly identified 78 of the 83 histologically negative cases, for a specificity of 94.0%. The 16 cases histologically diagnosed as ductal hyperplasia, which carries a high risk for subsequent malignancy, were studied in detail in an effort to define histologic and cytologic criteria for this entity. Using selected histologic criteria, 11 of these cases were graded as showing mild-to-moderate atypical hyperplasia and 5 as showing severe atypical hyperplasia. Three of the latter cases were similarly identified by an analogous cytologic grading; the other two cases had insufficient cytologic samples. The total results in this series of 114 cases support the use of stereotaxic FNA cytology in the diagnosis of these nonpalpable breast lesions, examples of which are illustrated. In particular, it may help to raise the low specificity yielded by mammography alone, which would represent a significant advance for the patient in terms of the accuracy, expediency and reduced cost of diagnosing these lesions.     

Significance of immunocytochemical expression of E-cadherin, N-cadherin and CD44 in serous effusions using liquid-based cytology

OBJECTIVE: To assess the diagnostic utility of E-cadherin (E-cad), N-cadherin (N-cad) and CD44 to discriminate adenocarcinoma cells from benign and malignant mesothelial cells in body cavity fluids and to clarify the origin of cancer cells. STUDY DESIGN: A total of 120 ThinPrep (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) cytologic specimens of serous effusions, which included 22 cases of reactive mesothelium, 6 cases of malignant mesothelioma and 92 cases of metastatic adenocarcinoma from various sites, were immunostained for E-cad, N-cad and CD44. RESULTS: Eighty-three of 92 metastatic adenocarcinomas (90.21%) expressed E-cad, while 1 of 6 malignant mesotheliomas and 1 of 22 cases of reactive mesothelium were positive for E-cad. All 6 cases of mesothelioma expressed N-cad, whereas most cases of metastatic adenocarcinomas were negative. CD44 immunoreactivity was seen in 18 of 22 (81.81%) benign effusions and in 21 of 92 (22.82%) metastatic adenocarcinomas. CONCLUSION: The combination of E-cad, N-cad and CD44 appears to be a useful panel for distinguishing metastatic adenocarcinoma, mesothelioma and reactive mesothelium and also for clarifying the exact histogenetic origin of cancer cells. This is of great importance in a few otherwise-insoluble cases because of differences in tumor treatment and prognosis.     

Peritoneal washing cytology in cervical carcinoma. Analysis of 109 patients

The peritoneal washing cytologies of 109 patients (112 procedures) undergoing laparotomy for cervical carcinoma were evaluated retrospectively and compared with the clinical and pathologic findings. Nine patients (8.3%) had malignant peritoneal washings (including three of four with washings initially termed "inconclusive"). Four (4.9%) of the 82 patients with squamous carcinoma and 3 (16.7%) of 18 with adenocarcinoma had positive washings. Five (5.6%) of 90 washings obtained at initial explorations were positive, as compared with 4 (18.2%) of 22 washings obtained as follow-up operations in recurrent cases. The 111 peritoneal washing cytologies with a corresponding histologic evaluation of the peritoneal cavity showed a good correlation; peritoneal washing cytology had an efficiency of 91.0%, a sensitivity of 52.9% and a specificity of 100%. Two cases in which the cytologies were considered positive only after review had negative peritoneal histologies; both patients died of progressive disease within 11 months. Peritoneal washing cytology was positive in 5 (5.9%) of 84 cases with FIGO stage 1 cancers, 2 (18.2%) of 11 cases with stage 2 cancers, 1 (33.3%) of 3 cases with stage 3 cancers, and 1 (10%) of 10 cases with recurrent tumors. Eight (88.9%) of nine patients with malignant peritoneal washings died of disease from 3 to 15 months following surgery; one showed no evidence of disease at 9 months. These results suggest that: (1) cervical carcinomas are infrequently associated with a positive peritoneal washing; (2) peritoneal washing cytology is more likely to be positive in cases of adenocarcinoma than in cases of squamous carcinoma; (3) peritoneal washings obtained at the time of surgery for recurrence are more likely to contain malignant cells than are washings obtained during initial exploration; (4) nonkeratinizing malignant squamous cells may be confused with reactive mesothelial cells; and (5) peritoneal washing cytology is a relatively insensitive technique for detecting advanced cervical disease, but correlates with a poor prognosis when positive.     

Prospective comparative cytologic study of direct peritoneal smears and lavage fluids in patients with epithelial ovarian cancer and benign gynecologic disease

Direct peritoneal samples obtained by scraping or brushing (with a Cytobrush) were compared to peritoneal lavages (washings) for the cytologic evaluation of patients with gynecologic disease. The direct samples were obtained during laparotomy or laparoscopy, following saline lavage if that was performed, and were immediately smeared on glass slides and fixed in 95% alcohol. Only 9 of the direct peritoneal samples taken from 64 patients with benign gynecologic disease were unsatisfactory for cytologic interpretation while 19 of the 33 lavage specimens simultaneously collected from these patients were considered unsuitable for analysis (P less than .001). Two direct smears from cases with benign histology were reported as suspicious. Nineteen patients with epithelial ovarian cancer also had cytologic specimens collected by direct sampling and by washing. The direct smears were positive for malignancy in 12 cases, suspicious in 4 cases and negative in 3 cases while the lavage samples were positive in 9 cases, suspicious in 4 cases, negative in 4 cases and unsatisfactory in 2 cases. These results indicate that direct peritoneal sampling is a simple and reliable alternative to peritoneal lavage and produces a significantly lower incidence of unsatisfactory specimens.     

Different modes of sialyl-Tn expression during malignant transformation of human colonic mucosa

Monoclonal antibodies TKH2 and B72.3, which react with the mucin-associated sialyl-Tn(STn) antigen, preferentially bind to cancerous but not normal colonic tissues. If O-acetyl groups are removed by saponification of tissues, MAb TKH2 will react with normal colonocytes, whereas MAb B72.3 remains non-reactive. To explain this difference in binding specificity, we tested both MAbs against synthetic constructs of single (monomeric) or clustered (trimeric) STn epitopes by enzyme immunoassay. Both MAb TKH2 and MAb B72.3 reacted with trimeric STn, but MAb TKH2 demonstrated greater binding than MAb B72.3 to monomeric STn. This suggests that normal colonic mucosa expresses monomeric STn epitopes, but that with transformation to malignancy, clustered STn epitopes appear. The appearance of clustered STn epitopes during colonic carcinogenesis represents a novel pattern of carbohydrate antigen expression and implicates alterations at the level of apomucins and/or glycosyltransferases responsible for cluster epitope formation.