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.     

Expression of cytokeratin 19 and protein p63 in fine needle aspiration biopsy of papillary thyroid carcinoma

OBJECTIVE: To analyze the immunocytochemical distribution of CK19 and p63 on archival cytologic smears of 27 papillary thyroid carcinomas (PTCs), 22 benign thyroid lesions and 5 malignant non-PTC lesions. STUDY DESIGN: Archival cytologic smears of 27 papillary carcinomas, 22 benign thyroid lesions and 5 malignant nonpapillary carcinomas were processed for immunocytochemical detection of CK19 and p63, and results were compared. RESULTS: CK19 showed strong cytoplasmic staining in 22/27 fine needle aspiration biopsies (FNABs) of PTCs, in 5 benign lesions and in 4 malignant lesions of the control group. p63 Positivity was present in FNABs of 20/27 PTC and in 1 FNAB of nodular hyperplasia. Eighteen FNABs of PTC (66.6%) showed both strong CK19 staining and p63-positive cells, whereas none of the control cases showed coexpression of CK19 and p63. CONCLUSION: Coexistence of strong CK19 positivity and p63-positive cells can enhance the cytologic diagnosis of PTC.     

Detection of benign or malignant origin of ascites with combined indirect immunoperoxidase assays of carcinoembryonic antigen and lysozyme

The indirect immunoperoxidase method was used to study the presence of the intracellular carcinoembryonic antigen (CEA) and lysozyme (LZ) in alcohol-fixed cytologic smears of peritoneal fluids from 2 patients with chronic active hepatitis, 31 patients with liver cirrhosis and 7 patients with malignant liver disease. In the two patients with hepatitis, LZ was positive in both CEA was positive in one and negative in the other. Of the 31 patients with liver cirrhosis, 21 (67.5%) were LZ positive, 27 (87%) were CEA negative and only 4 (13%) were CEA positive. Of the seven patients with malignant disease, six were CEA positive and six were LZ negative. It is of interest that 23 of 24 (96%) LZ-positive results and 28 of 29 (97%) CEA-negative results corresponded to negative cytologic diagnoses for malignancy. Cytologic diagnosis of "reactive mesothelial cells" seemed to correlate better (71%) with CEA-negative and LZ-positive results. The data suggest that the investigation of CEA and LZ in the cells of peritoneal fluids appears to have promise as an adjunct to cytology in differentiating benign from malignant origins of the fluid.     

Cytology of yolk-sac tumor of the ovary in ascitic fluid. Report of a case

The cytologic, serologic, immunocytochemical and histologic findings of a yolk-sac tumor of the ovary in which the diagnosis was suggested by the cytologic examination of ascitic fluid specimens are reported. The case emphasizes the importance of evaluating, in addition to smears, the cytologic findings of a cell block specimen (which is generally prepared from an effusion) to obtain more diagnostic clues. A preliminary cytomorphologic diagnosis of this highly malignant tumor is valuable as a guide in planning further immunocytochemical and serologic studies.     

Cytologic appearance of carcinosarcoma (malignant ameloblastoma and fibrosarcoma) of the maxilla. A case report.

The cytologic appearance of a carcinosarcoma (malignant ameloblastoma and fibrosarcoma) of the maxilla in a 63-year-old man is described. On his first admission the diagnosis of malignant ameloblastoma was made on biopsy. After five surgical excisions, radiotherapy and chemotherapy, the diagnosis was changed to carcinosarcoma because the stromal cells of the tumor had become malignant. Aspiration biopsy cytology of the tumor, with a cystic lesion found at the left suborbital area, revealed malignant epithelial cells, indicating malignant ameloblastoma. Imprint smears of both surgically resected and autopsy material showed two types of malignant neoplastic cells, of epithelial and mesenchymal origin.     

Usefulness of AgNOR technique and CEA expression in atypical metaplastic cells from cervical smears

OBJECTIVE: To evaluate the proliferating capacity of atypical metaplastic cells in cervical smears by AgNOR technique and image analysis and investigate the probable relation with squamous intraepithelial lesions (SIL) using immunocytochemical assay for carcinoembryonic antigen (CEA). STUDY DESIGN: Eight cervical smears were stained with Papanicolaou stain for diagnosis of atypical metaplastic cells. After removal of the stain the smears were processed with a silver colloidal solution and the AgNOR area determined by image cytometry. Differences in the mean AgNOR protein area between reactive metaplastic cells and controls were tested by Student's t test. The CEA was investigated by immunocytochemical staining in smears with atypical metaplastic cells and smears from high-grade squamous intraepithelial lesions (HSIL). RESULTS: The mean AgNOR areas from atypical metaplastic cells (4.55, 6.66, 4.68, 5.30, 4.97, 6.20, 6.28, and 7.35) were significantly greater those that of intermediate metaplastic cells and cells from low-grade squamous intraepithelial lesions (LSIL) (0.77, 0.99, and 0.82, respectively). The atypical metaplastic cells showed values of mean AgNOR area intermediate between that of basal cells (3.28) and HSIL cells (7.73) or neoplastic cells (16.12). The CEA was strongly expressed by the atypical metaplastic cells. CONCLUSION: The expression of CEA in the atypical metaplastic cells underlies the probable relation to SIL. Although the organizer region areas raised high values, it would be necessary to use a greater number of cases to define whether the AgNOR area is indicative of the proliferative activity of the atypical metaplastic cells.     

Fine needle aspiration cytology of metastatic malignant schwannoma. A case report

A metastatic malignant schwannoma diagnosed by fine needle aspiration (FNA) biopsy in a 56-year-old man is reported. Cytologic examination of smears and cell blocks prepared from aspirates of a vertebral mass suggested the presence of metastases from a previously excised malignant schwannoma on the right leg. Electron microscopic and immunocytochemical studies on the aspirate supported the diagnosis, as did the patient's clinical history and previous pathology and the radiographic demonstration of metastatic lesions in the lung. The cytologic findings (cells with oval-to-spindled nuclei and ill-defined cellular borders suspended within a delicately fibrillar eosinophilic matrix) are discussed in light of the histologic diversity of this lesion and the problems of distinguishing it from other sarcomas. The ability to diagnose metastatic malignant schwannoma by FNA emphasizes the value of this technique.     

Abrasive bronchial brushing cytology. A preliminary study of 200 specimens for the diagnosis of neoplastic and nonneoplastic bronchopulmonary lesions

Two hundred subjects with chronic respiratory symptoms with a suspicion of malignancy were selected for bronchial brushing cytology. Prior sputum examination had shown malignant squamous cells in two cases only. The cytologic appearances of the brushing smears were divided into five categories: 41 (20.5%) smears with positively malignant cells; 20 (10%) smears predominantly showing chronic inflammatory features; 31 (15.5%) smears with mainly acute inflammatory changes; 60 (30%) smears with normal cytologic features; and 48 (24%) smears unsatisfactory for cytologic interpretation. Thirteen patients with a positive cytology had a positive tissue biopsy for malignancy. Among the group with chronic inflammatory changes, acid-fast bacilli were identified in nine cases, and one smear showed frank tuberculous granuloma. In the unsatisfactory group, two cases showed malignant cells in the postbrushing sputum. There was one false-negative report for malignancy in the entire study. This study confirms the sensitivity and accuracy of bronchial brushing cytology in the diagnosis of various bronchopulmonary lesions, especially malignancy and pulmonary tuberculosis, in India.     

Decisive role of intermediate filament typing of tumor cells in the differential diagnosis of difficult fine needle aspirates

Thirty-six diagnostically difficult fine needle aspirates from enlarged lymph nodes and malignant soft tissue tumors, containing tumor cells with scanty or no obvious light microscopic features indicative of their differentiation, were assessed by a panel of six cytopathologists. Their diagnoses were recorded and then compared with the definitive diagnosis established by combining the cytologic findings with the results of intermediate filament typing of tumor cells in the smears using monoclonal antibodies specific for each filament type. The results show that use of these antibodies can markedly improve the accuracy of the cytologic diagnosis of tumor type as well as revise or prevent erroneous cytologic diagnoses in difficult cases. This pertains especially to the differential diagnoses of carcinoma versus malignant lymphoma, carcinoma versus malignant melanoma, carcinoma versus sarcoma and squamous carcinoma versus carcinoma of simple epithelia. Intermediate filament typing of tumor cells in aspirates as an objective histogenetic criterium makes the differential diagnosis of the difficult aspirates much more reliable and reproducible, provided that appropriate questions are asked, monoclonal antibodies with well-defined specificities are used and the antigenicity of the intermediate filaments in smears is preserved.     

Bronchial cytology in pleural mesothelioma. A report of 3 positive cases, including 1 diagnosed initially on bronchial brushings

OBJECTIVE: To evaluate retrospectively the value of bronchial aspiration cytology in patients with histologically proven pleural mesothelioma, reappraising positive smears in light of conventional microscopic features and, when feasible, immunocytochemical investigations. STUDY DESIGN: In 3 cases of mesothelioma with bronchial brushings positive for malignant cells, the cytologic features were correlated with the histologic findings. RESULTS: Salient microscopic features included scant to moderate cellularity arranged in micropapillary clusters, morular aggregates with scalloped borders and isolated malignant cells. Intercellular clear spaces or windows suggesting a brush border on cell membranes were also noted. In cases with available material, immunocytochemistry was positive for keratins, epithelial membrane antigen and calretinin and negative for carcinoembryonic antigen. All the cases were histologically confirmed epithelial mesotheliomas. CONCLUSION: In rare cases, pleural mesothelioma cells are shed within the airway lumina and can be detected in bronchoscopic cytology specimens. Cytologic features seem comparable to their analogues in pleural effusions. Although no single criterion appears diagnostic, their combined documentation could ensure correct interpretation, especially if supported by a limited immunocytochemical panel.     

Characterization of the epithelial components in pleomorphic adenoma of the salivary gland

OBJECTIVE: To clarify the cytomorphologic characteristics of luminal epithelial cells (LEC) and neoplastic myoepithelial cells (NMC) in pleomorphic adenoma (PA). STUDY DESIGN: Imprint cytologic smears stained with Papanicolaou stain were examined in 20 patients with PA (including recurrent cases). Immunocytochemistry was performed using the antibodies of epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA); cells positive for both CEA and EMA were interpreted as LEC and those negative as NMC. RESULTS: LEC were found in 9 of 20 cases as cell clusters in various shapes or as isolated cells with ample cytoplasm. NMC were classified into four types according to their visual patterns and cytoplasmic features: type A, isolated cells with ample cytoplasm; type B, isolated naked cells; type C, cluster of cells with ample cytoplasm; and type D, cluster of cells with scant cytoplasm. NMC were found in all 20 cases, with an absolute incidence of 100%, 90%, 65% and 50%, respectively. CONCLUSION: The different features of NMC (Types A-D) are essential to a specific differential diagnosis. This classification was useful to discriminate PA from other salivary gland tumors with NMC.     

The value of the immunoperoxidase slide assay in the diagnosis of malignant pleural effusions in breast cancer

Whether immunocytochemical studies of malignant pleural effusions due to breast cancer would increase the diagnostic yield as compared with conventional effusion cytology was examined in 30 cases with biopsy-proven metastatic spread to the pleura. Conventional cytology was performed on air-dried smears as well as on cytocentrifuge preparations stained with the May-Grünwald-Giemsa stain. Immunocytochemistry was performed with monoclonal antibodies against carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and human leukocyte antigen (HLA) and the peroxidase-antiperoxidase technique on glass slides after Ficoll-Hypaque centrifugation. By conventional cytology, 13 cases (43%) were positive for malignant cells, 6 cases (20%) were suspicious, and 11 cases (37%) were negative. In marked contrast, all 30 cases were immunocytologically positive for malignancy. Tumor cells in all cases demonstrated a positive reaction for EMA. Some mesothelial cells were also positive for EMA, but their reaction pattern was clearly distinguishable from that of the tumor cells. Twenty-one cases (70%) also showed CEA-positive tumor cells; mesothelial cells never reacted with CEA. Some tumor cells showed a loss of HLA expression. In conclusion, this immunocytologic method can be recommended as a routine procedure for greatly increasing the diagnostic yield of cytology in pleural effusions due to breast cancer.     

Fine needle aspiration biopsy of primary malignant fibrous histiocytoma of the lung

Malignant cells were found on the fine needle aspiration (FNA) biopsy smears from a primary tumor of the lung. The cytologic specimen contained a mixture of fibroblastlike cells, histiocytelike cells, giant cells and undifferentiated cells; mitotic figures were also found. Histologic, histochemical and electron microscopic studies confirmed the FNA cytologic suggestion of a primary malignant fibrous histiocytoma of the lung.     

Scratch cytologic findings on surgically resected solitary fibrous tumors of the pleura

OBJECTIVE: To ascertain the cytologic characteristics of solitary fibrous tumors of the pleura (SFTPs) on smear preparations. STUDY DESIGN: Fine needle aspiration cytology (FNAC) was initially attempted preoperatively in five cases, but the specimens were inappropriate for interpretation because only a few tumor cells were obtained. Therefore, scratch smears made at the time of operation were used. Papanicolaou and immunocytochemical staining was performed in all 10 cases, 2 of which were malignant. RESULTS: As expected, cellular tumors yielded more cells. The cytologic appearance was variable, showing spindle/bipolar, dendritic/stellate and intermediate cells. Atypical cells reminiscent of sarcoma were also present in cellular, benign tumors. Highly atypical epithelioid cells were obtained in two malignant cases. Immunocytochemically, the tumor cells were positive for CD34 and vimentin and negative for cytokeratin, regardless of histologic differences and cell shape. CONCLUSION: It seems difficult to diagnose SFTPs with certainty by FNAC, partly because the cell morphology of SFTPs resembles a wide variety of heterogeneous groups of spindle cell tumors and partly because only a few tumor cells were available in the FNAC specimens in the present study. However, a cytologic diagnosis of SFTP is possible if cytologic preparations yield CD34-positive cells with spindle/bipolar or dendritic/stellate morphology.     

Diagnosing endometrial carcinoma with cervical involvement by cervical cytology

OBJECTIVE: To assess the relationship of a cervical cytologic diagnosis based on number, size and degeneration of malignant clusters and necrotic background to cervical involvement of endometrial carcinoma. STUDY DESIGN: Cervical smears of 53 women with endometrial carcinoma were evaluated for cervical involvement. The cytologic diagnosis was compared with actual involvement, and accuracy was calculated. Retrospectively, cytologic features, including number, size and degeneration of malignant clusters and necrotic background, were analyzed in involved and noninvolved cases. RESULTS: Cervical involvement was confirmed in 15 patients (28.3%). The number and size of malignant clusters in the involved cases were significantly larger than those in the noninvolved cases (P < .001 and < .01, respectively). The proportion of degenerated malignant cells and necrotic background in involved cases were significantly higher than those in noninvolved cases (P < .05). Cytologic diagnosis had a sensitivity and specificity of 62.5% and 86.8%, respectively. CONCLUSION: Cervical smears of involved cases revealed a large number and large size of malignant clusters. These findings support cytologic diagnosis based on number, size and degeneration of malignant cells and necrotic background. Cervical cytology is useful to exclude cervical involvement because of its high specificity and can help detect cervical involvement because of its moderately high sensitivity.     

Cytology of vaginal and uterine sarcomas

OBJECTIVE: To retrospectively review, based on cytologic and histopathologic findings, the diagnoses of 13 patients with uterine sarcoma and 1 with vaginal sarcoma. STUDY DESIGN: There were 8 cases of uterine carcinosarcoma (CS), 2 of leiomyosarcoma, 2 of endometrial stromal sarcoma (ESS), 1 of endocervical stromal sarcoma (ECSS) and 1 of malignant fibrous histiocytoma (MFH) of the vagina. The presence of sarcomatous components was retrospectively investigated by microscopic observation of preoperative specimens from the endocervical canal and endometrial cells. Characteristic features of sarcomatous cells were then investigated by cytodiagnostic micrometry of malignant cells. RESULTS: Of the 14 patients, 1 with low grade ESS and 1 with homologous CS were diagnosed as negative for sarcomatous components. One case of high grade ESS had been overlooked, as were 4 cases of CS. Thus, 7 cases (50%) were diagnosed as positive for sarcomatous cells by preoperative cytologic observation. Based on these findings, 12 of the 14 cases (85.7%) were positive for sarcomatous elements on retrospective reexamination of the specimens. CONCLUSION: Careful attention should be paid to small sarcomatous cells since cases of ESS or ECSS with such cells show morphologic characteristics similar to those of stromatous cells. Furthermore, careful microscopic observation of an entire specimen is required to avoid misdiagnosis as carcinoma since it is easy to overlook sarcomatous elements in smears with carcinosarcoma if there are only a few sarcomatous cells.     

Parotid metastasis of Merkel cell carcinoma in a young patient with ectodermal dysplasia. Diagnosis by fine needle aspiration cytology and immunocytochemistry.

Fine needle aspiration (FNA) biopsy was performed on an intraparotid lymph node metastasis of a Merkel cell carcinoma of the eyelid in a 15-year-old girl with antecedent ectodermal dysplasia syndrome. The cytologic appearance of the aspirate and the results of immunocytochemical typing of intermediate filaments on the FNA smears provided a definitive diagnosis. The Romanowsky stain provided an excellent delineation of paranuclear intracytoplasmic "buttons," which appeared to contain both cytokeratin and neurofilaments by immunocytochemical studies. These findings confirm previous data emphasizing the role of light microscopic observations, supplemented by proper immunocytochemical investigations, in the differential diagnosis of metastatic Merkel cell carcinoma in fine needle aspirates.     

Carcinoembryonic antigen content in fine needle aspirates of the lung. A diagnostic adjunct to cytology.

Carcinoembryonic Antigen (CEA) was measured in 59 consecutive fine needle aspirates (FNAs) of the lung from 58 patients to determine if the CEA content would enhance the sensitivity of the cytologic diagnosis. Twenty-eight males and 30 females with tumors 1-40 cm in diameter were studied. Final diagnoses were correlated with the clinical history, radiologic studies, tissue (when available) and follow-up. Image-guided FNAs were performed by radiologists using a 22-gauge Chiba needle and 20-mL syringe with one to four passes per specimen. Cytologic examination included rapid assessment in the radiology suite and a final diagnosis in 24 hours. CEA was measured by enzyme immunoassay using monoclonal antibody. Nine benign aspirates and 50 malignant aspirates were diagnosed. The sensitivity of cytology was 86% and specificity, 100%. Using 5 ng/mL as the cutoff, the sensitivity of CEA for malignant aspirates was 50% and specificity, 90%. The combined sensitivity of CEA and cytology was 95%. The mean CEA in malignant aspirates was 131 ng/mL and in benign aspirates, 2.41. The highest mean CEA was seen in adenocarcinoma, 402.6 ng/mL. Lower CEA content was seen in epidermoid carcinoma (58.6 ng/mL), large cell carcinoma (8.09), oat cell carcinoma, metastatic carcinoma of the kidney and breast, thymoma and lymphoma (each less than 1 ng/mL). Elevated CEA alone was diagnostic in two aspirates of bronchioloalveolar carcinoma; carcinoma with an unknown primary source, three; and large cell carcinoma, one. The adjunctive use of CEA in FNAs of the lung enhances the sensitivity of the cytologic diagnosis.     

Cytologic features of metanephric adenoma of the kidney during pregnancy: a case report

BACKGROUND: Metanephric adenoma (MA) is a relatively rare neoplasm derived from metanephric blastema and composed of well-differentiated epithelial nephroblastic cells. In view of its invariably benign clinical outcome, a preoperative diagnosis of this tumor could be of critical importance. Since computed tomography and ultrasound imaging are not per se sufficient to unequivocally distinguish between MA and malignant neoplasms, fine needle aspiration cytology (FNAC) could be the only accurate method to establish a preoperative diagnosis of this tumor. However, cytologic appearance of MA is not well characterized. CASE: A 33-year-old pregnant woman presented with erythrocytosis. Transabdominal ultrasound examination disclosed a mass in her left kidney. FNA smears showed small, uniform cells with bland nuclei arranged in compact acinar and follicular structures; immunocytochemical staining revealed a diffuse, positive reaction for CD57, WT-1 and vimentin, and epithelial membrane antigen and alpha-methylacyl-CoA racemase yielded negative results. These cytologic and immunocytochemicalfindings led to a preoperative diagnosis of MA. After delivery, the diagnosis was confirmed on the surgical specimen. CONCLUSION: A diagnosis of MA could be established by FNAC supported by immunocytochemical analysis. The present case illustrates the clinical impact that this diagnosis could have on patient management.     

Cytology of recurrent ameloblastoma with malignant change. A case report

BACKGROUND: Ameloblastoma is a rare tumor of the jaw that arises from the odontogenic epithelium. Ameloblastomas have a propensity for local recurrence and, rarely, for metastasis. The term malignant ameloblastoma is reserved for those metastasizing tumors that retain the typical morphology of ameloblastoma. Fine needle aspiration (FNA) reports on ameloblastomas are scant, and those on malignant ameloblastomas are still more so. CASE: In a case of malignant ameloblastoma diagnosed by FNA cytology, the clinical presentation was that of a malignant neoplasm. FNA smears were highly cellular and showed isolated, scattered cells and small groups of basaloid cells and polygonal squamous epithelial cells. Stellate and spindle-shaped cells were also seen in the background. The cytologic diagnosis was subsequently confirmed on histopathology. CONCLUSION: The characteristic combination of cells in FNA smears facilitated the diagnosis of ameloblastoma. Since the biologic behavior of the tumor was that of a malignant neoplasm, the slides were reviewed. The cytologic smears did not exhibit sufficient features of malignancy to label the lesion malignant.