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.     

Chondroblastoma in fine needle aspirates.

The cytologic features of smears of fine needle aspirates from four chondroblastomas were studied. In an ideal fine needle aspiration biopsy sample of chondroblastoma, all the diagnostic details can be found: chondroid matrix surrounding individual round to oval mononuclear cells, calcifications among cells and multinucleate osteoclasts. Chondroid matrix, which we believe to be the decisive feature, and calcifications are seen better in Giemsa-than in Papanicolaou-stained smears.     

Gynecomastia: cytologic features and diagnostic pitfalls in fine needle aspirates.

OBJECTIVE: To illustrate some of the uncommon cytologic findings of gynecomastia, such as apocrine metaplasia, cellular atypia and foamy macrophages, that can be misinterpreted as evidence of malignancy. STUDY DESIGN: The clinical data and fine needle aspiration (FNA) cytologic material from 100 men with the diagnosis of gynecomastia were retrospectively reviewed. The excisional biopsy slides were available for 16 cases. For comparison, FNA smears from five men with breast lesions other than gynecomastia were studied. RESULTS: The patients ranged in age from 23 to 91 years. Cytologic findings were as follows: cohesive sheets of cells containing 20-1,000 cells (98%); scattered, single, bipolar cells (78%); spindle cells (68%); ductal epithelial atypia (26%); apocrine metaplasia (8%); and foamy histiocytes (12%). In nine cases the atypia was marked, and in two of them the possibility of malignancy could not be ruled out. Surgical follow-up on 16 patients, including the cases with marked atypia, showed gynecomastia. In one case, gynecomastia was associated with intraductal papilloma. No correlation between the underlying etiology and atypical cytologic features of gynecomastia was identified. CONCLUSION: Apocrine metaplasia and epithelial atypia are common findings in gynecomastia. Attention to the cell patterns, the presence of sheets of ductal cells and absence of atypical single cells will point to the correct diagnosis.     

Nucleolar organizer regions in the fine needle aspirates of lung tumours

Nucleolar organizer region associated proteins (AgNOR proteins) have been identified by means of an argyrophil technique in smears of 60 consecutive fine needle aspirates from lung tumours. AgNOR proteins were visualized as silver-positive granules distributed in loose, intranuclear aggregates. Variations in the number as well as differences in the distribution pattern of AgNOR granules were found among different types of tumours. Except for small cell lung carcinoma, the count of AgNOR granules increased when the differentiation of tumours decreased. In particular well differentiated tumours had relatively few AgNOR granules, distributed in cohesive aggregates. Poorly differentiated tumours had many AgNOR granules organized in loose clusters and small cell lung carcinoma had relatively few granules dispersed throughout the nucleoplasm, showing characteristics unique among all lung neoplasms. The application of the AgNOR technique in cyto-preparations is useful in discriminating between small cell and non-small cell lung carcinomas. Moreover, the pattern of distribution of AgNOR proteins may be of diagnostic value in the assessment of tumours displaying overlap in AgNOR counts.     

Immunocytochemistry of fine needle aspirates. A tactical approach

To maximize the potential of immunocytodiagnosis for fine needle aspiration (FNA) samples, it is necessary to be aware of the pitfalls and limitations of these techniques and to formulate a strategy to deal with the many variables involved. Five cases are presented to illustrate some of these variables, which include determining the adequacy of the FNA specimen, selecting tactics for cytologic and immunocytochemical studies, selecting methods for processing the FNA sample, preparing smears to enrich and preserve cells of interest, selecting enzyme labeling methods to optimize sensitivity and specificity, selecting monoclonal antibodies to make the study efficient and pertinent and interpreting the study results. The adequacy of the FNA specimen could be determined by an immediate cytologic assessment of the aspirate as it was obtained. Alcohol-fixed smears and formalin-fixed tissue sections prepared from the aspirate were used for diagnosis; the immunocytochemical studies were used as a diagnostic adjunct for accurate cell identification. Immunocytochemical studies were done on air-dried cytocentrifuge smears of pre-washed cells. While both immunoperoxidase and immunoalkaline phosphatase methods were suitable, we recommend the immunoperoxidase method for the study of aspirates from nonhemopoietic tissues and the immunoalkaline phosphatase method for the study of aspirates with many blood cells present. The proper selection of monoclonal antibodies and the interpretation of the results are best made in the context of the cytologic characteristics of the FNA sample and the clinical features of the patient.     

Amphicrine carcinoma of the lung. Diagnosis by fine needle aspiration cytology

A case of pulmonary carcinoma with dual (glandular and endocrine) differentiation diagnosed by fine needle aspiration cytology is reported. By light microscopy, the neoplastic cells showed mucicarmine, periodic-acid Schiff, and Grimelius silver positivity. On immunostaining, neuron specific enolase, chromogranin, calcitonin and serotonin were demonstrated. Electron microscopy revealed two different types of distinctive cytoplasmic inclusions in the same cell, namely: carcinoid type of neurosecretory granules and mucin droplets. Diagnostic criteria and possible histogenesis of this rare tumour entity are discussed.     

Asbestos bodies in fine needle aspirates of lung masses. Markers of underlying pathology

Analysis of 52 transthoracic-mass aspirates that contained asbestos bodies (ABs) showed the mass to be due to pathology other than (or superimposed upon) asbestosis in every case. Malignancy accounted for 30 masses, all of which were carcinomas except for one mesothelioma. The remaining 22 lesions were benign, with tuberculosis or lung abscesses accounting for the majority. Fine needle aspiration (FNA) detection of the pathology (benign or malignant) associated with ABs was diminished, probably due to asbestos-induced fibrosis. Other diagnostic methods, including bronchial studies, mediastinoscopy and even exploratory thoracotomy, were required to document 20% of the neoplasms and 50% of the benign lesions. The results of this series support the view that ABs in FNA specimens from localized or dominant parenchymal lung masses are significant markers of underlying pathology, whether or not cellular evidence of that pathology is observed in the aspirated material.     

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

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

Immunocytochemical analysis of cytocentrifuged fine needle aspirates. A study based on lung tumors aspirated in vitro

The value of Cytospin preparations of fine needle aspiration (FNA) biopsy material for immunocytochemical analysis was investigated using aspirates obtained from 23 resected human lung tumors. The results were compared with those on cryostat sections from the same tumors. The Cytospin preparations of the FNA biopsies gave the best immunostaining reactions and enabled a comprehensive range of monoclonal antibodies (MAbs) to be utilized. The quality of the Cytospin immunostaining compared favorably with that on cryostat sections of the same tumors and generally yielded a similar immunophenotype. However, the Cytospin preparations were not suitable for staining with MAb Ki67, which detects an antigen associated with cellular proliferation. With Ki67, conventionally prepared smears were much superior and enabled an assessment of tumor growth fraction that concurred with the growth fraction calculated from cryostat sections in most cases.     

Analysis of the causes of false negative cytology reports on breast cancer fine needle aspirates

Forty-six (2.9%) false negative reports were recorded among adequate fine needle aspirates from 1609 consecutive histologically proven carcinomas, observed from 1991 to 1993. False negatives were more frequent among younger women (<40 years=7.1; 40-49 years=4.0; 50-59 years=3.6; 60-69 years=1.7; >69 years=1.5%), lobular invasive subtypes (5.4%), and smaller tumours (pT1a=4.2; pT1b=7.6; pT1c=1.9; pT2=2.1; pT3-4=1.5%). the latter finding is probably ascribable to better differentiation and less precise sampling of small non-palpable tumours. No significant association was found between the false negative rate and the sampler's or reader's skill and experience. the former finding may be ascribed to the wide use of sonography guided aspiration, even for palpable masses, and the latter to the fact that readers were highly experienced and undergo periodic quality control of individual performance. False negatives were reclassified at reviews as true false negatives, reading errors or inadequates in 27, 11, and eight cases, respectively. the observed findings suggest that in most cases cytological faults were due to the absence of cytological atypia in cells sampled from well differentiated tumours, rather than to misinterpretation or sampling from adjacent normal tissues.     

Adult rhabdomyoma in fine needle aspirates. A report of two cases

BACKGROUND: Adult rhabdomyoma (ARh) is a rare, benign tumor arising most frequently in the head and neck region and sometimes mimicking malignant tumors clinically. Correct preoperative evaluation of this tumor is of crucial importance as its treatment is complete excision only and not radical surgery. CASES: Two patients with ARh, one tumor presenting near the submandibular gland and the other in the thyroid area, are reported. The first tumor was correctly diagnosed by fine needle aspiration cytology. The second, clinically suspected to be a colloid goiter, was preoperatively diagnosed as such cytologically as well. After the tumor was excised, reexamination of the cytologic specimen disclosed follicle cells admixed with single cells from ARh; these had been interpreted as colloid fragments at the time of primary evaluation. CONCLUSION: Fine needle aspiration evaluation of ARh may be problematic due to the rarity of the tumor and to the similarity of the tumor cells to normal striated muscle and to other tumors in which cells with abundant granular cytoplasm are characteristic. With an awareness of the cytologic features of this uncommon tumor, cytopathologists can render a correct diagnosis.     

Pitfalls in fine needle aspiration cytology.

A review of pitfalls encountered in fine needle aspiration cytology (FNAC) of all organs and tissues and based mainly on the author's 35-year experience of diagnostic FNAC in clinical practice is presented. Diagnostic difficulties are usually related to deviations from common cytological criteria that may occur in some lesions. Others are due to the effects of the sampling procedure or of the preparation of samples. A few basic rules are proposed, which may help to avoid some of the diagnostic pitfalls.     

Telomerase activity in thyroid fine needle aspirates

OBJECTIVE: To study the utility of telomerase activity (TA) detection in thyroid fine needle aspirates (FNAs). STUDY DESIGN: One hundred two thyroid nodules were studied: 70 in FNA samples and 32 in frozen tumors. From among FNA samples, there were 57 nodules of the goiter, 1 adenoma, 7 papillary carcinomas, 1 medullary carcinoma and 1 lymphoma. Three cases of thyroiditis were excluded. The 32 frozen tissue tumors consisted of 5 follicular adenomas, 4 follicular carcinomas and 23 papillary carcinomas. TA was analyzed by Telomerase PCR ELISA (Roche Diagnostics, Indianapolis, Indiana, U.S.A.). RESULTS: TA was negative in the 57 nonneoplastic nodules and 6 follicular adenomas and positive in 3 of 4 follicular carcinomas and 10 of 30 papillary carcinomas. TA sensitivity was 41.4% and specificity 100%. Sensitivity for malignancy was higher (85.7%) in FNAs than in TA. CONCLUSION: TA seems highly specific for neoplasms of the thyroid. Further studies are needed to confirm whether TA detection could contribute to identifying neoplasms when FNAs are inconclusive for malignancy and in cases of scanty material.