Nuclear grooves. Valuable diagnostic feature in May-Grünwald-Giemsa-stained fine needle aspirates of papillary carcinoma of the thyroid.

Recent reports have indicated the usefulness of nuclear grooves (clefts or notches) as an additional criterion for the diagnosis of papillary thyroid carcinoma in fine needle aspirates; most of these studies were carried out on alcohol-fixed material stained with the Papanicolaou stain or with hematoxylin and eosin, which yield good nuclear details. In the present study air-dried thyroid aspirates stained with the widely used May-Grünwald-Giemsa stain were evaluated. Nuclear grooves were observed in 88% of the May-Grünwald-Giemsa-stained aspirates from papillary thyroid carcinoma, usually in substantial numbers. A few grooved nuclei were seen in a small percentage of the other thyroid aspirates studied. These results show that nuclear grooves can also be used as a possible marker of papillary carcinoma of the thyroid in May-Grünwald-Giemsa-stained aspirates.     

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.     

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.     

Differentiation of Hashimoto's thyroiditis from thyroid neoplasms in fine needle aspirates

In order to refine the cytodiagnostic criteria for distinguishing Hashimoto's thyroiditis from thyroid neoplasms, aspirates from six cases of Hashimoto's thyroiditis, five Hürthle cell neoplasms and one papillary carcinoma associated with Hashimoto's thyroiditis were reevaluated. Distinguishing characteristics were cell arrangements, nuclear chromatin pattern and nucleolar appearance. Hashimoto's thyroiditis was characterized by flat sheets and clusters of epithelial cells with oncocytic changes or occasionally by cohesive tissue fragments with cells well oriented one to the other. Thyroid neoplasms were characterized by loosely cohesive, syncytial-type tissue fragments with crowded overlapping cells poorly oriented one to the other and/or numerous isolated single cells. The nuclear chromatin of Askanazy cells in Hashimoto's thyroiditis was bland and even while that of neoplastic cells was finely granular, coarsely granular or irregularly clumped. Macronucleoli were present in Hürthle cell tumors but not in the Askanazy cells of Hashimoto's thyroiditis. Epithelial cellularity, lymphoid cellularity, cellular polymorphism and nuclear pleomorphism were not useful criteria for making the differential diagnosis between the two conditions. An admixture of epithelial cells and lymphoid cells indicated Hashimoto's thyroiditis but was not helpful in ruling out an associated neoplasm.     

Karyometric marker features in fine needle aspirates of follicular adenoma of the thyroid

Karyometric measurements were performed on fine needle aspirates of clearly identifiable adenomatous areas and adjacent normal-appearing areas in the surgical specimens from ten patients with follicular adenomas of the thyroid. Similar measurements were made on aspirates from nine patients free of thyroid disease. A total of 95 karyometric features were evaluated for each nucleus. Analysis of variance of optical density values did not show a significant difference between the three types of nuclei. Discriminant analysis selected seven karyometric features that produced a statistically highly significant separation of adenoma nuclei from control nuclei. A similar analysis selected six features that produced a statistically highly significant discrimination of normal-appearing nuclei from control nuclei. The validity of these markers for distinguishing control nuclei from adenoma nuclei and normal-appearing nuclei adjacent to adenomas was demonstrated by analysis in further training and test sets. These findings parallel those previously demonstrated for invasive and microinvasive follicular carcinomas of the thyroid.     

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.     

Karyometric marker features in fine needle aspirates of invasive follicular carcinoma of the thyroid.

Karyometric measurements were performed on fine needle aspirates of clearly identifiable tumor areas and adjacent normal-appearing areas in the surgical specimens from ten patients with invasive follicular carcinoma of the thyroid. Similar measurements were performed on aspirates from nine patients free of thyroid disease (controls). A total of 95 karyometric features were evaluated for each nucleus. Analysis of variance of optical density values indicated (1) a similarity between tumor and normal-appearing nuclei from carcinoma cases, (2) a significant difference between those nuclei and control nuclei and (3) that most of the differences were due to the differences of tissue origin. Stepwise linear discriminant analysis selected ten features that produced a statistically highly significant separation of tumor nuclei from control nuclei. A similar analysis selected six features that produced a statistically highly significant discrimination of normal-appearing nuclei from control nuclei; the validity of those karyometric features as markers of malignancy in normal-appearing nuclei from tissues adjacent to invasive follicular carcinomas of the thyroid was demonstrated by analysis in further training and control sets of nuclei. This analysis in thyroid aspirates identified more marker features than did a previous similar analysis using tissue sections.     

Computerized morphometric study on fine needle aspirates of cellular follicular lesions of the thyroid

OBJECTIVE: To investigate the value of computerized nuclear morphometry in the differential diagnosis of cellular follicular lesions of the thyroid cytologically diagnosed on fine needle aspiration (FNA) smears. STUDY DESIGN: Sixty cases of FNA thyroid smears were cytologically diagnosed and classified as follows: 30 cases of follicular carcinoma, 20 cases of cellular hyperplastic nodules and 10 cases of follicular adenoma. Using an image analysis system, two morphometric variables, nuclear area and major axis length of the nucleus, were measured for each case. RESULTS: For both nuclear morphometric variables, statistical differences were found between carcinomas and hyperplastic nodules as well as between carcinomas and adenomas. No statistical differences were found between the nuclear variables in either hyperplastic nodules or adenomas. CONCLUSION: The results confirm the aim of our study, to establish nuclear morphometry by computerized image analysis as an additional tool in the differential diagnosis of thyroid follicular lesions cytologically diagnosed on FNA smears.     

Grave's disease. Appearance in cytologic smears from fine needle aspirates of the thyroid gland

The cytomorphologic features were analyzed in thyroid samples obtained by fine needle aspiration (FNA) from 54 cases proven to be Grave's disease (toxic goiter) by a multiparameter study. A fire-flare appearance of the follicular cells and a good cellularity of the smears were the features most frequently observed in these cases. Hürthle cell changes were present in 47% of the cases, and small numbers of lymphocytes were seen in smears from 41% of the cases. Epithelioid cell granulomata and multinucleated giant cells were observed in less than one-fourth of the cases. About half of the cases showed some degree of pleomorphism of the follicular cells. Twenty cases of toxic multinodular goiter were similarly analyzed; the features that distinguished this entity from Grave's disease were the absence of epithelioid cells and multinucleated giant cells in the FNA smears.     

Computerized microscopic analysis of prostatic fine needle aspirates. Comparison with breast aspirates

Computerized image analysis was employed to analyze fine needle aspiration smears of the prostate and breast using both high-resolution images of individual cells and medium-resolution images of scenes and clusters (contextual analysis). A linear discriminant analysis was used to demonstrate the computer's ability to discriminate between benign and malignant categories for both types of tissue. Correct classification as benign or malignant using contextual analysis was achieved in 22 of 26 prostatic aspirates and in 15 of 18 breast aspirates, as determined by comparison with histology. The addition of high-resolution single-cell analysis resulted in correct classification of 24 of 26 prostatic aspirates and all breast aspirates. For virtually all features, the distinction between benign and malignant was more subtle for prostatic than for breast tissue. The data indicate that contextual analysis may be less effective as an adjunct to high-resolution single-cell microscopy of prostatic specimens than it is for breast specimens.     

Diagnostic significance of coexpression of intermediate filaments in fine needle aspirates of human tumors

A study was undertaken of the diagnostic significance of the coexpression of intermediate filaments in fine needle aspirates of human tumors. Three types of coexpression were found: (1) true coexpression, in which tumor cells simultaneously express more than one intermediate filament protein; (2) pseudocoexpression, in which various tumor cell types from histogenetically different parts of a complex tumor show different results; and (3) false coexpression, in which tumor cells with one or two types of intermediate filaments are present together with benign cells expressing a different filament type. True coexpression of vimentin and keratin was documented in renal cell carcinomas, endometrial carcinomas, certain thyroid carcinomas and Hürthle cell adenomas. Coexpression of keratin and neurofilaments was seen in Merkel cell carcinomas, and coexpression of desmin and vimentin was found in leiomyosarcomas. Keratin, vimentin and neurofilament expression was seen in medullary thyroid carcinomas, and keratin, vimentin and glial fibrillary acidic protein expression was observed in pleomorphic adenomas of the salivary gland. Pseudocoexpression was noted in synovial sarcoma, epithelioid sarcoma, benign cystosarcoma phyllodes of the breast, teratocarcinoma, malignant granular cell tumor, progonoma, Wilms' tumor and triton tumor. Sources of false coexpression are also discussed.     

Ringlike structures in fine needle aspirates from the breast

Spherical ringlike structures of various sizes resembling Liesegang rings (LRs) are described in four fine needle aspirates (FNAs) from breast lesions over a period of 13 years. A characteristic finding in these structures was a distinct double layer outer wall with striations and an amorphous central nidus. Under polarized light they were non-refractile and no birefringence was noted in Congo red. Immunohistochemical stains for calcium, iron, mucus, glycogen, amyloid, cytokeratin and epithelial membrane antigen in all the cases were found to be negative. Since LRs can be mistaken for ova or parasites, their presence in aspirates of breast should be kept in mind to avoid misdiagnosis.     

Morphometric studies on nuclei in smears of fine needle aspirates from oxyphilic tumors of the thyroid

Morphometry was applied to smears of fine needle aspirates from 26 oxyphilic thyroid neoplasms. Thirteen tumors were considered benign as judged from histologic findings and clinical follow-up for 2 to 20 years after the operation. Thirteen tumors were considered malignant histologically; four of these had proven metastases. In each case the mean and standard deviation of the projected nuclear area were calculated from 200 nuclei in the smear. Our results indicate that morphometric estimation of mean nuclear size and/or degree of anisokaryosis is of no practical value in distinguishing between benign and malignant thyroid neoplasms of the oxyphilic type.     

Microfilariae in fine needle aspirates from epididymal lesions

Microfilariae of Wuchereria bancrofti were observed in fine needle aspiration smears from three epididymal nodules, and degenerating microfilariae suggestive of Brugia malayi were found in the smears from a fourth case. The smears in all four cases showed a polymorphonuclear inflammatory cell component as well as epithelioid cell granulomata. While blood eosinophilia was present in all four cases, eosinophilia was present in the aspiration smears in only one case. Microfilariae could be demonstrated in the peripheral blood in only one case.     

Planimetric studies on fine needle aspirates from follicular adenoma and follicular carcinoma of the thyroid

A planimetric study was performed on fine needle aspiration biopsy smears from 21 follicular thyroid adenomas, 13 follicular thyroid carcinomas and 7 nontoxic goiters. The nuclear and the cytoplasmic projected areas were measured in each smear on 50 cells with intact nuclei. The nuclear-cytoplasmic area was calculated. Significant differences in mean nuclear area were found between benign and malignant follicular neoplasms and between neoplastic cells and cells from nontoxic goiter. Planimetry of cells aspirated from follicular neoplasms permitted differentiation between carcinomas and adenomas with a high degree of statistical probability.