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.     

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.     

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.     

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.     

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.     

Tyrosine crystals in fine needle aspirates of a pleomorphic adenoma of the parotid gland

Tyrosine crystals were identified in the fine needle aspirate from a pleomorphic adenoma of the parotid gland. Such crystals have been seen before in tissue sections of pleomorphic adenomas, and they should be considered supportive evidence for a diagnosis of pleomorphic adenoma.     

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.     

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.     

MIB-1 immunohistometry of follicular adenoma and follicular carcinoma of the thyroid gland

OBJECTIVE: To analyze cellular proliferative activity, MIB-1 immunopositivity of normal tissue (n = 20), follicular adenoma (n = 30) and follicular carcinoma (n = 32) of the thyroid gland was analyzed by means of immunohistometry. STUDY DESIGN: Immunohistochemical reactions were performed on 3-micron sections from routinely formalin fixed and paraffin embedded surgical specimens using an indirect peroxidase method. The rate of immunostained cells was determined using the CM-2 TV image analysis system (Hund, Wetzlar, Federal Republic of Germany). Forty viewing fields (1.94 mm2) were measured with 20:1 objective magnification. An average of 5,965 cells were assessed in each case. RESULTS: Mean MIB-1 immunopositivity was higher in follicular carcinoma (average, 2.30%) and follicular adenoma (0.58%) than in normal thyroid tissue (0.14%). The distribution of single values differed significantly between groups (P < .001). To test the suitability of MIB-1 immunohistometry for the differential diagnosis of follicular adenoma and follicular carcinoma, different four-field tables with varying thresholds were calculated. Using a threshold of 0.9%, follicular carcinoma could be detected with a sensitivity of 75% (24/32) and a specificity of 83% (25/30). If a specificity of 90% is required (27/30), the sensitivity of the test decreases to 69% (22/32), based on a threshold of 1.1%. CONCLUSION: As some overlap of single values has to be considered, MIB-1 immunohistometry, although presenting new insights into the proliferative potential of thyroid lesions, is of only limited value for the differential diagnosis of follicular lesions in routine surgical pathology.     

Fine needle aspirates of follicular lesions of the thyroid gland. The intermediate-type smear

In order to evaluate fine needle aspirates of thyroid lesions with features intermediate between those of follicular neoplasms and colloid nodules, 38 aspirates in which a definitive diagnosis had not been made were reviewed. On review, ten aspirates were excluded from the "intermediate" category; seven were reclassified as unsatisfactory and one as a cellular colloid nodule. Two papillary carcinomas showed a complex pattern not identified in smears from other lesions; these aspirates were also classified separately for independent evaluation. The remaining 28 aspirates were characterized by syncytial-type tissue fragments with mild nuclear atypia. The association of syncytial-type tissue fragments and orderly sheets and fragments forming a honeycomb pattern in the same aspirate indicated a colloid nodule, though a two-disease process could not be excluded. Of the aspirates containing only syncytial-type tissue fragments, 50% were from adenomas, 25% were from carcinomas, and 25% were from colloid nodules. Criteria to distinguish between the various follicular lesions were not identified in these smears.     

Signet-ring follicular adenoma of the thyroid diagnosed by fine needle aspiration. Report of a case with cytologic description

BACKGROUND: Follicular cells of the thyroid may undergo squamous, oncocytic or clear cell metaplastic changes. Of these, the clear cell change with signet-ring formation is the most unusual, and follicular adenoma of the thyroid with signet-ring formation is extremely rare. We describe for the first time the cytologic features of a clear cell adenoma of the thyroid obtained by fine needle aspiration (FNA). CASE: A 48-year-old woman in a euthyroid state presented with a 2-cm, right-sided thyroid nodule. Smears obtained by FNA of the nodule revealed clusters of large signet-ring cells in a bloody background. The signet-ring cells were round to oval, with large cytoplasmic vacuoles and hyperchromatic, eccentric nuclei. Colloid in the background was very scanty. Histologic examination of the right hemithyroidectomy specimen revealed a signet-ring follicular adenoma. CONCLUSION: Lack of familiarity with signet-ring cell adenoma of the thyroid could lead to an erroneous diagnosis of metastatic signet-ring cell carcinoma.     

Morphometric analysis of fine needle aspirates from breast lesions

In an attempt to discover the morphometric variables with the most diagnostic power in the differentiation of benign from malignant breast disease, 20 unequivocally benign and 20 unequivocally malignant and histologically confirmed breast aspirates were examined on an image analyser. It was found that standard deviation of nuclear area was the most discriminant variable. Then 23 aspirates initially diagnosed as 'suspicious of malignancy' were measured by the same technique, and standard deviation of nuclear area correctly differentiated all but three cases.     

Multinational study of oestrogen and progesterone receptor immunocytochemistry on breast carcinoma fine needle aspirates

?. P. Marin?ek, N. Nolde, I. Kardum‐Skelin, R. Nizzoli, B. Önal, T. Rezanko, E. Tani, K. T. Ostovi?, P. Vielh, F. Schmitt and G. Kocjan
Multinational study of oestrogen and progesterone receptor immunocytochemistry on breast carcinoma fine needle aspirates Objectives: To collect data on the variability of immunocytochemical (ICC) procedures used to detect oestrogen/progesterone receptors (ER/PR) on cytological material; to test the reproducibility of results; and to identify the crucial points in the ICC procedures that affect the result. Methods: Ten laboratories from eight countries participated in a two‐part study. In the first part, one of the participants (the coordinator) prepared and distributed cytospins from a fine needle aspirate of a primary breast carcinoma. Laboratories performed ICC staining for ER/PR according to their own methods on the test slides and in‐house positive controls. Slides were returned to the coordinator together with information on the preparation of positive control slides and the ICC methodology used. In the second part, obligatory methods of fixation and antigen retrieval were specified. Evaluation of results included grading the number of positive cells, staining intensity, background staining, cytoplasmic staining, sample condition and cellularity. Participants evaluated their own results, which were subsequently evaluated by the coordinator. Results: There was great variability in the preparation of slides for in‐house controls and ICC methodology. The outcome of ICC staining of in‐house control slides was excellent in two laboratories, adequate in three, sub‐optimal in four and inadequate in one. Only six obtained a positive reaction on the test slides and not all were of a high quality. Results of the second run were greatly improved in terms of cellularity of in‐house positive control slides, and scores for the percentage of stained cells and staining intensity of control and test slides. Cytospins and monolayer (ThinPrep^®) preparations were superior to direct smears; methods of fixation and antigen retrieval were the key points in the staining process. Conclusions: Our experience points to the need for guidelines for hormonal receptor determination and external quality control on cytological material, in order for cytological methods to be used in routine clinical practice with a suitable degree of confidence.     

Immunocytochemistry on fine needle aspirates in paraffin miniblocks

A simplified method of processing of fine needle aspirates for paraffin miniblocks suitable for both morphologic and immunocytochemical evaluation is described. Aspirates were fixed in ethanol at 4 degrees C, dehydrated in acetone and xylene and embedded in paraffin (58 degrees C). All steps were carried out in a single Eppendorf centrifuge tube; the total process took less than four hours. Deparaffinized sections were stained using the alkaline phosphatase-antialkaline phosphatase technique with monoclonal and conventional antibodies helpful in the differential cytologic diagnosis of alcohol-fixed aspiration biopsy specimens. Antibodies to keratin, vimentin, desmin, neurofilaments, glial fibrillary acidic protein, leukocyte-common antigen, synaptophysin and immunoglobulin kappa and lambda light chains reacted positively on the miniblock material. Since the paraffin miniblocks combine the histologic pattern of the tumor with the differentiation-specific information provided by immunocytochemistry, their use can improve the accuracy of tumor typing in aspirates.     

Metastatic follicular thyroid carcinoma diagnosed by fine needle aspiration cytology: a report of 3 cases

BACKGROUND: Follicular thyroid carcinomas (FTCs) usually have a benign clinical course, with an excellent long-term prognosis and a propensity for vascular invasion. The most common sites of metastases are lung and bone. Only a few reports are available on fine needle aspiration biopsy findings from metastatic lesions of FTC. CASES: A 68-year-old man presented with a thyroid mass and skin nodule on the scalp. Skin nodule aspiration revealed metastatic FTC. A 52-year-old woman and 60-year-old man were investigated for chronic anemia. As part of the routine investigation, bone marrow aspiration and biopsy were performed from the posterior iliac crest and diagnosed as metastatic FTC. Further questioning revealed that the patients had undergone thyroidectomy 10 and 13 years earlier. The aspiration material in all 3 cases revealed epithelial cell clusters with marginal (fire-flare) vacuoles. CONCLUSION: Cytologic diagnosis of metastatic FTC has been reported rarely. Marginal (fire-flare) vacuoles aid in making the diagnosis of metastatic FTC.     

Cytomorphology and immunocytochemistry of fine needle aspirates from blastic non-Hodgkin's lymphomas

Fine needle aspirates from 54 consecutive patients with primary or recurrent blastic (high-grade malignant) non-Hodgkin's lymphomas (NHLs) were analyzed by cytomorphology and immunocytochemistry. The cytologic diagnoses induced follicular center-cell-derived (centroblastic or anaplastic centrocytic) lymphoma (31 cases), immunoblastic lymphoma (11 cases), lymphoblastic lymphoma (9 cases) and histiocytic lymphoma (3 cases). Immunocytochemistry showed a B-cell phenotype of the neoplastic lymphocytes in all lymphoblastic lymphomas, 29 follicle center-cell lymphomas and 4 immunoblastic lymphomas. Four of the immunoblastic lymphomas were of T-cell origin while one case was not evaluable due to necrosis. A histiocytic origin was confirmed in two of the three cases that had a cytologic diagnosis of histiocytic lymphoma; the third case was shown by immunocytochemistry to be a true Ki-1-positive large cell lymphoma. Histologic and immunohistochemical analysis were performed on surgical biopsies from 18 patients. The results were in agreement with those on the fine needle aspiration (FNA) material in 14 cases. Three lymphomas could be phenotyped on aspirated material while marker studies on excised material were inconclusive. One lymph node aspirate contained mostly necrotic cells, which were unsatisfactory for adequate immunocytochemistry. However, sections from a removed tonsil from the same patient could be used for conclusive histology and phenotyping. In conclusion, the high diagnostic accuracy of combined cytomorphologic and immunocytochemical assessment of FNA samples validates the use of the technique in the diagnostic work-up of blastic (high-grade malignant) NHLs. In fact, the diagnostic accuracy seems so high that the technique can safely be used in the final diagnosis of blastic NHLs.