Role of Fine-Needle Aspiration Cytology in the Management of Thyroid Nodules: Review of Experience With 1,925 Cases Helio Bisi, M.D., Ph.D., Rosalinda Y. Asato de Camargo, Adhemar Longatto Filho, M.S.
In this review article, the authors present their experience with the management of thyroid nodules usingfine-needle aspiration cytology as the primary method of investigation. Diagn Cytopathol 1992;8:504-510. 0 1992 wiiey-Liss, Inc Key Words: Thyroid gland; Thyroid cancer; Thyroid disorders
Fine-needle aspiration cytology (FNAC) of the thyroid nodules is a well-known method used to obtain tissue fragments, fluid specimens, or smears. ‘-I6 The first studies on the usefulness of FNAC were performed more than a halfcentury ago, but only recently has this procedure been used in Brazil. ’’-I9 FNAC is easy, of low cost, and very safe.’ An additional advantage is the avoidance of unnecessary surgery, along with a high accuracy in differentiating benign and malignant lesions. 2 , 13,20-46 The efficacy of FNAC depends on various factors: experience in selecting and aspirating the palpable thyroid nodules in order to obtain a representative cellularity of the smears, proper preparation of the smears, as fixation and staining, and finally, a good knowledge and familiarity with the histopathology of the thyroid lesions. Since our group had a great interest in and much previous experience with thyroid necropsy and surgical techniques (unpublished data), we decided to undertake FNAC studies. We reviewed a total of 4,703 (3.6%) cases of thyroid lesions from the 131,466 necropsies of the Pathology Department files, Medical School, Sao Paulo University. From this large amount of autopsy information we identified 4,358 cases of non-neoplastic lesions (3.3%) and Received July 31, 1991. Accepted December 13, 1991. From the Pathology Department, Medical School of Sao Paulo University; Endocrinology Clinics, Sao Paulo County Hospital; and Division of Pathology, Adolfo Lutz Institute, Sao Paulo, Brazil. Address reprint requests to Prof. Dr. Helio Bisi, Pathology Department (FMUSP), Av. Dr. Arnaldo-455, CEP 01246, Sao Paulo-SP, B r a d
Diagnostic Cyiopaihology, Vol 8, No 5
345 cases of neoplastic lesions (0.26%) distributed as follows: 12 1 adenomas, 109 primary malignant neoplasias, and 1 15 metastatic neoplasias. We also reviewed the surgical material from the same Pathology Department which had similar numbers of cases. With this past experience we decided to introduce FNAC as a routine method in the thyroid lesions seen in the County Hospital. We also decided to report our diagnosis according to “cellular patterns,” which informs the diagnosis with great accuracy; these cytologic findings, when associated with clinical findings, have been helpful in the evaluation of thyroid nodules. With this clinico-pathologic correlation we suggest to the clinician the possible entity in the thyroid, and also suggest the thyroid lesions correlated with these “cellular patterns,” whenever possible. The “cellular patterns” and the cytological criteria used in our study are outlined below.
Inflammatory Pattern UP) Hushimoto ’s Diseuse The smears reveal lymphocytic infiltration with different degrees of cell maturation, plasma cells, and macrophages; multinucleated giant cells are observed occasionally. Epithelial cells with oxyphilic and granular cytoplasm are frequent (Hiirthle cells). These cells can exhibit large hyperchromatic nuclei, coarse chromatin, and prominent nucleoli. On the other hand, some large and reactive lymphocytes with typical and/or atypical mitosis are seen. Both findings can be misinterpreted as malignancY-48-57
Nonspecijk Lymphocytic Thyroiditis In contrast with Hashimoto’s disease, the smears reveal rare or absent Hurthle cells; in addition, one sees a great
1992 W I L t k L I S . I N C
FNA IN MANAGEMENT OF THYROID NODULES
number of mature lymphocytes, follicular cells, and high concentrations of colloid.
Subacute Thyroiditis The smears exhibit lymphocytes, macrophages, and frequently multinucleated giant cells, associated with neutrophils and normal epithelial cells; oxyphilic cells (Hiirthle) are scanty. 53
Medullary Pattern (MP) Out of the classical M P plasma cell-like, with granular and oxyphilic cytoplasm (Hiirthle cell-like), the diagnosis of this group is usually done by a process of elimination.
General Considerations The follicular pattern has been the great dilemma of the FNAC method in thyroid nodules, because it can be diagnosed both as adenomatous goiter and as follicular well-differentiated neoplasm (Fig. 1). Adenomatous goiter has a multifocal follicular origin 66; its evolution distorts the gland architecture, compressing the blood vessels and leading to an ischemic necrosis and hemorrhagic cysts. In FNAC it is represented by a F P and numerous macrophages with hemossider in pigments, and abundant colloid proteic substrate. The collagen denaturation due to necrosis leads to distrophic calcification detectable by X-ray or ultrasound. These areas must be excluded in FNAC since they are not representative for study. In a recent study, we could also observe that some follicles are lined by Hiirthle cells and/or small oxyphilic cells67; in FNAC, smears presenting only these cells can lead to a misinterpretation as a Hiirthle cell neoplasm. Well differentiated follicular neoplasms are of monoclonal origin. 66 The solitary nodules have follicle cells resembling those of the adenomatous goiter. In Brazil, where the goiter incidence is very high, 69 the FP detected by FNAC is frequently synonymous with goiter; in countries where goiter is rare, FP will correspond to differentiated neoplasms, as adenomas or carcinomas. 70*7' In our experience, from the cases of FP, we misled the diagnosis in only 2.4%. The high incidence of goiter in Brazil is an alert to the cytopathologist to a more attentive interpretation of this pattern, to avoid wrong diagnosis (Tables I, 11). 2092',23,24,30359-65
Papillary Pattern (PP) The epithelial cells are seen in a papillary arrangements; inflammatory and plasma cells could be present and the colloid is scanty. The classic nuclear appearance is significant and fundamental for the diagnosis, mainly in cases in which the papilliform projections are absent. Round or oval nuclei are seen with nuclear inclusions and/or nuclear crease 5657; follicular arrangements can be found in some cases." The cytoplasm of these cells is frequently abundant; Hiirthle cells are rare in papillary projections. Psammoma bodies have been described but were rarely found in our material.
Follicular Pattern (FP) Epithelial cells are distributed in solid clusters or in follicular arrangements; isolated cells are frequently observed. The cytoplasm is scanty and rarely oxyphilic. The nuclei are round or oval with dense or slightly granular chromatin; nucleoli could be observed in cases with a granulous aspect of the nucleus. This pattern can be found in follicular neoplasms (benign and malignant) and adenomatous goiter. In our experience, a dense and homogeneous nuclear aspect suggests goiter; when the chromatin margin is granular and the nuclei irregular, we consider it to be a neoplastic condition.
Hiirthle Pattern (HP) The Hiirthle cells are present in trabecullar or follicular arrangement or in isolated distribution. The nuclei are mono- or pleomorphic, single or double. Granulous chromatin and prominent nucleoli are seen. The colloid is frequently scanty. In the H P are included Hiirthle cell adenoma and Hiirthle cell carcinoma. Cytoplasm of these cells is voluminous, oxyphilic, and slightly granular.
Undifferentiated Pattern (UP) Small, large multinucleated, and fusiform cells are the predominant elements in this pattern. Atypical mitosis is more frequently seen in the presence of fusiform and large multinucleated cells. In the case of an UP mainly composed Of there is no association with Other types, and the tumor exhibits a homogeneous patterns.
Cytologic Pattern Diagnosis in Thyroid F N A C
Medullary~' Undifferentiated Papillary Hiirthle Inflammatory Follicular
55 146 1,234
Oh 1 OOh
"Papillary carcinoma. Misdiagnosed as medullary due to ah\riice of inc1usion5. hCorrect diagnosi5 confirmed by h~stopathology. 'Correct diagnosis confirmed by clinical and laboratory findings predominantly, and histopathology.
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Diugnostic Cytoputhology, Vol 8. No 5
FNA IN MANAGEMENT OF THYROID NODULES Table 111. FNAC of Thyroid Gland, Selected Pitfalls
Table 11. Other Findinas in FNAC
Number oJ cases
Metastatic neoplasm Others (lipoma, calcification) Suspicious for malignancy Cysts (hemorrhagic, thyrogloss, thymic, serose, epidermoid inclusion) Insufficient material
3 5 34
Final surgical pathology diagnosis
Cause oJfalse diagnosis (cytologic pirfalls)
Immuno peroxidase-calcitonin (IC) was false-positive due to number of isolated plasma-cell like elements
IC negative, congo red stain positive projections, absence of papillary projections
Papillary occult carcinoma
Aspiration of peri-neoplastic area
The FNAC was performed in an area without inflammatory cell arrangements of large nodule goiter
Nuclear classic signs of papillary carcinoma were absent (also in the surgicalspecimen); presence of great number of Hiirthle cells
The inflammatory infiltrate of mature lymphocytes associated with small oxyphilic cells was misinterpreted as Hashimoto's Disease
Papillary carcinoma Hashimoto's disease
The FNAC only reached the inflammatory. .part of the lesion
aCorrect diagnosis based in surgical pathology and/or clinical follow up. hData not included in index accuracy.
The pure Hurthle pattern invariably suggests neoplasm (Fig. 2), but pitfalls exist. In 60% of dyshormonogenic goiter studied in our department (unpublished data), we found follicles lined by Hurthle cells that can lead to a false-positive diagnosis in some instances. Adenomatous goiter can also present with Hiirthle cells lining the follicles, but in these cases we observed a great concentration of proteic colloid substrate, macrophages with hemossiderin, and normal follicular cells. When the FNAC obtains only Hurthle cells, the differential diagnosis between benign or malignant lesions is impossible. 67 Papillary and undifferentiated patterns, in general, present no major difficulties for interpretation; our FNAC results were 100% in accordance with the biopsies (Figs. 3-6). When a suspicious medullary pattern exists, it is essential to stain with congo red or immunoperoxidase. 72,73 In the immunostaining, the hemorrhagic areas of lesions must be carefully interpreted, in order to avoid falsepositive results, 74 as could happen in the macrophages with the haemossiderin. In cases of medullary carcinoma without amiloid, the congo red stain does not aid in the diagnosis. The smears showing small cells do not present difficulties to a diagnosis of malignancy (Fig. 7); in addition, immunoperoxidase stain can differentiate carcinoma from lymphomas. Inflammatory pattern (Figs. 8, 9) can lead to false-negative diagnosis when the punction removes only the inflammatory cells, releasing the epithelial clusters (Table 111). 75976
Original cytologic pattern
As described in the literature, careful attention should be paid when dealing with cystic lesions. 7740 In a previous study, we found 44% of papillary carcinomas with cysts. " Our procedure is to drain these cysts, to provide material for cytological interpretation, and for therapeutic value. We do not use saline or tetracycline injection for sclerosing purposes, as indicated in the literature, 82-R4 since this procedure can complicate the long follow-up that is essential in these cases. The role of FNAC in the management of nodules of the thyroid gland on an outpatient basis is well established (Table IV). It should be used as the first procedure in the
Fig. 1. Follicular pattern (follicular carcinoma). Follicular cells arranged in acinus-like fashion with hyperchromatic nuclei (Papanicolau, X 500). Fig. 2. Hiirthle pattern. Small group of a Hiirthle cell tumor. Eccentric hyperchromatic nuclei with coarsely granular chromatin and granular cytoplasm (Leishmann, X 500). Fig. 3. Papillary pattern (papillary carcinoma). Sheet of cells with nuclear creases (arrow) (hematoxylin-eosin, X 800). Fig. 4. Papillary pattern (papillary carcinoma). Papillary configuration with intranuclear cytoplastic inclusions (isolated) and ground-glass nuclei (hematoxylin-eosin, X 500). Fig. 5. Undifferentiated pattern (undifferentiated carcinoma). Giant cell carcinoma: prominent nucleoli and atypical mitosis (arrow) (hematoxylineosin, x 800). Fig. 6. Undifferentiated carcinoma (giant cell carcinoma). Giant pleomorphic nuclei hyperchromatic with coarse chromatin and large nucleoli (arrow) (hematoxylin-eosin, x 800). Fig. 7. Medullary pattern (medullary carcinoma). Solid sheet of oval (sometimes polygonal or spindle) cells dispersed in homogeneous eosiriophilic amyloid (arrow) (hematoxylin-eosin, x 600). Fig. 8. Inflammatory pattern (Hashimoto's disease). Lymphocytic characteristic infiltration (hematoxylin-eosin, x 200). Fig. 9. Inflammatory pattern (Hashimoto's disease). Lymphocytic infiltration and large Hiirthle cell (arrow) with characteristic granular cytoplasm and hyperchromatic nuclei (hematoxylin-eosin, x 500).
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BISI ET AL. Table IV.
FNAC’s Literature Review (1979-1990)” Inadequacy
(ref. 20) Friedman et al., 1979 (USA) (ref. 5) Chu et al., 1979 (USA) (ref. 4) Colacchio et al., 1980 (USA) (ref. 21) Frable and Frable, 1980 (USA) (ref. 12) Varhaug et al., 1981 (Norway) (ref. I ) Schwartz et al., 1982 (USA) (ref. 2) Belanger et al., 1983 (Canada) (ref. 22) Rubenfeld et al., 1982 (USA) (ref. 23) Block et al., 1983 (USA) (ref. 24) Suen and Quenville 1983 (USA) (ref. 25) Brauer and Silver 1984 (USA) (ref. 26) Christensen et al., 1984 (Sweden) (ref. 27) Riestra et al., 1986 (Puerto Rico) (ref. 3) Bugis et al., 1986 (Canada) (ref. 28) Hsu and Boey, 1987 (Hong Kong) (ref. 29) Pandit and Kinare 1986 (India) (ref. 30) Andreoli et al., 1986 (Italy) (ref. 31) Squartini and Coscio 1986 (Italy) (ref. 32) Frable, 1986 (USA) (ref. 33) Silverman et al., 1986 (USA) (ref. 34) Goellner et al., 1987 (USA) (ref. 35) Hall et al., 1989 (USA) (ref. 13) Glinoer et al., 1987 (Belgium) (ref. 36) Gabrielli et al., 1989 (Italy) (ref. 37) Altavilla et al., 1990 (Italy) (ref. 92) Jones et al. 1990 (United Kingdom) Present series (Brazil)
265 109 300 I68 2 64 102 63 156 I21 304 224
8 0 0 6.5 16.3 9.8 9.0 5.0 16.5 5.0 0
43 I98 555 84 3,038 3,023 9 60 309 6,346 795 600 I39 2,433 175 1,925
99 96 97 96
95 90 2 86 99 98 98 97 96 84 90 94 9x 97 98 98 94 98 90 90 85 6 95.09 93.5 97.2
0 3.0 2.2 4.7 7 25.2 8 0 20 16.5 5 0 16.11 14 8.7
Rate (%) Fake negative
(n (n (n (n (n (n
(n = I ) (n = 2) (n = 4) (n = 2) 0 3.3 (n = 3) 1.6 (11 = 1) 0 0.9 (n = 1) 1.9 (n = 6) 0.7 (n = I ) 0 14 (n = 6) 1.5 (n = 3) 0.6 (n = 3) 0 0 0 0.8 ( n = 7 ) 0 0.3 (n = 1) 0.4 (n = 3) 5 (n = 7) 7.5 (n = 11) 0 8 (n = I ) 0
0.4 1.8 1.0 2.4 4.1 6.5 12.7 0.64 1.9 0.6 7.0 1.1 2.3 8.6 4.6 1.2 3.6 1.4 1.1
2.4 1.3 2.0 6.4 28.7 8 0.3
2) = 3) = 4) = 9) = 6) = 8) =
2) (n = 2) (n = 3) (n = 1) (n = 1) (n = 17) (n = 24) (n = I ) (n = 5) (n = 3) (n-11) 0 (n = 8) (n = I ) (n = 3) (n = 9) (n = 8) (n = 1) (n = 7) (11 =
0.4 1.8 1.3 1.2
98 92 86 95 74 45 92 98 70 97 88 80 93 43 81 89 83 94 92
99 97 98 97
98 89 77 88.7 71.4 92 95
96 84 100
98 98 99 I00 79 93 99 100
I00 100 99 100
99 88 93 81.3 100
“In the works that have no statistical index, we calculated it based on data mentioned by the authors
ULTBGSOUND +SINGLE NODULE+SURGERY B l l U L T 1 P I . E IODULES+FOLLOY
I T H HVPOECOGENIC HALO: SUPRESSICN FGLL ICULAR FATTEEN-EIIELE
Fig. 10. Flowchart
evaluation of the nodule. We believe that FNAC of the thyroid is a useful examination that provides essential information to the clinician. The use of immunoperoxidase techniques 72-75 and other information obtained
Diagnostic Cytopathology, Vol 8, No 5
through nuclear medicine (uptake of radioisotopes), scintscan, 8 5 and ultrasound could increase the accuracy of the evaluation of thyroid nodules when associated with FNAC. 88-92 (Fig. lo). %zX7
FNA IN MANAGEMENT OF THYROID NODULES
References I . Schwartz AE, Nieburgs HE, Davies TF, et al. The place of fine needle biopsy in the diagnosis of nodules of the thyroid. Surg Gynecol Obstet 1982;155:5458. 2. Belanger R, Guillet, et al. The thyroid nodule: evaluation of fineneedle biopsy. J Otolarygol 1983;12(2):109-111. 3 . Bugis SP, Young EM, Archibald SD, Chen VSM. Diagnostic accuracy of fine-needle aspiration biopsy versus frozen sections in solitary thyroid nodules. Am J Surg 1986;152:411416. 4. Colacchio TA, LoGerfo P, Feind CA. Fine needle cytologic diagnosis of thyroid nodules. Am J Surg 1980;140(4):568-71. 5. Chu EW, Hanson TA, Goldman JM, Robbins J. Study of cells in fine needle aspirations of the thyroid gland. Acta Cytol (Baltimore) 1979;23(4):309-3 14. 6. Gahan N, Rocmans P, et al. Place de la ponction a l’aiguille fine (PAF) dans le diagnostic clinique du nodule thyroidien froid. Ann Endocrinol (Paris) I98 1;42:543-544. 7. LoGerfo P, Colacchio T, et al. Comparison of fine-needle and coarse-needle biopsies in evaluating thyroid nodules. Surgery 1982; 92(5):835-838. 8. Goldfarb WB, Bigos TS, Eastman RC, et al. Needle biopsy in the assessment and management of hypofunctioning thyroid nodules. Am J Surg 1982;143:409412. 9. Hamberger B, Gharib H, et al. Fine needle aspiration biopsy of thyroid nodules: Impact on thyroid practice and cost of case. Am J Med 1982;73:381-384. 10. Norton LW, Wangensteen SL, et al. Utility of thyroid aspiration biopsy. Surgery 1982;73:381-384. 11. Parsi B, Hugues A, et al. La cytologie et les nodules thyroidiens isoles et froids. Semin Hop Paris 1980;56(13-14):666-669. 12. Varhaug JE, Segadal E, Heimann P. The utility of fine needle aspiration biopsy cytology in the management of thyroid tumors. World J Surg 1981;5:573-577. 13. Glinoer D, Verelst J, Ermans AM. Place et utilite de la ponction a I’aiguille fine dans l’evaluation clinique du nodule froid de la thyroide. Rev Med Brux 1987;8:1&16. 14. Hamaker RC, Singer MI, De Rossi RV, Shockey WW. Role of needle biopsy in thyroid nodules. Arch Otolaryngol 1983;109:225228. 15. Lowhagen T, Willems JS, Lundell G, Sundblad R, Granberg PO. Aspiration biopsy cytology in diagnosis of thyroid cancer. World J Surg 1981;5:61-73. 16. Miller JM. Needle biopsy of the thyroid: methods and recommendations. Thyroid Today 1982;1(1):1-5. 17. Bisi H, Camargo RYA, Bloise W. Citologia aspirativa da glandula tireoide. In Bogliolo Patologia. Editora G u a n a b a r a A a ediclo 1987: 901-903. 18. Fialho F, Oliveira CAB, Leal IIR, Camara DA, Mello CEB. Citopatologia nos carcinomas tireoidianos. Medicina Hoje 1980; 6(65):311-32 I. 19. Barros MAE, Barros AJ, Valeri F, Bisson F, Cunha AH. Biopsia de aspiraqlo corn agulha fina em nodulos tiroideanos 1985. Arq Bras Endocrinol Metab 1985;9(4):129-132. 20. Friedman M, Shimaoka K , Getaz P. Needle aspiration of 310 thyroid lesions. Acta Cytol (Baltimore) 1979;23(3):194203. 21. Frable MA, Frable WJ. Thin needle aspiration biopsy of the thyroid gland. Laryngoscope 198090:16 19-1 625. 22. Rubenfeld S, Wheeler TM, Spjut HJ. Fine-needle aspiration biopsy of thyroid nodules. Texas Med 1982;78:4144. 23. Block MA, Dailey GE, Robb JA. Thyroid nodules indeterminate by needle biopsy. Am J Surg 1983;146:72-78. 24. Suen KC, Quenville NF. Fine needle aspiration biopsy of the thyroid gland: a study of 304 cases. J Clin Pathol 1983;26:1036-1045. 25. Brauer RJ, Silver CE. Needle aspiration biopsy of thyroid nodules. Laryngoscope 1984;94:3842.
26. Christensen SB, Bondeson L, Ericson UB, Lindholni K. Prediction of malignancy in the solitary thyroid nodule by physical examination, thyroid scan, fine-needle biopsy and serum thyroglobulin. Acta Chir %and 1984;150:433439. 27. Riestra JL, Martinez, Villamarzo G, Rodriguez L. Fine needle aspiration of the thyroid: cyto-pathologic correlation. Bol Asoc Med Puerto Rico 1986;78(8):332-334. 28. Hsu C, Boey J. Diagnostic pitfalls in the fine needle aspiration of thyroid nodules. A study of 555 cases in Chinese patients. Acta Cytol. (Baltimore) 1987;31(6):699-704. 29. Pandit AA, Kinare SG. Fine needle aspiration cytology of thyroid. Indian J Cancer 1986;23:54-58. 30. Andreoli M, Falzoi F, Martini M, Nardi F. Valore diagnostico e terapeutico della citologia tiroidea pre-operatoria mediante aspirazione con ago sottile (FNA). Studio su 3038 lesioni nodulari. Minerva Med 1986;77:2069-2088. 3 1. Squartini F, Coscio GC. Patologia e diagnosi morfologica del concio tiroideo. Minerva Med 1986;77:2045-2048. 32. Frable WJ. The treatment of thyroid cancer. The role of FNA cytology. Arch Otolaryngol Head Neck Surg 1986;112:1200-1203. 3 3 . Silverman JF, West L, Finley JL, et al. Fine needle aspiration versus large-needle biopsy or cutting biopsy in evaluation of thyroid nodules. Diagn Cytopathol l986;2( l):25-30. 34. Goellner JR, Chaib H, Grant CS, Johnson DA. Fine-needle aspiration cytology of the thyroid, 1980 to 1986. Acta Cytol (Baltimore) 1987;31(5):587-590. 35. Hall TS, Layfield LJ, Philippe A, Rosenthal DL. Sources of diagnostic error in fine needle aspiration of the thyroid. Cancer 1989;63: 718-725. 36. Gabrielli M, Gaeti L, Melissari M. Citodiagnostica per agoaspirazione con ago sottile (FNAB) in displasie e neoplasie tiroidee osservate nel period0 1983-1987. Minerva Medica 1989;80(5):435438. 37. Altavilla G, Pascale M, Nenci I. Fine needle aspiration cytology of thyroid gland diseases. Acta Cytol (Baltimore) 1990;34(2):25 1-256. 38. Kendall CH. Fine needle aspiration of thyroid nodules: three years’ experience. J Clin Pathol 1989;42:23-27. 39. Gobien RP. Aspiration biopsy of the solitary thyroid nodule. Radio1 Clin North Am 1979;17(3):543-554. 40. Bourgeois P, Ardichvilli D, et al. La ponction thyroidienne i 1 aiguille fine: aide dans le diagnostic du cancer thyroidien. Rev Med Brux 1986;7:381-384. 41. Manenti A, Botticelli A. Ponction-biopsie percutanee des nodules froids thyroidiens. Chir Acta 1982;49:521-525. 42. Walfish PG. Routine needle biopsy in the management of hypofunctioning thyroid nodules. Thyroid nodules. Thyroid Today 1979;2(4): 1-6. 43. Bodo M, Dobrossyl L, Sinkovics 1, et al. Fine needle biopsy of thyroid gland. J Surg Oncol 1979;12:289-297. 44. Gagneten CB, Roccatogliata G, et al. The role of fine needle aspiration biopsy cytology in the evaluation of the clinically solitary thyroid nodule. Acta Cytol (Baltimore) 1987;31(5):595-598. 45. Nardi F. L’aspirazione con ago sottile nella diagnosi preo-peratoria in patologia tiroidea. Minerva Med 1986;77:2065-2067. 46. Hamburger JI. Consistency of sequential needle biopsy findings for thyroid nodules management implications. Arch lntern Med 1987; 147:97-99. 47. Bisi H, Asato de Camargo RY, Longatto Filho A, Carvalho MI, Bloise W, Mori NS. Citologia aspirativa da gllndula tiroide, com agulha fina em 1971 casos: Analiase critica. Arquivos Brasileiros Endocrinol Metab (in press). 48. Kini SR, Miller JM, Hamburger JI. Problems in the cytologic diagnosis of the “cold” thyroid nodule in patients with lymphocytic thyroiditis. Acta Cytol (Baltimore) 198 1;25(5):506-5 12. 49. Guarda LA, Baskin HJ. Inflammatory and lymphoid lesions of the thyroid gland. Am J Clin Pathol 1987;87:1&22. 50. Tani E, Skoong L. Fine-needle aspiration cytology and immunocytoDiagnostic Cytopaihology. Vol 8, No 5
BISI ET AL
62. 63. 64.
chemistry in the diagnosis of lymphoid lesions of the thyroid gland. Acta Cytol (Baltimore) 1989;33(1):48-52. Ravinsky E, Safneck JR. Differentiation of Hashimoto’s thyroiditis from thyroid neoplasms in fine needle aspirates. Acta Cytol (Baltimare) 1989;32(6):85&867. Friedman M, Shimaoka K , Ran U, et al. Diagnosis of chronic lymphocytic thyroiditis (nodular presentation) by needle aspiration. Acta Cytol (Baltimore) 1981;25(5):5 13-522. Jayaram G , Marwaha RK, Gupta RK, Sharma SK. Cytomorphologic aspects of thyroiditis. A study of 51 cases with functional immunologic and ultrasonographic data. Acta Cytol (Baltimore) 1987;31(6):687-693. Politi-Deligeorgi H. Nuclear crease as a cytodiagnostic feature of papillary thyroid carcinoma in fine-needle aspiration biopsies. Diagn Cytopathol 1987;3(4):307-310. Schniid KW, Lucciarini P, Ladurner D, et al. Papillary carcinoma of the thyroid gland. Analysis of 94 cases with preoperative fine needle cytologic examination. Acta Cytol (Baltimore) 1987;31(5): 591-594. Could E, Watzak L, Chamizo W, Abores-Saavedra J. Nuclear grooves in cytologic preparations. A study of the utility of this feature in the diagnosis of papillary carcinoma. Acta Cytol (Baltimore) 1989;33(1):1&20. Rupp M, Ehya H. Nuclear grooves in the aspiration cytology of papillary carcinoma of the thyroid. Acta Cytol (Baltimore) 1989; 33(1):21-26. Hugh JC, Duggan MA, Chang-Poon V. The fine-needle aspiration appearance of the follicular variant of thyroid papillary carcinoma: a report of three cases. Diagn Cytopathol 4(3):196-201. Kung ITM, Yuen RWS. Fine needle aspiration of the thyroid. Distinction between colloid nodules and follicular neoplasms using cell blocks and 21-gauge needles. Acta Cytol (Baltimore) 1989;33(1):5360. Cavallari V, Maiorana A, La Rosa GL, Maiorana MC, Scimone S, Fano RA. Morphometric studies on fine-needle aspirates from follicular proliferative lesions of the thyroid. Pathologica 1989;81:441446. Suen KC. How does one separate cellular follicular lesions of the thyroid by fine-needle aspiration biopsy? Diagn Cytopathol 1988; 4(1):78-8 I . Mazzaferri EL. Solitary thyroid nodule: diagnosis and management. Med Clin North Am 1988;72(5):1177-1211. Silver CE, Loiodice J, Johnson JM, Schreiber K. Needle aspiration biopsy of thyroid nodules. Surg Gynecol Obstet 1981; 152:469472. Nishiyama RH, Bigos T, Goldfarb WB, et al. The efficacy of simultaneous fine-needle biopsy of the thyroid gland. Surgery 1986;100(6): 1133-1 137. Silverman JF, West L, Larkinew, et al. The role of fine-needle aspiration biopsy in the rapid diagnosis and management of thyroid neoplasm. Cancer 1986;57:116&1170. Studer H, Ramelli F. Simple goiter and its variants: euthyroid and hyperthyroid multinodular goiters. Endocr Rev 1982;3:40. Bisi H, Longatto Filho A, Asato de Camargo RY, Fernandes VOS. IncidCncia da Metaplasia Oxifilica no Bocio e sua importsncia na correlaqao anatomo-patologica e na punqao biopsia por agulha fina. Arq Bras Endocrinol Metab 1989;33(3):51-54. Kini SR, Miller JM, Hamburger JI. Cytopathology of Hurthle cell lesions of the thyroid gland by fine needle aspiration. Acta Cytol (Baltimore) 198 1;25(6):647-65 1. Bisi H, Fernandes VSO, Asato de Camargo RY, Koch L, Abdo AH, Brito T. The prevalence of unsuspected thyroid pathology in 300 sequential autopsies, with special reference to the incidental carcinoma. Cancer l989;64: 1888-1 893. Rosen IB, Wallace C, Strawbridge HG, Walfish PG. Reevaluation
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77. 78. 79.
87. 88. 89. 90. 9 1.
of needle aspiration cytology in detection of thyroid cancer. Surgery 198 1;90(4):747-756. Miller TR, Abele JS, Greenspan FS. Fine needle aspiration blopsy in the management of thyroid nodules. West J Med 1981;90(4):747756. Delellis RA, Rule AH, Spiler I, et al. Calcitonin and carcinoembryonic antigen as tumor markers in medullary thyroid carcinoma. Am J Clin Pathol 1978;70:587-594. Rastad J, Wilander E, Lindgren PG, et al. Cytologic diagnosis of a medullary carcinoma of the thyroid by Sevier-munger silver staining and calcitonin immunocytochemistry. Acta Cytol (Baltimore) 1987; 3 I ( 1):4547. Nickols CD. Simple technique to identify haemosiderin in immunoperoxidase stained sections. J Clin Pathol 1984;37(10):119@ 1191. Gal R, Aronof A, Gertzmann H, Kessler E. The potential value of the demonstration of thyroglobulin by immunoperoxidase techniques in fine needle aspiration cytology. Acta Cytol (Baltimore) l978;3 l(6):713-7 16. Permanetter W, Nathrath WBJ, Lohrs U. Immunohistochemical analysis of thyroglobulin and keratin in benign and malignant thyroid tumours. Virchows Arch [A] 1982;398:221-228. Chlap Z, Szot W. Valeur diagnostic des ponctions des kystes thyroidiens. Semin Hop Paris 1980;7-8:362-364. Goellner JR, Johnson DA. Cytology of cystic papillary carcinoma of the thyroid. Acta Cytol (Baltimore) 1982;26(6):797-799. Muller N, Cooperberg PL, Suen KCH, Thorson SC. Needle aspiration biopsy in cystic papillary carcinoma of the thyroid. AJR 1985; 144:251-25 3. Rosen IB, Provias JP, Walfish PG. Pathologic nature of cystic nodules selected surgery needle aspiration biopsy. Surgery 1986; 100(4):606-6 13. Bisi H, Fernandes VSO, Longatto Filho A, Asato de Carmargo RY. IncidCncia de cistos em carcinoma papilifero da tireoide. Arq Bras Endocrinol Metabol 1988;32(4):94-96. Lee JK, Tai FT, Lin HD, Chou YH, Kaplan MM, Ching KN. Treatment of recurrent thyroid cysts by injection of tetracycline or Minocycline. Arch Intern Med 1989;149:599-601. Hegedus L, Hansen JM, Karstrup S, Torp-Pedersen S, Juul N. Tetracycline for sclerosis of thyroid cysts. A randomized study. Arch Intern Med 1988;148:1116-1118. Treece GL, Georgetis WJ, Hofeldt FD. Resolution of recurrent thyroid cysts with Tetracycline instillation. Arch Intern Med 1983; 143:2285-2287. Focacci C, Salvo D, Crupi M, La Vecchia G. Scintigrafia e termografia per lo studio della tiroide. Radio1 Med (Torino) 1977;9:781782. Walfish PG, Hazani E, et al. A prospective study of combined ultrasonography and needle aspiration biopsy in the assessment of the hypofunctioning thyroid nodule. Surgery 1977;82(4):474482. Mendonqa LK. Echographic diagnosis of benign and malignant thyroid nodules. Toshiba Medical Review 1989;28:1-6. Lever JV, Trott PA, Webb AJ. Fine needle aspiration cytology: review article. J Clin Pathol 1985;38:1-1 I . Yao Y. Thyroid nodules-benign or malignant? Postgrad Med J 1977;61:65. Hamburger JI. Fine needle biopsy diagnosis of thyroid nodules. Perspective. Thyroidology 1988;1 :21-34. Hugues FC, Baudet M, Laccourreye H. Le nodule thyroidien. Une etude retrospective de 200 observations. Ann Oto-Laryng (Paris) 1989;106:77-81. Jones AJ, Aitman TJ, Edmonds CJ, et al. Comparison of fine needle aspiration cytology, radioisotopic and ultrasound scanning in the management of thyroid nodules. Postgrad Med J 1990;66:914917.