- Email: [email protected]
Fine-needle aspiration cytology of thyroid
doi:10.1054/ycdip.2002.0118, available online at http://www.idealibrary.com on
SELF-ASSESSMENT
Fine-needle aspiration cytology of thyroid ANSWERS Answer 1 Cytological preparations from this case show the background of thin colloid and many macrophages, some containing haemosiderin (Fig. 1). Occasional sheets of follicular thyroid epithelium are present mimicking papillary aggregates (Fig. 2). The cells within it are bland, evenly sized and have very little cytoplasm. In addition, sheets of larger cells with central nuclei, prominent nucleoli and more abundant cytoplasm with pulled out edges are present (Fig. 3). It is important to note that cells from both Figures 2 and 3 are very few in number, against a generally bland background, as seen in Figure 1. These features are typical of a benign colloid cystic goitre. The ‘papillary’ cluster in Figure 2 and apparent cellular pleomorphism in Figure 3 are both part of the spectrum of changes seen in this condition. The important feature pointing to the lesion being non-neoplastic is the presence of abundant colloid with relatively sparse follicular cells. The morphology of follicular cells alone, without regard to the colloid/cell ratio, may be misleading in this case and in thyroid cytology in general. Although papillary carcinoma may often be cystic, the occasional ‘papillary’ cell arrangement does not indicate papillary carcinoma. Bizarre cytoplasmic features are often due to degenerative changes, or in this case, due to the distension of the epithelial lining of the cysts. The lesion can safely be reported as benign, not requiring further intervention unless clinically symptomatic. The e⁄cacy of ¢ne-needle aspiration cytology (FNAC) and its role in the management of a nodular goitre are established.1 The accuracy of cytological diagnosis approaches 95%.2 FNAC of the thyroid has a high negative predictive value, which is useful to reassure the majority of patients presenting with thyroid enlargement.3 The combination of clinical ¢ndings with those of the FNAC is a reliable approach to the management of benign thyroid nodules.4 Because of the high prevalence of malignancy in thyroid nodules that are large (3 cm or larger), cystic/solid, or large and cystic/solid, and the possible false-negative FNAC diagnosis of these lesions, thyroid lobectomy for diagnosis should be considered in these patients even when FNAC ¢nding is interpreted as benign.5 Management of non-neoplastic thyroid nodules diagnosed by FNAC is controversial. While clinical follow-up with repeat FNAC for enlarging
thyroid nodules is recommended in some studies, others recommend repeat FNAC in follow-up of all benign thyroid nodules after several months or years, in order to identify possible misdiagnosed malignant lesions. Merchant et al. showed that the routine performance of repeated FNAC in the follow-up of patients with benign nodular thyroid disease, with or without any clinical changes, is of limited usefulness. Clinical factors rather than repeat FNAC may be more important in surgical management of patients with benign nodular thyroid disease.6
Answer 2 Very cellular FNAC smears are composed mainly of lymphoid cells with islands of epithelium among them (Fig. 4). High-power view of the epithelium reveals large cells with abundant cytoplasm and nuclei of variable size, often with prominent nucleoli. Cytoplasm is abundant and well outlined. Small lymphocytes are interspersed within the epithelium (Fig. 5). Some of the epithelial clusters have a less well-de¢ned cytoplasm and are merging at the edges with the surrounding lymphocytes, lymphoblasts and plasma cells (Fig. 6). Follicular dendritic cells may also be seen in other parts of the preparations. The features are typical of lymphocytic thyroiditis. Lymphocytic thyroiditis is an autoimmune disease of the thyroid a¡ecting mainly middle-aged women but may be seen in both sexes and in all ages including children.The condition usually passes unrecognized clinically until there is a sizeable, often di¡use, swelling of the thyroid gland. Patients do not have any speci¢c clinical history and often have confusing results of other investigations, in particular the isotope scan which tends to show a mixed pattern of radio-iodine uptake in an ultrasonically solid nodule. Thyroid antibodies (antithyroglobulin and antimicrosomal) are usually raised but they may not represent the ¢rst line of investigation of a thyroid nodule. The condition is progressive and eventually results in replacement of thyroid epithelium with lymphoid cells. Patients do not need surgery but long-term medical surveillance and treatment according to the endocrine status. FNAC is highly sensitive in diagnosing lymphocytic (Hashimoto’s) thyroiditis, with a diagnostic accuracy rate of 92%.7 Re£ecting the progressive nature of the disease, the ratio of lymphoid cells and epithelium in the FNAC is
204
variable, depending on the stage of the disease and the site of aspiration. It is often the case that several samples contain atypical looking epithelium showing Hurthle (Ashkenazy) cell change, with no associated lymphoid cells. These may be seen only in the minority of smears or only in part of the smear. Particularly important is to note the presence of lymphoid follicle centre cells. The presence of even a few plasma cells in the aspirate with atypical epithelium should prompt the search for more lymphoid cells and, clinically, the investigation of antibodies. Occasionally, it is di⁄cult to appreciate the di¡erence between follicular dendritic cells and follicular epithelium of the thyroid which is trapped within the lymphoid cells. Sometimes follicular dendritic cells of the residual follicle centre fragment may appear as granulomata. Di¡erential diagnosis of lymphocytic thyroiditis includes thyroid lymphoma.8 Although thought to arise in lymphocytic thyroiditis, in our experience this is a very uncommon disease, often causing symptoms of compression and sometimes tracheal deviation at presentation.9 Cell population in thyroid lymphoma is usually monotonous and residual follicle centre fragments may not be seen. High-grade lymphoma is an aggressive disease and is usually not a signi¢cant diagnostic challenge from the pathological point of view. Low-grade lymphoma, however, can sometimes be di⁄cult to distinguish from chronic lymphocytic thyroiditis. Although mostly of B cell phenotype, not all low grade lymphomas in the thyroid originate from the marginal zone of the lymphoid follicles (MALT). The distinction between the di¡erent types of lymphomas has signi¢cant impact on the patient’s prognosis, treatment, and follow-up.10 In our experience, the main pitfall in diagnosis of lymphocytic thyroiditis is not in the morphology of lymphoid cells but in the epithelium. This can be very atypical, particularly in cases of long-standing lymphocytic thyroiditis, containing large cells with prominent anisonucleosis and well-de¢ned cytoplasm, similar to those of papillary carcinoma.Other potential pitfalls may be in the abundance or scarcity of background in£ammation, low cell yield and co-existing toxicity and malignancies. Epithelial preponderance over in£ammation, nuclear crowding, severe atypia and cell discohesion should raise the possibility of a neoplasm in spite of other features of autoimmune thyroiditis.11 However, the atypia is often the pointer of the pitfall since well-di¡erentiated carcinomas rarely display any signi¢cant degree of cell atypia. Di¡erential diagnosis includes Hurthle cell adenoma, which at times cannot be distinguished from Hashimoto’s thyroiditis.12
Answer 3 This is a very cellular aspirate composed of many epithelial cells with a background of blood and little or no colloid (Fig. 7). High power shows that cells are
CURRENT DIAGNOSTIC PATHOLOGY
arranged in individual ‘follicles’, most of which are ‘complete’ and some contain thick colloid in the centre (Fig. 8). No lymphoid cells, macrophages or other speci¢c features are seen. This is a ‘follicular lesion’, most probably neoplastic. Clinical characteristics (large diameter, ¢xation of the mass and young age of the patient13) may be used for more accurate assessment of the risk of the presence of a malignant lesion when FNAC of a thyroid nodule is reported as ‘suspicious for follicular neoplasm’. FNAC in this case is a triage method for selecting patients needing surgery. It is usually not possible to distinguish between follicular adenoma and follicular carcinoma from the FNAC material alone although morphometric parameters have been suggested.14 Papillary carcinomas, however, do have speci¢c features which allow them to be identi¢ed speci¢cally pre-operatively.15 The main differential diagnosis for the pathologist in this case is not between adenoma and carcinoma but between colloid ‘adenomatous’ hyperplastic/non-neoplastic nodule in a multinodular goitre and a neoplasm.16 This distinction is often di⁄cult but is not very common if the FNAC is performed under standard conditions so that the cell/ colloid ratio may be relied upon. Non-neoplastic conditions, although they may be cellular, often have an abundance of colloid in the background while adenomas and carcinomas typically lack it. Moreover, because of vascularity of the neoplastic process, a poorly sampled follicular carcinoma may appear hypocellular and may not show the cell pleomorphism expected of a malignant tumour. Good sampling technique and clinico-pathological correlation is therefore essential in this area of endocrine pathology if con¢dence in the FNAC as a method of surgical triage is to be maintained. Thyroperoxidase (TPO) immunostaining of FNAC from solitary, scintigraphically cold nodules of the thyroid gland has proved to be an important and reliable diagnostic tool for distinguishing between benign and malignant nodules. Thus, patients might be spared further surgery if not otherwise indicated.17 In this case, surgery was recommended and the histological ¢ndings were those of a follicular adenoma. FNAC has decreased costs substantially because it facilitates selection of patients who need to undergo surgical excision.18 Selecting patients for operation on the basis of results of FNAC has more than doubled the yield of carcinoma. Negative (benign) and positive (malignant) cytological results are conclusive; careful clinical follow-up of benign nodules and surgical excision of malignant nodules are recommended. Non-diagnostic results are inconclusive; further evaluation by repeated FNAC, ultrasound-guided biopsy or isotope scanning is necessary. Suspicious cytological results are also inconclusive and are associated with a 20% chance of malignant involvement; surgical treatment is necessary for clari¢cation. FNAC is a safe, simple, reliable and cost-
FINE -NEEDLE ASPIRATION CYTOLOGYOF THYROID
205
e¡ective means of ¢rst-line investigation of thyroid nodules.
11. Kumarasinghe MP, De Silva S. Pitfalls in cytological diagnosis of autoimmune thyroiditis. Pathology1999; 31: 1^7. 12. MacDonald L,Yazdi HM. Fine needle aspiration biopsy of Hashimoto’s thyroiditis. Sources of diagnostic error. Acta Cytol 1999; 43: 400 ^ 406. 13. Schlinkert RT, van Heerden JA, Goellner JR, Gharib H, Smith SL, Rosales RF et al. Factors that predict malignant thyroid lesions when ¢ne-needle aspiration is ‘suspicious for follicular neoplasm’. Mayo Clin Proc 1997; 72: 913^916. 14. DeshpandeV, Kapila K, Sai KS,Verma K. Follicular neoplasms of the thyroid. Decision tree approach using morphologic and morphometric parameters. Acta Cytol 1997; 41: 369^376. 15. Kumar PV,Talei AR, Malekhusseini SA, Monabati A,Vasei M. Follicular variant of papillary carcinoma of the thyroid. A cytological study of 15 cases. Acta Cytol 1999; 43: 139^142. 16. Busseniers AE, Oertel YC. ‘Cellular adenomatoid nodules’ of the thyroid: review of 219 ¢ne-needle aspirates. Diagn Cytopathol 1993; 9: 581^589. 17. Christensen L, Blichert-Toft M, Brandt M, Lange M, Bjerregaard Sneppen S, Ravnsbaek J et al.Thyroperoxidase (TPO) immunostaining of the solitary cold thyroid nodule. Clin Endocrinol 2000; 53: 161^169. 18. St. Louis JD, Leight GS, Tyler DS. Follicular neoplasms: the role for observation, ¢ne needle aspiration biopsy, thyroid suppression, and surgery. Semin Surg Oncol 1999; 16: 5^11.
REFERENCES 1. Godinho-Matos L, Kocjan G, Kurtz A. Contribution of ¢ne needle aspiration cytology to diagnosis and management of thyroid disease J Clin Pathol 1992; 45: 391^395. 2. Gharib H. Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations, and e¡ect. Mayo Clin Proc 1994; 69: 44 ^ 49. 3. Leonard N, Melcher DH. To operate or not to operate? The value of ¢ne needle aspiration cytology in the assessment of thyroid swellings. J Clin Pathol 1997; 50: 941^943. 4. Mazzawi SJ, Rosen G, Luboshitzky R, Dharan M. Management of benign thyroid nodules based on the ¢ndings of ¢ne-needle aspiration. J Otolaryngol 2000; 29: 95^97. 5. Meko JB, Norton JA. Large cystic/solid thyroid nodules: a potential false-negative ¢ne-needle aspiration. Surgery 1995; 118: 996 ^1004. 6. Merchant SH, Izquierdo R, Khurana KK. Is repeated ¢ne-needle aspiration cytology useful in the management of patients with benign nodular thyroid disease? Thyroid 2000; 10: 489^ 492. 7. Nguyen GK, Ginsberg J, Crockford PM, Villanueva RR. Hashimoto’s thyroiditis: cytodiagnostic accuracy and pitfalls. Diagn Cytopathol 1997; 16: 531^536. 8. Fenton JE, Stack J, Kelly P, O’DwyerTP. Lymphoma and Hashimoto’s thyroiditis. J Laryngol Otol 1995; 109: 781^783. 9. Schole¢eld JH, Quayle AR, Harris SC, Talbot CH. Primary lymphoma of the thyroid, the association with Hashimoto’s thyroiditis. Eur J Surg Oncol 1992; 18: 89^92. 10. Kossev P, Livolsi V. Lymphoid lesions of the thyroid: review in light of the revised European^American lymphoma classi¢cation and upcoming World Health Organization classi¢cation. Thyroid 1999; 9: 1273^1280.
This self-assessment was compiled by G. Kocjan, Department of Histopathology, Royal Free and University College London Medical School, University College Hospital, London,UK Tel.: +44 (0)207679 6027; E-mail: [email protected]
SELF-ASSESSMENT
Fine-needle aspiration cytology of thyroid ANSWERS Answer 1 Cytological preparations from this case show the background of thin colloid and many macrophages, some containing haemosiderin (Fig. 1). Occasional sheets of follicular thyroid epithelium are present mimicking papillary aggregates (Fig. 2). The cells within it are bland, evenly sized and have very little cytoplasm. In addition, sheets of larger cells with central nuclei, prominent nucleoli and more abundant cytoplasm with pulled out edges are present (Fig. 3). It is important to note that cells from both Figures 2 and 3 are very few in number, against a generally bland background, as seen in Figure 1. These features are typical of a benign colloid cystic goitre. The ‘papillary’ cluster in Figure 2 and apparent cellular pleomorphism in Figure 3 are both part of the spectrum of changes seen in this condition. The important feature pointing to the lesion being non-neoplastic is the presence of abundant colloid with relatively sparse follicular cells. The morphology of follicular cells alone, without regard to the colloid/cell ratio, may be misleading in this case and in thyroid cytology in general. Although papillary carcinoma may often be cystic, the occasional ‘papillary’ cell arrangement does not indicate papillary carcinoma. Bizarre cytoplasmic features are often due to degenerative changes, or in this case, due to the distension of the epithelial lining of the cysts. The lesion can safely be reported as benign, not requiring further intervention unless clinically symptomatic. The e⁄cacy of ¢ne-needle aspiration cytology (FNAC) and its role in the management of a nodular goitre are established.1 The accuracy of cytological diagnosis approaches 95%.2 FNAC of the thyroid has a high negative predictive value, which is useful to reassure the majority of patients presenting with thyroid enlargement.3 The combination of clinical ¢ndings with those of the FNAC is a reliable approach to the management of benign thyroid nodules.4 Because of the high prevalence of malignancy in thyroid nodules that are large (3 cm or larger), cystic/solid, or large and cystic/solid, and the possible false-negative FNAC diagnosis of these lesions, thyroid lobectomy for diagnosis should be considered in these patients even when FNAC ¢nding is interpreted as benign.5 Management of non-neoplastic thyroid nodules diagnosed by FNAC is controversial. While clinical follow-up with repeat FNAC for enlarging
thyroid nodules is recommended in some studies, others recommend repeat FNAC in follow-up of all benign thyroid nodules after several months or years, in order to identify possible misdiagnosed malignant lesions. Merchant et al. showed that the routine performance of repeated FNAC in the follow-up of patients with benign nodular thyroid disease, with or without any clinical changes, is of limited usefulness. Clinical factors rather than repeat FNAC may be more important in surgical management of patients with benign nodular thyroid disease.6
Answer 2 Very cellular FNAC smears are composed mainly of lymphoid cells with islands of epithelium among them (Fig. 4). High-power view of the epithelium reveals large cells with abundant cytoplasm and nuclei of variable size, often with prominent nucleoli. Cytoplasm is abundant and well outlined. Small lymphocytes are interspersed within the epithelium (Fig. 5). Some of the epithelial clusters have a less well-de¢ned cytoplasm and are merging at the edges with the surrounding lymphocytes, lymphoblasts and plasma cells (Fig. 6). Follicular dendritic cells may also be seen in other parts of the preparations. The features are typical of lymphocytic thyroiditis. Lymphocytic thyroiditis is an autoimmune disease of the thyroid a¡ecting mainly middle-aged women but may be seen in both sexes and in all ages including children.The condition usually passes unrecognized clinically until there is a sizeable, often di¡use, swelling of the thyroid gland. Patients do not have any speci¢c clinical history and often have confusing results of other investigations, in particular the isotope scan which tends to show a mixed pattern of radio-iodine uptake in an ultrasonically solid nodule. Thyroid antibodies (antithyroglobulin and antimicrosomal) are usually raised but they may not represent the ¢rst line of investigation of a thyroid nodule. The condition is progressive and eventually results in replacement of thyroid epithelium with lymphoid cells. Patients do not need surgery but long-term medical surveillance and treatment according to the endocrine status. FNAC is highly sensitive in diagnosing lymphocytic (Hashimoto’s) thyroiditis, with a diagnostic accuracy rate of 92%.7 Re£ecting the progressive nature of the disease, the ratio of lymphoid cells and epithelium in the FNAC is
204
variable, depending on the stage of the disease and the site of aspiration. It is often the case that several samples contain atypical looking epithelium showing Hurthle (Ashkenazy) cell change, with no associated lymphoid cells. These may be seen only in the minority of smears or only in part of the smear. Particularly important is to note the presence of lymphoid follicle centre cells. The presence of even a few plasma cells in the aspirate with atypical epithelium should prompt the search for more lymphoid cells and, clinically, the investigation of antibodies. Occasionally, it is di⁄cult to appreciate the di¡erence between follicular dendritic cells and follicular epithelium of the thyroid which is trapped within the lymphoid cells. Sometimes follicular dendritic cells of the residual follicle centre fragment may appear as granulomata. Di¡erential diagnosis of lymphocytic thyroiditis includes thyroid lymphoma.8 Although thought to arise in lymphocytic thyroiditis, in our experience this is a very uncommon disease, often causing symptoms of compression and sometimes tracheal deviation at presentation.9 Cell population in thyroid lymphoma is usually monotonous and residual follicle centre fragments may not be seen. High-grade lymphoma is an aggressive disease and is usually not a signi¢cant diagnostic challenge from the pathological point of view. Low-grade lymphoma, however, can sometimes be di⁄cult to distinguish from chronic lymphocytic thyroiditis. Although mostly of B cell phenotype, not all low grade lymphomas in the thyroid originate from the marginal zone of the lymphoid follicles (MALT). The distinction between the di¡erent types of lymphomas has signi¢cant impact on the patient’s prognosis, treatment, and follow-up.10 In our experience, the main pitfall in diagnosis of lymphocytic thyroiditis is not in the morphology of lymphoid cells but in the epithelium. This can be very atypical, particularly in cases of long-standing lymphocytic thyroiditis, containing large cells with prominent anisonucleosis and well-de¢ned cytoplasm, similar to those of papillary carcinoma.Other potential pitfalls may be in the abundance or scarcity of background in£ammation, low cell yield and co-existing toxicity and malignancies. Epithelial preponderance over in£ammation, nuclear crowding, severe atypia and cell discohesion should raise the possibility of a neoplasm in spite of other features of autoimmune thyroiditis.11 However, the atypia is often the pointer of the pitfall since well-di¡erentiated carcinomas rarely display any signi¢cant degree of cell atypia. Di¡erential diagnosis includes Hurthle cell adenoma, which at times cannot be distinguished from Hashimoto’s thyroiditis.12
Answer 3 This is a very cellular aspirate composed of many epithelial cells with a background of blood and little or no colloid (Fig. 7). High power shows that cells are
CURRENT DIAGNOSTIC PATHOLOGY
arranged in individual ‘follicles’, most of which are ‘complete’ and some contain thick colloid in the centre (Fig. 8). No lymphoid cells, macrophages or other speci¢c features are seen. This is a ‘follicular lesion’, most probably neoplastic. Clinical characteristics (large diameter, ¢xation of the mass and young age of the patient13) may be used for more accurate assessment of the risk of the presence of a malignant lesion when FNAC of a thyroid nodule is reported as ‘suspicious for follicular neoplasm’. FNAC in this case is a triage method for selecting patients needing surgery. It is usually not possible to distinguish between follicular adenoma and follicular carcinoma from the FNAC material alone although morphometric parameters have been suggested.14 Papillary carcinomas, however, do have speci¢c features which allow them to be identi¢ed speci¢cally pre-operatively.15 The main differential diagnosis for the pathologist in this case is not between adenoma and carcinoma but between colloid ‘adenomatous’ hyperplastic/non-neoplastic nodule in a multinodular goitre and a neoplasm.16 This distinction is often di⁄cult but is not very common if the FNAC is performed under standard conditions so that the cell/ colloid ratio may be relied upon. Non-neoplastic conditions, although they may be cellular, often have an abundance of colloid in the background while adenomas and carcinomas typically lack it. Moreover, because of vascularity of the neoplastic process, a poorly sampled follicular carcinoma may appear hypocellular and may not show the cell pleomorphism expected of a malignant tumour. Good sampling technique and clinico-pathological correlation is therefore essential in this area of endocrine pathology if con¢dence in the FNAC as a method of surgical triage is to be maintained. Thyroperoxidase (TPO) immunostaining of FNAC from solitary, scintigraphically cold nodules of the thyroid gland has proved to be an important and reliable diagnostic tool for distinguishing between benign and malignant nodules. Thus, patients might be spared further surgery if not otherwise indicated.17 In this case, surgery was recommended and the histological ¢ndings were those of a follicular adenoma. FNAC has decreased costs substantially because it facilitates selection of patients who need to undergo surgical excision.18 Selecting patients for operation on the basis of results of FNAC has more than doubled the yield of carcinoma. Negative (benign) and positive (malignant) cytological results are conclusive; careful clinical follow-up of benign nodules and surgical excision of malignant nodules are recommended. Non-diagnostic results are inconclusive; further evaluation by repeated FNAC, ultrasound-guided biopsy or isotope scanning is necessary. Suspicious cytological results are also inconclusive and are associated with a 20% chance of malignant involvement; surgical treatment is necessary for clari¢cation. FNAC is a safe, simple, reliable and cost-
FINE -NEEDLE ASPIRATION CYTOLOGYOF THYROID
205
e¡ective means of ¢rst-line investigation of thyroid nodules.
11. Kumarasinghe MP, De Silva S. Pitfalls in cytological diagnosis of autoimmune thyroiditis. Pathology1999; 31: 1^7. 12. MacDonald L,Yazdi HM. Fine needle aspiration biopsy of Hashimoto’s thyroiditis. Sources of diagnostic error. Acta Cytol 1999; 43: 400 ^ 406. 13. Schlinkert RT, van Heerden JA, Goellner JR, Gharib H, Smith SL, Rosales RF et al. Factors that predict malignant thyroid lesions when ¢ne-needle aspiration is ‘suspicious for follicular neoplasm’. Mayo Clin Proc 1997; 72: 913^916. 14. DeshpandeV, Kapila K, Sai KS,Verma K. Follicular neoplasms of the thyroid. Decision tree approach using morphologic and morphometric parameters. Acta Cytol 1997; 41: 369^376. 15. Kumar PV,Talei AR, Malekhusseini SA, Monabati A,Vasei M. Follicular variant of papillary carcinoma of the thyroid. A cytological study of 15 cases. Acta Cytol 1999; 43: 139^142. 16. Busseniers AE, Oertel YC. ‘Cellular adenomatoid nodules’ of the thyroid: review of 219 ¢ne-needle aspirates. Diagn Cytopathol 1993; 9: 581^589. 17. Christensen L, Blichert-Toft M, Brandt M, Lange M, Bjerregaard Sneppen S, Ravnsbaek J et al.Thyroperoxidase (TPO) immunostaining of the solitary cold thyroid nodule. Clin Endocrinol 2000; 53: 161^169. 18. St. Louis JD, Leight GS, Tyler DS. Follicular neoplasms: the role for observation, ¢ne needle aspiration biopsy, thyroid suppression, and surgery. Semin Surg Oncol 1999; 16: 5^11.
REFERENCES 1. Godinho-Matos L, Kocjan G, Kurtz A. Contribution of ¢ne needle aspiration cytology to diagnosis and management of thyroid disease J Clin Pathol 1992; 45: 391^395. 2. Gharib H. Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations, and e¡ect. Mayo Clin Proc 1994; 69: 44 ^ 49. 3. Leonard N, Melcher DH. To operate or not to operate? The value of ¢ne needle aspiration cytology in the assessment of thyroid swellings. J Clin Pathol 1997; 50: 941^943. 4. Mazzawi SJ, Rosen G, Luboshitzky R, Dharan M. Management of benign thyroid nodules based on the ¢ndings of ¢ne-needle aspiration. J Otolaryngol 2000; 29: 95^97. 5. Meko JB, Norton JA. Large cystic/solid thyroid nodules: a potential false-negative ¢ne-needle aspiration. Surgery 1995; 118: 996 ^1004. 6. Merchant SH, Izquierdo R, Khurana KK. Is repeated ¢ne-needle aspiration cytology useful in the management of patients with benign nodular thyroid disease? Thyroid 2000; 10: 489^ 492. 7. Nguyen GK, Ginsberg J, Crockford PM, Villanueva RR. Hashimoto’s thyroiditis: cytodiagnostic accuracy and pitfalls. Diagn Cytopathol 1997; 16: 531^536. 8. Fenton JE, Stack J, Kelly P, O’DwyerTP. Lymphoma and Hashimoto’s thyroiditis. J Laryngol Otol 1995; 109: 781^783. 9. Schole¢eld JH, Quayle AR, Harris SC, Talbot CH. Primary lymphoma of the thyroid, the association with Hashimoto’s thyroiditis. Eur J Surg Oncol 1992; 18: 89^92. 10. Kossev P, Livolsi V. Lymphoid lesions of the thyroid: review in light of the revised European^American lymphoma classi¢cation and upcoming World Health Organization classi¢cation. Thyroid 1999; 9: 1273^1280.
This self-assessment was compiled by G. Kocjan, Department of Histopathology, Royal Free and University College London Medical School, University College Hospital, London,UK Tel.: +44 (0)207679 6027; E-mail: [email protected]