Indications of Thyroid FNAB
	The main indication of FNAB is the preoperative selection of thyroid nodules. On clinical grounds, nodular thyroid diseases are classified as solitary nodules or multinodular goiters. The use of FNAB is well established in these two groups of clinical nodular disease. The widespread use of high-resolution echography has, however, lead to the recognition that non-palpable nodules are surprisingly frequent. The role of FNAB in this group is rather controversial. Non-nodular thyroid enlargement or enlarged cervical lymph nodes may also harbor cancer and require FNAB for diagnosis. The indications of FNAB for the detection of thyroid cancer in these different conditions will be briefly discussed. Solitary thyroid nodule: when a solitary thyroid nodule is evidenced by palpation, it is important to rule out the presence of a cancer and of an autonomously functioning thyroid nodule (AFTN), which may lead to hyperthyroidism. Cancer and AFTN account for approximately 5% and 10 % of all nodules, respectively. The large majority of solitary thyroid nodules are, therefore, benign and asymptomatic. There is a general consensus that FNAB and ultrasensitive TSH are the two most accurate tools to diagnose cancer and hyperthyroidism, respectively, and should be both used as first line diagnostic tests. When serum TSH is normal, thyroid nodules are supposed to be hypofunctioning and thyroid scintigraphy is unnecessary. As no clinical or echographic feature can exclude cancer in hypofunctioning nodules, all of them should be examined by FNAB5-7. In contrast, when TSH is low/suppressed, an AFTN is suspected and scintigraphy should be carried out for confirmation. As AFTNs have a very low cancer risk (in the range of 0.2-0.5 %), FNAB is indicated only in selected cases with clinically suspected features (e.g. rapid growth of solid areas, hard consistency, etc.). Multinodular goiter: multinodular goiters are especially common in endemic goiter areas with deficient iodine intake. They may also harbor AFTNs and/or malignant nodules. As for solitary nodules, a serum TSH determination will be important to raise the suspect of AFTN. For long time nodules in the context of a multinodular goiter have been believed to have a low cancer risk. However, it has become clear that the cancer risk in multinodular goiters is similar to that found in solitary nodules8,9. Therefore, all palpable nodules, except for AFTNs, discovered in the context of a multinodular goiter should be also examined by FNAB. At present, over 70 % of american physicians do use FNAB as a key diagnostic approach in multinodular goiter10. A fast growing multinodular goiter, involving one or both thyroid lobes, should raise the suspect of either an anaplastic thyroid cancer or a thyroid lymphoma. A prompt cytological diagnosis is crucial in determining a timely and appropriate therapy for these two aggressive malignancies. Subclinical thyroid nodular disease. Non-palpable thyroid nodules are found in 25-50% of the population by using ultrasound screening11. However, such a screening is not recommended at present and, therefore, these nodules may come to the clinician's attention following a neck echography carried out either for a single palpable nodule or an apparently diffuse goiter or a non-thyroid disease. Approximately one third of patients with a single palpable nodule are diagnosed additional non-palpable nodules when examined by echography. Non-palpable nodules are a heterogeneous group: they may be either single or multiple and with variable size. Even relatively large nodules (> 2 cm) located deeply or in the context of a goiter, may escape detection by physical examination12. The use of US-FNAB now allows examining nodules of few millimeters in size. However, cytological examination of all non-palpable nodules is considered cost ineffective and a reasonable approach is to limit FNAB to two groups of non-palpable nodules: a) nodules >= 1.5cm13, b) nodules < 1.5 cm when suspected to be small aggressive cancers (e.g. history of exposure to radiations, familiarity for thyroid cancer, suspect of medullary carcinoma, presence of enlarged locoregional lymph-nodes, etc.). The rational of these recommendations is based on the fact that, although small asymptomatic nodules may be malignant in 3-4% of cases, the large majority of these occult carcinomas do not actually progress to a clinical disease. Several studies indicate that, while the prevalence of occult thyroid cancers is very high (on average = 36 per 1,000 people, range, 4.5-356), clinical thyroid cancers occur much less frequently (approximately 2.5 per 1,000)14. Therefore, diagnosing and treating these tumors would lead to unnecessary costs and morbidity. Graves' and Hashimoto's disease. In Graves' patients the occurrence of thyroid nodules and cancer was considered rare. However, different lines of evidence now indicate that palpable thyroid nodules are approximately 3-fold more frequent than in the general population and carry an increased cancer risk15. There is also evidence that thyroid cancer associated to Graves' disease may behave more aggressively and have a poorer outcome than in uthyroid patients16. For these reasons, it is wise to screen Graves' patients for thyroid nodules and to examine nodules by FNAB. Hashimoto's thyroiditis may be also associated with thyroid carcinoma or with a thyroid lymphoma17. Furthermore, diffuse sclerosing papillary carcinoma, a histological variant of papillary carcinoma characterized by a diffuse involvement of an entire lobe or the whole gland, may mimic chronic thyroiditis18. For these reasons, FNAB is a very useful tool to confirm the diagnosis of Hashimoto’s disease and to exclude association with malignancies. Enlarged cervical lymph-nodes. FNAB is a powerful tool to diagnose thyroid cancer metastases in patients with a thyroid nodule and enlarged cervical lymph nodes. It is also very useful to identify small metastatic lymph nodes in the post-operative followup of patients operated for a thyroid cancer. The identification of metastatic thyroid cancer cells in standard cytological smears is, however, complicated by the frequent occurrence of inflammatory lymphadenopaties and metastases of non-thyroid malignancies. The use of ancillary techniques (see below) has an important role when examining enlarged lymph nodes for detecting thyroid cancer.