Review of Literatures

Review of Literatures Fine needle biopsy was popular in the Scandinavian countries some four decades ago. Though FNAC for any palpable tumor was first introduced in America in the 1920s by Martin, Ellis and Stewart (an early opponent of exfoliative cytology) and subsequently largely abandoned in America, the procedure was adopted in Sweden where through the efforts of Franzen, Zayicek Soderstram and others it has become a routine and extremely well-documented technique used in the diagnosis of palpable or localised tumor 1,2,28. Fox summarised that fine needle aspiration biopsy is a major diagnostic tool in Scandinavia 28. The procedure is rapid, inexpensive and technologically simple yet it has found only limited, albeit increasing, acceptance in medical practice outside Scandinavia. Although the differences between Scandinavian and other medical systems may explain why the technique is not used more widely, there seems to be an underlying reluctance among medical communities to accept subjective types of innovation compared with objective innovation. Smeds states that, in the hands of an experienced cytologist aspiration, cytology is a safe and hitherto the best diagnostics tool in the evaluation of nodular thyroid lesions 13. In histologically verified case series 50-90% of confirmed thyroid cancers can be detected by aspiration biopsy, the sensitivity being dependent on sampling errors, microscopic misinterpretation and the variation in attitude towards intermediate diagnosis in the decision for diagnostic surgery. The number of proven benign cases that are correctly identified as such by biopsy varies accordingly and approximately 75% (specificity). In comparison with imaging procedures, including those giving information of functional activity, the combined sensitivity and specificity rates of aspiration cytology come closest to the ideal discriminatory situation. In combination with case history and careful clinical examination, fine-needle aspiration cytology is the best guidance for an optimal selection of patient for

therapeutic and diagnostic surgery. Future development of sensitive markers for malignant degeneration will probably increase the selective power of this diagnostic technique. Agrawal evaluated the diagnostic accuracy of fine-needle aspiration cytology (FNAC) in thyroid nodules in 100 consecutive cases, which subsequently underwent thyroidectomy between the years 1989-1991. FNAC as diagnostic test for thyroid nodules demonstrated an accuracy of 90.9%, a sensitivity of 76.5%, a specificity of 95.9% with a false positivity of 2%, false-negativity of 4%, positive and negative predictive values of 86.7% and 92.2%, respectively. A correct classification of the carcinoma type on the basis of FNAC was possible only in 69% patients. As a result, FNAC is the first line of investigation in most non-toxic nodular goitres and often the only procedure necessary to obtain an accurate diagnosis. However, it is recommended only adjunct to clinical judgement and is not intended to replace it 14. Hussain et al in 1993 evaluated the use of fine needle aspiration cytology (FNA) in the management of the solitary thyroid nodule and set up a thyroid cytology service in a district general hospital 9. One hundred and eight patients underwent FNA and then went on to have thyroid lobectomy. The results of cytology were compared with histology. The percentage of cancers was 8% and of benign legions 92%. The overall accuracy of FNA was 86%. If one includes a suspicious cytology as positive then six of seven cancers were diagnosed by FNA. Also, 49 benign colloid nodules were accurately diagnosed by FNA. They conclude that fine needle aspiration cytology is a useful adjunct to the management of the solitary cold thyroid nodule and should be used with other clinical information to decide the best form of treatment for the patient. During a six-year prospective study of clinically isolated thyroid swelling (ITS), Cusick et al found that 148 (37%) of 395 swellings were cystic as defined by the aspiration of fluid during fine-needle aspiration cytology (FNAC) 16. In the 106 (72%) patients operated upon, 47% of cystic swellings 9

were neoplastic and 14% were malignant. In men 29% of cystic swellings were found to be malignant and 11% of such cystic lesions in women were malignant. Only 12 cystic ITS were permanently abolished by aspiration and FNAC was inaccurate in predicting neoplasia. The incidence of malignancy in cystic ITS is higher than generally accepted and most cysts not abolished by aspiration should be removed. Ng et al in 1989 assessed the cost effectiveness of fine needle aspiration cytology (FNAC) as a selection criterion for surgery in solitary thyroid nodules compared to scintigraphy and ultrasonography 4. Ninety-eight patients who had FNAC and histological confirmation, scintigraphy and/or ultrasonography were studied. The use of combine diagnostic discriminants of positive FNAC, Clinical suspicion and age above 50 years detected all malignancies and would have resulted in fewer patients being subjected to surgery-51%(fnac) vs. 90% (scans, U/S). This resulted in cost saving of $ 800 per patients seen. They conclude therefore that FNAC should be the diagnostic modality of choice and that the routine use of scintigraphy and ultrasonography is not justifiable. The role of fine needle aspiration cytology of thyroid nodules was analysed in 116 cases by Hamaker et al in 1983. Forty-six percent of the patients with cold solid nodules were operated on with a 1% known false-negative and a 5% false-positive result. Ninety-four percent of the aspirations provided adequate cytologic material for evaluation. They proposed it as a new approach to the assessment and management of the thyroid nodule with fine-needle aspiration as the initial step in the evaluation 18. To determine whether the routine use of fine-needle aspiration (FNA) cytology reduces the rate of unnecessary surgery, the surgical pathology of 54 thyroidectomy patients who had preoperative FNA was compared to the results obtained with 24 thyroidectomy patients who did not have preoperative FNA by Bouvet et al in 1992. Twenty-nine (85.3%) of the 34 patients who had a positive FNA were confirmed by histology to have a thyroid neoplasm; in 24 patients, the neoplasm was malignant. Two of the 10

17 patients who had a negative FNA but underwent thyroidectomy based on other factors were found to have thyroid cancer. Only 8 (33.3%) of the 24 surgical specimens of patients who did not have an FNA were found to be malignant. FNA had a sensitivity of 93.5% and a specificity of 75.0%. The results indicate that the routine use of FNA for patients with thyroid nodules reduces the incidence of an unnecessary surgery. Furthermore, FNA alone is sufficient to identify most patient at risk and is, therefore cost-effective. However the presence of other findings suspicious of malignancy should preclude clinical decision-making based on FNA alone 11. Layfield et al evaluated the utility of clinical features for the selection of patients with thyroid lesions suitable for diagnosis by fine-needle aspiration cytologic study. They reviewed 149 cases with complete clinical histories, laboratory evaluation, fine-needle aspirates, and histologic study of indexed lesions 6. Review of these data demonstrated that only the presence of lymphadenopathy was of statistical value in the distinction of benign from malignant nodules. Moreover, once an aspiration diagnosis of follicular neoplasm had been made, no clinical, radiologic, or laboratory test aided in the distinction of follicular adenoma from follicular carcinoma. Willems and Lowhagen analysed the role of fine needle cytology in the management of thyroid disease in 1981 20.Fine-needle aspiration cytology of the thyroid gland is a low-cost office procedure, which even in children does not require regional anaesthesia. The method is safe, without appreciable complications or side effects. Since the needling is readily accepted by patients, it can be repeated when necessary. A morphological diagnosis is then rapidly obtainable and time-consuming and expensive investigations are bypassed. In the hands of experienced cytopathologists, fine-needle biopsy is a reliable means of selecting patients for surgery, thereby reducing the frequency of operations for benign lesions. The cytological reports enables the clinician to recognise the conditions which will benefit from non-surgical management, for example colloid goitre, 11

thyroiditis and lymphoma, and also to plan surgical strategy in papillary, medullary and anaplastic giant cell neoplasm's. In follicular neoplasms, aspiration biopsy cytology does not permit reliable distinction between adenoma and carcinoma. With combined consideration of aspiration biopsy cytology and scintiscans, however, it is possible to distinguish nonneoplastic from neoplastic follicular proliferation. In cases where cytological study does not give a specific or conclusive diagnosis, broad disease categories such as inflammatory or neoplastic states can be recognised. Even for these patients, therefore, the method can serve as a guide in the further management. In post-therapy follow-up of thyroid neoplasms, aspiration biopsy cytology permits rapid detection of recurrence. Lucas et al stated that, fine-needle aspiration cytology (FNAC) has become a widespread procedure for the study of thyroid nodules (TN) 21. Some authors recommend the practice of repeated punctures for their follow-up. This study was done to determine the usefulness of repeated FNAC in patients with benign nodular thyroid disease. They studied 251 fineneedle re-aspirations performed on 116 females aged 45.6 +/- 14 years. The time elapsed between each consecutive FNAC was one year. No patients presented any changes in the size or consistency of their nodular goitres during this period; all FNAC were carried out by the same physicians in the same thyroid area according to the Lowhagen technique, with the minimum of two or three aspirations of each nodule, and processed in the same way and valued by the same cytologist without any knowledge of cytological diagnoses. These were done using strict classical criteria (Lowhagen). 105 out of 116 patients (90.51%) with two consecutive FNAC (210) showed identical cytological diagnoses in the two specimens studied. The remaining 11 patients (9.48%) with two FNAC were diagnosed with colloid goitre and cyst alternately. Fifteen out of 19 patients (78.94%) with three FNAC showed identical cytological diagnoses in the three samples and the rest (21%) also demonstrated alternate diagnoses of colloid goitre and cyst. Their results show that the routine performance of 12

repeated FNAC in the follow-up of females with benign nodular thyroid disease, without any clinical changes, is a limited usefulness. Ng et al evaluated the impact of the routine use of fine-needle aspiration cytology (FNAC) on the management of solitary thyroid nodules 22. 102 consecutive patients were assessed in regard to the proportion of patients being subjected to surgery and the corresponding yield of malignancy. This cohort was compared with a historical control where FNAC was not routinely applied as diagnostic selection criterion the percentage of patient operated on had decreased from 95% to 60%(P less than 0.001) without any significant decrease in the field of malignancy: 18.6% vs. 17.6% (P = 0.97). The yield of malignancy of patients operated on had increased from 18.4% to 26.2%. Of those not subjected to surgery, 14 patients or 14% of the original cohort experienced spontaneous complete resolution of their nodules after mean follow-up period of 5.5 months (s.d.=3.5) (non rejected group). In the retrospective evaluation of diagnostic discriminants to maximise yield of malignancy while minimising unnecessary surgery for thyroid nodules, the use combined parameters and expensive investigations of radionuclid scans and ultrasonography. In conclusion, the decreased proportion of patients requiring surgery and cost saving while maintaining the yield of malignancy. From 1982 to 1987, 2433 lesions of the thyroid gland in 1796, patients were examined by fine-needle aspiration (FNA) by Altavilla 23. Cytopathology classified 66.91% of the aspirates as benign, 10.76% as thyroiditis, 4.89% as suspected ( unspecified) neoplasia, 1.31% as positive for malignancy and 16.11% (392) as unsatisfactory. The histologic diagnoses in 257 cases were compared with cytologic diagnoses to determine the accuracy of FNA cytology of thyroid lesions, yielding a sensitivity of 71.43% a specificity of 100% and an accuracy of 95.09%. This data strongly supports thyroid FNA as an important preoperative diagnostic tool. Follicular carcinomas were difficult to cytologically differentiate from non malignant follicular neoplasms and papillary 13

thyroid carcinomas less than 2 cm in diameter in elderly patients were frequently misdiagnosed or diagnosed only as suspect lesion. Radetic et al assessed the reliability of aspiration in thyroid nodes in 2190 cases 10. Cytological findings was negative in 1841 patients; accurate in 1763 (95.8%). Suspicious cytology proved malignant in 82 of 252 patients (32.5%). Positive cytology was accurate in 88 out of 97 cases (90.7%). In 1942 benign goitres, cytology was accurate in 90.8% of patients, false suspicious in 8.7% and false positive in 0.5%; the highest of percentage of misdiagnosis was in adenomas (15.8%) and thyroiditis (19.0%). In 248 malignant goitres, cytology was accurate in 35.5% of patients, suspicious in 33.1%, and false negative in 31.4 %. False negative cytology was found in 44% of follicular cancers, 22.2% of papillary and medullarry, and 12.9% anaplastic. The most frequent false-negative cytologic diagnosis was the adenomatous goitre. The accuracy of cytology was statistically higher in papillary cancers than in follicular (77.8% vs. 56.0%), in undifferentiated tumours than in differentiated (83.7% vs. 65.0%), and in adenomatous non-toxic goitres than adenomas, thyroiditis and toxic goitres (80.3% vs. 42.7%), (20.1% and 13.4%). Positive preoperative fine-needle aspiration biopsy cytology is worthwhile and reliable finding; it fails in less than 10% of patients. Negative cytology, however, does not exclude malignancy in thyroid nodes; it is false negative in more than 30% of cancers. Cusick, in his prospective analysis of over six years of cytological predictions compared with histological findings 16. The positive predictive value of aspiration cytology for detecting malignant disease was 100% and the sensitivity was 83%. The sensitivity for the detection of neoplasia (frank malignancy together with follicular adenomas) was 76%. The specificity was 58% and the overall accuracy was 69%. Recalculation of data in previous papers with strict criteria showed the accuracy of aspiration cytology to be variable and lower than is widely accepted. Since the introduction of aspiration cytology 21% fewer operations for isolated thyroid swellings have bean performed. 14

As a basis of selection for surgical excision of isolated thyroid swellings according to the prediction of neoplasia fine-needle aspiration cytology is less reliable than is widely accepted. It is an adjunct to management rather than a definitive test, and negative cytological results do not excludes neoplastic disease. Further study should take account of the implications of repeated clinic attendances for review and aspiration as these may culminate in delayed surgical treatment. In1989 Loy- et al attempted to assess the accuracy of radionuclide scan, ultrasonography and fine-needle aspiration biopsy as diagnostic tools in distinguishing malignant from benign nodular thyroid lesions in Singapore 5. The medical case records of 537 patients referred to the department of nuclear medicine were analysed. Ninety-four percent of the solitary thyroid nodules delineated on scintiscan were cold. The incidence of malignancy in solitary cold thyroid nodules was 8%, and that in multinodular goitres was 2.3%. The sensitivity of both radionuclid scan and ultrasonography in detecting cancer was 100%, but the specificity was disappointingly low i.e. 3.6% for radionuclid scan and 21% for ultrasonography. The sensitivity for fine-needle aspiration biopsy was 85%, and the specificity 96%. Fine-needle aspiration cytology is indisputable as an accurate diagnostic tool in differentiating malignant from benign thyroid lesions, and should be the first test to be used in the diagnostic workup of nodular thyroid disease. However, both radionuclid scan and ultrasonography remain crucial in the subsequent management of patient with thyroidectomy done for thyroid cancer. The other major roles are in the management of thyroiditis, thyrotoxicosis and confirmation of ectopic thyroid tissue. Giansanti et al 24, analysed a result of 1886 fine-needle cytoaspiration of solid, palpable thyroid nodules cold on scintiscanning, performed between 1 st January 1978 and 31 st December 1986. In total 36 diagnosis of malignancy were made (1.9%). The result of cytologic and histologic examinations were compared in 114 cases to verify the diagnostic accuracy of this method; there was agreement in 98 cases and 15

discordance in 16 consisting of 13 false negatives (11.4) and 3 false positives (2.6%). The sensitivity was 77.9%, specificity 94.5%, and efficiency 86%. These values are in the range of those reported in the literature and confirmed the validity of fine-needle aspiration cytology in the pre-operative diagnosis of thyroid neoplasms. Gagneten et al 19. evaluated the role of fine needle aspiration cytology in the evaluation of the clinically solitary thyroid nodule in 1987. The imputation that a clinically solitary nodule is suspicious sign of carcinoma has been the cause of too many surgical procedures as well as the subject of much controversy. This study evaluated the effectiveness of fine-needle aspiration (FNA) biopsy cytology in diagnosing the uninodular goitres in 286 patients who presented with clinically solitary nodules. The final diagnosis in these cases included carcinoma (4.7%), adenoma (6.3%), autonomous nodule (11.0%), colloid goitre (45.8%), colloid cyst (17.4%) and chronic thyroiditis (13.4%). The proportion of patients with cancer in this group was the same as in patients with multinodular and diffuse goitres. These finding call attention to (1) the fact that any thyroid disease may appear as uninodular goitre and (2) the frequency with which lymphocytic thyroiditis was cytologically diagnosed, even in cases with negative titres. The cytologic diagnosis of benign disease has contributed to a reduction in the number or unnecessary surgical procedures, only 24.1% of their patients with uninodular goitres underwent surgery. According to P.Harsoulis 29 fine needle aspiration biopsy cytology (ABC) was performed in 1100 patients with nodular goitre, who had either a solitary cold nodule or dominant hypofuntioning nodules within a multinodular or diffusely enlarged gland. Surgery was performed in patients based on clinical an cytological criteria, and the histology of the surgical specimens was correlated with the cytological findings. ABC specimens were sufficient for cytological diagnosis in 190 patients and were classified as malignant (positive), suspicious or benign. In 37 patients who had a final histological diagnosis of malignancy, cytology was positive or suspicious in 33 and benign in 4. In the remaining 153 16

patients with benign histology there were 7 positive or suspicious aspirates and 146benign.The 37 malignancies included papillary carcinoma in 26 patients (24 positive or suspicious and 2 benign in cytology), Hurtle cell tumour in 6 (6 positive), follicular carcinoma in 1 (negative), anaplastic carcinoma in one (suspicious), medullary carcinoma in 2 (1positive,1 negative), and lymphoma in 1(positive). The overall sensitivity of ABC method for cancer was 89.2%, the diagnostic specificity 95.4%, the false positive rate was 17.5% and false negative rate 2.6%. The overall accuracy of the method was 94.2%. It was concluded that papillary and Hurthle cell carcinoma could be diagnosed accurately with ABC but it we recommended that the method be used in conjunction with clinical information and other conventional diagnostic procedures. Al-Sayer 3 analysed fine needle aspiration cytology in isolated thyroid swellings. Cytological findings were not disclosed. It did not influence management and were compared later retrospectively with histological diagnosis. It was found that sensitivity for detection of neoplasia was 86%, overall accuracy 92%, and positive predictive value 96%. When cytological findings were used to influence management the frequency of operation for isolated thyroid swellings decreased by 25%. And the proportion of operation for neoplasia increased from 31 to 50%. In terms of bed occupancy the potentially avoidable surgical workload for benign disease was reduced by 34%. It was concluded that aspiration cytology, carried out at the first clinic attendance makes a sound basis for selective surgery and leads to economy in the management of isolated thyroid swellings. Anderson and Webb 2 analysed the fine needle aspiration biopsy in diagnosis of thyroid cancer. Conventional criteria for evaluation of thyroid nodule were inaccurate in identifying the small proportion of malignant neoplasm. The diagnostic accuracy of fine needle aspiration biopsy (FNAB) for cytology was therefore assessed in 562 patients with nodular thyroid disease, 373 of whom (66.4%) had histological confirmation of the cytological diagnosis. Sixty-one aspiration biopsy were positive for malignancy and the diagnosis was confirmed histologically in 59 of these 17

(96.7%). Thus, there were 2 false positive cytology. Four of 63 patients with proven carcinoma had benign cytological diagnosis, a false positive rate of 6.3%. In 57 of the 59 malignancies (96.6%) correctly diagnosed by FNAB, the histological type of the tumor was successfully identified. Overall 367 of 373 patients received correct cytological discrimination between benign and malignant nodules, an overall accuracy of 98.4% for FNAB. The sensitivity of the test was 93.7% and the specificity 99.4%. Besides being safe cost effective and reliable FNAB directs the appropriate selection of the patients for surgery and enables the correct operations to be perfomed for each type of tumour. 18