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The papillary thyroid carcinoma (PTC) is the most frequent endocrine cancer and it is the most common thyroid cancer (85-95%). Potential risk factors for the incidence of the PTC include radiation exposure, iodine deficiency, family history of thyroid cancer. The PTC is usually indolent and the prognosis is favourable, with a 10 year survival generally reported to exceed 90%. The palpation and growth of thyroid nodules are the more frequent clinical manifestations of the PTC which can be evaluated by physical examination, neck ultrasound and fine needle aspiration cytology (FNAC). The therapeutic management of PTC includes surgical treatment combined with 131I therapy and life long TSH suppressive thyroid hormone replacement. The external beam radiation can be taken into account in select aggressive tumours. Nevertheless the good prognosis of the PTC, the prevalence of persistence or recurrent disease is not trans-curable. The biomolecular studies can permit to individuate the more aggressive PTC subtypes. A more significant attention of the clinical examination, US and FNAC to the thyroid nodular disease will be able to guarantee a more precocious diagnosis and a radical surgical treatment.

Purpose: The purposes of this study were to investigate the efficacy of radiocolloid lymphoscintigraphy and of handheld gamma probe procedure for sentinel lymph node biopsy (SLNB) in papillary thyroid carcinoma (PTC) and to evaluate its results in clinical staging., Materials and Methods: Sixty-five PTC consecutive patients entered the study. Patients underwent radiocolloid lymphoscintigraphy before surgery. Intraoperative sentinel lymph node (SLN) localization was performed using a handheld gamma probe. They were followed up at 2, 6 months, and yearly., Results: SLN metastases were diagnosed in 52%. Fifty-one patients underwent ablative 131-I therapy. The mean Tireoglobulin level in N0 vs N1 cases was 2.2 ng/ml vs 4.73 (p = 0.03) and 0.68 vs 2.1 ng/ml (p = 0.005) before and after 131-I therapy, respectively., Conclusions: In patients classified N0 by SLNB, ablative 131-I therapy could be avoided.

Background: The prognosis of patients with papillary thyroid carcinoma (PTC) is usually favorable; however, a subset of patients can develop local recurrence or distant metastases. The aim of this study was to evaluate the prognostic factors influencing the recurrence and the survival rate in 950 PTC patients., Materials and Methods: From 1990 to 2005, 950 consecutive patients affected by PTC were operated on at our Department. We analyzed the prognostic role of the following parameters: gender, age at initial treatment, extent of thyroid surgery, node dissection, tumor size, node metastases, distant metastases, stage, and 131-I therapy., Results: Seventy-nine patients (8.3%) developed locoregional or distant metastases after an average follow-up of 7.8 years (range 2-17 years); in particular local recurrence was observed in 25 cases and distant metastases in 54 cases. The global 10- and 15-year survival rates were 91.38% and 88.69%, respectively. At univariate analysis, all variables were significantly correlated with recurrence (P = .001) except gender (P = .3); moreover, gender (P = .2), node dissection (P = .5), and node metastases (P = .06) were not significant on 10- and 15-year survival. At multivariate analysis the age at first treatment, T4, M+, stage IV, the extent of thyroid surgery, and the 131-I therapy resulted to be significant and independent prognostic factors (P < .001)., Conclusion: Our data, in disagreement with other staging systems, suggest that gender does not play a significant role both in recurrence and survival. Moreover, the 131-I therapy was a statistically significant prognostic factor at univariate and multivariate analyses.

Aim: Papillary thyroid microcarcinoma (PTMC), a tumor measuring =or<1 cm according to the World Health Organization (WHO) histologic classification, is the most common histologic variant of thyroid cancer. The aim of this study was to evaluate the long-term outcome of surgical treatment for PTMC at a single institution with a view to differentiate therapy options based on risk of progression of disease by comparing our results with those reported in the literature., Methods: The study sample was a total of 587 cases of PTMC treated surgically at our institution between 1990 and 2006. PTMC was an incidental finding (PTMC-I) in 325 (55.4%) cases, diagnosed preoperatively (PTMC-D) at echography and needle-aspiration biopsy in 229 (39%), and occult with metastasis (PTMC-O) in 33 (5.6%). Patients were grouped into two classes (PTMC diameter =or>5 mm or <5 mm) and compared against prognostic factors: sex, age, type of PTMC (PTMC-I, PTMC-D, PTMC-O), extent of surgery, lymph node dissection, lymph node metastasis, iodine-131 (131-I) therapy, state of disease, relapses. These parameters were then compared against tumor size (PTMC diameter =or>5 mm or <5 mm), excluding cases of PTMC-O with metastasis., Results: Comparison of the two groups divided by tumor size, across the entire sample and after PTMC-O cases were excluded, revealed significant differences in the type of PTMC, frequency of partial thyroidectomy, presence of lymph node metastasis, iodine-131 therapy, life status and recurrence rate., Conclusion: Published PTMC studies were analyzed for definition of the disease, incidence, therapy, prognosis, and follow-up results and compared with our data. The results of our analysis argue against use of the term ''microcarcinoma'' in the wider sense since the three PTMC categories (PTMC-I, PTMC-D, PTMC-O) present different behaviour patterns. When cases of PTMC-O with clinically manifest metastasis were excluded, none of the patients with PTMC <5 mm in diameter were reoperated for tumor recurrence and all are currently free of disease. In conclusion In PTMC <5 mm in diameter, whether PTMC-I and PTMC-D, and without evidence of lymph node involvement, partial thyroidectomy may be a viable approach to treatment. By contrast, occult PTMC with metastasis is prognostically important and should therefore be treated like tumors =or>5 mm in diameter.

The present study aims to evaluate the accuracy of sentinel lymph node (SLN) mapping performed by intratumoral injection of blue dye in a large series of patients with papillary thyroid cancer (PTC). 153 consecutive patients were enrolled in the study. All patients had a preoperative cytological diagnosis of PTC, and none had clinical or ultrasonographic (US) evidence of nodal involvement. At surgery, vital patent V blue dye was injected into the malignant thyroid nodule. Subsequently, total thyroidectomy, central compartment (CC) node dissection, and median inferior jugulocarotid node dissection of laterocervical compartment, ipsilateral to the primary tumour, were performed. The excised thyroid, the blue-positive SLN and blue-negative lymph nodes were sent for frozen section and definitive histophatologic analysis. At surgery, blue-positive SLN were found in 107/153 patients (69.9%), of whom 36 (33.6%) had micrometastasis in SLN; moreover, in 13 of these 36 patients (36.1%), other nodes were found to be metastatic. In the remaining 71/107 blue-positive SLN patients, both the SLN itself and the other removed nodes were found negative for the presence of metastatic disease. In 4 cases, a normal parathyroid gland and in 3 cases fibro-adipous tissue were blue-stained and mistakenly removed as SLN (7 false positive results). On the other hand, SLN was blue-negative in 46/153 patients (30.1%), of whom 7 patients (15.2%) had micrometastases in blue-negative lymph nodes. On the basis of these data, the blue dye procedure for SLN detection appears inappropriate as a standard of care in PTC due to a relatively high number of false negative and false positive results.

Aim: To investigate an "optimal" therapeutic management of patients with papillary thyroid microcarcinoma (PTMC)., Methods: We evaluated a group of 403 consecutive patients affected by PTMC operated on by the same surgeon. Prognostic factors were evaluated by uni- and multivariate statistical analysis., Results: After a mean follow-up of 8.5 years, 372 patients were living without disease (undetectable serum thyroglobulin levels), 24 patients were living with disease (increased serum thyroglobulin levels), 6 patients were deceased due to causes different from thyroid cancer, and 1 patient was deceased due to metastatic thyroid cancer. No statistically significant prognostic factor was found at uni- and multivariate analysis. However, it is worth noting that in patients with a larger primary tumour (size> or =5mm) and treated by partial thyroidectomy alone, the prevalence of recurrent disease was higher than in patients treated by total thyroidectomy and (131)I administration., Conclusion: It appears reasonable to perform total thyroidectomy (possibly associated with central compartment node dissection), (131)I whole body scan (followed by (131)I therapy when necessary) and TSH-suppressive hormonal therapy in patients with PTMC.

Aim: How far to extend surgical treatment of papillary thyroid carcinoma (PTC) is still an open question. A contribution may derive from intraoperative lymphatic mapping because, in other malignancies, the procedure has become an important aid in defining lymph node status. The aim of this study was to evaluate the feasibility of sentinel lymph node (SLN) mapping performed by intratumoural injection of vital blue dye to guide nodal dissection in PTC., Methods: One hundred and ten patients were selected for the study, all of them had a preoperative diagnosis of PTC, but no clinical or ultrasonographic evidence of nodal involvement. Following cervicotomy and exposition of the thyroid gland, vital blue dye was injected into the malignant thyroid nodule. Subsequently, total thyroidectomy and lymph node dissection were carried out, and the thyroid, the SLN(s) and the other lymph nodes were sent for frozen section and definitive histologic evaluation., Results: Intraoperative lymphatic mapping located sentinel lymph nodes in 74 cases (67.3%); the SLN was detected in the laterocervical compartment (LC) in 4 cases (5.4%), with the ''sick'' of the CC. In 23 of these 74 patients (31.1%) the SLN(s) were positive for micro-metastases and in 15 cases (65.2%) both the SLN and other resected nodes were found positive. In the 51 cases in whom the SLN was disease-free, the other nodes were also negative. Of the 36 cases in whom the SLN was not detected, in 4 cases (11.1%) a parathyroid gland was stained and in 1 case (2.8%) fibroadipous tissue was stained. To date, of the 23 patients with positive-SLN 22 patients are living without disease (95.6%), 1 patient is living with disease (4.4%); all patients with negative SLN are living without disease; of the 36 patients without staining of the SLN, 35 are living without disease (97.2%) and 1 patient is deceased for reasons different from PTC (2.8%)., Conclusions: On the basis of this study, we underline some disadvantages in using Blue Patent V dye in SLN biopsy procedure as: a) the risk of disruption and interruption of the lymphatics from the tumour; b) blue dye uptake by a parathyroid gland which is successively mistakenly removed; c) the ''seak'' of the CC that doesn't permit to disclose SLN that lies outside the central compartment.

How far to extend the surgical treatment of papillary thyroid carcinoma (PTC) is still an open question. A contribution may come from intra-operative lymphatic mapping because, in other malignancies, the procedure has become an important aid in defining lymph node status. To assess the feasibility of using the sentinel lymph node (SLN) technique with the intratumoral injection of Patent Blue V dye to guide nodal dissection in PTC, 29 patients with a preoperative diagnosis of PTC and no clinical or ultrasonographic evidence of nodal involvement underwent cervicotomy and exposure of the thyroid gland, followed by Patent Blue V dye injection into the thyroid nodule. Total thyroidectomy was subsequently performed, resecting the lymph nodes at levels III, IV, VI and VII. The thyroid, SLN and the other lymph nodes were snap-frozen and submitted for both intra-operative and subsequent definitive pathological evaluation. Intra-operative lymphatic mapping located the SLN in 22/29 patients (75.9%) and the SLN revealed neoplastic involvement in 4/22 (18.2%); other lymph nodes were also positive in 2 cases. In the 18 patients whose SLNs were not metastatic, the other nodes were also disease-free. The SLN technique thus seems helpful in avoiding unnecessary lymph node dissection in PTC without spread to the SLN.

The authors report three cases of primary hyperparathyroidism (HPT) in patients with differentiated thyroid carcinoma (DTC) developed a few years after initial surgical and radiometabolic treatment of DTC. The early diagnosis of HPT in these patients was made possible because of laboratory tests performed during follow-up, including the assay of serum calcium and serum phosphorus levels. Scinti-graphy using 99mTc-MIBI enabled the correct preoperative localisation of a single parathyroid adenoma in two of these patients and multiglandular pathology in the third.

Two cases of papillary thyroid carcinoma coexisting with a parathyroid adenoma are reported. A double-tracer pertechnetate-MIBI subtraction scan combined with neck ultrasound correctly visualized the site of the parathyroid adenoma despite the presence of thyroid nodule(s) located in the opposite thyroid lobe in one case and in both thyroid lobes in the other case. In both patients, the papillary thyroid carcinoma was cold with Tc-99m pertechnetate and hot with MIBI. Total thyroidectomy and parathyroidectomy of a solitary parathyroid adenoma were performed in both patients. Pertechnetate-MIBI subtraction scanning associated with neck ultrasound appears to be a useful imaging technique to detect parathyroid adenoma before operation in patients with concomitant thyroid nodular disease. A MIBI-hot and Tc-99m pertechnetate-cold thyroid nodule can indicate the possible presence of a malignant lesion.

Methods: A total of 463, out of 677 patients operated on for papillary thyroid carcinoma between 1967-1995, were selected, on the basis of a 5-year minimal follow-up (max 28, mean 11.15 +/- 5.29), for uni and multivariate analysis of survival curves. Patient sex, age over and under 45 years, tumour size smaller and larger than 15 mm, stage, any TNM parameter, histological variety, surgical procedure on the thyroid and nodes were the factors assessed in order to express the prognosis., Results: Male:female ratio was 1:3, the mean age 42.2 years; only 25.9% of patients presented with smaller than 15 mm tumor, about 57% with positive nodes and 8.85% with distant metastases; total or near total thyroidectomy was performed in 86% and nodal dissection in 70% of patients. The 5, 10, 15, 20 year survival rate resulted to be 96.94%, 94.36%, 91.38% and 88.69%; 23 patients, but none aged less than 45 years, died (poorly differentiated and locally advanced carcinoma). Age over 45 years, T4 and M+ stages resulted of high prognostic importance while nodal involvement, interrelated with T and M, showed no independent impact; stage gradually worsened but no difference was found between stage I and II. Adverse effect of male sex resulted from its interrelation with more advanced stages. The relapse rate was found higher in male sex and in patients aged over 45 years, interrelated with T and N extension: no tumor smaller than 15 mm recurred and no relation was found between recurrence and surgical procedure., Conclusions: Longer follow-up is needed to compare the higher curative effectiveness of total thyroidectomy and nodal dissection versus more conservative treatments.

Out of 677 patients, who underwent surgery for papillary thyroid carcinoma between '67-'95, we selected for survival uni and multivariate analysis 463 patients with over 5 years of minimal follow up (max 28, mean 11.15 +/- 5.29). Patient's sex, age (over and under 45) tumour size (smaller and larger than 15 mm), stage, any TNM parameter, hystological variety, surgical procedure on the thyroid and nodes were the factors assessed in order to establish the prognosis. Male:female ratio was 1:3, average age 42.2 +/- 0.68; only 25.9% of the patients presented smaller than 15 mm tumors, about 57% positive nodes and 8.85% distant metastases; total or near total thyroidectomy was performed in 86% of the cases and nodal dissection in 68.47%. The 10, 15, 20 year survival rate resulted to be 94.36%, 91.38% and 88.69%; 23 patients (4.96%) died of poorly differentiated and locally advanced carcinoma, but none of them was younger than 45. Age over 45, T4 and M+ stage parameters and dedifferentiated histotype resulted of high value while nodal involvement, interrelated with T and M, showed no independent impact; stage gradually got worse but no difference was found between stage I and II, or T1 and T2. Surgical treatment has not resulted to affect survival, whereas lymphnodes involvement is correlated with complications. Adverse effect of male sex resulted from its interrelation with more advanced stages. A significantly higher relapse rate was found in males and in patients over 45, interrelated with T and N extension: no tumor smaller than 15 mm recurred and no relation was found between recurrence and surgical procedure. Longer follow-up is needed to compare the more conservative treatments with total thyroidectomy and nodal dissection.

A series of 112 patients reoperated on for differentiated thyroid cancer is analyzed; 60 patients (38 with papillary and 22 with follicular cancer) underwent ex-principio to completion of a non total thyroidectomy and 52 (37 with papillary and 15 with follicular cancer) to repeat surgery for local relapse. At a mean follow-up of 8.7 years, all the 38 patients with papillary cancer reoperated on for completion are alive and disease-free, while of those with follicular cancer 4 are dead, 2 are alive with carcinoma and 16 (72.7%) are disease free. A reoperation for relapse was performed on the thyroid in 11, on the thyroid and nodes in 23 patients (all had initially received partial thyroidectomy), and on nodes alone in 28 patients. At a mean follow-up of 10.2 years, 20 patients (54%) with papillary and 7 (46.6%) with follicular cancer are alive and disease-free, 8 patients with papillary and 1 with follicular cancer are alive with disease and the remainder are dead due to the tumour. Although there is no sure evidence that total thyroidectomy provides higher survival and fewer recurrences, since many factors, predominantly age influence the prognosis, total thyroidectomy is recommended as a minimal procedure to avoid less safe and less radical subsequent reoperation.

Thyroid carcinoma represents less than 2% cancers although there is an increasing incidence, mainly of the papillary variety, due in part to improved diagnostic procedures. In contrast there is a remarkably higher prevalence of occult foci in detailed autopsy studies (up to 34%) suggesting the possibility of a spontaneous regression for most of them. Only 1-2% of latent tumours grow larger and become clinically important through environmental, genetic and cellular factors (two-mutational event model by Knudson). Each single histological subgroup has different influencing factors: X ray exposure, iodide diet intake, coexisting (autoimmune and non) thyroid disease such as thyroiditis, Graves' disease, goitre, dyshormonogenesis, heredity and altered cellular oncogenes have been considered. Of a series of 715 thyroid cancers operated on between 1967 and 1992 we analyze sex ratio, mean age, radiation exposure, coexisting thyroid disease, familial occurrence.

In a surgical series of 277 consecutive patients operated on the thyroid for benign diseases, a high prevalence rate (10.5%) of occult papillary carcinoma was found by means of an accurate histologic examination. Indications for surgery were euthyroid multinodular goiter in 25 patients, autonomously hyperfunctioning adenoma in 2 and Graves' disease in 2 patients. Neoplastic foci were unilaterally found in 25 cases but multifocally in 6 and bilaterally in 4 cases: the diameters ranged from 2-10 mm. After operation (14 subtotal and 15 total thyroidectomies), all patients received TSH-suppressive doses of T4. At a mean follow-up of 5.6 years, neither local recurrences nor lymph node or distant metastases had occurred; no patient died of the tumor. In keeping with other surgical and autopsy series, the prevalence of occult thyroid carcinoma in a normal population is calculated to be about 5-10%, whereas it is known that the prevalence of clinically evident thyroid cancer is only 0.05%. This means that only 1-2% of occult carcinomas may evolve in an overt tumor during life. In view of such an epidemiologic difference and the favorable course of our patients, although the mean follow-up is rather short, we suggest that lobectomy plus T4 treatment may be considered an adequate therapeutic approach in patients with occult papillary thyroid carcinoma.

A case of extremely severe hyperthyroidism due to bone metastasis of papillary thyroid cancer is described. Hyperthyroidism began in this patient soon after the discovery of pelvic metastasis and worsened after total thyroidectomy and after the first dose of radioiodine. The administration of methimazole, prednisone and multiple, fractioned and small doses of radioiodine cured the hyperthyroidism and stabilized the neoplastic growth. Hyperthyroidism lasted for at least six months and hypothyroidism appeared only after seven months. Thus, the fractionation of the doses of radioiodine together with antithyroid drugs appears to be an effective treatment in patients with hyperthyroidism due to metastatic thyroid cancer.

Twenty-six patients with papillary and 4 with medullary thyroid carcinoma were examined by HRUS before surgery in order to evaluate its accuracy in detecting lymph node metastasis (N) of the neck from thyroid carcinoma. All patients underwent total thyroidectomy and nodal dissection. HRUS was accurate in 73% of cases in N staging, while clinical staging was accurate in 60% of cases only. In 50% of patients HRUS provided with interesting additional information, such as disclosing lymphadenopathy in 8 patients with no clinical evidence, proving nodal involvement in 5 cases, and showing extranodal extension in 5 cases. HRUS allowed the observation of anechoic necrotic areas and microcalcified nodes. On the other hand, according to our results, HRUS cannot either discriminate metastatic from benign nodal involvement, or identify mediastinal adenopathy. False negatives are possible due to micrometastatic areas in normal size nodes. Nevertheless, HRUS proved to be a valuable aid to complete clinical examination of the neck, and a good guide for the surgeon during nodal neck dissection.