Single Institution Experience in the Management of Locally Advanced (pT4) Differentiated Thyroid Carcinomas.

BACKGROUND: Locally infiltrating (T4) differentiated thyroid carcinomas (DTC) represent a challenge. Surgical strategy and adjuvant therapy should be planned balancing morbidity and oncologic outcome. A series of patients with T4 DTC who underwent multidisciplinary evaluation and treatment is reported. The main study endpoints were the oncologic outcome, complication rates, and risk factors for tumor recurrence. PATIENTS AND METHODS: All DTC cases operated between 2009 and 2021 were reviewed and T4 DTC cases were identified. En bloc resection of inferior laryngeal nerve (ILN), tracheal, and/or internal jugular vein (IJV) was performed in cases of massive infiltration. In cases of pharyngoesophageal junction (PEJ) invasion, the shaving technique was always applied. RESULTS: Among 4775 DTC cases, 60 were T4. ILN infiltration was documented in 45 cases (en bloc resection in 9), tracheal infiltration in 14 (tracheal resection in 2), PEJ invasion in 11 (R0 resection in 7 cases and < 1 cm residual tissue in 4 cases), IJV resection in 6, and laryngeal in 2. In total, 11 postoperative ILN palsy, 23 transient hypoparathyroidisms, and 2 hematomas requiring reoperation were registered. Final histology showed 7 pN0, 22 pN1a, and 31 pN1b tumors. Aggressive variants were observed in 47 patients. All but 1 patient underwent radioiodine treatment, 12 underwent adjuvant external beam radiation therapy (EBRT), and 2 underwent chemotherapy. At a median follow-up of 58 months, no tumor-related death was registered, and seven patients required reoperation for recurrence. Tracheal invasion was the only significant factor negatively impacting recurrence (p = 0.045). CONCLUSIONS: A multidisciplinary approach is essential for the management of T4 DTC. Individualized and balanced surgical strategy and adjuvant treatments, in particular EBRT, ensure control of locally advanced disease with acceptable morbidity.

Distal outpatients hemodynamic treatment of chronic venous insufficiency of the lower limbs: a new proposal.

The etiology of the venous insufficiency of the lower limbs is related to the increase of the district pressure. This occurs in case of pressure overload of the afferent compartment with a progressive increase of the gradient until the reversal of the flow direction. Varicose veins would be the effect and not the cause of the pressure overload which must always be researched in the efferent (draining) compartment. The gradient inversion in a compartment causes a reflux circuit (venous shunt) only if - in addition to the escape point - one re-entry point is also active, The closure of the escape point does not solve the etiological moment of the district pressure overload. It is therefore a symptomatic treatment that cannot reduce the potential of the system to cause recurrences. During walking, reflux will cause Transmural Pressure Peaks (PPT): in diastole if the reflux is systolic; in systole if the reflux is diastolic; in diastole and in systole if the reflux is diastolic-systolic. On this basis, it has been proposed CHIVA 2 distal outpatient treatment without CHIVA 1 with interesting haemodynamic effects. In the subcutaneous area by the pressure overload block it improves compartment drainage, reduces the peak of trans-mural pressure and the caliber of the varicose veins. In the intrafascial district: reduces peak and trans-mural walking pressure; does not change the drainage of the reflux; can restore an antegrade flow. KEY WORDS: Hemodyamic venous treatment, Vricose veins, Venous Hemodynamic Map (VHM).

Is There Any Reliable Predictor of Functional Recovery Following Post-thyroidectomy Vocal Fold Paralysis?

BACKGROUND: Predicting definitive outcomes of post-thyroidectomy vocal fold paralysis (VFP) is challenging. We aimed to identify reliable predictors based on intraoperative neuromonitoring (IONM) and flexible fiberoptic laryngostroboscopy (FFL) findings. METHODS: Among 1172 thyroid operations performed from April to December 2021, all patients who exhibited vocal fold paralysis (VFP) at post-operative laryngoscopy were included. IONM data, including type of loss of signal (LOS), were collected. Patients underwent FFL, with arytenoid motility assessment, at 15, 45 and 120 days post-operatively. Patients were divided into two groups: those who recovered vocal fold motility (VFM) by the 120th post-operative day (recovery group) and those who did not (non-recovery group). RESULTS: Fifty-nine VFP cases (5.0% of total patients) met the inclusion criteria. Eight patients were lost at follow-up and were excluded. Overall, 9 patients were included in the non-recovery group (0.8% of total patients) and 42 in the recovery group. Among various predictive factors, only arytenoid fixation (AF) at the 15th post-operative day and Type I LOS were significant predictors for no VFM recovery (p = 0.007, RR = 9.739, CI:1.3-72.3 and p = 0.001, RR = 9.25, CI:2.2-39.3 for AF and Type I injury, respectively). The combination of type of LOS and arytenoid motility at the 15th post-op day yielded satisfactory predictive values for the progression of transient VFP to permanent. CONCLUSIONS: Arytenoid motility at the 15th post-op day and type II LOS are associated with recovery of VFM. Type of LOS and FFL could be included in the follow-up protocols of patients with VFP to reliably predict clinical outcomes.

Molecular Characterization of Thyroid Follicular Lesions in the Era of "Next-Generation" Techniques.

It is unequivocally recognized that thyroid nodules are frequently detected in the adult population and mostly characterized by benign lesions (up to 70% of them), with only 5%-15% malignant lesions. The evaluation of thyroid lesions with fine-needle aspiration cytology (FNAC) represents one of the first and most useful diagnostic tools in the definition of their nature. Despite the fact that the majority of thyroid lesions are correctly diagnosed as either benign (70%-75%) or malignant (5%-10%) entities, the remaining nodules (20%-25%) represent the "gray zone" of follicular lesions, which belong to indeterminate categories, according to the different classification systems. This indeterminate group of lesions includes both benign and malignant entities, which cannot be easily discriminate with morphology alone. In these last decades, the increasing role of molecular testings, feasibly performed on cytological material combined with the discoveries of specific genetic alterations in the field of thyroid pathology, has opened the pace to their more accurate and specific contribution on cytology. In fact, in 2015, in the revised management guidelines for patients with thyroid nodules and well-differentiated thyroid cancers (WDTCs), the American Thyroid Association (ATA) confirmed the performance of molecular testing in thyroid indeterminate cytology, and the same performance was addressed in recent update of the management of thyroid nodules in the second edition of the Bethesda system for reporting thyroid cytopathology (TBSRTC). In the current review, we discuss the role of molecular tests for the different thyroid diagnostic categories of the Bethesda system for reporting thyroid cytopathology, mostly focusing our attention on the follicular and indeterminate lesions.

Does Locally Advanced Thyroid Cancer Have Different Features? Results from a Single Academic Center.

BACKGROUND: Despite the fact that the majority of thyroid cancers are indolent, 15% of patients with well-differentiated carcinoma including papillary thyroid carcinoma (PTC) present with locally advanced thyroid cancer (LATC) at diagnosis. The current study analyzes a cohort of patients with LATC focusing on their risk for local recurrence, distant metastases, and overall survival. MATERIALS AND METHODS: From January 2010 to December 2020, 65 patients with LATC were retrieved, including 42 cases with preoperative cytological samples. BRAFV600E and TERT mutations were performed on both cytology and histopathology specimens in this cohort. RESULTS: Among the 65 cases, 42 (65%) were women. The median age was 60.1 years. Histological diagnoses included 25 (38.4%) with classic PTC and 30 (46.1%) aggressive variants of PTC, mostly tall cell variant (17 cases, 26.1%). Multifocality was seen in 33 cases (50.8%). All patients had nodal metastases. The most common site of extrathyroidal extension was the recurrent laryngeal nerve (69.2%). Staging revealed 21 cases were stage I, none were stage II, 33 were stage III, and 7 were stage IVa and 4 stage IVb. No differences were found between well and poorly/undifferentiated thyroid cancers. CONCLUSION: These data suggest that locally advanced thyroid cancers, including variants of PTC, exhibit a more aggressive biological course and should accordingly be more assertively managed.

Post-thyroidectomy hypocalcemia: Is a routine preferable over a selective supplementation?

BACKGROUND: Comparative studies among protocols for the management of post-total thyroidectomy (TT) hypocalcemia are lacking. We compared the effectiveness of PTH-driven selective supplementation (PD-SS) and routine calcium and calcitriol supplementation with preoperative calcitriol administration in preventing symptomatic hypocalcemia (SH) and readmission. METHODS: Three-hundred consecutive patients undergoing TT were assigned to 3 groups: the PD-SS group, the high-dose routine supplementation (HD-RS) group and the low-dose routine supplementation (LD-RS) group. RESULTS: Mean post-operative stay was shorter in HD-RS patients when compared to PD-SS and LD-RS (p < 0.001). Significantly more patients in the PD-SS group experienced SH (p = 0.042). The rate of post-operative hypocalcemia was not significantly different among the groups (p = 0.063). No readmission for SH or hypercalcemia occurred. CONCLUSIONS: HD-RS emerged as the most effective treatment to prevent SH, without increasing the risk of readmission for calcitriol-related hypercalcemia. Basing on the present results, HD-RS should be recommended as the preferable protocol.

Is it possible to intraoperatively modulate the extent of thyroidectomy in small papillary thyroid carcinoma?

BACKGROUND: Thyroid lobectomy is the preferred option for small, unifocal papillary thyroid carcinoma. Involvement of the central neck lymph nodes is an indication for total thyroidectomy plus central neck dissection. We aimed to verify if frozen section examination of ipsilateral central neck nodes can identify the subgroup of patients scheduled for thyroid lobectomy intraoperatively who could benefit of more extensive initial operative treatment. METHODS: Ninety-four consenting patients with clinically unifocal cN0 papillary thyroid carcinoma underwent thyroid lobectomy plus ipsilateral central neck dissection with frozen section examination. If the frozen section examination was positive for metastases, a completion thyroidectomy and a bilateral central neck dissection were accomplished during the same procedure. RESULTS: Frozen section examination identified occult nodal metastases in 25 of the 94 patients who then underwent immediate completion thyroidectomy and bilateral central neck dissection. Overall, central neck node metastases were found at final histology in 35 cases: occult micrometastases were observed in additional 9 patients and nodal metastases ≥2 mm in additional 1 patient. CONCLUSION: Intraoperative assessment of nodal status obtained with ipsilateral central neck dissection and frozen section examination is able to change the extent of thyroidectomy in about one-fourth of patients scheduled for thyroid lobectomy. Frozen section examination appears a safe and effective strategy to decrease the need of a second-step completion procedure and, theoretically, the risk of recurrence.

Extremely Late Recovery of Unusual Cervical Ankylosing Spondylitis-Related Dysphagia: Anesthesiologic, Surgical, and Pathophysiological Considerations, and Review of the Literature.

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory disease that involves above all the spine and the pelvis. In the spine, the inflammatory processes cause the formation of syndesmophytes between the vertebral bodies and the ossification of ligaments, with bony overgrowth. In this setting, dysphagia is a rare but severe complication and only a few cases have been reported in the literature. CASE DESCRIPTION: We describe the case of a 50-year-old man suffering from AS, with a 6-month history of severe dysphagia caused by bone compression of the esophagus at the C3-5 level. Because the patient underwent a 10-kg weight loss 2 months after clinical onset, a gastrostomy tube placement was needed. Complete surgical excision of the bone overgrowth via an anterior cervical approach was performed, but despite continuous intensive swallowing rehabilitation therapy, the patient failed to improve in the first following months. Surprisingly, the patient started to improve 18 months after the operation, with a complete recovery from dysphagia 24 months after. CONCLUSIONS: Among the 5 reports (including the present case) available in the current literature with a clear dysphagia recovery follow-up, the present case (the second one harboring gastrostomy) is associated with the slowest complete recovery published so far. This unusually late recovery suggests a possible role not only of the mechanical decompression of the esophagus but also of the degeneration/regeneration ratio of the myenteric plexus, along with local neurotransmitters sensitivity changes, to better understand the dysphagia recovery time course of this unique patient.

A large series of hyalinizing trabecular tumors: Cytomorphology and ancillary techniques on fine needle aspiration.

BACKGROUND: Hyalinizing trabecular tumors (HTTs) are rare, essentially benign, follicular cell-derived thyroid neoplasms characterized by a trabecular growth pattern and nuclear pseudoinclusions. Their cytological findings are misleading, because these tumors are often misinterpreted on fine needle aspirate cytology as malignant lesions, such as papillary thyroid cancer and/or medullary thyroid cancer, leading to unnecessary total thyroidectomy. The aim of this study was to analyze the cytomorphological features and application of ancillary techniques in a series of HTTs. METHODS: Of 26 histological cases of HTT collected from September 2001 to December 2018, 18 cases had concomitant cytopathology. Cytological cases were processed with liquid-based cytology (LBC). Immunocytochemistry for HBME-1 and galectine-3 as well as molecular testing for BRAFV600E mutation were performed on both LBC and histological specimens. RESULTS: The 18 lesions with fine needle aspirate cytology ranged in size from 5 to 45 mm. Cytological diagnoses included: 1 benign lesion favoring goiter (5.5%), 4 atypia of undetermined significance (22.2%), 6 follicular neoplasms (33.3%), 5 suspicious for malignancy favoring papillary thyroid cancer (28%), and 2 malignant (11%). Hence, 89% HTT had a negative concordant immunopanel, and they were 100% wild-type BRAFV600E . CONCLUSION: The majority of our HTTs (83.3%) were diagnosed in the indeterminate Bethesda categories, suggesting that their cytomorphological features pose issues for reaching a conclusive cytological diagnosis. The ancillary test results in our series support the fact that HTT is a benign neoplasm.

Echocolor Doppler morpho-functional study of the jugulo-subclavian confluence in chronic cerebro-spinal venous insufficiency and multiple sclerosis patients.

OBJECTIVES: The aim of this work is to measure the mean diameter of the confluence jugulo- subclavian, the impact of different types of jugular confluences and the correlation between the types of confluences and the Valsalva maneuver (jugular reflux) in subjects with Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and Multiple Sclerosis. METHOD: We investigated by Echo-Color-Doppler (ECD) 103 subjects (67 F 36M) of mean age 45 ± 12 years (a minimum of 22 to a maximum of 79 years, with a median of 44 and a modal value 42 years), mean EDSS of 4.7 and average disease duration of 12 years. RESULTS: The 103 right jugular veins investigated had an average diameter of 8.4 ± 2.4 mm (minimum 4.0, maximum 14.9 mm; median 7.9; modal value 7.6 mm). Three form types were found: 56 cylindrical, 29 conical and 18 funnel. Valsalva maneuver was positive in 30 patients. The 103 left jugular investigated had an average diameter of 8.9 ± 2.4 mm (minimum 2.8, maximum 14.4 mm; median of 8.8; modal value 8.7 mm). The form types were found: 42 cylindrical, 45 conical and 16 funnel. Valsalva maneuver was positive in 30 patients. CONCLUSIONS: The mean diameter of the jugular veins was 8.7 mm. Internal jugular veins with cylindrical morphology have a diameter smaller than other forms; this difference is statistically significant. The different morphology of the jugular vein confluence does not increase the possibility of a reflux because the positive Valsalva maneuvers are not statistically significant when compared to the various types. KEY WORDS: CCSVI, EchoColorDoppler Map, Jugulo-Subclavian Confluence Diameter.

Complications of Neck Dissections in Papillary Thyroid Carcinoma: A Modified Procedure to Reduce Parathyroid Morbidity.

BACKGROUND/AIM: Hypoparathyroidism is the most significant morbidity after neck dissection for thyroid cancer. Addition of lateral neck dissection (ND) to central ND combined with total thyroidectomy (TT) increases the risk of postoperative hypoparathyroidism compared to TT plus central ND. The aim of this study was to verify if a modified procedure and different access to the neck for lateral ND may improve safety. PATIENTS AND METHODS: In 62 patients with papillary thyroid cancer (PTC) undergoing TT plus central and lateral ND between 2010 and 2013, lateral ND was performed as first step approaching the neck via extrathyroideal space. Calcium in serum and parathormone (PTH) were determined preoperatively, intraoperatively and during the follow-up. RESULTS: Twenty patients (32%) developed postoperative hypocalcemia. Calcium levels and PTH completely recovered for 58 out of 62 patients from 3 to 6 months after surgery. After a mean of 12 months' follow-up, only four patients (6.5%) had developed permanent hypoparathyroidism. The incidence of parathyroid complication after TT plus central ND and lateral ND did not differ from postoperative hypoparathyroidim after TT plus central ND. CONCLUSION: The presented surgical procedure may provide a better outcome in terms of parathyroid morbidity.

Complications in thyroid surgery. Harmonic Scalpel, Harmonic Focus versus Conventional Hemostasis: A meta-analysis.

BACKGROUND: To evaluate the incidence of postoperative complications, hemostatic effects and safety of Total Thyroidectomy (TT) performed using the Harmonic Scalpel (HS), the Harmonic Focus (HF) or Conventional Hemostasis (CH). METHODS: The meta-analysis was performed according to PRISMA guidelines. A literature search was conducted from 2003 to 2014 and stringent criteria were required for inclusion. Thirteen studies concerning an overall population of 1458 compared HS versus CH, whilst 8 studies with 1667 patients compared HF versus CH. RESULTS: There was a significant reduction of operative time (Mean Difference [MD] = -25.49 min.; 95% CI -32.43 to -18.55), intraoperative blood loss (MD = -30.49 mL; 95% CI -53.01 to -7.97), postoperative drainage volume (MD = -12.90 mL; 95% CI -22.83 to -2.98) and postoperative pain (MD = -0.87; 95% CI -1.27 to -0.46) in patients underwent TT with HS. Regarding HF group, a significant reduction of operative time (MD = -25.99 min., 95% CI -34.56 to -17.41), length of hospital stay (MD = -0.57; 95% CI -0.97 to -0.17), transient hypocalcemia (OR = 0.56; 95% CI 0.39 to 0.81) and postoperative pain (MD = -1.33 days; 95% CI -2.49 to -0.17) resulted. CONCLUSIONS: HS TT can be a safe, useful and fast alternative to conventional TT. The newer HF can reduce the rate of hypocalcemia. Future RCTs of larger patient cohorts with more detailed data of postoperative complications, cost-effectiveness and cosmetic results, randomization procedures, intention-to-treat analyses and blinding of outcome assessors are needed to draw more meaningful conclusions.

Well-differentiated thyroid cancer with a minor poorly differentiated component: clonal heterogeneity through the prognostic role of CXCR4 and BRAF analysis.

Well-differentiated carcinoma (WDC) accounts for up to 90% of all thyroid cancers. The presence of a minor poorly differentiated (PD) component (mainly insular pattern) might represent an additional critical parameter for patients' prognosis and outcome. The role of both CXCR4 (a chemokine inducing cytoskeletal rearrangement and cell adhesion) and BRAF mutation have been studied in WDC (mainly papillary thyroid cancer and its variants), highlighting their critical role in tumor progression, local infiltration, and metastases. We discussed the clonal heterogeneity through the prognostic role of CXCR4 and BRAF mutation in WDC with a minor PD/insular component. Of our 16 WDC cases with a PD/insular component, up to 40% underwent surgery. The cases were subclassified according to the PD percentage as (1) <20% PD and (2) 20% to 40% PD, and were studied for CXCR4 expression and BRAF mutation. CXCR4 and molecular testing were distinctly performed on both components of each lesion. The majority of the cases (69%) showed an extrathyroid and metastatic dissemination. Regardless of the 2 categories, we had 8/16 (50%) patients with disease-free status. CXCR4 was negative in all 16 cases, whereas 3 of them (19%) had a mutated BRAF only in the WDC component of the lesion. WDCs with a minor PD pattern, even when <20%, showed more aggressive features than pure WDCs and should be entirely considered as PD carcinoma. The absence of CXCR4 expression and BRAF mutation in cancers with a minor PD component underlined different pathogenic and metastatic processes in comparison with WDCs.

Thyroglossal duct cyst cancer most likely arises from a thyroid gland remnant.

Thyroglossal duct cancer is a rare entity, occurring in 1.5 % of all thyroglossal duct cysts (TDC). A definitive consensus about its neoplastic origin has not been established as two contrasting theories exist, one proposing an origin in extra-thyroid remnants and the other a metastatic localization of a primary thyroid cancer. We compare morphological and molecular characteristics of both thyroglossal and thyroid carcinomas in a case series from our institute. We evaluated histology of 80 TDC. In 12 cases, prior cytological evaluation had been performed by liquid-based cytology (LBC). The BRAF gene was examined for mutations, and the histology of both thyroglossal duct and synchronous thyroid carcinoma was reevaluated. In 9 out of 80 (11 %) TDC cases, a papillary thyroid cancer (PTC) was diagnosed. In five out of nine (56 %) thyroglossal carcinomas, a synchronous thyroid cancer was diagnosed: 3 PTC and 2 follicular variant PTC (FVPC). In five thyroglossal carcinomas, mutated BRAF (V600E) was found, three in PTC and in thyroglossal as well as in the synchronous tumor in the thyroid. All the patients are in a disease-free status and still alive. Our results suggest that the majority of thyroglossal carcinomas most likely develop as a primary malignancy from a thyroid remnant. Neither the presence of V600E BRAF mutations nor that of a well-differentiated thyroid carcinoma changed the outcome or disease-free survival. We suggest that a diagnosis of thyroglossal carcinoma should be followed by a detailed evaluation of the thyroid gland. In the absence of clinical and radiological thyroid alterations, follow-up as for thyroid cancer is the correct management.

Papillary thyroid microcarcinoma: proposal of treatment based on histological prognostic factors evaluation.

BACKGROUND: Papillary thyroid cancer accounts for approximately 80% of thyroid tumors and its incidence has increased over the past decades. Papillary thyroid microcarcinomas (PMCs), defined by the World Health Organization as less than 1.0 cm in size, are identified with greater frequency. The majority of patients with PMCs follows a benign clinical course, however a subgroup of these carcinomas is as aggressive as bigger tumors. Risk factors related with poor outcome have not been defined and the optimal treatment has not been proved. The authors investigated histologic prognostic factors predicting high risk patients considered for more aggressive treatment and propose reviewed therapeutic guidelines based on analysis of histopathologic features which determined the recurrence rate. STUDY DESIGN: One hundred forty nine patients with PMC who underwent surgery were retrospectively analyzed. Clinical and histopathologic parameters potentially predicting patient outcome and recurrent disease were statistically investigated, after a minimum follow-up of 5 years. RESULTS: After a median follow-up of 5.4 years 28 of 149 patients experienced recurrent disease. All of them were reoperated on and newly treated with radioiodine administration. The multivariate statistical analysis identified extrathyroidal invasion (Odds Ratio, OR, 58.54; P=0.013), the solid pattern (OR,25.77; P>0.001), the tumor multifocality (OR, 15.80; P= 0.005), and the absence of tumor capsule (OR, 9.74; P=0.015) as significant and indipendent risk factors for the appearance of PMCs recurrences. Of note, none of the PMC "incidentally" discovered at histopathological examination alone experienced recurrent disease during follow-up. CONCLUSIONS: Although most PMC have favourable long-term prognosis, some patients (19% in our series) presented aggressive clinical course strongly correlated with some histopathologic features (extrathyroidal invasion, tumor multifocality, solid pattern and absence of capsule) who need to be investigated and for whom a radical therapeutic approach is recommended based on total thyroidectomy and regional lymphadenectomy followed by radioiodine administration.

The role of thyroid fine-needle aspiration cytology in the pediatric population: an institutional experience.

BACKGROUND: The current study was conducted to investigate the role of thyroid fine-needle aspiration cytology (FNAC) in the authors' pediatric series. Thyroid pediatric FNAC has been reported to have conflicting sensitivity and specificity in different series. The authors evaluated their thyroid cytological series mainly for the categories of 1) follicular/indeterminate neoplasms with atypical cells of indeterminate significance (FN/AUS) and 2) suspicious for malignancy (SM). In this setting, the application of immunocytochemistry (ICC) is likely to allow a correct diagnosis. METHODS: A total of 64 of 247 pediatric FNACs (26%) that were processed with liquid-based cytology had surgical follow-up. An ICC panel (Hector Battifora mesothelial cell-1 [HBME-1] and galectin-3) was performed on liquid-based cytology. A positive immunopanel was defined by a concordant positivity. RESULTS: These 64 cases were cytologically diagnosed as 4 cases of cystic hemorrhagic lesions, 23 benign lesions (BL), 17 FN/AUS cases, 11 SM cases, and 9 positive for malignancy (PM) cases. All PM and BL cases were histologically confirmed. The rate of malignancy was 31.2%, including 1 case of follicular carcinoma, 9 cases of classic papillary thyroid carcinomas (PTC), and 10 PTC variants (7 follicular variant of PTC, 1 macrofollicular variant, and 2 sclerosing diffuse variants). The immunopanel was performed on the categories of FN/AUS, SM, and PM. The data highlighted a concordant positive ICC in 87% of malignancies and a concordant negative ICC in 100% of benign follicular adenomas. CONCLUSIONS: Thyroid FNAC represents a valuable/feasible tool in childhood. The higher incidence of histological malignancies justifies the cytological application of ancillary techniques (ie, ICC or molecular panels), thereby enabling a more adequate surgical selection based on the effective distinction of high-risk and low-risk lesions mainly for the categories of FN/AUS and SM.

Diagnostic and prognostic role of HBME-1, galectin-3, and ß-catenin in poorly differentiated and anaplastic thyroid carcinomas.

AIM: Thyroid cancer represents the first endocrine malignant neoplasm, accounting for 1% of human malignancy. The majority of which are well-differentiated cancer representing up to 90% of thyroid cancer and pursuing a favorable clinical course. The groups of poorly differentiated thyroid cancer (PDC) and anaplastic thyroid cancer (ATC) have a poor outcome and need a strict clinical surveillance. MATERIALS AND METHODS: Thirty-four cases including 23 PDC/insular cancer and 9 ATC were examined for the expression of an immunohistochemical panel made up by HBME-1, galectin-3, and ß-catenin and correlated either with histologic prognostic parameters or the overall surveillance. RESULTS: HBME-1 and galectin-3 were expressed in 100% of the PDC/insular cases and in none of the ATC cases. The data for ß-catenin pointed out an 80% expression (12/15) in the PDCs and only a focal and nonspecific positivity in the ATCs. A ß-catenin-positive expression was found in all patients with a worse outcome/death and in the presence of vascular invasion and metastatic disease. All 3 PDC patients with ß-catenin negativity are alive, whereas only 41% (5/12) are alive in the ß-catenin-positive group. CONCLUSIONS: Our data set up the idea that PDC represents an intermediate step in the biological process of dedifferentiation of thyroid tumors toward ATC. This shift is underlined by the ß-catenin expression, which seems to be related to a worse prognostic behavior. HBME-1 and galectin-3 show a similar pattern in PDC compared with well-differentiated carcinoma, whereas they are not expressed, as well as ß-catenin, in anaplastic carcinomas.

Aggressive papillary thyroid microcarcinoma: prognostic factors and therapeutic strategy.

BACKGROUND AND AIM: Papillary thyroid carcinomas smaller than 1 cm are classified as papillary microcarcinomas (PMCs). Papillary microcarcinomas are usually considered low-risk tumors; however in some cases, PMCs behave aggressively and metastasize early, giving rise to clinically metastatic disease. Debate exists in the literature about prognostic factors and therapeutic management to PMC. We report here the long-term experience of our referral center for malignant thyroid disease. METHODS: We retrospectively analyzed 149 consecutive patients with PMC who underwent surgery at our institution between 2000 and 2005; 49 of them (33% of cases) were treated also with radioiodine therapy. Clinical and histopathological parameters potentially predicting patient outcome and recurrent disease were statistically investigated, after a minimum follow-up of 5 years. RESULTS: After a median follow-up of 5.4 years (range, 5-11 years), 28 (19%) of 149 patients experienced recurrent disease. All of them were reoperated on and newly treated with radioiodine administration. Of these 28 patients, 27 are living without disease, whereas 1 patient died due to metastatic thyroid cancer to lungs. The multivariate statistical analysis identified extrathyroid invasion (odds ratio [OR], 58.54; P=0.013), the solid pattern (OR, 25.77; P<0.001), the tumor multifocality (OR, 15.80; P=0.005), and the absence of tumor capsule (OR, 9.74; P=0.015) as significant and independent risk factors for the appearance of PMC recurrences. Of note, in most patients who experienced recurrent disease, the PMC had been diagnosed preoperatively and often for the presence of cervical clinically evident lymphadenopathy. On the other hand, none of the PMC "incidentally" discovered at histopathological examination alone experienced recurrent disease during follow-up. CONCLUSIONS: Although most PMCs have an indolent course, there is a fraction (19% in our series) of patients with PMC and aggressive behavior strongly correlated with some histopathological features (extrathyroid invasion, solid pattern, tumor multifocality, and absence of a capsule) who need to be individualized and for whom a radical therapeutic approach is recommended based on total thyroidectomy and lymphadenectomy followed by radioiodine administration.

Prospective evaluation of total thyroidectomy versus ipsilateral versus bilateral central neck dissection in patients with clinically node-negative papillary thyroid carcinoma.

BACKGROUND: Prophylactic central neck dissection (PCND) for papillary thyroid carcinoma (PTC) is controversial. We compared 3 different approaches to the management of central compartment nodes in patients with clinically unifocal and N0 PTC. METHODS: A total of 186 patients were prospectively assigned to one of the following procedures: total thyroidectomy (TT), TT plus ipsilateral PCND (Ipsi-PCND), and TT plus bilateral PCND (Bil-PCND). RESULTS: No difference was found concerning demographic, clinical or pathologic characteristics (P = NS). More patients in the Bil-PCND group had transient hypocalcemia (P < .001). One patient in the Bil-PCND group experienced permanent hypoparathyroidism (P = NS). One transient and one permanent unilateral laryngeal nerve palsy occurred in the Ipsi-PCND group (P = NS). Significantly more patients in the Bil-PCND and Ipsi-PCND groups had node metastases recognized (26 vs 18 vs 6; P < .001). Six of 26 pN1 patients (23%) in the Bil-PCND group had bilateral metastases. No difference was found concerning mean postoperative basal and stimulated thyroglobulin and mean postoperative radioiodine uptake. One patient in the Ipsi-PCND group experienced recurrent disease (P = NS). CONCLUSION: TT seems adequate treatment for most patients with clinically N0 PTC. PCND could be considered for a more accurate staging. Ipsi-PCND could be a valid option, but it includes the risk of overlooking contralateral metastases.