Incidental thyroid carcinoma in an endemic goiter area in Italy: histopathological features and predictors of a common finding.

PURPOSE: The occurrence and histopathological features of incidental thyroid carcinoma (ITC) vary considerably among populations from different geographical regions. The aim of this study is to assess the prevalence and histopathological characteristics of ITC in patients who underwent thyroid surgery for apparently benign thyroid diseases in an endemic goiter area in Italy. METHODS: A total of 649 consecutive patients (531 females and 118 males; mean age, 52.9 ± 11.0 years), who underwent thyroid surgery at the Endocrine Surgery Unit of the tertiary care "Renato Dulbecco" University Hospital (Catanzaro, Italy) in the period between years 2017 and 2022, were included in this retrospective study. A comprehensive histopathological examination was performed on surgically excised thyroid tissue. Logistic regression analysis was employed to identify potential predictors of ITC. RESULTS: The histopathological examination revealed the presence of ITC in 81 patients, accounting for 12.5% of the total study population. The female to male ratio was found to be 6.4 to 1. Among the patients with ITC, 72 had papillary carcinoma (PTC), with 53 of these tumors being microcarcinomas (microPTC). Additionally, 5 patients had follicular thyroid carcinoma, 2 patients had low-risk follicular cell-derived thyroid neoplasms, 1 patient had an oncocytic carcinoma, and 1 patient had a medullary thyroid carcinoma. Logistic regression analysis demonstrated a significant association between female sex and incidental microPTC. CONCLUSIONS: These findings provide further evidence of the common occurrence of ITC, typically in the form of microPTC, among individuals who undergo thyroid surgery for apparently benign thyroid diseases.

[Clinical importance of thyroid gland cytology]. / Klinische Bedeutung der Schilddrüsenzytologie.

The cytological evaluation of fine needle biopsies (FNB) of the thyroid gland crucially depends on a close cooperation between clinicians and cytopathologists. Scintigraphy, sonography as well as clinical data and patient history are necessary for a correct interpretation of the indications for FNB; moreover, these data are of outstanding importance for cytopathologists for the correct interpretation of the cytomorphological findings. This overview describes the present standards in the acquisition, technical workup and cytopathological interpretation of thyroid gland tissue obtained by FNB, particularly focusing on the rapidly growing relevance of additional molecular pathological investigations to increase the diagnostic accuracy of thyroid FNB.

[Experience of using phytopreparation Alba (root extract of the Potentilla alba) in complex treatment of thyroid pathology in children and adolescents].

This article presents the background for including phytopreparation Alba (root extract of the Potentilla alba) into complex treatment of thyroid pathology. The findings confirm visible reduction of size of the thyroid gland and normalizing its functions in children and adults with the thyroid gland with normal or enhanced function treated by Alba per oral.

Pathology and the surgical management of goitre in an endemic area initiating supplementary iodine nutrition.

UNLABELLED: Goitre in the West African sub-region is caused by iodine deficiency and goitrogens in the diet. Supplementary iodine nutrition on a mass scale was started in Ghana in 1996. In areas where iodine deficiency have been corrected the histological pattern of goitre changes and this influences surgical decision making. Data on the histological types of goitre in our institution is lacking. OBJECTIVE: To define the histopathological types of goitre in this initial period of iodine supplementation and relate this to the types of thyroid surgeries that were performed. METHODS: It was a prospective study of consecutive patients who underwent thyroidectomy from January 2003-December 2007. Descriptive statistics was employed in analyzing the data RESULTS: Five hundred and twenty eight cases were studied made up of 470 (89%) females and 58 (11%) males with mean age of 41.98 yrs, SD ± 12.90 yrs. The excised mean thyroid tissue weight was 161.4 g, SD ± 116.3 yrs. Hyperplastic goitres were 373 (70.7%), toxic goitre 70 (13.3%), adenoma 37 (7.0%), carcinoma 25 (4.7%) and thyroiditis 23 (4.4%). Papillary carcinoma accounted for 56% (14) cancers. Subtotal thyroidectomy was performed in 278 (52.7%) of patients, near total thyroidectomy 107 (20.3%), lobectomy 98 (18.6%),total thyroidectomy 24 (4.5%), excision or completion thyroidectomy 20 (3.8%) and de-bulking 1 patient. Overall, complications occurred in 32 patients (6.1%) and were made up mostly of haemorrhage in 10 (1.9%), Hypocalcaemia 10 (1.9%), unilateral Recurrent Laryngeal Nerve(RLN) injury 3 (0.57%), Tracheal collapse 3 (0.57%) and Bilateral RLN injury 2 (0.4%). CONCLUSION: The introduction of iodine supplementation on a mass scale in Ghana is yet to have its fullest impact on thyroid diseases. Goitres are still large and cause pressure effects. Toxic, inflammatory and malignant goitres are gaining prominence, and surgery for malignant goitre was oncologically inadequate.Near total thyroidectomy is recommended as the minimum surgery to avert the need for completion thyroidectomies in view of the lack of preoperative pathological diagnosis of thyroid lesions.

Impaired glucose metabolism is a risk factor for increased thyroid volume and nodule prevalence in a mild-to-moderate iodine deficient area.

OBJECTIVE: Insulin resistance (IR) is a key factor involved in the pathogenesis of impaired glucose metabolism. IR is associated with increased thyroid volume and nodule prevalence in patients with metabolic syndrome. Data on the association of thyroid morphology and abnormal glucose metabolism are limited. This prospective study was carried out to evaluate thyroid volume and nodule prevalence in patients with pre-diabetes and type 2 diabetes mellitus (DM) in a mild-to-moderate iodine deficient area. MATERIALS AND METHODS: Data were gathered on all newly diagnosed patients with pre-diabetes and type 2 diabetes mellitus between May 2008 and February 2010. 156 patients with pre-diabetes and 123 patients with type 2 DM were randomly matched for age, gender, and smoking habits with 114 subjects with normal glucose metabolism. Serum thyroid-stimulating hormone (TSH) and thyroid ultrasonography was performed in all participants. RESULTS: Mean TSH level in the diabetes group (1.9±0.9 mIU/L) was higher than in the control group (1.4±0.8 mIU/L) and the pre-diabetes group (1.5±0.8 mIU/L) (P<0.0001 for both). Mean thyroid volume was higher in the pre-diabetes (18.2±9.2mL) and diabetes (20.0±8.2mL) groups than in controls (11.4±3.8mL) (P<0.0001 for both). Percentage of patients with thyroid nodules was also higher in the pre-diabetes (51.3%) and diabetes groups (61.8%) than in controls (23.7%) (P<0.0001 for both). CONCLUSIONS: The results suggest that patients with impaired glucose metabolism have significantly increased thyroid volume and nodule prevalence.

Accuracy of ultrasound elastography in the diagnosis of thyroid cancer in a low-risk population.

OBJECTIVE: Stiffness has been associated to malignancy in prostate and breast, as well as thyroid. Ultrasound elastography objectively measures tissue elasticity, and previous studies have described it as a high sensitivity and specificity technique for the detection of malignant thyroid nodules in high-risk populations. The aim was to assess the accuracy of elastography in a population with low risk of malignancy. DESIGN AND PATIENTS: 128 consecutive patients with nodular goiter were recruited. Elastography and ultrasound-guided fine-needle aspiration were performed. When malignancy was suspected by citology, surgery was recommended. Thyroid nodules were classified by elastography according the criteria described by Ueno, and an alternative classification. Sensitivity, specificity, predictive values, and odds ratio were calculated. RESULTS: Most patients were female, aged 56.1 year, with single nodule (52.0%) or multinodular goiter (45.6%), and a few thyroiditis (2.4%). The majority of nodules were mostly elastic. Fine-needle aspiration found 86% of benign nodules, 9.3% of indeterminate, and 4.7% possibly malignant. After surgery, 3 malignant nodules were confirmed, all of them being papillary carcinomas. All the malignant nodules were mostly elastic, as well as 75% of indeterminate nodules. Low values of sensitivity and specificity were found for elastic nodules being benign and hard nodules malignant. CONCLUSION: In a low-risk population for thyroid cancer, elastography lacks accuracy for the diagnosis of malignant nodules.

Involvement of inducible costimulator ligand (ICOSL) expression in thyroid tissue in hyperthyroidism of Graves' disease patients.

BACKGROUND: The role of costimulatory molecules expressed on lymphocytes and thyrocytes in hyperthyroidism has attracted increasing attention and research has shown a close correlation between variant expression of these molecules on lymphocytes and thyrocytes and the development of GD. MATERIALS AND METHODS: [corrected] Thyroid tissues were collected from GD patients during surgery and from Hashimoto disease (HT) and non-toxic goiter (NTG) patients as controls. ICOSL expression on infiltrated B cells and TFC was detected by flow cytometry (FCM), reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Variation in ICOSL expression on TFC in primary cultures was analyzed in the absence or presence of cytokines using FCM assays. The role of ICOS-ICOSL signaling in proliferation, thyroid hormone production and thyroglobulin (Tg) release was investigated in primary TFC cultures using ICOS gene transfected L929 cells (ICOS-L929 cells) and the blocking ICOSL antibody (11 C4) in MTT assays and radioimmunoassays. RESULTS AND DISCUSSION: ICOSL expression on infiltrated B cells and TFC was detected in GD patient tissue. However, ICOSL expression was only detected on infiltrated B cells in control HT and NTG patient tissue. ICOSL expression on TFC was induced in vitro by the proinflammatory cytokines IFN-γ, IL-6 and TNF-α. Compared with mock transfected L929 (mock-L929) control cells, ICOS-L929 cells promoted significant proliferation of primary cultured TFC, with increased thyroid hormone and Tg production (all P < 0.01). TFC proliferation and production of thyroid hormones and Tg were inhibited significantly in the presence of ICOSL blocking antibody (11 C4) (all P < 0.05). Our observations suggest that ICOS-ICOSL signal plays a direct role in proliferation and differentiation of TFC and may exert important effects in the initiation, maintenance and exaggeration of autoimmune responses in local tissue.

Thyroid malignancy among goitrous thyroid lesions: a review of hospital-based studies in Malaysia and Myanmar.

Endemic goitre is a major concern in many parts of the world, including Southeast Asia. Goitrous thyroid lesion is postulated as a precursor lesion to thyroid cancer (TC). This paper reviews the prevalence rates and characteristics of TC among cases of goitrous thyroid-swelling in different parts of Malaysia and Myanmar. Recorded data from hospital-based retrospective studies of thyroid cases, whose study periods ranged from three to 11 years, were analysed. These included research findings from the author's publications as well as other published review articles of retrospective analyses. The incidence of TC varies among gender, age, race/ethnicity and histological type. There appears to be a higher rate of occurrence among females aged 21-60 years. Papillary thyroid carcinoma is the more common histological type compared to follicular cancer. This review also presents a descriptive analysis and discussion on studies conducted in other countries. Further exploration is warranted in order to uncover the possible risk factors for the rising incidence of TC.

Indications for surgery and significance of unrecognized cancer in endemic multinodular goiter.

BACKGROUND: The exclusion of cancer in endemic goiter is often difficult mainly because of the high number of nodules and the as-yet unclear natural history of diagnosed cancer in endemic goiter patients. In a large number of consecutive patients who were to undergo total thyroidectomy for endemic multinodular goiter, we assessed indications for surgery and thyroid cancer outcome. METHODS: All patients who were to undergo total thyroidectomy for diffuse multinodular goiter on histological examination between January 1990 and October 2008 were evaluated. RESULTS: Of the 1,161 patients included in the study, 252 were cases of thyroid cancer (21.7%). Sensitivity of thyroid ultrasound (US) and fine-needle aspiration cytology (FNAC) for cancer detection was 30.3 and 64.1%, respectively. Differentiated thyroid carcinoma accounted for most of the tumors (96%), with 54.8% of them being papillary microcarcinomas, while bilateral-multicentric cancer occurred in 20.3%. In multivariate analysis, younger age (p = 0.06), sonographic findings (p = 0.03), and presence of histological thyroiditis (p = 0.09) were independently associated with the occurrence of tumors with diameter greater than 2 cm. The percentage of transient and permanent postoperative complications were approximately 25 and below 2%, respectively. After a median follow-up time of 78.5 months, overall recurrence rate was 6.7% and disease-specific mortality was 1.2%. CONCLUSION: As US and FNAC did not consistently detect cancer in patients with diffuse multinodular goiter in our endemic area, evidence-based indications for surgery in this group of patients is needed, although radical surgery and favorable tumor histology offer favorable outcomes in commonly diagnosed thyroid cancer after total thyroidectomy for endemic multinodular goiter.

[When is thyroid fine-needle biopsy most effective?]. / Wann ist die Feinnadelbiopsie der Schilddrüse am effektivsten?

The essentially desirable standardisation of various European and American guidelines for the evaluation of thyroid nodules has led to the recommendation to perform fine-needle biopsy (FNB) in all nodules >1 cm in order to detect clinically occult thyroid carcinoma early. However, in iodine-deficient areas such as Germany (where thyroid nodules are found in approximately 25% of the adult population) this recommendation would substantially increase both the number of FNB and thyroid operations without significantly increasing the cancer detection rate. The recommendation for FNB in Germany, therefore, should be restricted to hypofunctioning ("cold") nodules >1 cm.

Histopathological evaluation of recurrent goiter.

The recurrent goiter is the regrowth of thyroid tissue after thyroidectomy. An inadequate surgical removal of the thyroid gland, lack of substitution therapy and pathological stimulation of the thyroid growth can all promote the recurrence. The aim of this study was to find the connection between the histopathological findings during the first and second operation and the recurrence of goiter. The study group consisted of 29 women and 1 man. The mean time to recurrence was 15 years. The most frequent histopathological finding during the first and second operation was struma nodosa. According to our observations different histopathological findings were found in 63.4% cases after primary and secondary thyroidectomy. Some genetic investigations showed that nodules in recurrent goiters did not derive from nodules left during the first operation but from a group of cells which had high growth potential. Thus, not only the operation technique and substitution after operation are key factors of successful therapy of goiter, but also other factors which stimulate the re-growth of thyroid tissue.

Routine ultrasound-guided aspiration cytology for evaluation of palpable thyroid nodules in an endemic area: is it justified?

PURPOSE: To prospectively evaluate the efficacy of routine ultrasound-guided fine-needle aspiration cytology (FNAC) of thyroid nodules in an endemic area and to analyze the factors influencing it. METHODS: Patients with thyroid nodules were randomly subjected to either conventional palpation-guided fine-needle aspiration cytology (PFNAC) or ultrasound-guided fine-needle aspiration cytology (USFNAC). The results of cytology were compared with the final histopathologic diagnosis in 112 patients who had undergone surgery. The performance of both methods was individually analyzed in solid nodules, cystic nodules, and solitary and multinodular goitres. RESULTS: Overall, USFNAC showed a significantly higher sensitivity (83.3% vs 54.6%, p < .001), positive predictive value (100% vs 85.7%, p < .001), and greater diagnostic accuracy (96.5% vs 89.1%, p = .052) compared with PFNAC. The sensitivity of USFNAC was significantly higher compared with that of PFNAC in cystic and complex nodules (75% vs 50%, p < .001) but not in solid nodules (77.8% vs 75%, p > .05). USFNAC was more sensitive and more accurate than PFNAC for detection of malignancy in multinodular goitres (66.7% vs 50%, p < .05; 95.6% vs 86.2%, p < .05, respectively). CONCLUSION: The superiority of "routine" USFNAC over PFNAC is mainly due to its better performance in cystic nodules and multinodular goitres. Hence, routine USFNAC can be recommended in areas where such lesions constitute the majority of thyroid nodules.

Prevalence of malignancy in goitre--a review of 718 thyroidectomies.

BACKGROUND: Thyroid malignancies are a heterogeneous group oftumours which show considerable variability in biological behaviour, histological appearances and response to therapy. Thyroid cancer is uncommon and represents only 1% of all malignancies. Objective was to determine the prevalence of malignancy in patients presenting with goitre. This prospective, observational study was conducted at Department of Surgery, Fauji Foundation Hospital, Rawalpindi from January 1999 to December 2008. METHODS: All patients requiring surgery for goitre were included in the study. Postoperatively histopathologies of specimens were evaluated in all patients. RESULTS: 718 patients were operated and post operative histopathology specimens were reviewed. 2.92% of patients were found to have malignancy. Prevalence of papillary and follicular carcinoma was 33.33% each. Anaplastic carcinoma was found in 23.81% of patients followed by Hurthle cell carcinoma in 9.53% of patients. CONCLUSION: All postoperative thyroid specimens should be subjected to histopathology. Prevalence of follicular carcinoma and anaplastic carcinoma is relatively higher in our country due to high incidence of iodine deficiency goitre.

Thyroid surgery in Burkina Faso, West Africa: experience from a surgical help program.

BACKGROUND: Endemic goiter caused by iodine deficiency is still very common in sub-Saharan Africa and is a surgical challenge because of the often large size of the goiters. METHODS: A retrospective analysis was made of patients who underwent operation for thyroid diseases during a surgical help program in Leo/Burkina Faso during a 7-year period from 2001 to 2008. RESULTS: A total of 253 cases presented with goiters grade III (WHO classification) were operated on: 134 hemithyroidectomies, 108 hemithyroidectomies combined with subtotal contralateral resection, and 11 total thyroidectomies were performed. The recurrent laryngeal injury rate was 0.8%, and the re-exploration rate for bleeding was 1.2%. Median hospital stay was 3.1 days. Histological examinations showed Graves' disease in 6 cases, and multinodular goiter in 231 cases. Follicular cancer was found in 15 cases, and anaplastic carcinoma was found in 1 case. CONCLUSIONS: Thyroid surgery can be performed with low complication rates under basic surgical conditions. Because of the size and pathology of the goiters, total thyroidectomy is the method of choice. However, considering the risk of the development of hypothyroidism due to poor understanding or difficult access to medication, a limited resection, e.g., hemithyroidectomy, is the most optimal operative strategy.

The role of iodine in the evolution of thyroid disease in Greece: from endemic goiter to thyroid autoimmunity.

The thyroid gland is dependent on dietary iodine for the production of thyroid hormones, normal iodine requirement being about 150-200 microg/day. Long-term deficiency in iodine intake is associated with the development of goiter. When the prevalence of goiter in a population rises above 5-10%, the problem is considered endemic. Greece is a country with a recent history of moderate iodine deficiency, endemic goiter being prevalent in the 1960s in inhabitants of mountainous regions. Despite recognition of the problem, an iodine prophylaxis program was never officially implemented. Instead, "silent iodine prophylaxis" took place during the 1980s and 1990s with Greece's improvement in socioeconomic conditions. This resulted in the elimination of iodine deficiency and a parallel decrease in the prevalence of goiter among schoolchildren in formerly iodine deficient areas. However, the transition from iodine deficiency to iodine sufficiency or excess was followed by the emergence of autoimmune thyroiditis, especially among young girls, indicating that exposure to excess iodine may trigger thyroid autoimmunity. Thus, the modification of an environmental factor, ie dietary iodine, over the last 40 years in Greece has been associated with changes in the phenotypic expression of thyroid disease from endemic goiter to goiter associated with autoimmune thyroiditis.

Predictive factors for recurrent non-toxic goitre in an endemic region.

AIMS: We aimed to determine the risk factors for recurrence and to assess the complication rate associated with surgery for benign, recurrent goitre. METHODS: We studied 125 consecutive patients with recurrent goitre who underwent re-operative thyroid surgery (group one). Patients in the control group were randomly selected from those undergoing their first procedure during the same period (group two). Age, initial surgery, presence of multinodular goitre, presence of carcinoma in the resected thyroid tissue, interval between initial operation and re-operation, and complications were analysed and compared for the two groups. RESULTS: The mean age (+/- standard deviation) was found to be significantly greater in group one compared with group two. The mean age at the time of primary thyroid operation was found to be significantly less in group one compared with group two. The interval between the initial and the re-operative procedures was a mean of 15.8+/-eight years. Initial surgery was conservative. Papillary thyroid carcinoma was found in 14/125 (11 per cent) of group one patients. The incidence of complications was found to be significantly higher in group one compared with group two. CONCLUSION: The incidence of recurrent goitre has been directly related to conservative thyroid surgery and to the retention of large amounts of remnant tissue. To avoid recurrent goitre and possible re-operative complications, total or near-total thyroidectomy should be performed in all patients with bilateral, multinodular goitre, especially in endemic regions.

Chronic iodine overload and apoptosis in cold nodules from endemic multinodular goiters.

As apoptosis and necrosis are known to exist during experimental goiter development and involution, we studied them in ten Tunisian multinodular endemic goiters, five of them having received a chronic excess of iodine during six months. Apoptotic thyrocyte nuclei have been counted on hematoxylin-eosin stained semi-thin sections. Using immunoperoxidase on paraffin sections, bcl-2 and bax immunoreactivities have been evidenced, and CD34 positive microvessels counted; ultra-thin sections have also been observed. After six months of iodine overload, apoptotic thyrocytes were ten times more numerous; CD34 positive endothelial cells were diminished by one half bcl-2 immunoreactivity disappeared in thyrocytes and a bax one appeared in thyroid follicular and endothelial cells. Presence of numerous apoptotic follicular and endothelial cells was confirmed using electron microscopy. Chronic iodine excess induces apoptosis and necrosis of thyroid follicular and endothelial cells, leading to thyroglobulin accumulation in connective tissue.

Prospective analysis of 518 cases with thyroidectomy in Turkey.

OBJECTIVE: Thyroid malignancies can present in different manners, among them as asymptomatic solid nodule being the most puzzling. Nodules have been found in the 60-70 % of autopsy specimens and it is very important to rule out the malignancies in such cases. Incidence of carcinomatous changes is reported in 5-15 % of solitary nodules. We present the results of prospective study on 418 thyroidectomies with the aim to review the experience of our unit, to establish the correlation between clinical presentation and histopathology, to discuss the malignancy rates and surgical complications. PATIENTS AND METHODS: Five hundred eighteen consecutive cases of thyroidectomy 419 female (80.8 %), and 99 male (19.2 %) patients performed between January 2002 and October 2004 were included in this prospective study. RESULTS: In 71 (13.7 %) cases the malignancy was found by paraffin specimens, the highest prevalence of malignancy being found in patients with nodular goiter (NG-18 %) followed by 14.6 % in multinodular goiter (MNG). The sensitivity of preoperative fine needle cytology (FNAC) was 83.3 % with false positive rate of 1.3 %. Complications were seen in 5.2 % of cases of which 4 (0.7 %) had hypoparathyroidism and 7 (1.3 %) had recurrent laryngeal nerve injury. All patients observed came from endemic area. Family history nearly doubles the risk of malignancy. CONCLUSIONS: In an endemic area the nodular goiter is the most common. Preoperative cytology, although sensitive, gives a considerable number of false positive results. Results of thyroid surgery at a high volume centre are satisfactory with very low rates of recurrent laryngeal nerve and parathyroid injury. Probability of malignant transformation in a long standing thyroid swelling should always be kept in mind. There appears to be an increase in prevalence of thyroid malignancies in Turkey after Chernobyl disaster.

Clinical presentation and treatment of hyperthyroidism associated with thyroid cancer.

OBJECTIVE: Hyperthyroidism apparently does not protect the patients from thyroid cancer as believed before. In contrast, hyperthyroidism with concurrent thyroid cancer can be diagnosed after pathological examination of unsuspect nodules. The aim of this study was to evaluate the coexistence of hyperthyroidism and thyroid carcinoma and to discuss the advantages of total thyroidectomy in such cases. METHODS: Between January 2002 and October 2004, 120 hyperthyroid patients underwent surgical treatment in our clinic. All patients with hyperthyroidism in this study underwent fine-needle aspiration biopsy and cytologic examination. Frozen section evaluation was performed in all of these patients during the operation. RESULTS: Among these patients 10 had concurrent thyroid cancer. Only one of these patients was examined by fine needle aspiration biopsy prior to operation, while the rest of malignancies was diagnosed from unsuspect nodules. CONCLUSIONS: The selection of appropriate operation procedure appears very important to find out and treat concurrent thyroid cancers. We diagnosed 90 % of thyroid cancers incidentally. If there are no technical difficulties, we prefer total thyroidectomy for the patients with toxic multinodular goiter and Graves' disease with nodules.