Intraepithelial Neutrophils in Thyroid Fine-Needle Aspiration: A Portent of Aggressive Thyroid Cancer?

We report three patients with papillary thyroid carcinoma in whom fine-needle aspiration (FNA) showed neutrophils within tumor cells. All three patients presented with large neck masses; at excision, two proved to be tall cell variants of papillary cancer. Nodal metastasis, extrathyroidal extension, and vascular invasion were found in both cases. One patient has experienced recurrent disease; the other has an increasing thyroglobulin titer but no clinically appreciable recurrence. The third patient refused further therapy, but brain metastases were noted clinically; this patient died of disease. In each case, FNA showed tumor clusters with characteristic nuclear features, papillary groups, and psammoma bodies. Neutrophils were present in the cytoplasm of tumor cells in the absence of necrosis. Immunostaining for proliferating cell nuclear antigen (PCNA), MIB-1 (Ki-67), and p53 tumor suppressor gene product was markedly positive. Intraepithelial neutrophils have not been previously reported in differentiated thyroid tumors. We postulate that these neoplasms produce specific leukocyte-attracting cytokines analogous to those produced by anaplastic and poorly differentiated thyroid carcinomas. We believe the finding of intraepithelial leukocytes in the absence of necrosis in thyroid FNA specimens represents a characteristic of clinically aggressive differentiated papillary neoplasms; in our small series, each represented a tall cell variant of papillary carcinoma.     

Should Core Needle Biopsy be Used in the Evaluation of Thyroid Nodules?

Fine needle aspiration (FNA) is the first choice in thyroid nodules suspected of harboring malignancy on sonography in routine practice. However, sampling with core needle biopsy (CNB) is also being used, especially in cases with repeated nondiagnostic/indeterminate diagnoses. The aim of this study was the retrospective evaluation of CNB samples. A total of 604 thyroid CNB samples registered in the Department of Pathology at Bezmialem Foundation University Medical Faculty within the 1-year period between June 2014 and June 2015 were re-evaluated by correlation with previous FNA and later resection results. CNB was divided into diagnostic groups of insufficient, malignant, suspicious for malignancy, no evidence of malignancy/benign, atypia of uncertain significance (AUS)/follicular lesions of uncertain significance (FLUS), and follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN). Among the 604 cases, 15 cases (2.48 %) were classified as malignant and 9 cases (1.49 %) as suspicious for malignancy. No evidence of malignancy was seen in 512 cases (84.76 %). There were 26 (4.3 %) cases in the AUS/FLUS-FN/SFN group, and the sample was inadequate in 42 cases (6.95 %). Resection was performed for 17 of the cases classified as malignant or suspicious for malignancy, and all were found to be malignant. There were also 10 resected cases with a diagnosis of no evidence of malignancy, and all were found to be benign. We think that sampling with CNB may be useful especially in repeating inadequate biopsies or cases diagnosed with AUS/FLUS that have hesitations regarding clinical management. Larger series including comparisons with FNA and resection results are required.     

Response of Pituitary—Thyroid Axis to a Short-Term Shift in Deuterium Content in the Body

Bulletin of Experimental Biology and Medicine - We studied functional changes in rat pituitary—thyroid axis after a short-term shift in deuterium body content. Male Wistar rats consumed...     

Does Fine-Needle Aspiration Cytology Optimize the Surgical Management of Thyroid Disorders in Endemic Goiter Region?

Aim The aim of this study was to determine the diagnostic value of fine-needle aspiration cytology (FNAC) before thyroidectomy in an endemic goiter region. Methods One hundred patients with preoperative FNAC of thyroid nodules who underwent thyroidectomy were recruited. FNAC were classified into five groups. 0, no thyroid cells; 1, normal thyroid cells; 2, degenerative thyroid cells without evidence of malignacy; 3, follicular or oncocytary neoplasia; and 4, malignant thyroid cells. FNAC was compared with postoperative histopathological diagnoses. Results Only 76% of the FNAC allowed an adequate cytological examination. In 15 patients (15%), carcinomas were found in the postoperative histopathological diagnosis (including four follicular carcinomas). In the 48 patients of FNAC groups 3 and 4, nine carcinomas (18.7%) were found (including four follicular carcinomas). In the 28 patients of groups 1 and 2, there was only one papillary carcinoma (3.5%). In the 24 patients of group 0, there were two papillary, two follicular, and one anaplastic carcinomas (total of 20.8%). The sensitivity, specificity, and likelihood ratio (LR) of the FNAC for benign nodules were 90%, 40.9%, 0.24, respectively. The LR for malignant nodules was 13.2, and that for follicular neoplasia was 0.55. Conclusions Despite the high prevalence of carcinoma in an endemic goiter region, FNAC disappointed its diagnostic expectation. The lower specificity of FNAC may be caused by a higher prevalence of thyroid nodules in an endemic goiter region or by the absence of a specialized cytopathologist. T. Osei-Agyemang and I. Hassan contributed equally to this work. Presented in part to Second Biennial Congress of the European Society for Endocrine Surgeons (ESES), May 18–20, 2006, Krakow (Poland)     

Thyroid peroxidase in the differential diagnosis of thyroid gland lesions. A marker of biological behavior or differentiation?

Human thyroid peroxidase (hTPO) is a membrane protein with a key role in the thyroid hormones synthesis. Loss of hTPO was described in malignant tumours of the thyroid gland. hTPO was tested as a marker of malignancy. Immunohistochemical study of hTPO in 321 thyroid lesions (45 malignant tumours, 72 benign tumours, 199 benign non-tumours lesions, and 5 normal thyroid glands) is presented. The sensitivity of hTPO in predicting malignancy in thyroid is 64%, and the specificity is 87%. Thus, hTPO is of limited value in the diagnosis of thyroid malignancy. The authors discuss the role of hTPO as a marker of differentiation.     

Hypoxia Induces Epithelial-Mesenchymal Transition in Follicular Thyroid Cancer: Involvement of Regulation of Twist by Hypoxia Inducible Factor-1α

Purpose

Although follicular thyroid cancer (FTC) has a relatively fair prognosis, distant metastasis sometimes results in poor prognosis and survival. There is little understanding of the mechanisms contributing to the aggressiveness potential of thyroid cancer. We showed that hypoxia inducible factor-1α (HIF-1α) induced aggressiveness in FTC cells and identified the underlying mechanism of the HIF-1α-induced invasive characteristics.

Materials and Methods

Cells were cultured under controlled hypoxic environments (1% O₂) or normoxic conditions. The effect of hypoxia on HIF-1α, and epithelial-to-mesenchymal transition (EMT) related markers were evaluated by quantitative real-time PCR, Western blot analysis and immunocytochemistry. Invasion and wound healing assay were conducted to identify functional character of EMT. The involvement of HIF-1α and Twist in EMT were studied using gene overexpression or silencing. After orthotopic nude mouse model was established using the cells transfected with lentiviral shHIF-1α, tissue analysis was done.

Results

Hypoxia induces HIF-1α expression and EMT, including typical morphologic changes, cadherin shift, and increased vimentin expression. We showed that overexpression of HIF-1α via transfection resulted in the aforementioned changes without hypoxia, and repression of HIF-1α with RNA interference suppressed hypoxia-induced HIF-1α and EMT. Furthermore, we also observed that Twist expression was regulated by HIF-1α. These were confirmed in the orthotopic FTC model.

Conclusion

Hypoxia induced HIF-1α, which in turn induced EMT, resulting in the increased capacity for invasion and migration of cells via regulation of the Twist signal pathway in FTC cells. These findings provide insight into a possible therapeutic strategy to prevent invasive and metastatic FTC.     

Novel Cause of ‘Black Thyroid’: Intraoperative Use of Indocyanine Green

The antibiotic minocycline is virtually pathognomonic for brown-black discoloration of the thyroid gland referred to as ‘black thyroid’. Black thyroid’ is an incidental finding in patients taking the drug who undergo thyroid surgery for another indication and is not of known clinical significance. However, its recognition is important so as not to raise concern for a disease process. Here, we present the first case of ‘black thyroid’ attributable to the iodine-containing compound indocyanine green. Intraoperative indocyanine green was administered as part of a research protocol transoral robotic-assisted surgery for a base of tongue cancer in a 44-year-old man. Hemithyroidectomy was subsequently performed during the same operation for further evaluation of an indeterminate thyroid nodule. The resected thyroid lobe was dark, nearly black in color, and histologically showed extensive brown pigment deposition in the follicular epithelial cells and colloid, mimicking minocycline-induced ‘black thyroid’. In this case, however, the patient was not taking minocycline; instead the ‘black thyroid’ was attributed to the iodine-containing compound indocyanine green. Indocyanine green is a hereto unreported cause of ‘black thyroid’ with histopathologic features that are remarkably similar to that induced by minocycline. Indocyanine green should be included the differential diagnosis of ‘black thyroid’. Clinical history is important so as not to raise concern for a disease process.     

“The Diagnostic Accuracy of Thyroid Nodule Fine-Needle Aspiration Cytology Following Thyroid Surgery: a Case–Control Study”

Thyroid surgery may cause regional scarring and some degree of fibrotic process which may extend into the perithyroidal soft tissues. This may result in problems when collecting thyroid fine-needle aspiration biopsy (FNAB) samples and evaluating the cellular abnormalities. This study aimed to determine if a history of thyroid surgery is a risk factor for nondiagnostic (ND) FNAB results. Patients with ≥1 discrete nodular lesion of the thyroid who underwent FNAB were included. The patients with a history of thyroid surgery constituted group 1, and the others constituted group 2. The factors which may influence FNAB results, including age, gender, presence of Hashimoto’s thyroiditis, and ultrasound characteristics, were also evaluated. Group 1 included 123 patients with 200 nodules, and group 2 included 132 patients with 200 nodules. The two groups were similar with respect to demographic characteristics of the patients and ultrasonographic features of the nodules including diameter, content (cystic or solid), echogenicity, margin, and calcifications (P?>?0.05). In all, 176 (44 %) of the participants had ND FNAB results. The median time interval between thyroid surgery and FNAB was 15 years [range, 1–45 years; interquartile range (IQR) 13 years]. Significantly more nodules in group 1 had ND FNAB results than in group 2 [98 (49 %) vs 78 (39 %), respectively, P?=?0.028]. Multivariate analysis revealed that history of thyroid surgery was independently associated with ND FNAB [odds ratio (OR) 1.55, 95 % confidence interval (CI) 1–2.33, P?=?0.033]. A history of thyroid surgery increases the risk of initial ND FNAB.     

Long-Term Immunological Study in Graves’ Disease Treated with Thyroid Arterial Embolization

OBJECTIVE: The aim of this study was to investigate long-term immunological changes after the treatment of Graves' disease (GD) with thyroid arterial embolization and the effect of thyroid arterial embolization on the body's immunological functions. MATERIALS AND METHODS: Forty-one patients with clinically and laboratorily ascertained GD were treated with thyroid arterial embolization and followed up for 3-54 months following embolization. Prior to embolization and at 1, 3, 6, 12, and 36 months following embolization, thyroid autoimmune antibodies were tested respectively, including thyroid stimulating antibody (TSAb), thyrotropin antibody (TRAb), thyroglobulin antibody (TGAb), and thyroid microsomal antibody (TMAb), as well as subgroup lymphocytes of CD16+CD56+, CD19+, CD3+, CD3+CD4+ and CD3+CD8+. The autoimmune status of GD patients prior to embolization and the dynamic changes of the immunological function after embolization were analyzed. RESULTS: The therapy of thyroid arterial embolization could effectively decrease the activity/titer and positive rate of TRAb and the ratio of CD4+/ CD8+ to normal levels at 6 months following embolization, while the ratio of CD3+CD8+ increased gradually to normal level at 1 year following embolization. In patients with recurrence, TSAb and TRAb remained at a higher level, while the rate of CD3+CD8+ and the ratio of CD4+/CD8+ were not statistically significantly different from those before embolization. CONCLUSION: Immunological functional disorder exists in GD patients. The treatment method of thyroid arterial embolization can effectively resume the basic immunological function to normal range while patients with recurrence have no significant improvement, suggesting that thyroid arterial embolization has an effective role in adjusting the immunological function.     

Thyroid volume by ultrasound in boys and girls 6–16 years of age under marginal iodine deficiency as related to the age of puberty

Summary The results of thyroid volume estimation with the aid of ultrasound in a total of 921 boys and girls 6–16 years of age are reported. The thyroid volume was found to be increasing slowly between the age of 6 and 12 years, but somewhat more remarkable increase occurred at 13 and 14 years of age. However, in both sexes it was nearly doubled at the age of 15–16 years as compared with the values at 13–14 years irrespective of body weight. The thyroid growth rate (as calculated from the least squares analysis of the correlation between thyroid volume and body weight) in girls was significantly higher (P< 0.001) than in boys. In spite of long-term mandatory iodine prophylaxis the average urinary excretion of iodine as estimated in 69 randomly selected subjects was 78.06 g/g creatinine (geometrical mean). It may be suggested that such intake of iodine, though marginally deficient, may be satisfactory up to the age of about 12–14 years, while it appeared to be inadequate for the adolescents at the age of puberty.     

Hürthle Cells Adenoma of the Thyroid with Post-surgical Implants in the Neck: Clinical,Morphological, and Molecular Analysis of Three Cases

Thyroid implants in the soft tissue of the neck are very rare findings of traumatic, iatrogenic, or neoplastic origins. We describe the clinico-pathological and molecular analysis of three cases with an initial diagnosis of follicular adenoma, Hürthle cell variant (FA-HCT), which developed cervical thyroid implants at 60, 59, and 36 months after thyroid surgery, followed by further neck recurrences, and, eventually, by distant metastases. A systematic review of all histopathological samples of both the primary lesions and the neck implants was performed. Molecular study included the analysis of pan-RAS and BRAF mutations and RET/PTC1, RET/PTC3, and PAX8/PPARγ rearrangements. The review of the original slides and of additional re-cuts of each block of the thyroid lesions did not show any sign of capsular and/or vascular invasion; thus, the original diagnoses of FA-HCT were confirmed. When sampling adequacy was considered, it turned out that the capsule was completely evaluable in case #3, whereas 85 % was evaluable for case #1 and less than 50 % for case #2. We cannot exclude that cases #1 and #2 were carcinomas that had not been completely sampled. The first occurring neck implants showed neither histological signs of malignancy nor the presence of lymphoid tissue. However, further neck recurrences had different histological aspects, with a clear infiltrative growth. Moreover, a mesenchymal reaction forming a sort of capsule was observed around oncocytic cells along with signs of vascular invasion. Molecular analysis revealed no alterations in the genes and rearrangements studied. Oncocytic thyroid implants in the neck soft tissue should be regarded as metastasis, even in the absence of clear-cut signs of malignancy and in the case of a bona fide diagnosis of Hürthle cells adenoma of the thyroid.     

Thyroid and parathyroid tumours in patients submitted to X-ray scalp epilation during the tinea capitis eradication campaign in the North of Portugal (1950–1963)

Tinea capitis attained epidemical proportions in the fifth and sixth decades in Portugal, as in other countries. Before starting the utilization of griseofulvin in 1959, the best approach to treat tinea capitis infection was X-ray scalp epilation combined with topical antimycotic ointments. A long-term side effect of this therapy is thyroid disease, namely thyroid cancer; data on parathyroid lesions (hyperplasia, adenoma and carcinoma) are scarce. We observed clinically 1,375 individuals irradiated in childhood for tinea capitis treatment in the North of Portugal with the main purpose of evaluating thyroid and parathyroid tumours as possible sequelae of the irradiation treatment. For each individual, a cervical ultrasound and a serum calcium measurement were proposed. Fine needle aspiration cytology was suggested whenever ultrasound thyroid nodules presented suspicious features. We observed a 54 % frequency of thyroid nodules and a 2.8 % frequency of thyroid carcinoma (38/1,375). Nineteen of the 38 (50 %) carcinomas were diagnosed by us, whereas the remaining 19 carcinomas had been diagnosed and treated prior to our observation. The carcinomas were significantly more frequent in women than in men. Benign excised lesions were also significantly more frequent in women and in patients irradiated at younger ages. Seven women, considered asymptomatic until our clinical observation, had laboratory signs of hyperparathyroidism. The data we have obtained, namely high thyroid cancer frequency, corroborate previous data from childhood irradiated cohorts and highlight the need for the close follow-up of these populations in order to identify and treat early undiagnosed head and neck lesions. No evidence of increased parathyroid disease was found in this cohort of head and neck X-irradiated patients.     

Initial Report of the Results of Percutaneous Laser Ablation of Benign Cold Thyroid Nodules: Evaluation of Histopathological Changes After 2 Years

Percutaneous laser ablation (PLA) is a new method to be used for reducing the volume of symptomatic cold benign thyroid nodules. We aimed to introduce the long-term histopathological effects of PLA procedure in thyroid nodules. A 42-year-old male patient with 18.7-mL nodule volume was transferred a total of 720 J of energy with 3-W power. A 50-year-old female patient with 14.1-mL volume nodule was transferred a total of 3,300 J with 5-W power. A 61-year-old female patient with 49.7-mL volume nodule was transferred a total of 4,200 J with 5-W power. The thyroidectomy materials were examined histopathologically 2 years later. In histopathologic examination, it was observed that the periphery of ablated area was organized with hyalinized connective tissue and the center was organized with necrosis and carbon particles. Concurrently, in the center, we detected calcifications and colloid and foreign-body giant cells against colloid in one patient. We did not encounter any pathologic findings in the tissue adjacent to ablated area. In the cold benign thyroid nodules taken out by thyroidectomy 2 years after PLA procedure, necrosis and hyalinization were detected histopathologically. PLA procedure in cold benign thyroid nodules seems to be safe according to long-term histopathological findings.