Prognostic risk factors for rare oncocytic variantin 101 cases of papillary thyroid carcinoma.

OBJECTIVE: Oncocytic variant (OV) is an unusual subtype of papillary thyroid cancer whose histopathologic diagnostic criteria, clinicopathologic features and biological behavior are different and have not been comprehensively studied, characterized in literature. Previous studies present conflicting results upon its prognosis. We investigated demographic and clinicopathologic risk factors affecting its prognosis while presenting our clinical experience. SUBJECTS AND METHODS: This is a retrospective cohort study reviewing 101 patients of OV from an archive of 4500 well-differentiated thyroid cancer patients treated with iodine-131 (131I) between 1991 and 2017. Predefined parameters of age, gender, tumor size (TS), total 131I dose, time to recurrent disease, overall survival, extrathyroidal extension, multifocality, vascular invasion, accompanying other variants, capsular status of thyroid gland, initial cervical lymph node (LN) metastases, preablation stimulated thyroglobulin level, background thyroiditis and stage were evaluated by statistical comparison between metastatic and nonmetastatic groups. RESULTS: Seventeen cases (17%) developed metastases/recurrence, 70% of the recurrences occured before 24 months. Four patients (4%) died during the follow-up. Metastatic sites were usually cervical LN, local recurrence in thyroid bed and lungs. Multivariate analysis revealed stage (IV) and TS were the main parameters impacting recurrence/metastases. In the follow-up, isolated cervical LN metastases were found in 41% of metastatic cases, while 12% had sole recurrence in thyroid bed. Eighty eight percent of the metastatic disease included locoregional (cervical) and/or remote LN. The recurrences were associated with initial thyroid masses greater than 3.5cm in diameter. CONCLUSION: We found that the prognosis of OV is not poor in our series. Stage (IV) and tumor size are the main risk factors in metastatic development.

Gammagrafía paratiroidea con 99mTc-MIBI: valor complementario de la paratohormona en el aspirado y análisis histopatológico de los tipos de células en los adenomas paratiroideos / Complementary role of parathormone washout test to 99mTc-MIBI parathyroid scintigraphy and histopathologic analysis of cell types in parathyroid adenomas

Objetivo: La gammagrafía paratiroidea (GP) puede ser negativa o equívoca (N/E) en un número considerable de casos con alta sospecha clínica y bioquímica de adenoma de paratiroides (AP). Los objetivos de este estudio fueron investigar el papel complementario de la determinación de paratohormona en punción con aguja fina (PTH en PAAF) con la GP en pacientes con hiperparatiroidismo primario (HPTP) y evaluar los aspectos histopatológicos de los AP en comparación con los resultados de GP. Material y métodos: Fueron incluidos en el estudio 38 pacientes con HPTP remitidos para realizar GP. Diecisiete pacientes tuvieron resultados gammagráficos y ecográficos concordantes con AP (grupo A). Veintiún pacientes con GP N/E pero sospecha de AP en la ecografía formaron el grupo B. Se realizó PTH en PAAF en todos los pacientes y todos fueron operados. Se extirpó un adenoma en cada uno de ellos y en todos los casos se establecieron las características histopatológicas. Resultados: El tamaño del tumor en la ecografía fue mayor en aquellos pacientes cuyos adenomas se vieron en la GP (p<0,001). Los porcentajes de células principales, oxífilas y claras en AP no fueron estadísticamente diferentes entre los grupos. El nivel de paratohormona sérica y PTH en PAAF no fueron estadísticamente significativos entre los grupos A y B (p=0,095 y p=0,04, respectivamente). Conclusión: Aunque no existe un valor umbral definitivo, la sensibilidad de la GP aumenta con el tamaño de la lesión. Mientras que el contenido de células principales y oxífilas tiende a reducirse en los AP con GP N/E EP, la tasa de células claras aumenta sustancialmente. La combinación de GP con la ecografía y la PTH en PAAF aumenta la sensibilidad de detección y localización de los AP

Objective: Parathyroid scintigraphy (PS) can be negative or equivocal (N/E) in a considerable number of cases with highly suspicious clinical findings and biochemical results for parathyroid adenoma (PA). The aims of this study were to investigate the complementary role of parathormone washout test (PWT) to PS in patients with primary hyperparathyroidism (PHPT) and evaluate histopathologic aspects of PAs in comparison with PS results. Material and methods: Thirty-eight patients with PHPT referred for PS were included in the study. Seventeen patients had both scintigraphic and ultrasonographic findings concordant with PA (Group A). Twenty-one patients having N/E PS, but suspected lesions for PA on ultrasonography (US) formed Group B. PWT was performed for all patients and they underwent the surgical intervention. An adenoma was removed in all patients and the histopathologic cell characteristics were established. Results: The tumor size on US was larger in those patients whose adenomas were seen on the PS (P<.001). The percentages of chief (or principal), oxyphilic and clear cells in PAs were not statistically different between the groups. Serum parathormone level and PWT were not statistically significant between Group A and Group B (P=.095 and P=.04, respectively). Conclusion: Although there is not a definitive threshold value, the sensitivity of PS increases with lesion size. While chief cell and oxyphilic cell content of PAs tend to deplete in N/E PS, clear cell rate increases substantially. Combining PS with both US and PWT increases the sensitivity of detection and localization of PAs

Complementary role of parathormone washout test to 99mTc-MIBI parathyroid scintigraphy and histopathologic analysis of cell types in parathyroid adenomas. / Gammagrafía paratiroidea con 99mTc-MIBI: valor complementario de la paratohormona en el aspirado y análisis histopatológico de los tipos de células en los adenomas paratiroideos.

OBJECTIVE: Parathyroid scintigraphy (PS) can be negative or equivocal (N/E) in a considerable number of cases with highly suspicious clinical findings and biochemical results for parathyroid adenoma (PA). The aims of this study were to investigate the complementary role of parathormone washout test (PWT) to PS in patients with primary hyperparathyroidism (PHPT) and evaluate histopathologic aspects of PAs in comparison with PS results. MATERIAL AND METHODS: Thirty-eight patients with PHPT referred for PS were included in the study. Seventeen patients had both scintigraphic and ultrasonographic findings concordant with PA (Group A). Twenty-one patients having N/E PS, but suspected lesions for PA on ultrasonography (US) formed Group B. PWT was performed for all patients and they underwent the surgical intervention. An adenoma was removed in all patients and the histopathologic cell characteristics were established. RESULTS: The tumor size on US was larger in those patients whose adenomas were seen on the PS (P<.001). The percentages of chief (or principal), oxyphilic and clear cells in PAs were not statistically different between the groups. Serum parathormone level and PWT were not statistically significant between Group A and Group B (P=.095 and P=.04, respectively). CONCLUSION: Although there is not a definitive threshold value, the sensitivity of PS increases with lesion size. While chief cell and oxyphilic cell content of PAs tend to deplete in N/E PS, clear cell rate increases substantially. Combining PS with both US and PWT increases the sensitivity of detection and localization of PAs.

Evaluation of predictor variables of diagnostic [18F] FDG-PET/CT in fever of unknown origin.

BACKGROUND: Fever of unknown origin (FUO) is defined as an illness having fever which lasts at least 3 weeks of duration and is higher than 38.3 ºC on several measurements. The causes are infections, malignancies, noninfectious inflammatory diseases and miscellaneous. If [18F]FDG-PET/CT helps the final diagnosis, it is called contributory. The aim of the study is to evaluate the predictor variables effecting a contributory PET/CT for the diagnosis. METHODS: This is a retrospective cohort study conducted between June 2006 and May 2015 including 76 patients. The evaluated predictor variables are age, sex, ESR, CRP, fibrinogen, ferritin, albumin, haemoglobin level, platelet count, total leukocyte count, neutrophil percentage, lymphocyte percentage, ALP, LDH, ALAT, ASAT, GGT, total bilirubin, CK, RF, ANA, urinanalysis, chest radiography, abdominal US, lymphadenopathy, duration of fever, comorbid diseases and previous therapies. RESULTS: ESR (P=0.001), CRP (P=0.001), fibrinogen (P=0.009), lymphopenia (P<0.001), neutrophilia (P<0.001), ferritin (P<0.001), leukocytosis (P=0.003), duration of fever before PET/CT (<3 months) were found to be statistically significant for positive contribution of PET/CT results to the diagnosis. CONCLUSIONS: [18F]FDG-PET/CT is helpful and contributory for the diagnosis of FUO in patients having higher levels of CRP, ESR, ferritin, fibrinogen, leukocytosis, neutrophilia and shorter durations of fever (<3 months).

Impact of tall cell variant histology on predicting relapse and changing the management of papillary thyroid carcinoma patients.

OBJECTIVE: There has been much discussion recently about the risk category of tall cell variant (TVC) histology and its effects on the management of papillary thyroid carcinoma (PTC). We, therefore, undertook a retrospective study to compare stage-matched risk factors and recurrence rates between classical PTC (cPTC) patients and patients with TCV histology. SUBJECTS AND METHODS: A total of 3128 well-differentiated thyroid carcinoma patients who were treated and followed-up for more than 5 years in our clinic from 1995 to 2016 were included in this study. There were 2783 PTC (89%) patients, 1113 (40%) of them were cPTC and 56 (2%) of them were TCV patients. RESULTS: In all stages, the stage-matched incidence of extrathyroidal extension (ETE), lymphovascular invasion and initial lymph node metastases were significantly higher in TCV patients than in cPTC patients (P<0.001). Recurrence was in 10 of 27 patients (37%) with TCV and in 91 of 890 (10%) patients with cPTC diagnosed in stage I (odds ratio (OR)=5.16); in 4 of 6 patients with TCV and 18 of 84 (21%) patients with cPTC in stage II (OR=7.33); in 5 of 6 patients with TCV and 11 of 46 (23%) patients with cPTC in stage III (OR=15.90); and in 13 of 17 patients with TCV and 31 of 93 (33%) patients with cPTC in stage IV (OR=6.50). Stage-matched recurrence rates were found significantly higher in all stages of TCV patients than in cPTC patients (OR=8.49, P<0.001). Recurrence with distant metastases was seen more frequently in TCV patients than in cPTC patients (P<0.001) and treatment of metastatic disease was more difficult in TCV patients. CONCLUSION: Tall cell variant was an independent poor prognostic factor in papillary thyroid carcinoma patients even if they were diagnosed at early stages of the disease. Patients with tall cell variant histology required more aggressive therapeutic approach and closer follow-up than classical patients.

Risk factors and stratification for recurrence of patients with differentiated thyroid cancer, elevated thyroglobulin and negative I-131 whole-body scan, by restaging 18F-FDG PET/CT.

OBJECTIVE: In nearly 20%-30% of patients with differentiated thyroid carcinoma (DTC) relapse and 7% of them die during the next 10 years after initial diagnosis. In 10%-30% of patients with DTC after ablation therapy during the follow-up show a negative iodine-131 (131I) whole-body screening test (131I WBS) and increased serum thyroglobulin (Tg) level. Loss of ability of DTC metastatic lesions to trap 131I is associated with pure survival and often aggressive disease. Several studies have shown that in DTC cases non trapping 131I, fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) can detect recurrence or metastases with high sensitivity (80%-90%). The purpose of this study was to investigate the clinicopathologic features and other related risk factors of patients with DTC having elevated Tg levels and negative 131I WBS in which recurrence was detected by 18F-FDG PET/CT. We tried to study and stratify patients in this grey zone who could benefit from 18F-FDG PET/CT for the detection of metastases/recurrence according to predefined risk factors not investigated by other researchers. SUBJECTS AND METHODS: We studied retrospectively 165 DTC patients with elevated Tg levels and a negative 131I WBS during their follow-up between 2004-2015. Metastases/recurrence was found in 49% of the patients on restaging with 18F-FDG PET/CT and were compared with nonmetastatic group according to predefined risk factors. These factors were also evaluated in true positive and false negative cases. RESULTS: The sensitivity and specificity of 18F-FDG PET/CT for detecting recurrent/metastatic disease were 90% and 98.5%, respectively. No apparent predefined risk factor impacting a false negative 18F-FDG PET/CT was found. Findings in follicular carcinoma, Hürtle cell carcinoma and papillary carcinoma were not different from positive PET findings. The variants of papillary carcinoma also had no statistically difference with regard to 18F-FDG results. CONCLUSION: The most important factors affecting a true positive 18F-FDG PET/CT study were: ETE, high total 131I dose and the SUVmax values over 4.5.

Clinicopathologic features and prognostic factors of tall cell variant of papillary thyroid carcinoma: comparison with classic variant of papillary thyroid carcinoma.

OBJECTIVE: Tall cell variant (TCV), an aggressive form of papillary thyroid carcinoma (PTC), frequently presents with extrathyroidal disease and recurrence. The aim of this study was to evaluate the clinicopathologic features and outcomes of patients with TCV by comparing them with a larger group of patients with classic variant of papillary thyroid carcinoma (cPTC). PATIENTS AND METHODS: A total of 2500 patients with differentiated thyroid carcinoma were treated and monitored during a 23-year period (1992-2015). Of them, 2250 (90%) had PTC and 235 (9.5%) had follicular thyroid carcinoma. Of the 2250 patients, 862 (38.3%) and 70 (3.1%) had cPTC and TCV, respectively. Cases of TCV and cPTC of PTC were compared on the basis of risk factors. RESULTS: Patients with TCV were significantly older compared with cPTC patients (P<0.001). Tumor size was significantly bigger (P=0.01) and preablation thyroglobulin level was significantly higher (P<0.001) in TCV patients than in cPTC patients. The incidence of capsule invasion, extrathyroidal extension, and vascular invasion was significantly higher in TCV (P=0.003, <0.001, and 0.011, respectively). The incidence of initial lymph node metastasis was significantly higher in TCV (P<0.001). Patients with TCV were mostly at an advanced stage compared with patients with cPTC (P<0.001). Development of local or distant metastasis during the follow-up was significantly higher in TCV than in cPTC. Sex and multifocality were not statistically significant. CONCLUSION: TCV has a higher incidence of local or distant metastasis and mortality rate. Thus, it must be treated with the highest possible I ablation doses and followed up carefully.

Evaluation of radiographic and metabolic changes in bone metastases in response to systemic therapy with (18)FDG-PET/CT.

BACKGROUND: The aim of the study was to retrospectively evaluate radiographic and metabolic changes in bone metastases in response to systemic therapy with (18)FDG-PET/CT and determine their roles on the evaluation of therapy response. PATIENTS AND METHODS: We retrospectively evaluated radiographic and metabolic characteristics of bone metastases in 30 patients who were referred for the evaluation of response to systemic therapy with (18)FDG-PET/CT. All patients underwent integrated (18)FDG-PET/CT before and after treatment. RESULTS: The baseline radiographic patterns of the target lesions in responders group were lytic, sclerotic, mixed and CT negative; after treatment the radiographic patterns of all target lesions changed to a sclerotic pattern and attenuation increased (p = 0.012) and metabolic activity decreased (p = 0.012). A correlation was found between decreasing metabolic activity and increasing attenuation of the target lesions (r = -0.55) (p = 0.026). However, in nonresponders group, the baseline radiologic patterns of the target lesions were lytic, blastic, mixed and CT negative; after treatment all lytic target lesions remained the same and one CT negative lesion turned to lytic pattern and the attenuation of the target lesions decreased (p ± 0.12) and metabolic activity increased (p = 0.012). A correlation was found between increasing metabolic activity and decreasing attenuation (r = -0.65) (p = 0.032). An exception of this rule was seen in baseline blastic metastases which progressed with increasing in size, metabolic activity and attenuation. CONCLUSIONS: This study shows that the metabolic activity of lesions is a more reliable parameter than the radiographic patterns for the evaluation of therapy response.

Role of cardiac ultrafast cameras with CZT solid-state detectors and software developments on radiation absorbed dose reduction to the patients.

Myocardial perfusion imaging (MPI) is one the most contributing nuclear medicine technique to the annual population dose. The purpose of this study is to compare radiation-absorbed doses to the patients examined by conventional cardiac SPECT (CSPECT) camera and ultrafast cardiac (UFC) camera with cadmium-zinc-telluride (CZT) solid-state detectors. Total injected activity was reduced by 50 % when both stress and rest images were acquired and by 75 % when only stress images were taken with UFC camera. As a result of this, the mean total effective dose was found significantly lower with UFC camera (2.2 ± 1.2 mSv) than CSPECT (7.7 ± 3.8 mSv) (p < 0.001). Further dose reduction was obtained by reducing equivocal test results and unnecessary additional examinations with UFC camera. Using UFC camera, MPI can be conveniently used for the detection of coronary artery disease (CAD) much less increasing annual population radiation dose as it had been before.

Clinical impact of (18)F-FDG PET/CT on initial staging and therapy planning for breast cancer.

The purpose of this study was to determine the clinical significance of (18)F-FDG PET/CT on initial staging and therapy planning in patients with invasive breast cancer. One hundred and forty-one consecutive, biopsy proven preoperative and 195 postoperative high-risk breast cancer patients who were referred for PET/CT for initial staging were included in this retrospective study. The clinical stage had been determined by conventional imaging modalities prior to the PET/CT scan. Of the 141 examined preoperative patients, 19 had clinical stage I (T1N0), 51 had stage IIA (12 T2N0 and 39 T1N1), 49 had stage IIB (2 T3N0 and 47 T2N1), 12 had stage IIIA (11 T3N1, 1 T2N2), 2 had stage IIIB (2 T4N1) and 8 had stage IV. PET/CT modified the staging for 26% of stage I patients, 29% of stage IIA patients, 46% of stage IIB patients, 58% of stage IIIA patients and 100% of stage IIIB patients. PET/CT scans detected extra-axillary regional lymph nodes in 14 (9.9%) patients and distant metastasis in 41 (29%) patients. PET/CT scans detected multifocal lesions in 30 (21%) patients, multicentric lesions in 21 (14%) patients and malign foci in the contralateral breast (bilateral breast cancer) confirmed by biopsy in 5 (3.5%) patients. Of the examined 195 postoperative patients PET/CT detected axillary lymph nodes in 22 (11%) patients, extra-axillary regional lymph nodes in 21 (10%) patients and distant metastasis in 24 (12%) patients. PET/CT findings altered plans for radiotherapy in 22 (11%) patients and chemotherapy was adapted to the meta-static diseases in 24 (12%) patients. PET/CT was revealed to be superior to conventional imaging modalities for the detection of extra-axillary regional metastatic lymph nodes and distant metastases. These features make PET/CT an essential imaging modality for the primary staging of invasive breast cancer, particularly in patients with clinical stages II and III.

Iodine-131 treatment and high-resolution CT: results in patients with lung metastases from differentiated thyroid carcinoma.

Between 1984 and 2002, pulmonary metastases were detected in 42 (4%) out of 1,023 patients with differentiated thyroid carcinoma (DTC) in our department. The age at diagnosis ranged from 6 to 77 years. Lung metastases were diagnosed by both increased thyroglobulin (Tg) levels and positive uptake of iodine-131 on scans, and/or positive radiological findings. The primary tumours were histologically classified as papillary (30 patients), follicular (nine patients) and poorly differentiated (two tall cell, one insular carcinoma). The duration of follow-up ranged from 24 to 228 months. The end-results of the (131)I therapy were evaluated. The treatment of choice was (131)I therapy of metastases after total thyroidectomy plus lymph node dissection (if lymph node metastases were present). Applied single and total (131)I activities were 1.8-10.4 GBq and 5.5-43.7 GBq, respectively. Lung metastases were present at the time of diagnosis in 30 patients and developed during the follow-up period in the remaining 12. Twelve patients with extensive metastases died of thyroid carcinoma and another died due to secondary malignancy (malignant mesothelioma). Ten patients with lung metastases remain completely free of disease and are probably cured, while another seven were stable at the time of study. Three- and five-year survival rates were 86% (36/42) and 76% (32/42), respectively. To define the diagnostic value of high-resolution computed tomography (HRCT) and identify the distinctive features of lung metastases from DTC, 22 patients were further examined with HRCT within 2 weeks of the initial diagnosis of lung metastases and the results were compared with chest X-ray findings. HRCT detected metastases in 10 out of 14 patients with a normal chest X-ray and confirmed metastases in all patients with positive (n=5) and suspicious (n=3) chest X-ray. HRCT did not show any abnormalities in four patients with positive lung uptake on (131)I whole-body images. Stage of disease, existence of distance metastases other than to the lung, and HRCT characteristics were significant prognostic variables. Lung metastases from DTC can be cured with (131)I therapy in a considerable number of patients, especially when they are not associated with other distant metastases; they should therefore be treated at an early stage. HRCT clearly improved diagnostic ability in the evaluation of lung metastases compared with chest X-ray and should be the primary method when radiological correlation is needed. The main, and new, finding of the study is that HRCT not only improves diagnostic ability but is also of prognostic value.