Comparison of clinical characteristics of patients with follicular thyroid carcinoma and Hürthle cell carcinoma. / Comparación de las características clínicas en pacientes con carcinoma folicular de tiroides y carcinoma de células de Hürthle.

INTRODUCTION: Hürthle cell carcinoma (HCC) is an uncommon thyroid cancer historically considered to be a variant of follicular thyroid carcinoma (FTC). The aim of this study was to assess the differences between these groups in terms of clinical factors and prognoses. PATIENTS AND METHODS: A total of 230 patients (153 with FTC and 77 with HCC) with a median follow-up of 13.4 years were studied. The different characteristics were compared using SPSS version 20 statistical software. RESULTS: Patients with HCC were older (57.3±13.8 years vs. 44.6±15.2 years; P<.001). More advanced TNM stages were also seen in patients with HCC and a greater trend to distant metastases were also seen in patients with HCC (7.8% vs. 2.7%, P=.078). The persistence/recurrence rate at the end of follow-up was higher in patients with HCC (13% vs. 3.9%, P=.011). However, in a multivariate analysis, only age (hazard ratio [HR] 1.10, confidence interval [CI] 1.04-1.17; P=.001), size (HR 1.43, CI 1.05-1.94; P=.021), and histological subtype (HR 9.79, CI 2.35-40.81; P=.002), but not presence of HCC, were significantly associated to prognosis. CONCLUSION: HCC is diagnosed in older patients and in more advanced stages as compared to FTC. However, when age, size, and histological subtype are similar, disease-free survival is also similar in both groups.

Favorable Outcome of Hurthle Cell Carcinoma of the Thyroid Treated With Total Thyroidectomy, Radioiodine, and Selective Use of External-Beam Radiotherapy.

OBJECTIVES: There is controversy about the prognosis of Hurthle cell carcinoma of the thyroid. The purpose of this project is to report the outcome of a well-defined group of patients treated at a single institution in the modern era. METHODS: Sixteen patients met the following inclusion criteria: Treatment with curative intent at our institution between January 1, 1997, and December 31, 2010. Primary treatment with total thyroidectomy with or without neck dissection. Age >18 years at the time of thyroidectomy. Confirmation by a pathologist of the diagnosis of a primary Hurthle cell carcinoma of the thyroid based on ≥75% Hurthle cells with extension through the tumor capsule. No areas of poorly differentiated (insular) or undifferentiated (anaplastic) carcinoma. Stage T1-3, NX-1b, M0. All patients received radioiodine immediately after thyroidectomy (remnant ablation, n=14) or as adjuvant for a recurrence (n=2). External-beam radiotherapy to the neck as adjuvant therapy after thyroidectomy was used in 2 patients and after resection of a neck recurrence in 1 patient. RESULTS: Five-year actuarial rates with a median 6 years of follow up on surviving patients were as follows:Overall and cancer-specific survival: 92% (1 death from Hurthle cell carcinoma). Relapse-free survival (no visible tumor and unstimulated thyroglobulin ≤1.0): 65%. CONCLUSIONS: Our experience suggests that the outcome of Hurthle cell carcinoma of the thyroid is favorable in adults with stage T1-3 NX-1b M0 disease who are managed with total thyroidectomy, radioiodine, and-in selected cases-external-beam radiotherapy. We do not have the ability to compare our results to other management strategies.

Parathyroid carcinoma and oxyphil parathyroid adenoma: an uncommon case of misinterpretation in clinical practice.

A 46 year-old male presented with persistently high level of serum parathyroid hormone (PTH), despite successful resection of an oxyphilic cell parathyroid adenoma of the left lower gland. Renal function and serum calcium were normal, leading to vitamin D deficiency being considered. Tc99m-sestamibi parathyroid scintigraphy showed no capitation, but a cervical ultrasound demonstrated an increase in the lower parathyroids. Surgery confirmed that the right gland was normal but the left corresponded to parathyroid carcinoma. The patient developed severe hypocalcemia, with PTH values being consistent with hypoparathyroidism for a few months. However, a progressive increase in calcium and PTH serum levels indicated recurrence of disease. Tc99m-sestamibi scintigraphy demonstrated hyperfixation in topography of the left inferior parathyroid and the patient was subjected to a third and more extensive surgery, with removal of lymph nodes and adjacent thyroid tissue. Serum calcium and PTH remained elevated, requiring loop diuretics and intravenous bisphosphonates to control hypercalcemia. Cervical radiotherapy was implemented as adjuvant therapy. After two months the patient complained of dyspnea, and a CT scan of the chest demonstrated areas of parenchymal condensation, suggestive of actinic pneumonitis. At the 2-year follow-up no major issues were evident.

131I SPECT/CT in the follow-up of differentiated thyroid carcinoma: incremental value versus planar imaging.

UNLABELLED: Planar 131I scintigraphy is routinely used to detect radioiodine-avid metastases of differentiated thyroid carcinoma (DTC). However, the modality has limitations, such as low sensitivity and lack of anatomic landmarks. We investigated whether SPECT with integrated low-dose CT may have additional value over planar imaging in detecting residue and metastases in DTC patients. METHODS: We studied 117 consecutive thyroidectomized DTC patients. On 2 different hybrid dual-head gamma-cameras (55 patients on one camera and 62 on the other), 108 patients underwent 131I diagnostic imaging and SPECT/CT, and 9 underwent posttherapeutic 131I planar imaging and SPECT/CT. We assigned an incremental value to SPECT/CT when it provided better identification and interpretation of the foci of radioiodine uptake, more correct anatomic localization and characterization, and precise differentiation between tumor lesions and physiologic uptake. RESULTS: Planar imaging showed 116 foci of uptake in 52 of 117 patients, and SPECT/CT showed 158 foci in 59 of 117 patients, confirming all foci seen on planar imaging but identifying an additional 28 occult foci in 10 of 52 patients. Fourteen occult foci were shown on SPECT/CT in 7 further patients whose planar imaging findings were negative. SPECT/CT correctly characterized 48 foci unclear on planar imaging, also defining location and extent. SPECT/CT was a determinant in classifying as neoplastic those foci for which planar imaging seemed to exclude malignancy, discriminating between residue and lymph node metastases in the neck, some of which were adjacent to salivary glands and had been missed on planar imaging. SPECT/CT also showed occult lesions in the mediastinum, abdomen, and pelvis and identified small bone metastases unsuspected on planar imaging. Globally, SPECT/CT had an incremental value over planar imaging in 67.8% of patients, modified therapeutic management in 35.6% of positive cases, and avoided unnecessary treatment in 20.3% of patients with only single benign lesions or physiologic uptake. CONCLUSION: 131I SPECT/CT improved planar data interpretation, showing a higher number of DTC lesions, more precisely localizing and characterizing DTC foci, and more correctly differentiating between physiologic uptake and metastases, thus permitting the most appropriate therapeutic approach to be chosen. A wider use of this method is suggested complementary to planar imaging in selected DTC patients.

Clinicopathological characteristics and long-term outcome in patients with distant metastases from differentiated thyroid cancer.

BACKGROUND: Distant metastases are seen in a minority of patients with differentiated thyroid carcinoma (DTC) but account for most of its disease-specific mortality. Studies on the long-term outcome of patients with distant metastases are controversial. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 660 patients with differentiated thyroid carcinoma followed at our institution from 1994 to 2004. Forty-four patients (6.7%) had distant metastases, with a prevalence of 4.8% for papillary thyroid cancer, 21% for follicular thyroid cancer, and 10% for Hurthle cell cancer. Primary near-total thyroidectomy followed by I(131) radiation was performed in 97% of patients with metastases (86% operated on in 1980-2003). Mean age at thyroidectomy was 49+/-19 years, and the female-to-male ratio was 1.9:1. RESULTS: The distant metastasis occurred synchronously with the primary tumor in 45.5% and after a median follow-up of 9 years in the others. Affected sites were lungs (n=24), bones (n=11), lungs and bones (n=9), brain (n=3), and uterus (n=1). Median duration of follow-up was 12 years (range: 1-42 years) from thyroidectomy and 5.5 years (range: 1-24 years) from diagnosis of distant metastases. The 5- and 10-year survival rates (all causes) after diagnosis of distant metastases were 88% and 77%, respectively. No significant differences in survival curves were found by age, sex, metastasis site, histopathology, or interval to distant metastasis. CONCLUSIONS: We conclude that complete resection of the thyroid gland at diagnosis and high-dose adjuvant radioactive iodine are associated with improved survival in patients with metastatic DTC.

Locally advanced thyroid cancer.

PURPOSE OF REVIEW: The purpose of this review is to summarize existing literature with respect to locally advanced thyroid cancer and define the intricacies of preoperative evaluation, surgical management of involved sites and postoperative treatment. RECENT FINDINGS: Locally invasive thyroid cancer is an uncommon disease process, which carries significant morbidity and mortality. Current treatment modalities include appropriate surgery, radioactive iodine treatment and external beam radiation therapy. Proper evaluation of the extent of disease, with complete gross tumor removal, is paramount in managing this difficult problem. Surgical treatment is still the mainstay for locally advanced thyroid cancer. SUMMARY: Little progress has been made in advancing the treatment of locally advanced thyroid cancer. Patient identification, evaluation and proper surgical management with adjuvant therapy, still remain the most effective course of treatment. Aggressive surgical treatment including removal of all gross tumor and still preserving vital structures along with adjuvant therapy is likely to offer the best results. There is a very high incidence of locoregional and distant failure in this group of patients. The understanding and recognition of histopathological variations, such as poorly differentiated thyroid cancer is also important. New molecular markers are needed to help identify and predict aggressive tumor behavior.

131I therapeutic efficacy is not influenced by stunning after diagnostic whole-body scanning.

PURPOSE: To determine if stunning can be seen with a 185-MBq (5-mCi) dose of iodine 131 (131I) at diagnostic whole-body scanning and, if stunning is seen, determine if there is any 131I therapeutic efficacy. MATERIALS AND METHODS: A retrospective review of findings involving 166 patients who underwent thyroidectomy for differentiated thyroid carcinoma was performed. Diagnostic 131I scans were compared with postablation scans for evidence of stunning. Stunning was defined when the diagnostic scan showed activity that was subsequently decreased on the postablation scan. The sample population was divided into two groups: group NS, patients with no stunning, and group S, patients with stunning. Patients were considered successfully treated if no functioning thyroid tissue and/or metastases were seen on follow-up diagnostic scans. Fisher exact and Student t tests were used to evaluate the statistical significance of therapy success rates, clinical characteristics, and scanning parameters between the two groups. RESULTS: Group NS included 135 (81.3%) of 166 patients, with 36 (26.7%) of 135 lost to follow-up. Group S included 31 (18.7%) of 166 patients, with eight (26%) of 31 patients lost to follow-up. There was no significant difference (P =.61) in treatment success rates between group NS (87 of 99, 88%) and group S (21 of 23, 91%). The treatment success rates for thyroid remnants were 87% (48 of 55) for group NS and 91% (10 of 11) for group S (P =.63). Treatment success rates for metastases (mostly lymph nodes) were 89% (39 of 44) for group NS and 83% (10 of 12) for group S (P =.55). CONCLUSION: Thyroid stunning can occur with 185 MBq of 131I in diagnostic imaging. However, data did not show any effect of stunning on the efficacy of 131I therapy for differentiated thyroid carcinoma.

Conservative management of incidental contrast-enhancing renal masses as safe alternative to invasive therapy.

OBJECTIVES: To describe small contrast-enhancing renal masses suggestive of cancer that were managed conservatively with watchful waiting and serial computed tomography scans. Advanced diagnostic imaging has led to the increased incidental detection of renal masses in patients whose multiple comorbid conditions preclude invasive management. METHODS: A retrospective review was conducted of 29 consecutive patients with 29 incidentally detected asymptomatic renal masses less than 3.5 cm in diameter that were managed conservatively with watchful waiting (because of patient wishes or multiple comorbid conditions) and serial computed tomography scans. RESULTS: The average patient age was 70 years (range 51 to 88), and the average duration of follow-up imaging was 32 months (range 10 to 89). The average number of follow-up computed tomography scans was 4.9 per patient (range 1 to 11). The average width of the renal masses at diagnosis was 1.83 cm (range 0.4 to 3.5), and the average change in size per year was 0.12 cm for all patients. Four patients underwent radical nephrectomy because of growth of the renal mass (n = 1) or patient wishes (n = 3). The histologic findings in 3 of these 4 patients were consistent with renal cell carcinoma. Two patients underwent radiofrequency ablation of the masses. At last follow-up, metastatic disease had not developed in any patient, and no patient had died of renal cell carcinoma. Two patients had died of other causes. CONCLUSIONS: The results of our study showed that when comorbid conditions or patient wishes preclude invasive treatment, contrast-enhancing renal masses less than 3.5 cm wide that are suggestive of cancer can be safely managed with watchful waiting and serial computed tomography scans.

Large remnant 131I ablation as an alternative to completion/total thyroidectomy in the treatment of well-differentiated thyroid cancer.

BACKGROUND: An alternative to completion thyroidectomy for well-differentiated thyroid carcinoma is to ablate the remnant lobe with 131 I. The purpose of this study is to review our own experience with large remnant ablation. METHODS: A retrospective review of 169 patients with well-differentiated thyroid cancer treated at one institution over a 14-year period was undertaken. Seventy-one patients who underwent partial thyroidectomy (PT) followed by 131 I ablation were identified. This group was compared to 98 patients treated with total thyroidectomy (TT). RESULTS: Mean follow-up was 6.2 years for the 71 PT + 131 I versus 4.7 years for the 98 TT patients (P = .184). Recurrence occurred in 4 of 71 PT + I 131 patients (5.6%) versus 9 of 98 TT patients (9.2%) (P = .393). Other than a tendency for the size of the primary to be slightly larger and for the histology to be follicular carcinoma in the PT + 131 I patients, the 2 groups were nearly identical in age, gender, and other prognostic factors such as capsular invasion and metastases. CONCLUSIONS: Large-dose ablation with 131 I is a viable alternative to completion thyroidectomy. Recurrence rates over an average 6-year period are similar to TT. Long-term monitoring of these cohorts is required.

[Follow-up of children and young adults with differentiated thyroid cancer treated with radioiodine]. / Seguimiento de niños y jóvenes adultos con cáncer diferenciado de tiroides (CDT) tratados con radioyodo.

This is a retrospective study carried out in a group of 30 patients with differentiated thyroid cancer (age at diagnosis equal to or less than twenty years old). The aim of the study is to evaluate outcome after 131I therapy. Patients were classified into three groups on the basis of initial surgery, pathology and scintigraphic results: group I (thyroid extent), group II (locoregional extent), and group III (distant metastatic disease). Clinical parameters, 131I scans, serum thyroglobulin determinations and 131I therapeutic administered doses were evaluated in the follow-up. Some other complementary techniques such as chest X-ray and pulmonary function tests are also described. Scintigraphic absence of thyroid tissue has been observed in 83% of the cases; high thyroglobulin level is still detectable in 34% of the patients as a single evidence of disease, and 21% remain without any abnormal clinical, scintigraphic or analytical findings. Total doses administered have increased in groups I, II and III respectively, and have also been inversely proportional to the extension of lymph node surgery. At present, all the patients are alive and in good general condition. According to the results obtained, we conclude that children and young adults with DTC should undergo periodical 131I therapeutic doses in case of positive scans (once total thyroidectomy has been realized, with or without lymph node resection depending on the extension of disease). In our experience, the use of radioiodine is effective and safe in the follow-up of children and youngs with DTC.

Outcome in patients with differentiated thyroid cancer with negative diagnostic whole-body scanning and detectable stimulated thyroglobulin.

BACKGROUND: Management of patients with differentiated thyroid carcinoma with negative diagnostic radioiodide scanning and increased serum thyroglobulin (Tg) concentrations is a widely debated problem. High-dose iodine-131 treatment of patients who have a negative (131)I diagnostic whole-body scan (WBS) is advocated. However, the therapeutic benefit of this "blind" treatment is not clear. OBJECTIVE: To investigate the course of serum Tg during thyroid hormone suppression therapy (Tg-on) and clinical outcome in patients with negative diagnostic (131)I scanning and increased serum Tg concentrations during thyroid hormone withdrawal (Tg-off), after treatment with high-dose (131)I. DESIGN: Retrospective single-center study. METHODS: Fifty-six patients were treated with a blind therapeutic dose of 150 mCi (131)I. Median follow-up from this treatment until the end of observation was 4.2 Years (range 0.5-13.5 Years). RESULTS: The post-treatment WBS revealed (131)I uptake in 28 patients, but none in the remaining 28 patients. In this study the Tg-on values did not change after treatment in either the positive or the negative post-treatment WBS group. During follow-up, 18 of the 28 patients with a positive post-treatment WBS achieved complete remission, compared with 10 of the 28 patients with a negative post-treatment WBS. Nine patients in the negative group died, but no patients died in the positive post-treatment group (P=0.001). CONCLUSIONS: High-dose iodine treatment in diagnostically negative patients who have a negative post-treatment scan seems to confer no additional value for tumor reduction and survival. In patients with a positive post-treatment scan, high-dose iodine treatment can be used as a diagnostic tool to identify tumor location, and a therapeutic effect may be present in individual cases.

Prognostic factors in patients with Hürthle cell neoplasms of the thyroid.

BACKGROUND: Hürthle cell neoplasms, often considered a variant of follicular thyroid neoplasms, represent 3% of thyroid carcinomas. Only a handful of publications have focused on the biologic behavior, prognostic factors, and treatment outcomes of Hürthle cell carcinoma. The objective of the current study was to identify the clinical and pathologic features of Hürthle cell carcinomas that predict disease progression or death. METHODS: The authors reviewed medical records of patients who were treated for Hürthle cell carcinoma (HCC) and Hürthle cell adenoma (HCA) at The University of Texas M. D. Anderson Cancer Center from March 1944 to February 1995, including follow-up information. The pathologic diagnosis was confirmed by one of the authors. RESULTS: The authors identified 127 patients with Hürthle cell neoplasms, 89 patients with HCC and 38 patients with HCA. Seven patients with HCC had foci of anaplastic thyroid carcinoma. Survival for this subgroup was worse compared with the overall group and was analyzed separately. The HCC group was significantly older (age 51.8 years vs. age 43.1. years) and had larger tumors (4.3 cm vs. 2.9 cm) compared with the HCA group. No differences were seen in gender or previous radiation exposure. Forty percent of patients in the HCC group died of thyroid carcinoma, whereas no patients in the HCA group died of the disease. There has been no improvement in all-cause and disease specific mortality in the past 5 decades for patients with these neoplasms. Conventional staging systems predicted mortality with minor differences. Of the patients with known metastasis, 38% showed radioiodine uptake. Univariate analysis identified older age, higher disease stage, tumor size, extraglandular invasion, multifocality, lymph node disease, distant metastasis, extensive surgery, external beam radiation therapy, and chemotherapy as factors that were associated with decreased survival. Tumor encapsulation was associated with improved survival. Although radioactive iodine treatment had no overall effect on survival, subgroup analysis showed that patients who received radioactive iodine for adjuvant ablation therapy had better outcomes compared either with patients who did not receive radioactive iodine or with patients who received radioactive iodine as treatment for residual disease. Multivariate analysis indicated that older age and larger tumor size predicted worse survival through an association with worse behaving tumors (multifocal, less encapsulated, and with extraglandular invasion). The decreased survival in patients with lymph node metastases may be explained by its association with distant metastases. The association of extensive surgery, external beam radiation therapy, and chemotherapy with worse survival also disappeared once those factors were analyzed together with other prognostic factors, such as distant metastases. CONCLUSIONS: Several clinical and pathologic prognostic factors were identified in patients with HCC and HCA. Older age and larger tumor size predicted reduced survival. Radioactive iodine therapy may confer a survival benefit when it is used for adjuvant ablation therapy, but not when residual disease is present. The authors could not demonstrate a survival benefit for the use of extensive surgery, external beam radiation therapy, or chemotherapy.

Hürthle cell carcinoma.

Patients with Hürthle cell carcinoma (HCC) of the thyroid often have aggressive tumors and generally have a worse prognosis than those with papillary or follicular thyroid carcinomas. A total thyroidectomy with ipsilateral central neck lymphadenectomy and a modified radical neck dissection, if central or lateral nodes are positive, are indicated for HCC. The completeness of this procedure should be assessed by radioiodine scan 3 to 4 months after surgery. Any thyroid remnant should be ablated with radiolabeled iodine 131 to eliminate all tissue at risk and to facilitate the use of serum thyroglobulin in surveillance for tumor recurrence. Fewer than 10% of these cancers take up radioiodine. Recurrent disease is treated surgically with good palliation and appreciable prolongation of life. Local excision and neck dissection for recurrent neck disease or pulmonary wedge resection for lung metastasis has been shown to be effective. All patients with HCC should be given thyroid hormone because most of these tumors have thyrotropin receptors. External beam radiation may be considered for patients with unresectable disease, but this is considered palliative.

Oxyphil parathyroid adenoma associated with primary hyperparathyroidism and marked post-operative hungry bone syndrome.

A rare case of functioning oxyphil parathyroid adenoma associated with primary hyperparathyroidism and marked hungry bone syndrome was revealed in a 29-year-old man with hypercalcemia and elevated circulating parathyroid hormone (PTH) level. A large parathyroid tumor weighing 8.4 g was resected and proved to be an oxyphil adenoma. Hypocalcemia was sustained after the operation, despite intensive calcium supplementation. During the postoperative 8 months, bone mineral density at the lumbar spine increased dramatically from 0.892 g/cm2 to 1.244 g/cm2, and whole body bone mineral content increased from 1,913.4 g to 2,419.2 g. This case gives insight to the reversibility of bone loss in this disorder.

Pancreatic pseudocyst resolution after parathyroidectomy for hyperparathyroidism.

Hyperparathyroidism is a rare cause of pancreatic inflammatory disease. Appropriate treatment of coexistent hyperparathyroidism and pancreatitis, especially when complicated by pseudocyst formation, is unsettled. We describe two patients with primary hyperparathyroidism who developed pancreatitis associated with multiple pseudocysts. The largest cyst in each patient was 9 and 5 cm, respectively. After correction of hyperparathyroidism and normalization of serum calcium levels by removal of a parathyroid adenoma, the pseudocysts resolved in both patients, as documented with computed tomography. We conclude that uncomplicated pancreatic pseudocysts in patients with primary hyperparathyroidism can be treated expectantly. Surgical correction of hyperparathyroidism and normalization of serum calcium levels should precede pancreatic intervention when possible, since pseudocyst resolution is likely and the risks of postoperative hypercalcemia are avoided.