Tyrosine kinase inhibitor treatment and long-term follow-up for metastatic malignant struma ovarii.

Metastatic malignant struma ovarii (MMSO) is a very rare disease (in the United States, less than one case in 10 million females annually). However, this incidence rate is due to a paucity of data regarding diagnosis, treatment, and follow-up. Herein, we describe the case of a 14-year-old female who presented with MMSO, which later metastasized and was followed up on for over 10 years. The patient underwent right oophorectomy surgery and was then treated with a combination of radioactive iodine followed by iodine scans to detect the absorption of radioiodine in the metastatic sites, and radiation therapy to treat skeletal lesions. She subsequently received treatment with the tyrosine kinase inhibitors (TKIs), sorafenib and then lenvatinib, as treatments for advanced disease, thereby achieving long-term disease stability. This case report, which adds to the limited data available on MMSO treatment, suggests that patients treated with a combination of radioactive iodine, radiation therapy, and TKIs can result in good responses and long-term overall survival.

Graves disease and metastatic hormonal-active Hürthle cell thyroid cancer: A case report.

RATIONALE: A hormone-active metastatic Hürthle cell thyroid carcinoma (HCTC) and Graves disease (GD) present a therapeutic challenge and is rarely reported. PATIENT CONCERNS: We present a 64-year-old male patient, who had dyspnea and left hip pain lasting 4 months. He had clinical signs of hyperthyroidism and a tumor measuring 9 cm in diameter of the left thyroid lobe, metastatic neck lymph node and metastases in the lungs, mediastinum, and bones. DIAGNOSIS: Laboratory findings confirmed hyperthyroidism and GD. Fine-needle aspiration biopsy and cytological investigation revealed metastases of HCTC in the skull and in the 8th right rib. A CT examination showed a thyroid tumor, metastatic neck lymph node, metastases in the lungs, mediastinum and in the 8th right rib measuring 20 × 5.6 × 4.5 cm, in the left acetabulum measuring 9 × 9 × 3 cm and parietooccipitally in the skull measuring 5 × 4 × 2 cm. Histology after total thyroidectomy and resection of the 8th right rib confirmed metastatic HCTC. INTERVENTIONS: The region of the left hip had been irradiated with concomitant doxorubicin 20 mg once weekly. When hyperthyroidism was controlled with thiamazole, a total thyroidectomy was performed. Persistent T3 hyperthyroidism, most likely caused by TSH-R-stimulated T3 production in large metastasis in the 8th right rib, was eliminated by rib resection. Thereafter, the patient was treated with 3 radioactive iodine-131 (RAI) therapies (cumulative dose of 515 mCi). Unfortunately, the tumor rapidly progressed after treatment with RAI and progressed 10 months after therapy with sorafenib. OUTCOMES: Despite treatment, the disease rapidly progressed and patient died due to distant metastases. He survived for 28 months from diagnosis. LESSONS: Simultaneous hormone-active HCTC and GD is extremely rare and prognosis is dismal. Concomitant external beam radiotherapy and doxorubicin chemotherapy, followed by RAI therapy, prevented the growth of a large metastasis in the left hip in our patient. However, a large metastasis in the 8th right rib presented an unresolved problem. Treatment with rib resection and RAI did not prevent tumor recurrence. External beam radiotherapy and sorafenib treatment failed to prevent tumor growth.

Efficacy and toxicity of sorafenib in the treatment of advanced medullary thyroid carcinoma: A systematic review and meta-analysis.

INTRODUCTION: The aim of this study is to investigate and summarize the treatment efficacy and adverse effects (AEs) of sorafenib in the treatment of metastatic medullary thyroid carcinomas (MTCs). METHODS: We included studies reporting the treatment efficacy or drug toxicity of sorafenib as a single therapeutic agent in MTCs. Pooled incidence and its 95% confidence interval (CI) for complete response, partial response (PR), stable disease (SD), and sorafenib-related AEs were calculated using random-effect model. RESULTS: Eight trials with 101 metastatic MTCs were included for meta-analyses. The overall PR and SD were 21% (95% CI = 9-33) and 58% (95% CI = 41-75), respectively. Hand-foot syndrome, diarrhea, alopecia, mucositis, skin rash, fatigue, and hypertension were the most commonly observed AEs. CONCLUSION: Our results show that sorafenib treatment has a modest effect and might be a candidate treatment in patients with metastatic MTCs who have failed other therapeutic regimens.

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.

Impact of combined FDG-PET/CT and MRI on the detection of local recurrence and nodal metastases in thyroid cancer.

BACKGROUND: Suspected recurrence of thyroid carcinoma is a diagnostic challenge when findings of both a radio iodine whole body scan and ultrasound are negative. PET/CT and MRI have shown to be feasible for detection of recurrent disease. However, the added value of a consensus reading by the radiologist and the nuclear medicine physician, which has been deemed to be helpful in clinical routines, has not been investigated. This study aimed to investigate the impact of combined FDG-PET/ldCT and MRI on detection of locally recurrent TC and nodal metastases in high-risk patients with special focus on the value of the multidisciplinary consensus reading. MATERIALS AND METHODS: Forty-six patients with suspected locally recurrent thyroid cancer or nodal metastases after thyroidectomy and radio-iodine therapy were retrospectively selected for analysis. Inclusion criteria comprised elevated thyroglobulin blood levels, a negative ultrasound, negative iodine whole body scan, as well as combined FDG-PET/ldCT and MRI examinations. Neck compartments in FDG-PET/ldCT and MRI examinations were independently analyzed by two blinded observers for local recurrence and nodal metastases of thyroid cancer. Consecutively, the scans were read in consensus. To explore a possible synergistic effect, FDG-PET/ldCT and MRI results were combined. Histopathology or long-term follow-up served as a gold standard. For method comparison, sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were calculated. RESULTS: FDG-PET/ldCT was substantially more sensitive and more specific than MRI in detection of both local recurrence and nodal metastases. Inter-observer agreement was substantial both for local recurrence (κ = 0.71) and nodal metastasis (κ = 0.63) detection in FDG-PET/ldCT. For MRI, inter-observer agreement was substantial for local recurrence (κ = 0.69) and moderate for nodal metastasis (κ = 0.55) detection. In contrast, FDG-PET/ldCT and MRI showed only slight agreement (κ = 0.21). However, both imaging modalities identified different true positive results. Thus, the combination created a synergistic effect. The multidisciplinary consensus reading further increased sensitivity, specificity, and diagnostic accuracy. CONCLUSIONS: FDG-PET/ldCT and MRI are complementary imaging modalities and should be combined to improve detection of local recurrence and nodal metastases of thyroid cancer in high-risk patients. The multidisciplinary consensus reading is a key element in the diagnostic approach.

Eficacia y seguridad de sorafenib en el tratamiento de pacientes con diagnóstico de carcinoma de tiroides diferenciado, metastásico, irresecable, refractario a tratamiento con yodo radioactivo / Efficacy and safety of sorafenib in the treatment of patients with differentiated, metastatic, unresectable thyroid carcinoma refractory to treatment with radioactive iodine

INTRODUCCIÓN: Antecedentes: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) ha recibido la solicitud de evaluar el uso e la seguridad y eficacia de sorafenib en el tratamiento de pacientes con diagnóstico de carcinoma de tiroides, metastásico, irresecable, refractario a tratamiento con yodo radioactivo detnro del sistema de EsSalud, indicación actualmente no contempla en el petitorio de medicamentos.Generalidades: El cáncer de tiroides es la neoplasia endocrin más frecuente, representando más del 90% de todas las neoplasias endocrinas. Se estima que a nível mundial la incidencia de cáncer de tiroides es mayor en los países desarrollados que en los países en desarrrollo, específicamente 11.1 casos por cada 100 000 habitantes y 4.7 casos por cada 100 000 habitantes, respectivamente. Sin embargo, la mortalidad por cáncer de tiroides es menos en los países desarrollados que en los países en desarrollo, específicamente 0.4 muertes por cada 100 000 habitantes y en 0.7 muertes por cada 100 000 habitantes, respectivamente. Tecnología Sanitaria de Interés: Sorafenib: Sorafenib es un compuesto sintético, inhibidor de quinasas múltiple con capacidad de inhibir tanto los VEGFR-1, VEGFR-2, VEGFR-3 y el receptor beta del factor de crecimiento derivado de las plaquetas, así como la expresión de los genes RET (incluyendo la translocación RET/PTC), RAF (incluyendo la mutación BRAFV600E, C-RAF y B-RAF), c-kit y Flt-3 (25,26).Desde el punto de vista farmacológico, sorafenib alcanza concentraciones séricas máximas a las 2.5-12-5 horas post administración oral, pero se asocia con una biodisponibilidad del 38%-49% que disminuye significativamente con la ingesta de grasas. METOLOGÍA: Estrategia de Búsqueda: La presente evaluación de tecnología fue preparada y revisada por el equipo técnico del IETSI. Las siguientes fuentes ha sido revisadas y consultadas con la intención de buscar la mejor evidencia disponible que directamente responda a la pregunta PICO de esta evaluación. American Thyroid Association (ATA) de los Estados Unidos, British Thyroid Association (ETA) del Reino Unido, Canadian Agency for Drugs and Technologies in Health (CADTH), Cochrane Library, Canadian Agency for Drugs and Technologies in Helath (CADTH), Cochrane Library, Cumulative Index to Nursing and Allied Health Literatura (CINAHL), Embase, European Society of Medical Oncology (ESMO) de Europa, European Thyroid Association (ETA) de Europa, Institute for Health Technology Assessment Ludwing Boltzmann Gelsellschaft (LBIHTA) de Austria, Medline/Pubmed, National Guideline Clearinghouse (NGC) de los Estados Unidos, National Institute for Health Research (NIHR) del Reino Unido, Scopus, Scopus, Scottihs Medicines Consortium (SMC), Translating Research into Practice (TRIP Database)Web of Science. RESULTADOS: Luego de revisar un total de 853 referencias resultados de nuestra búsqueda bibliográfica, logramos filtrar 166 referencias relevantes para nuestra pregunta PICO de interés, de los cuales sólo 21 referencias fueron finalmente selecionadas para nuestro análisis, toda vez que constituían referencias que respondían a la pregunta PICO de interés de este dictamen, incluyendo tres guias de práctica clínica, tres meta-análisis, una evaluación de tecnología y 14 referencias todas procedentes de un ensayo clínico de fase III. CONCLUSIONES: A la fecha no se dispone de evidencia que sustente de maera consistente un beneficio neto de sorafenib como alternativa de tratamiento más eficaz, segura en el manejo de pacientes con diagnóstico carcinoma de tiroides, metastásico, irresecable, refractario a tratamiento con yodo radioactivo. La evidencia disponible, sugiere que sorafenit tiene una ventaja relativa sobre el placebo solo en términos de desenlaces intermedios como la sobrevida libre de progresión y tasa de respuesta parcial, pero no se tiene evidencia que éstas se traduzcan en un beneficio en cuanto a desenlaces clínicos finales de alta relevancia desde la perspectiva del paciente, como la sobrevida global y la calidad de vida; es más, existe evidencia consistente que sorafenib conctituye un riesgo mayor eventos adversos serios y evidencia que sugiere que este medicamento puede incrementar el riesgo muerte por cualquier causa durante el lapso de seguridad del tratamiento. El hecho que la evidencia al momento existente establece que las ganancias atribuibles al sorafenib se da solo en desenlaces clínicos intermedios de relativo significado clínico desde la perspectiva del paciente (como la sobrevida livre de progresión y tasa de respuesta), que no se traducen en otros desenlaces de alta relevancia para el paciente (como la sobrevida global y la calidad de vida), y que ocurre a costa de un mayor riesgo (con evidencia bastante consistente incluso proveniente de meta-análisis) de muerte por culquier causa y de eventos adversos serios, limita seriamente la posibilidad de recomendar el uso de este medicamento algún beneficio neto para estos pacientes.El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI, no aprueba el uso de sorafenib en Pacientes adultos con carcinoma de tiroides diferenciado, metastásico, irresecable, refractario a tratamiento con yodo radioactivo.

Outcomes for patients with papillary thyroid cancer who do not undergo prophylactic central neck dissection.

BACKGROUND: The role of prophylactic central neck dissection (CND) in the management of papillary thyroid cancer (PTC) is controversial. This report describes outcomes of an observational approach in patients without clinical evidence of nodal disease in PTC. METHODS: All patients who had surgery between 1986 and 2010 without CND for PTC were identified. All patients had careful clinical assessment of the central neck during preoperative and perioperative evaluation, with any suspicious nodal tissue excised for analysis. The cohort included patients in whom lymph nodes had been removed, but no patient had undergone a formal neck dissection. Recurrence-free survival (RFS), central neck RFS and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. RESULTS: Of 1798 patients, 397 (22.1 per cent) were men, 1088 (60.5 per cent) were aged 45 years or more, and 539 (30.0 per cent) had pT3 or pT4 disease. Some 742 patients (41.3 per cent) received adjuvant treatment with radioactive iodine. At a median follow-up of 46 months the 5-year DSS rate was 100 per cent. Five-year RFS and central neck RFS rates were 96.6 and 99.1 per cent respectively. CONCLUSION: Observation of the central neck is safe and should be recommended for all patients with PTC considered before and during surgery to be free of central neck metastasis.

METASTATIC RADIOIODINE AVID STRUMA OVARII ASSOCIATED WITH PSEUDO-MEIGS' SYNDROME.

We report a case of 21 years old lady who presented with ascites, left adnexal mass and elevated CA-125. With suspicion of ovarian malignancy, she underwent left salpingo-oophorectomy with omental biopsy. Histopathology revealed: 'follicular variant of papillary thyroid carcinoma arising in struma ovarii' with metastatic papillary thyroid carcinoma in omental and peritoneal nodules. Patient underwent total thyroidectomy followed by radioactive iodine therapy for metastatic omental and peritoneal disease. Post-therapy whole body scan, revealed extensive I-131 avid disease metastatic disease involving the chest, abdomen, pelvis and the musculoskeletal system. Patient was treated with multiple doses of high dose radioactive iodine. She became symptom free on supra-physiologic doses of oral thyroxin however her high thyroglobulin levels and residual radioiodine avid metastatic disease required further treatment. In literature a few cases of struma ovarii have been reported with elevated CA-125 and associated pseudo-Meigs' syndrome. The treatment for this rare disease is still not standardized and poses a therapeutic challenge. Our case emphasizes the need for a multidisciplinary approach for managing struma ovarii.

Tyrosine kinase inhibitor treatments in patients with metastatic thyroid carcinomas: a retrospective study of the TUTHYREF network.

OBJECTIVE: Tyrosine kinase inhibitors (TKIs) are used to treat patients with advanced thyroid cancers. We retrospectively investigated the efficacy of TKIs administered outside of clinical trials in metastatic sites or locally advanced thyroid cancer patients from five French oncology centers. DESIGN AND METHODS: THERE WERE 62 PATIENTS (37 MEN, MEAN AGE: 61 years) treated with sorafenib (62%), sunitinib (22%), and vandetanib (16%) outside of clinical trials; 22 had papillary, five had follicular, five had Hürthle cell, 13 had poorly differentiated, and 17 had medullary thyroid carcinoma (MTC). Thirty-three, 25, and four patients were treated with one, two, and three lines of TKIs respectively. Primary endpoints were objective tumor response rate and progression-free survival (PFS). Sequential treatments and tumor response according to metastatic sites were secondary endpoints. RESULTS: Among the 39 sorafenib and 12 sunitinib treatments in differentiated thyroid carcinoma (DTC) patients, partial response (PR) rate was 15 and 8% respectively. In the 11 MTC patients treated with vandetanib, 36% had PR. Median PFS was similar in second-line compared with first-line sorafenib or sunitinib therapy (6.7 vs 7.0 months) in DTC patients, but there was no PR with second- and third-line treatments. Bone and pleural lesions were the most refractory sites to treatment. CONCLUSIONS: This is the largest retrospective study evaluating TKI therapies outside of clinical trials. DTC patients treated with second-line therapy had stable disease as best response, but had a similar median PFS compared with the first-line treatment.

Prognostic prediction of BRAF(V600E) and its relationship with sodium iodide symporter in classic variant of papillary thyroid carcinomas.

BACKGROUND: The aim of this study was to evaluate the prognosis of the classic variant of papillary thyroid carcinomas with the BRAF(V600E) mutation and 131I treatment failure in those tumors due to lower functional sodium iodide symporter expression. METHODS: 109 papillary thyroid carcinomas were associated with clinicopathologic features. The BRAF(V600E) mutation was evaluated by direct sequencing and sodium iodide symporter protein was determined by immunohistochemistry. RESULTS: We found that the BRAF(V600E) mutation was significantly associated with the classic variant of papillary thyroid carcinomas and was independent of tumor size, the presence of extrathyroid invasion and lymph node metastasis, advanced TMN stages, and a high risk of disease recurrence. Moreover, the BRAF(V600E) mutation was associated with a statistically significant lower functional NIS protein expression in the classic variant of papillary thyroid carcinomas. However, those statistically significant relationships were not found in the follicular variant of papillary thyroid carcinomas. CONCLUSIONS: The BRAF(V600E) mutation might be associated with a more aggressive phenotype and a poor prognosis, causing less NIS-mediated 131I uptake due to a lower functional NIS protein expression in the classic variant of papillary thyroid carcinomas. Our current study appears to be valuable for predicting prognosis and is of important clinical significance for surgery and 131I treatment in patients with the classic variant of papillary thyroid carcinomas.

Optimal surgical management of well-differentiated thyroid cancer arising in struma ovarii: a series of 4 patients and a review of 53 reported cases.

BACKGROUND: Well-differentiated thyroid cancer arising in struma ovarii is rare. The optimal management of this entity remains undefined. Unilateral cystectomy, unilateral salpingo-oophorectomy (USO), or total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH/BSO), in addition to total thyroidectomy and radioactive iodine (RAI) ablation, have been employed by various groups. We hypothesized that in patients with thyroid cancer arising within struma ovarii, pelvic surgery alone would be sufficient, provided there is no evidence of gross extra-ovarian extension. METHODS: We review a series of four patients from a single institution and 53 cases from the literature, comparing the extent of treatment and outcomes. Our literature review focused on low-risk patients with struma ovarii confined to the ovary, without evidence of gross extra-ovarian spread or distant metastases. Cumulative recurrence rate was determined by using the Kaplan-Meier method. RESULTS: We report the treatment of four patients with well-differentiated thyroid cancer arising within struma ovarii. Patients underwent USO, BSO, or TAH/BSO. One patient underwent prophylactic total thyroidectomy in anticipation of RAI treatment, and was found to have a synchronous papillary thyroid carcinoma. All patients clinically remain without evidence of disease at a median follow-up of 9 (range 0.8-13) years. Treatment strategies in 53 cases from a review of the literature varied. The pooled cumulative recurrence rate of 57 cases with struma ovarii confined to the ovary was 7.5% at 25 years. CONCLUSIONS: Thyroid cancer arising in struma ovarii is rare. Controversy exists regarding the extent of pelvic resection and management of the thyroid gland. In our series of four patients, all patients are alive without evidence of disease, and the 25-year recurrence rate of 57 cases was low (7.5%), despite a variety of approaches to surgical resection and adjuvant treatment. Extensive pelvic surgery and prophylactic total thyroidectomy to facilitate RAI therapy may be reserved for patients with gross extra-ovarian extension or distant metastases.

Papillary thyroid carcinoma patients assessed to be at low or intermediary risk after primary treatment are at greater risk of long term recurrence if they are thyroglobulin antibody positive or do not have distinctly low thyroglobulin at initial assessment.

BACKGROUND: In papillary thyroid carcinoma (PTC), recurrences during long-term follow-up (R-LTFU) occur even in those who appear to have an excellent prognosis after initial thyroid surgery and usually, radioactive iodine (i.e., "primary treatment"). Initial studies that predict R-LTFU are not well defined. Values for serum thyroglobulin (Tg) measurements when serum thyrotropin (TSH) is >30 µU/mL, as a result of either recombinant TSH or L-thyroxine withdrawal, referred to here as stimulated Tg (STg), have been previously evaluated. The aim of the current study was to determine the parameters associated with R-LTFU in patients with PTC categorized as having low-risk disease 9 to 12 months after their primary treatment. METHODS: This was a retrospective study of 469 patients with PTC with a mean follow-up 5.8±3.9 years. Study patients had to have no uptake in the first postablative diagnostic (131)iodine whole body scan (WBS) performed 9-12 months after primary treatment, a normal cervical ultrasonography (C-US), and STg of <2 ng/mL if their test for antithyroglobulin antibody (anti-Tg) was negative. The first two criteria were required for patients with a positive anti-Tg test, and their nominal serum Tg concentrations were not analyzed. RESULTS: Twelve patients developed recurrences (2.6%) in cervical region. Greater tumor size, higher STg, and positive anti-Tg tests at initial evaluation were associated with greater R-LTFU. The recurrence rates were 1.5% (7/450) and 26% (5/19), respectively, in patients with negative and positive anti-Tg tests at initial evaluation. Recurrence-free survival was lower in the patients with initial lymph node metastases, positive anti-Tg tests, and STg of ≥0.3 ng/mL at the first postablative WBS (p=0.022, 0.001, 0.035, respectively, by log-rank test). Regression analysis in patients who were anti-Tg negative revealed that STg ≥0.3 ng/mL at this first WBS was the only parameter related to recurrence (p=0.031, odds ratio: 10.30, confidence interval: 1.23-83.3). CONCLUSION: Patients with PTC traditionally categorized as low risk during their first 9 to 12 months after primary treatment have a greater risk of R-LTFU if their postablative STg is ≥0.3 ng/mL, or they have positive anti-Tg, even at this early stage. Periodic C-US is important in these patients and should probably be more frequent in patients with PTC who have positive anti-Tg tests or STg ≥0.3 ng/mL in the first year after diagnosis.

Distant, solitary skeletal muscle metastasis in recurrent papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common differentiated thyroid carcinoma. Metastases usually occur in regional lymph nodes or to lungs. Distant metastases to skeletal muscle are rare. Here, we report a patient with a solitary metastasis to skeletal muscle. PATIENT FINDINGS: A 31-year-old woman was found on routine physical examination to have a 1-cm nodule in the right thyroid lobe. The patient underwent endoscopic total thyroidectomy with central cervical lymph node dissection in April 2008. Pathological analysis showed a 1.5 × 0.9 cm PTC in the right thyroid lobe with extension into perithyroidal soft tissue and lymph node involvement (all six central lymph nodes examined were positive). After surgery, she received 100 mCi of radioactive iodine. Subsequently, the patient was found to have a lateral neck recurrence and, therefore, underwent right unilateral modified radical neck dissection followed by additional radioactive iodine ablation. In February 2010, her serum thyroglobulin was 19.4 ng/mL, but the neck ultrasound was negative. However, a fluorodeoxyglucose (FDG) positron emission tomography scan showed focal FDG uptake in the vastus medialis muscle of the right distal femur. A 0.9 × 0.5 cm, well-defined, whitish mass in the vastus medialis muscle was confirmed on histopathology to be metastatic PTC. SUMMARY: Here, we report an adult woman who presented with a thyroid nodule that was noted to be PTC on histopathology after total thyroidectomy. Almost 2 years later, she was noted to have had focal FDG uptake consistent in the region of the right femur. A solitary metastasis of PTC in the right vastus medialis muscle was resected. A MEDLINE (Medical Literature Analysis and Retrieval System Online) search showed that this is only the third report of PTC with a distant, solitary skeletal muscle metastasis. CONCLUSIONS: Distant skeletal metastasis in PTC is very rare. Until the availability of FDG to detect skeletal metastasis of PTC, they may have been more difficult to discern.

A case report of thyroid gland metastasis associated with lung metastasis from colon cancer.

Thyroid gland metastasis of malignant tumors is observed in 1.9% to 9.5% of histologically examined autopsy cases. Thyroid metastasis from colon cancer is extremely rare and the prognosis is poor. Here we report a case of lung metastasis and thyroid gland metastasis following sigmoid colon cancer surgery. In 2000, a 58-year-old woman underwent a sigmoid colectomy for sigmoid colon cancer. In 2005, a metastatic lung tumor was detected by chest CT. The patient underwent a partial thoracoscopic resection of the left lung in April 2005. On a CT scan taken 3 years and 4 months after the lung resection, a tumor mass was observed in the left lung and a low-absorption region with an unclear border was seen in the left lobe of the thyroid gland. Thyroid aspiration cytology showed adenocarcinoma, and a diagnosis of thyroid gland metastasis from sigmoid colon cancer was made. In April 2008 a subtotal thyroidectomy was performed. Following surgery, the patient underwent chemotherapy with mFOLFOX6 and bevacizumab. Nevertheless a number of lung metastases and expressions of lung metastasis were subsequently observed. Histopathological examination revealed a number of metastases of differentiated papillary adenocarcinoma in the thyroid gland from colon cancer.

Alternative therapeutic approaches in the treatment of primary and secondary dedifferentiated and medullary thyroid carcinoma.

The prognosis of patients with surgically unresectable differentiated thyroid tumors deteriorates significantly if radioiodine therapy is or becomes ineffective, considering the limited role of conventional chemotherapies in these patients. Several alternative approaches have been investigated for the treatment of patients with advanced thyroid malignancies in recent years. Among targeted therapies, tyrosine kinase inhibitors have resulted in the most encouraging responses and could soon be, along with redifferentiation therapy, the possible palliative strategies. Radiopeptide therapy, especially with beta emitter-labeled DOTANOC, which shows a great affinity to the somatostatin receptors expressed by thyroid tumor cells, might also be an attractive approach considering its comparatively low rate of side effects. However, the indication should be evaluated on individual basis. Medullary thyroid carcinoma shows a worse overall prognosis compared with the other differentiated thyroid tumors especially because of its natural resistance to radioiodine therapy. However, among possible palliative strategies, (131)I-meta-iodobenzylguanidine therapy is a noteworthy therapeutic approach in patients experiencing metastasized medullary thyroid carcinoma. In summary, recent developments in the treatment of patients with advanced thyroid malignancies have shown promising results, raising the hope for better outcomes in these patients in future.

A case of acromegaly and disseminated follicular thyroid carcinoma.

INTRODUCTION: A particularly challenging case of concurrent acromegaly and follicular thyroid carcinoma in a patient of the Clinic of Endocrinology, UJCM in Krakow is discussed. CASE DESCRIPTION: A 59-year-old male with post total thyroidectomy performed in 2005 and histopathologically confirmed metastases of the follicular thyroid carcinoma to the lungs was admitted to the Clinic in April 2006 for complementary ¹³¹I treatment. Acromegaly was treated in 1996 by trans-sphenoidal surgery. In December 2005 a relapse of pituitary adenoma was shown by MRI, which correlated with increased levels of hGH and IGF-1. Biochemical control of acromegaly was achieved with Sandostatin LAR. Pre-therapeutic whole-body scintigraphy (WBS) revealed numerous conjoined hot spots of ¹³¹I accumulation in both lungs and in thyroid remnants. In May and November 2006 the patient received ¹³¹I treatment. Post-therapeutic WBS in November 2006 revealed complete ablation of the thyroid remnants. Laboratory tests confirmed lowering of thyroglobulin concentration. In the years 2007, 2008, and 2009 the patient was qualified for therapy with ¹³¹I aided by rhTSH, achieving further reduction of Tg levels. Post-therapeutic WBS performed in 2009 revealed weak bilateral tracer uptake in the lung parenchyma. In 2010, chest CT revealed fibrosis in left lung segments, no infiltrative changes, and no lymph node enlargement. Patient follow-up continues at our Department. CONCLUSIONS: Disseminated thyroid cancer in a patient with pituitary insufficiency may be successfully treated by rhTSH-supported ¹³¹I treatment.

Treatment with sorafenib in advanced thyroid cancer - a case report.

Papillary thyroid cancer (PTC) usually has a good prognosis. The treatment, including total thyroidectomy and complementary radioiodine (RAI) therapy, gives complete remission in 90% of patients. However, in 10% of subjects with metastatic disease, the prognosis is poor. In the group of patients with disease progression and no 131I uptake, searching for new therapeutic modalities before all tyrosine kinase inhibitors and other antiangiogenic agents is necessary. The study presents the case of a 55-year-old male with advanced PTC /pT3mNxMo/ diagnosed in 1993. Primary treatment by total thyroidectomy and 131I ablation led to complete remission. In 2000 local as well as lymph node recurrence was diagnosed and successively treated by surgery. In 2006 an increasing serum thyroglobulin level was noted and a single lung metastasis was diagnosed and operated on. In 2007 new foci in CNS and vertebral column with no 131I uptake were stated. Further progression (bones, CNS, and pterygoid muscle) was confirmed by PET-CT. The patient underwent neurosurgical metastasectomy twice and palliative CNS and vertebra's radiotherapy. Liver metastases were diagnosed in 2009. Treatment with increasing doses of thalidomide (up to 800 mg/d) was administered for 3 months with a good tolerance; however, the therapy was withdrawn due to cancer progression. Next, sorafenib (800 mg/d) was given for 16 weeks. Radiological examination performed after 16 weeks confirmed stable disease, whereas 2 months later, after sorafenib withdrawal due to lack of treatment possibility, further progression was observed. Metronomic chemotherapy with Adriamycin was instituted which gave disease stabilization for 6 months. The patient died with advanced disseminated disease due to pulmonary embolism. We present this case to document no adverse effects of therapy with sorafenib in a patient with brain DTC metastases. Sorafenib therapy was only short-term, but no progression occurred in this time.

Well-differentiated thyroid carcinoma: comparison of microscopic and macroscopic disease.

BACKGROUND: The rapid increase in the incidence of well-differentiated thyroid cancer in recent years is the result of smaller thyroid tumors (1 cm or less) being diagnosed more frequently. Few studies are available regarding the appropriate approach to this previously known postmortem incidental finding, and their results remain controversial. METHODS: In 2005, our center started a registry of all patients with nonmedullary thyroid carcinoma who were followed at our institute. In the present study, data on the background, clinical, and outcome characteristics were collected from the registry for 225 patients with microscopic disease and 543 patients with macroscopic disease. RESULTS: Patients with microscopic disease were slightly older (51 vs. 47.5 years, p = 0.003), had a higher female to male ratio (189:37 vs. 419:123; p = 0.06), and were affected more by papillary carcinoma (98.2% vs. 85.5%; p < 0.001). Multifocal disease was documented in 50.2% of the patients with microscopic disease and 46.8% of the patients with macroscopic disease (NS), and bilateral disease, in 42.6% and 36.8%, respectively (NS). Corresponding rates for the two groups for other tumor-related factors were as follows: lymph node involvement at initial treatment, 25.7% and 30% (NS); distant metastases, 2.4% and 5.1% (p = 0.16); persistent/recurrent disease, 11% and 32% (p < 0.001); and new distant metastases, 2.65% and 6.5% (p = 0.07). At a median follow-up of 5 years, 96% of the microscopic carcinoma group were disease free compared to 77% of the macroscopic group (p < 0.001). CONCLUSION: The differences between patients with microscopic and macroscopic well-differentiated thyroid carcinoma may not justify a different therapeutic approach.

Papillary thyroid carcinoma and microcarcinoma: is there a need to distinguish the two?

BACKGROUND: The clinical significance of papillary thyroid microcarcinoma (PTMC) tumors < or =1 cm is widely debated. The objective of this study was to compare conventional papillary thyroid carcinoma (PTC) (tumors >1 cm) to PTMC and assess for differences in tumor characteristics and patient outcome. METHODS: A retrospective chart review of patients with PTC or PTMC who were followed for a minimum of 3 years postoperatively and managed at a single academic institute was performed. RESULTS: Of 202 patients in the study, 66 (32.7%) had PTMC and 136 (67.3%) had conventional PTC. Patient and tumor characteristics including tumor multifocality, extrathyroidal extension, angiolymphatic invasion, and lymph node metastasis were similar between both groups. Twenty-one percent of the PTMC tumors were discovered incidentally. Patients with conventional PTC were significantly more likely to undergo treatment with radioactive iodine therapy compared to PTMC patients (86.4% vs. 66.7%, respectively, p < 0.003). Disease recurrence was observed in 40 patients and was not statistically different between the two groups; 11 (16.7%) in PTMC and 29 (21.3%) in conventional PTC, p = 0.57. Within the PTMC group, tumors of patients that recurred were significantly larger than those who remained disease free (8.1 mm vs. 6.4 mm, p < 0.05). None of the patients with incidental PTMC had disease recurrence. Angiolymphatic invasion was the only significant prognostic indicator of recurrence on multivariate analysis (p < 0.02). CONCLUSIONS: Nonincidental PTMC can have aggressive tumor features and disease recurrence similar to conventional PTC. These tumors should be managed like any other papillary thyroid malignancy.