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.

Pituitary metastases of Hürthle cell carcinoma of the thyroid.

An 85-year-old man was referred to endocrinology following the discovery of an incidental pituitary mass on cranial imaging which was thought to be a non-functioning adenoma during an admission with headaches, lethargy, confusion and hyponatraemia. He had a history of Hürthle cell carcinoma of the thyroid treated with total thyroidectomy, ablative radioiodine therapy and thyroxine replacement. Subsequently, he developed metastatic spread to the neck, lungs and skeleton. About 9 months later, the patient had deterioration of vision. MRI showed a rapidly expanding pituitary mass with compression of the optic chiasm. Biochemical investigations confirmed hypocortisolism and hypogonadism. The patient underwent trans-sphenoidal resection of the pituitary mass followed by external beam radiotherapy to the pituitary bed. Histopathology confirmed a metastatic deposit of Hürthle cell carcinoma, which is a rare and aggressive variant of follicular thyroid carcinoma.

Axillary lymph node metastases from thyroid carcinoma: Report of seven cases.

Axillary lymph node metastasis (ALNM) of well- or poorly-differentiated thyroid cancer is rare. Notably, there are only 14 single case reports available; therefore, the mechanism of metastasis is unclear at this point. Because we encountered seven cases at a single institution, we were able to infer the mechanism of ALNM of thyroid cancer. The seven cases treated at our institution were analyzed retrospectively. In addition, 14 cases reported from other institutions were reviewed. All seven patients we treated and the 10 patients, among the 14, from other institutions were postoperative recurrences. All seven patients we treated had lymph node metastases near the venous angle, and invasive manipulation had been performed during the previous surgery. Therefore, we can presume that fibrosis at the venous angle caused by ablative surgery or tumor invasion could have resulted in anomalous lymphatic flow from the neck to the axilla. Hence, the subclavian region would probably need to be dissected besides axillary dissection. All 21 cases underwent surgical treatment for ALNM. Metastatic lymph nodes in the venous angle, subclavian or axilla, occasionally invade or adhere to the vessels. Hence, a surgical strategy is required in those cases rather than molecular targeted therapy or radioactive iodine irradiation.

Patient and tumor factors contributing to distant metastasis in well-differentiated thyroid cancer: a retrospective cohort study.

BACKGROUND: Distant metastasis in thyroid cancer significantly reduces survival in patients with well-differentiated thyroid carcinoma (WDTC). There is limited information available to clinicians regarding pathological features that confer a higher risk of distant metastasis (DM). This study aimed to identify patient and tumor factors that were associated with the development of DM over time in patients with WDTC. METHODS: A retrospective cohort analysis of patients with WDTC (n = 584) at our institution was performed between 2007 and 2017. A total of 39 patients with DM and 529 patients with no DM (NDM) were included. Patient demographics, tumor characteristics and patient survival were compared between the DM and NDM groups using a univariate analysis. Multivariate Cox-proportional hazards model was used to evaluate the risk of developing distant metastasis over time. Kaplan-Meier analysis was used to compare survival between the DM and NDM groups. RESULTS: Distant metastasis had a substantial impact on disease-specific survival (DSS) at 5 and 10-years in the DM group; 71.0% (SE 8.4%) and 46.9% (SE 11.6%) respectively, compared to 100% survival in the NDM group (p < 0.001). The DM group had significantly higher proportions of males, lymphovascular invasion (LVI), nodal metastasis (NM), large tumor size (TS), extrathyroidal extension (ETE), positive resection margins, multifocality, follicular thyroid cancer (FTC), tall cell variant of papillary thyroid cancer (PTC), and Hurthle cell carcinoma (HCC), when compared to the NDM group (p < 0.05). A TS ≥ 2 cm (Hazard Ratio (HR) 1.370), NM (HR 3.806) and FTC (HR 7.068) were associated with a significantly increased hazard of developing distant metastasis in patients with WDTC. CONCLUSIONS: TS ≥ 2 cm, NM and FTC are associated with a significantly increased propensity for developing DM in our cohort of WDTC patients.

Metástasis cutánea de carcinoma tiroideo folicular de células de Hürthle / Cutaneous metastasis from Hürthle cell follicular thyroid carcinoma

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Be Aware of the Patient With Benign Follicular Thyroid Lesion Histology and Rising Thyroglobulin Level.

OBJECTIVE: The accurate diagnosis of thyroid follicular/Hürthle cell tumors is challenging and a matter of controversy. We present a series of patients in whom a misclassification of follicular/Hürthle cell thyroid lesions as benign has led to devastating clinical outcomes. METHODS: The Thyroid Cancer Registry of Rabin Medical Center was screened for patients with metastatic differentiated thyroid carcinoma (DTC) who had been initially diagnosed with benign follicular lesion between 1974 and 2015 and treated with hemithyroidectomy. Clinical, pathologic, and outcome data were collected from the medical files. Adequate pathology specimens, when available, were re-evaluated. RESULTS: Seven patients met the inclusion criteria. The original pathologic diagnosis was follicular adenoma in 4 patients and Hürthle cell adenoma in 3 patients. Five patients had bone metastases, of whom one also had lung metastases and one, liver metastases. One patient had both cervical and lung metastases, and 1 patient had only meta-static neck lymph nodes. Six patients had a final diagnosis of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), and 1 patient was diagnosed as having follicular thyroid cancer metastasis by bone biopsy. In 3 of the patients, capsular invasion was detected retrospectively; only 1 patient had evidence of vascular invasion. All 7 patients had high levels of thyroglobulin at diagnosis of metastatic DTC. CONCLUSION: Misclassification of follicular thyroid lesions as benign may lead to progressive disseminated DTC. To minimize the clinical risk of misdiagnosis, especially if a thorough evaluation of the specimens by an experienced pathologist is unfeasible, we suggest long-term follow-up of serum thyroglobulin levels. ABBREVIATIONS: DTC = differentiated thyroid carcinoma; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma.

Malignant Solitary Fibrous Tumor Metastatic to Widely Invasive Hurthle Cell Thyroid Carcinoma: A Distinct Tumor-to-Tumor Metastasis.

We illustrate a case of synchronous malignant solitary fibrous tumor of the thoracic cavity, and widely invasive thyroid Hurthle cell carcinoma. The Hurthle cell carcinoma was found to harbor distinct areas of malignant solitary fibrous tumor. This is a unique case of tumor-to-tumor metastasis that, to the best of our knowledge, has not been previously reported.

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.

Pioglitazone Therapy of PAX8-PPARγ Fusion Protein Thyroid Carcinoma.

Context: A subset of thyroid carcinomas expresses an oncogenic paired box 8 (PAX8) and peroxisome proliferator activated receptor γ (PPARγ) fusion protein (PPFP). The PPARγ/PPFP ligand pioglitazone is highly therapeutic in a transgenic mouse model of PPFP thyroid carcinoma, but whether pioglitazone is therapeutic in patients with PPFP thyroid carcinoma is unknown. Case Description: Tumor blocks from 40 patients with progressive thyroid cancer despite standard-of-care therapy were screened for PPFP, and the tumor from only one patient (2.5%) was positive. The patient had a 6.0-cm acetabular soft tissue metastasis from Hürthle cell carcinoma that caused severe pain on weight bearing and had a serum thyroglobulin level of 1974 ng/mL. After 24 weeks of therapy with pioglitazone, the metastatic lesion was 3.9 cm, the thyroglobulin level was 49.4 ng/mL, and the patient was pain-free. Thirteen months after discontinuation of pioglitazone, the metastatic lesion was 3.6 cm, the thyroglobulin level was 4.7 ng/mL, and the patient remained pain-free. Conclusions: Pioglitazone may be therapeutic in patients with PPFP thyroid cancer. However, thyroid cancers that are progressive despite standard-of-care therapy appear to only rarely express PPFP.

Detection of micrometastases by flow cytometry in sentinel lymph nodes from patients with renal tumours.

BACKGROUND: Stage is an important prognostic factor in renal tumours and dissemination to regional lymph nodes is associated with poor outcomes. Lymph nodes are routinely assessed by immunohistochemistry and microscopic evaluation, a time-consuming process where micrometastases might go undiagnosed. We evaluate an alternative method for detecting metastatic cells in sentinel nodes (SNs) by flow cytometry. METHODS: A total of 15 nodes from 5 patients diagnosed with renal tumours were analysed by flow cytometry. Staining for the intracellular marker cytokeratin 18 (CK18) with the surface markers carbonic anhydrase IX (CA9) and Cadherin 6 were used in flow cytometry analysis. Peripheral blood mononuclear cells (PBMCs) with the addition of known concentrations of cancer cell lines were analysed to investigate the sensitivity of micrometastasis detection. RESULTS: Stability of the assay was marked by low intra-assay variability (coefficient of variance ⩽16%) and low inter-assay variability (R2=0.9996-1). Eight nodes in four patients were positive for metastasis; six of them were considered being micrometastatic. These metastases were undetected by routine pathology and the patients were restaged from pN0 to pN1. CONCLUSIONS: Flow cytometry is able to detect micrometastases in lymph nodes of renal tumour patients that were undetected under H&E examination.

Oncocytic adenomas of thyroid-mimicking benign or metastatic disease on 18F-FDG-PET scan.

BACKGROUND: The literature is sparse concerning 18F-fluorodeoxyglucose (18F-FDG) accumulation in the Hürthle cell neoplasm (HCN) of the thyroid. Given the difficulty of accurately diagnosing HCN, even with ultrasound (US) and fine needle aspiration biopsy (FNAB), the ability to accurately characterize these lesions by 18F-FDG positron emission tomography (PET) would be of value. PURPOSE: To describe six cases of oncocytic proliferation in the thyroid gland that mimics the presence of metastatic disease and was detected incidentally by an 18F-FDG PET scan. MATERIAL AND METHODS: We conducted whole-body 18F-FDG PET examinations for cancer staging in 1862 oncological patients from 2012 to 2013. Among them, six subjects (4 women, 2 men; age range, 45-85 years) with focal-enhanced 18F-FDG accumulation in the thyroid gland were selected from the study population. This study group was further investigated using 99 m-Tc-pertechnetate scintigraphy, US, and FNAB. Two experienced nuclear physicians reviewed the images. Gray-scale US and color Doppler (CD) sonographic examinations of the thyroid were undertaken for all subjects using a sonographic device Logiq 5 Expert (GE Medical Systems, Osaka, Japan) equipped with a 7-12 MHz linear array transducer. RESULTS: In all six cases, abnormal 18F-FDG uptake was found locally in the thyroid. The average SUVmax of the HCN was 5.8 (range, 2.6-16). In all six cases, 99 m-Tc-pertechnetate scintigraphy showed a cold spot. Compared with normal parenchymal vascularity, five of the six masses were shown to be hypervascular by CD ultrasonography. CONCLUSION: On PET scans, oncocytic proliferations of the thyroid may mimic metastases of other malignancies. The focal-enhanced uptake of 18F-FDG PET may be associated with a focal increase in the metabolic activity of the thyroid parenchyma due to the presence of oncocytes. Our study emphasizes the importance of obtaining cytological evidence before making a diagnosis of metastatic disease.

An in vivo mouse model of metastatic human thyroid cancer.

BACKGROUND: Mouse models of metastatic human cancers are important tools in preclinical studies for testing new systematic therapies and studying effectors of cancer metastasis. The major drawbacks of current mouse models for metastatic thyroid cancer are that they have low metastasis rates and do not allow in vivo tumor detection. Here, we report and characterize an in vivo detectable metastasis mouse model of human thyroid cancer using multiple thyroid cancer cell lines. METHODS: Human anaplastic thyroid cancer cell lines 8505C, C-643, SW-1736, and THJ-16T; follicular thyroid cancer cell lines FTC-133, FTC-236, and FTC-238; and Hürthle cell carcinoma cell line XTC-1 were transfected with a linearized pGL4.51[luc2/CMV/Neo] vector or transduced with lentivirus containing Luc2-eGFP reporter genes. The stably transfected cells were injected intravenously into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. Tumors were detected with an in vivo imaging system-Xenogen IVIS. Vemurafenib, a BRAF inhibitor, was used to treat lung metastases generated from 8505C-Luc2 cells with a BRAF(V600E) mutation to test the accuracy of the model to evaluate response to therapy. RESULTS: Intravenous injection of as few as 30,000 8505C-Luc2 cells produced lung metastases in 100% of the injected mice, and many of these mice also developed bone metastases at a later stage of the disease. Similarly, metastatic tumors also developed in all mice injected with C-643-Luc2, THJ-16T-Luc2, FTC-133-Luc2, FTC-236-Luc2, FTC-238-Luc2, and XTC-1-Luc2 cells. The metastases were easily detectable in vivo, and tumor progression could be dynamically and accurately followed and correlated with the actual tumor burden. Furthermore, disease progression could be easily controlled by adjusting the number of injected cells. The in vivo treatment of 8505C xenograft lung metastases with vemurafenib dramatically reduced the growth and signal intensity with good correlation with actual tumor burden. CONCLUSIONS: Herein we report an in vivo detectable mouse model of metastatic human thyroid cancer that is reliable and reproducible. It will serve as a useful tool in the preclinical testing of alternative systematic therapies for metastatic thyroid cancer, and for functional studies of thyroid cancer tumor biology in vivo.

"Hidden" bone metastasis from thyroid carcinoma: a clinical note.

The (131)I-iodide ((131)I) whole-body scan, for thyroid carcinoma is at times difficult to interpret. In a diagnostic whole body (131)I scan of a patient with follicular carcinoma, a posterior skull lesion was partially hidden by overlapping facial structures. On lateral head view, the abnormality was clearly evident. SPECT/CT and MRI showed the lesion originated in the occipital bone and had enlarged into the posterior fossa. The mass was surgically removed and the patient received (131)I therapy for residual tissue. The study demonstrates a pitfall in the reading of two dimensional radioiodine images which can be overcome by SPECT or lateral imaging.

Pituitary metastases from the oncocytic variant of follicular thyroid carcinoma: a case report and diagnostic dilemmas.

Metastases to the pituitary gland and sella turcica are uncommon. The distinction between primary and secondary metastatic pituitary tumours is challenging as carcinomas from distant sites might closely resemble, both clinically and histopathologically, non-functional adenomas or primary pituitary carcinomas. Among metastases to pituitary gland ones from thyroid carcinoma are extremely rare. We present a unique case of a 53-year-old male patient with a past history of thyroid carcinoma who underwent repeated surgeries over a period of 7 years for a sellar-parasellar mass with paranasal sinus involvement. Morphologically, the tumour was composed of solid sheaths of monomorphic cells exhibiting oncocytic features. In electron microscope images, the cytoplasm of tumour cells was filled with numerous mitochondria. The tumour was negative for pituitary hormones but exhibited immunoreactivity for cytokeratin AE1/AE3, thyroglobulin and thyroid transcription factor 1 (TTF-1). Based on the clinical data and immunophenotypic profile, the tumour was finally diagnosed as an oncocytic variant of follicular thyroid carcinoma. To our knowledge, this is probably the first report of such peculiar histopathological variant of follicular thyroid carcinoma metastasizing to the pituitary gland. The diagnostic dilemmas considering oncocytic features of the presented case are discussed.

Small cell variant of renal oncocytoma with liver metastases: a case report.

Renal oncocytoma is a renal neoplasm considered to be benign. A small cell variant comprising predominantly of oncoblasts is rare. Metastases from a renal oncocytoma are extremely rare. A case of small cell variant of renal oncocytoma with liver metastases is described.

A case report of adrenocortical carcinosarcoma with oncocytic and primitive neuroectodermal-like features.

Adrenocortical carcinosarcomas are rare aggressive neoplasms; only a few have been reported to date, all with dismal prognosis. These were reported as having varying morphology. We have encountered a case of adrenal carcinosarcoma with an undifferentiated component bearing similarities to primitive neuroectodermal tumors and other areas of oncocytic differentiation. The 48-year-old woman patient presented with abdominal pain and unintended, excessive weight loss. Computed tomographic imaging revealed a tumor located adjacent to the liver and kidney necessitating a partial nephrectomy and hepatectomy. Histologically, the tumor exhibited malignant features. Melan-A, inhibin, calretinin, cytokeratin AE1/AE3, synaptophysin, and neuron-specific enolase were positive immunohistochemically. The patient developed metastasis within 2 months of surgery and is currently alive with disease after chemotherapy. Adrenal carcinosarcoma is a rare highly aggressive malignancy with a wide morphologic spectrum. Recognition of variant morphology and applying correct immunohistochemical studies will aid in reaching an accurate diagnosis.

Tumour-to-tumour metastases: prostate carcinoma metastasising to a renal oncocytoma.

This is a case report of prostate carcinoma metastasising to a renal oncocytoma. The report demonstrates the unusual presentation of metastases from a common cancer to a common benign tumour, and reviews the rare phenomenon of tumour-to-tumour metastases.