Pink-on-pink: hepatocellular carcinoma metastatic to oncocytic carcinoma of the thyroid.

Hepatocellular carcinoma typically metastasizes within the liver and may involve extrahepatic sites such as the lungs, adrenal glands, and bones at advanced stages. However, hepatocellular carcinoma metastasis to the thyroid is very uncommon and tumor-to-tumor metastasis from a hepatocellular cancer to a thyroid neoplasm is extremely rare. In this report, we present a case of a 70-year-old man with a hepatocellular carcinoma metastasizing to oncocytic thyroid carcinoma, emphasizing the importance of clinical history and of a multidisciplinary approach, as well as the usefulness of site-specific immunohistochemical markers, in diagnosing and managing cases of Rosai's metastasis, especially when donor and recipient neoplasms share similar histologic features.

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.

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.

Molecular Characterization of Metastatic Oncocytoma With Exceptional Response to Treatment: A Case Report.

Comprehensive molecular characterization and effective therapy in a rare case of metastatic renal oncocytoma.

Optimizing therapy for radioactive iodine-refractory differentiated thyroid cancer: current state of the art and future directions.

The majority of patients with differentiated thyroid cancer are cured with standard primary treatments including surgery, radioactive iodine and TSH suppression. A small proportion of patients who develop radioactive iodine-refractory metastatic disease have few treatment options. Recent discovery of the molecular mechanisms that contribute to thyroid cancer tumorigenesis and its progression have revealed key targets that are currently being evaluated in clinical trials. In the last decade several novel targeted therapies have shown encouraging results and have brought hope to patients with advanced disease. However, identifying the subpopulation of patients who may benefit from systemic therapies remains a challenge as the use of these therapeutic modalities is associated with high toxicity rates and most patients have a long indolent phase where the tumor is stable or slowly progressive and asymptomatic. The objective of this review is to summarize the management of patients with metastatic, radioactive iodine refractory differentiated thyroid cancer.

Motesanib diphosphate in progressive differentiated thyroid cancer.

BACKGROUND: The expression of vascular endothelial growth factor (VEGF) is characteristic of differentiated thyroid cancer and is associated with aggressive tumor behavior and a poor clinical outcome. Motesanib diphosphate (AMG 706) is a novel oral inhibitor of VEGF receptors, platelet-derived growth-factor receptor, and KIT. METHODS: In an open-label, single-group, phase 2 study, we treated 93 patients who had progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer with 125 mg of motesanib diphosphate, administered orally once daily. The primary end point was an objective response as assessed by an independent radiographic review. Additional end points included the duration of the response, progression-free survival, safety, and changes in serum thyroglobulin concentration. RESULTS: Of the 93 patients, 57 (61%) had papillary thyroid carcinoma. The objective response rate was 14%. Stable disease was achieved in 67% of the patients, and stable disease was maintained for 24 weeks or longer in 35%; 8% had progressive disease as the best response. The Kaplan-Meier estimate of the median duration of the response was 32 weeks (the lower limit of the 95% confidence interval [CI] was 24; the upper limit could not be estimated because of an insufficient number of events); the estimate of median progression-free survival was 40 weeks (95% CI, 32 to 50). Among the 75 patients in whom thyroglobulin analysis was performed, 81% had decreased serum thyroglobulin concentrations during treatment, as compared with baseline levels. The most common treatment-related adverse events were diarrhea (in 59% of the patients), hypertension (56%), fatigue (46%), and weight loss (40%). CONCLUSIONS: Motesanib diphosphate can induce partial responses in patients with advanced or metastatic differentiated thyroid cancer that is progressive. (ClinicalTrials.gov number, NCT00121628.)

A delayed fatal metastatic Hürthle cell carcinoma.

Hürthle (oxyphilic or oncocytic) cell carcinoma is a variant of follicular cell carcinoma of thyroid. Although this entity of thyroid cancer is well known, its occurrence in young patients has scarcely been reported. We report a case of a 26 year-old male patient, at the time of diagnosis, of Turkish origin, who developed a tracheal, pulmonary and mediastinal metastatic Hürthle cell carcinoma with bilateral cervical and mediastinal lymphadenopathies. This case illustrates an aggressive and metastatic cancer at the time of diagnosis and resistant to all treatment options including surgery, chemotherapy and radioactive iodine.

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.

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.

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.

Metastatic Hürthle cell carcinoma of the thyroid presenting as ulcerated scrotum nodules.

Cutaneous metastasis from Hürthle cell carcinoma of the thyroid is an extremely rare phenomenon. As far as we can determine, there has been only a single case documented. Our patient, a 68-year old man with a history of Hürthle cell carcinoma of the thyroid, had cutaneous nodules in the scrotum and right chin. Histologic and immunohistochemical examinations confirmed the diagnosis of metastatic Hürthle cell carcinoma of the thyroid. To the best of our knowledge, this is the first reported case of scrotal skin metastasis. This case emphasizes the importance of thorough clinicopathologic correlation for any patient with a malignant scrotal cutaneous neoplasm with Hürthle cell or oncocytic differentiation.

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.

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.

Effectiveness of peripheral thyrotropin receptor mRNA in follow-up of differentiated thyroid cancer.

Thyroid cells in peripheral circulation have been linked to thyroid cancer (TC). These cells express thyrotropin receptor (TSHR) messenger RNA (mRNA), which has been studied as a marker of initial TC diagnosis. We examined the utility of TSHR mRNA in long-term follow-up of TC patients. From 2002 to 2007, TSHR mRNA was prospectively measured by quantitative reverse-transcription polymerase chain reaction (RT-PCR) from peripheral blood samples in 259 patients, and those followed > or =3 months since initial thyroidectomy were studied. TSHR mRNA levels were correlated to thyroglobulin (Tg), imaging studies, and disease status during follow-up. Thirty-four patients underwent 20 +/- 14 months median follow-up for papillary (n = 31, 91%), follicular (n = 2) or Hurthle cell (n = 1) TC. Advanced-stage disease occurred in 24% at presentation, and 11 (32%) developed cervical node metastases or recurrence requiring reoperation during follow-up. Of 52 simultaneous TSHR mRNA and serum Tg measurements, 52% were concordant. TSHR mRNA missed disease in 21% patients, but was better than Tg in 27%, including all those with Tg antibodies. TSHR mRNA concurred with whole-body scan detectable disease for 11/14 patients (79%) and accurately predicted overall TC disease status in 77% patients. In discordant cases, TC recurrence was apparent from other imaging modalities [positron emission tomography (PET) scan or ultrasound]. TSHR mRNA in conjunction with Tg diagnosed TC recurrence with 90% sensitivity and 94% specificity. We conclude that TSHR mRNA demonstrates high concordance rates with present methods of detecting TC recurrence, and appears to be more accurate in patients with Tg antibodies. As a novel adjunct, TSHR mRNA may enhance long-term management of TC patients.

A case of liver metastasis from an oncocytoma with a focal area of chromophobe renal cell carcinoma: a wolf in sheep's clothing.

In 2004, the World Health Organization classified the renal oncocytomas as benign neoplasms of the kidney. There are reports of subtypes of renal tumors, with similar histological morphology to oncocytoma, but with malignant potential, one of these tumors is the eosinophilic variant of chromophobe renal cell carcinoma. It is important to characterize the histological features and the subtype of tumor, as this predicts biological behavior and cancer-specific survival rate. A rare case of a liver metastasis from a focal area of eosinophilic variant of chromophobe renal cell carcinoma mixed in oncocytoma in a 69-year-old woman is reported. Although some renal tumors may contain oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma histology, caution should be exercised while diagnosing oncocytomas in needle biopsies as there may be unsampled area of chromophobe carcinoma which has a potential for metastatic spread representing a wolf in sheep's clothing.

Recurrent cancer of the parotid gland: how well does salvage surgery work for locoregional failure?

PURPOSE: Many articles have discussed the clinical features of previously untreated parotid cancer, but the clinical characteristics and treatment of recurrent parotid cancer have not yet been fully described. MATERIALS: We retrospectively reviewed 20 patients with recurrent parotid cancer and analyzed the therapeutic strategies and the prognostic factors. RESULTS: Twelve patients (60%) underwent definitive surgery, including 3 who underwent skull base surgery. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) in the surgery group were 66.7 and 64.1%. In the definitive surgery group, the presence of lymph node metastasis and high-grade malignant histopathology were associated with a poor prognosis (p < 0.01). On the other hand, the presence of facial palsy at presentation, the surgical margin, the time of relapse and the T stage did not affect the DFS in our series. CONCLUSIONS: The results suggest that aggressive definitive surgery may be justified for the treatment of recurrent parotid cancer. The presence of lymph node metastasis and the histopathological malignancy grade are poor prognostic factors for OS and DFS.

[Differentiated thyroid cancers]. / I carcinomi tiroidei differenziati.

The Authors, after a review of the topic of thyroid cancer, focus on the epidemiology, aetiology and diagnosis of well-differentiated thyroid cancers. They then describe their own case series and their many years' experience in treating the patients affected by this pathology, which is generally regarded as having low malignancy. Nowadays the Authors consider the treatment of choice the total thyroidectomy with central compartment lymphectomy, eventually associated with metabolic radiotherapy.

Metastatic adrenocortical oncocytoma: a case report.

With only 51 cases reported in the literature to date, adrenocortical oncocytoma is an exceedingly rare pathological variant of adrenal neoplasms. The first case of metastatic adrenocortical oncocytoma is reported along with an update of the literature. A role for radiotherapy in the palliative setting is demonstrated.