Breast metastasis of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and regional neck metastasis is more common than distant metastasis. If present, metastasis most frequently occurs in lungs and bones. Follicular variant of papillary thyroid carcinoma (FVPTC) is a mixture of the classic and follicular thyroid carcinoma and metastasizes in the same fashion as the PTC with cervical lymph nodes as the most common site. A case of atypical presentation of FVPTC with rib metastasis is reported. We present a case of an old man with a left-sided palpable breast mass for 2 months in duration without breast pain. Initially, the breast mass was categorised as Breast Imaging Reporting and Data System (BI-RADS) 4a via ultrasonography. Subsequent immunohistochemistry demonstrated that the mass was metastatic thyroid cancer. Consequently, a CT scan revealed a tumour originating from the rib. The patient was finally diagnosed with metastatic FVPTC.

Predictive Factors of Lymph Node Metastasis in Follicular Variant of Papillary Thyroid Carcinoma.

BACKGROUND: Compared with conventional papillary thyroid carcinoma (PTC), follicular variant of PTC (FV-PTC) shows less aggressive behavior and better prognosis. Nonetheless, regional lymph node (LN) metastasis was found in 22.8% of FV-PTC patients. Because LN metastasis is a proven predictor of recurrence in PTC, it is important to assess LN metastasis in FV-PTC patients. METHODS: We retrospectively reviewed 134 FV-PTC patients who underwent thyroidectomy with neck dissection. RESULTS: Central LN metastasis (CLNM) and lateral LN metastasis (LLNM) were found in 50 (37.3%) and 16 (11.9%) patients, respectively. In the multivariate analysis for CLNM, male sex (adjusted OR 4.735, p = 0.001), nonencapsulated form (adjusted OR 2.863, p = 0.022), and tumor size >1.0 cm (adjusted OR 3.157, p = 0.008) were independent predictors of high prevalence of CLNM in FV-PTC patients. In the multivariate analysis for LLNM, microscopic extrathyroidal extension (ETE) (adjusted OR 3.939, p = 0.041) and CLNM (adjusted OR 13.340, p = 0.001) were independent predictors of high prevalence of LLNM in FV-PTC patients. CONCLUSIONS: Meticulous perioperative evaluation and prophylactic central neck dissection may be beneficial for FV-PTC patients with male sex, nonencapsulated form, and tumor size >1.0 cm. Moreover, cautious perioperative evaluation of lateral neck LN may be mandatory for FV-PTC patients with microscopic ETE and CLNM.

Role of Ultrasound in Predicting Tumor Invasiveness in Follicular Variant of Papillary Thyroid Carcinoma.

BACKGROUND: Follicular variant of papillary thyroid carcinoma (FVPTC) is traditionally divided into infiltrative and encapsulated types. Adding to this classification, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a reclassification of a subset of cases (encapsulated tumors without lymphovascular or capsular invasion). The purpose of this study was to assess the role of ultrasound (US) in predicting tumor invasiveness in FVPTC. METHODS: From January 2014 to May 2016, preoperative US examinations were performed on 151 patients with 152 FVPTCs who underwent surgery. Based on a pathologic analysis, the FVPTCs were categorized into three groups: NIFTP, invasive encapsulated FVPTC (iE-FVPTC), or infiltrative FVPTC (I-FVPTC). Each nodule was categorized based on the US pattern according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and the American Thyroid Association (ATA) guidelines. The correlation between tumor invasiveness and the K-TIRADS or ATA category was investigated using Spearman's rank correlation coefficient. RESULTS: Among the 152 FVPTCs, there were 48 (31.6%) NIFTPs, 60 (39.5%) iE-FVPTCs, and 44 (28.9%) I-FVPTCs. US characteristics of the FVPTCs differed significantly according to tumor invasiveness (p ≤ 0.030). Tumor invasiveness showed a significant positive correlation with K-TIRADS (tumors of all sizes: r = 0.591, p < 0.001; tumors ≥1.0 cm: r = 0.427, p < 0.001) and ATA categories (tumors of all sizes: r = 0.532, p < 0.001; tumors ≥1.0 cm: r = 0.466, p < 0.001). According to both K-TIRADS and ATA guidelines for all-sized tumors, the most common subtype was NIFTP in low-suspicion nodules (52.6% and 51.6%), iE-FVPTC in intermediate-suspicion nodules (52.7% and 54.2%), and I-FVPTC in high-suspicion nodules (82.5% and 69.4%). After surgery, lymph node metastases were confirmed in two (4.2%) NIFTP cases, three (5.0%) iE-FVPTC cases, and eight (18.2%) I-FVPTC cases (p = 0.001). The results of the BRAF mutation analysis were not significantly different between the groups (p = 0.507). CONCLUSIONS: Increasing tumor invasiveness from NIFTP to iE-FVPTC to I-FVPTC is positively correlated with the level of suspicion on US using both K-TIRADS and ATA guidelines.

Primary Thyroid Carcinoma with Low-Risk Histology and Distant Metastases: Clinicopathologic and Molecular Characteristics.

BACKGROUND: Distant metastases (DM) are a rare occurrence in well-differentiated thyroid carcinoma. The aim of this study was to analyze the clinical, pathologic, and molecular features of primary thyroid carcinoma with low-risk histology that develop DM. METHODS: A detailed clinicopathologic review and targeted next-generation sequencing were performed on a cohort of well-differentiated thyroid carcinoma lacking gross extrathyroidal extension, extensive vascular invasion, or significant lymph node metastases but exhibiting DM. RESULTS: Primary well-differentiated thyroid carcinoma with low-risk histologic features and DM was a rare occurrence, accounting for only 3% of metastatic non-anaplastic thyroid carcinoma. All 15 cases meeting the inclusion criteria harbored DM at presentation. The majority (11/15) of these tumors were follicular variant of papillary thyroid carcinoma (PTC), especially the encapsulated form (n = 8). The remaining patients harbored encapsulated Hürthle cell carcinoma (n = 2), encapsulated follicular carcinoma (n = 1), and an encapsulated papillary carcinoma classical variant (n = 1). Of the 12 encapsulated carcinomas, 10 had capsular invasion only and no vascular invasion. Ninety-two percent of the tumors exhibited extensive intra-tumoral fibrosis. Among the eight tumors that were subjected to next-generation sequencing analysis, a RAS mutation was the main driver (5/8), and TERT promoter mutation was highly prevalent (6/8). In four cases, TERT promoter mutations were associated with RAS or BRAF mutations. BRAF-mutated classical variant of papillary carcinoma also presented with DM but was less common (1/8). In 11/15 cases, the clinician was able to diagnose distant disease based on the clinical presentation. In 3/4 incidental cases that were genotyped, TERT promoter mutations were found. CONCLUSIONS: When DM occur in primary thyroid carcinoma with low-risk histology, they are almost always found at presentation. The majority are encapsulated follicular variant of PTC with capsular invasion only. TERT promoter mutations occur at a higher rate than that seen in PTC in general and may help explain the aggressive behavior of these histologically deceptive primary carcinomas.

Extremely Well-Differentiated Papillary Thyroid Carcinoma Resembling Adenomatous Hyperplasia Can Metastasize to the Skull: A Case Report.

We describe herein histologic, immunohistochemical, and molecular findings and clinical manifestations of a rare case of an extremely well differentiated papillary thyroid carcinoma (EWD-PTC). Similarly, it is also difficult to diagnose follicular variant papillary thyroid carcinoma (FVPTC), whose diagnosis is still met with controversy. A recently reported entity of well-differentiated tumor of uncertain malignant potential (WDT-UMP) is added to the diagnostic spectrum harboring EWD-PTC and FVPTC. We report this case, because EWD-PTC is different from FVPTC in its papillary architecture, and also from WDT-UMP in its recurrence and metastatic pattern. These morphologically deceptive entities harbored diagnostic difficulties in the past because the diagnosis depended solely on histology. However, they are now diagnosed with more certainty by virtue of immunohistochemical and molecular studies. We experienced a case of EWD-PTC, which had been diagnosed as adenomatous hyperplasia 20 years ago and manifested recurrence with lymph node (LN) metastasis 7 years later. After another 7 years of follow-up, a new thyroid lesion had developed, diagnosed as FVPTC, with LN metastasis of EWD-PTC. One year later, the patient developed metastatic FVPTC in the skull. Immunohistochemically, the EWD-PTC was focally positive for CK19, negative for galectin-3, and focally negative for CD56. Molecular studies revealed BRAF-positivity and K-RAS negativity. The FVPTC in the left thyroid showed both BRAF and K-RAS negativity. In conclusion, EWD-PTC and FVPTC share similar histologic features, but they are different tumors with different molecular biologic and clinical manifestations. A large cohort of EWD-PTC should be included in further study.

Follicular variant of papillary thyroid carcinoma: distinct biologic behavior based on ultrasonographic features.

BACKGROUND: Follicular variants of papillary thyroid carcinoma (FVPTCs) have dichotomous ultrasonographic (US) features. We investigated the differences in the biologic behavior of FVPTC according to US features. METHODS: We reviewed the US findings, pathologic reports, and medical charts of 75 consecutive patients with FVPTC who underwent surgery at our institution from January 2006 to December 2008. FVPTCs were divided into PTC-like and follicular neoplasm (FN)-like based on US findings. PTC-like nodules were defined as having at least one accepted malignant feature (a taller-than-wide shape, an infiltrative margin, marked hypoechogenicity, and micro- or macrocalcifications), whereas FN-like nodules showed oval solid features without malignant features. The prognostic factors were compared. RESULTS: Of the 75 FVPTCs, 42 (56%) were PTC-like and 33 (44%) were FN-like. The mean tumor size of PTC-like FVPTC was significantly smaller than that of FN-like FVPTC (p=0.0483). PTC-like FVPTC showed a significantly higher rate of multifocality than FN-like FVPTC (48% and 15% respectively; p=0.0031). Extrathyroidal extension occurred in 55% of PTC-like FVPTCs compared to 12% of FN-like FVPTCs (p=0.0001). Lymph node metastasis was more frequent in PTC-like FVPTC than in FN-like FVPTC (36% vs. 12%; p=0.0197). PTC-like FVPTC had a higher stage than FN-like FVPTC (p=0.0001). These significant factors persisted in multivariate analysis. Only one recurrence and one distant metastasis were identified, and both occurred in PTC-like FVPTC. CONCLUSIONS: FVPTC with malignant US features seems to behave in a more aggressive fashion than FVPTC without malignant US features. US can help predict the behavior of FVPTC.

Multifocal choroidal metastases from thyroid carcinoma: a case report.

We present the case of a 62-year-old female patient, with follicular variant of papillary thyroid carcinoma, which presented to our department for a severe decrease in vision at right eye level. Despite a complex therapy, that included a near-total thyroidectomy, thyroid I-131 ablation, suppressive therapy with LT4, and external beam radiotherapy with cobalt- 60, the patient developed multiple lung, mediastinal, liver, and bone metastases, followed after 1 year, by multifocal choroidal metastases. The complex ocular investigations performed for the diagnosis and follow-up of the choroidal metastases are presented. A review of the literature was also performed. The rarity of choroidal metastases in patients with thyroid carcinoma imposes, for their detection, periodic ocular examinations.

Peroperative detection with a gamma probe of pelvic metastasis after differentiated thyroid carcinoma in female patients: about two cases and management reflections.

BACKGROUND: Distant metastases of differentiated thyroid cancers are exceptionally localized in the soft tissues and the pelvic cavity. This last event complicates diagnosis, especially in female patients because of false positive nuclear imaging and unrelated iodine uptakes. False positive due to body secretions, urinary and fecal iodine retention and iodine uptake by non-thyroid tissues or ectopic thyroid tissue and bone metastasis of differentiated thyroid carcinoma. METHODS: We present two cases of metastasectomy, guided by a peroperative gamma probe and intraoperative frozen sections of the specimens. In females patients because of potentially false positive nuclear imaging and iodine uptakes unrelated to pathology, it is very difficult to identify a pelvic metastasis. Our experience of two cases underlines these pitfalls and the possibilities to avoid them: the use of 131 Iodine SPECT/CT whole body scan, peroperative gamma probe and intraoperative frozen sections of specimen. CONCLUSION: Preoperative localization needs a precise 3D imaging and the surgical treatment must be guided by a peroperative gamma probe and frozen sections.

Deaths due to differentiated thyroid cancer: a South Island, New Zealand experience: 1984-2009.

AIM: To assess differentiated thyroid cancer (DTC) deaths from the northern half of New Zealand's South Island. METHODS: Retrospective review of Christchurch Hospital Thyroid Clinic and Oncology Department clinical records of resident patients who died of differentiated thyroid cancer of follicular cell origin over the 25-year period 1984-2009. RESULTS: During the 25-year study period 25 patients died from differentiated thyroid cancer. All patients (17 female, 8 male) were Caucasian, with median age 65 years (47-86 years) at presentation. Most (24/25) patients presented with advanced (15 Stage IV, 9 Stage III) disease. Three patients initially presented with cervical lymphadenopathy and four patients with distant metastases--three patients with bone metastases, and one with a pleural effusion. The pathological classification of the tumours included 14 papillary cancers (four were follicular variants), six follicular cancers and five Hurthle cell cancers. The majority of primary tumours were large (>4 cm) and 11 were locally invasive. However one patient had a small (1.3 cm) papillary cancer and presented with a pleural effusion. Surgical removal of the primary tumour was attempted in 24 of the 25 patients, 18 received postoperative radioiodine 131I therapy, and three had external beam radiation therapy. The median survival from diagnosis was 5.5 years (0.2-22 years) with two Stage IV patients (both with Hurthle cell cancers) dying within 4 months. The majority of patients died of metastatic disease but seven died of local disease. CONCLUSIONS: During the 25-year study period, 25 patients died of differentiated thyroid cancer which approximates to one DTC death per year in our region. The median age at diagnosis was 65 years with no patients <45 years of age, and the female to male ration was 2.1:1. Most patients presented with advanced disease--7 patients (28%) had distant metastases. Hurthle cell cancers were over-represented (20%) in our series.

Radioiodine therapy of metastatic lesions of differentiated thyroid cancer.

Seventy years after the first successful radioiodine treatment of metastatic differentiated thyroid cancer (DTC), radioiodine (131I) therapy for this type of tumor is still without alternative. During the last decade, some key issues such as individual dosimetry, and preparation of 131I therapy by recombinant human TSH have been addressed, but this has not yet lead to conclusive results; furthermore a number of questions related to indication, preparation, and treatment protocol of 131I therapy still remain unanswered. In this review, we will address the literature pertaining to the latest developments in the field of 131I therapy of advanced DTC and we will give an overview of the state of the art regarding patient preparation, dosimetry, and therapy.

Unusual CNS presentation of thyroid cancer.

As advanced therapies allow cancer patients to live longer, disease failure in the central nervous system increases from limited therapeutic penetration. Primary thyroid malignancies rarely metastasize to the brain and have a small number of investigations in literature on the subject. The majority of brain metastases involve the brain parenchyma, reflecting the mass and blood distribution within the brain and central nervous system. Here, we report two cases of the most common differentiated thyroid cancers; follicular thyroid cancer having brain involvement from extra-axial growth and papillary thyroid cancer having brain involvement from a single intraventricular metastasis, presumed as metastasis from the vascular choroid plexus. Both of our cases had widespread systemic involvement. For our follicular thyroid cancer, brain involvement was a result of extra-axial growth from cavarial bone, and our papillary thyroid cancer had brain involvement from a single intraventricular metastasis that was initially resected and nearly a year later developed extensive brain involvement. Unlike the usual gray-white junction metastases seen in the majority of metastatic brain tumors, including thyroid, our cases are uncommon. They reflect differences in tumor biology that allows for spread and growth in the brain. Although there is growing genetic knowledge on tumors that favor brain metastases, little is known about tumors that rarely involve the brain.

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.

Rare metastases of differentiated thyroid carcinoma: pictorial review.

Differentiated thyroid cancer (DTC) is usually indolent with good prognosis and long-term survival. However, DTC distant metastasis is often a grave event and accounts for most of its disease-specific mortality. The major sites of distant metastases are the lung and bone. Metastases to the brain, breast, liver, kidney, muscle, and skin are rare or relatively rare. Nevertheless, recognizing rare metastases from DTC has a significant impact on the clinical decision making and prognosis of patients. (131)I single photon emission computed tomography/computed tomography ((131)I-SPECT/CT) can provide both metabolic and anatomic information about a lesion; therefore, it can better localize and define the (131)I-WBS findings in DTC patients. In this pictorial review, the imaging features of a range of rare metastases from DTC are demonstrated, with a particular emphasis on the (131)I-SPECT/CT diagnostic aspect.

Metastasis of follicular variant of papillary thyroid carcinoma masquerading as primary temporal bone tumour.

OBJECTIVE: We describe the first published case of papillary thyroid carcinoma metastatic to the temporal bone. CASE REPORT: A 64-year-old woman presented with a large left temporal bone mass centred in the jugular foramen, initially thought to be a paraganglioma or schwannoma. She was simultaneously being investigated for a left-sided thyroid nodule, which was found to be unremarkable on repeated fine needle aspiration cytology. A biopsy of the temporal bone mass indicated that it was of thyroid origin. The patient underwent total thyroidectomy, which enabled a final diagnosis of follicular-variant papillary thyroid carcinoma with metastasis to the temporal bone. CONCLUSION: Although biopsy is not the usual management for many types of temporal bone mass, pathological investigation is recommended if the tumour has an atypical growth rate, location, spread and/or radiological features. Metastasis of papillary thyroid carcinoma to the skull base is extremely rare, and correct diagnosis is essential in order to pursue an effective treatment plan.