Humans ; Thyroid Neoplasms/pathology* ; Carcinoma, Papillary/pathology* ; World Health Organization ; Adenocarcinoma, Follicular/pathology*

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.
Adenocarcinoma, Follicular/pathology/secondary ; Adult ; Carcinoma, Papillary, Follicular/pathology/*secondary ; Female ; Galectin 3/analysis ; Humans ; Hyperplasia/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Skull Neoplasms/*secondary ; Thyroid Neoplasms/*pathology

Follicular variant papillary thyroid cancer (FVPTC) is the second most common subtype after conventional PTC. We compared ultrasonographic (US) features of FVPTC to those of conventional PTC according to tumor size. We reviewed US findings, pathologic reports, and medical charts of 249 PTC patients with surgically proven disease (83 FVPTCs, 166 conventional PTCs) at our institution from January 2007 to December 2012. FVPTCs were divided into PTC-like and follicular neoplasm (FN)-like based on sonographic characteristics. PTC-like features were defined as having at least one malignant feature (taller-than-wide shape, infiltrative margin, marked hypoechogenicity, and micro-calcifications), whereas FN-like cancers showed oval solid features without malignant features. FVPTCs showed a higher rate of FN-like features than conventional PTCs. Of 166 conventional PTCs, 13 (7.8%) had FN-like features and 153 (92.2%) had PTC-like features, whereas of the 83 FVPTCs, 31 (37.3%) had FN-like features and 52 (62.7%) had PTC-like features. Macro-FVPTCs showed a higher rate of FN-like features than micro-FVPTCs (P < 0.001). Of 21 macro-FVPTCs, 18 (85.7%) had FN-like features and 3 (14.3%) had PTC-like features, whereas of the 62 micro-FVPTCs, 13 (21%) had FN-like features and 49 (79%) had PTC-like features. There were no differences in multifocality, extrathyroidal invasion, and lymph node metastasis between PTC-like FVPTCs and FN-like FVPTCs. FVPTCs showed fewer sonographic malignant features than conventional PTCs. In particular, FVPTCs larger than 1 cm had a more frequent benign sonographic appearance. Therefore, if fine-needle aspiration result is suspicious for PTC in a nodule larger than 1 cm with no suspicious US features, the possibility of FVPTC might be considered.
Adult ; Carcinoma, Papillary, Follicular/*diagnostic imaging/pathology ; Demography ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Thyroid Neoplasms/*diagnostic imaging/pathology ; *Ultrasonography

Adenocarcinoma, Follicular ; classification ; metabolism ; pathology ; Adenoma ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; Carcinoma, Papillary ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Signal Transduction ; Thyroid Neoplasms ; classification ; metabolism ; pathology

Adenocarcinoma, Follicular ; classification ; diagnosis ; pathology ; Carcinoma, Papillary ; diagnosis ; pathology ; surgery ; Humans ; Lymphatic Metastasis ; Thyroid Neoplasms ; diagnosis ; pathology ; surgery

Diffuse follicular variant papillary thyroid carcinoma (DFVPTC) is a rare variant papillary thyroid carcinoma. DFVPTC typically occurs in young females, extensively involves one lobe or both lobes entirely with frequent nodal metastasis and vascular invasion. In contrast to the other subtypes of follicular variant, DFVPTC has biologically aggressive behavior. We present a case of DFVPTC arising in a 69-yr-old male patient. He presented hoarseness for a few months. Following diagnosis of malignancy on aspiration cytology, total thyroidectomy with neck dissection was performed. The tumor involved both lobes of thyroid, encroaching the surrounding structures including tracheal cartilage and esophagus. Multiple lymph node metastasis and vascular invasion were also found. The patient passed away due to the unexplained bleeding of surgical site.
Aged ; Antigens, CD56/metabolism ; Carcinoma, Papillary, Follicular/*diagnosis/pathology/surgery ; Galectin 3/metabolism ; Humans ; Immunohistochemistry ; Keratin-19/metabolism ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Male ; Thyroid Neoplasms/*diagnosis/pathology/surgery ; Thyroidectomy ; Tomography, X-Ray Computed

Adenocarcinoma, Follicular ; genetics ; metabolism ; pathology ; Carcinoma, Papillary ; genetics ; metabolism ; pathology ; Carcinoma, Renal Cell ; genetics ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Kidney Diseases, Cystic ; genetics ; metabolism ; pathology ; Kidney Neoplasms ; genetics ; metabolism ; pathology ; Thyroid Neoplasms ; genetics ; metabolism ; pathology ; Translocation, Genetic

Adenocarcinoma, Follicular ; metabolism ; pathology ; Adenoma, Chromophobe ; metabolism ; pathology ; Adenoma, Oxyphilic ; metabolism ; pathology ; Angiomyoma ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; Carcinoma, Papillary ; metabolism ; pathology ; Carcinoma, Renal Cell ; classification ; metabolism ; pathology ; ultrastructure ; Diagnosis, Differential ; Humans ; Kidney Neoplasms ; classification ; metabolism ; pathology ; ultrastructure ; Thyroid Neoplasms ; metabolism ; pathology

OBJECTIVETo explore the expression of thyroid stimulating hormone (TSH) receptor in differentiated thyroid carcinoma and its clinical significance.

METHODSSeventy-four patients with differentiated thyroid carcinoma treated in our department from January 2009 to January 2011 were selected as the observation group, and 28 patients with nodular goiter were selected as the control group. Expression of TSH receptor in the two groups were detected by immunohistochemistry.

RESULTSThe positive rate of TSH receptor expression in the observation group was 55.4 (41/74), significantly lower than that of the control group (89.3%, 25/28), with a significant difference between the two groups (χ(2) = 10.21, P < 0.05). In the observation group, the positive rate of TSH receptor expression was 75.9% (22/29) in the stage I patients, 47.8% (11/23) in the stage II patients, 38.9%6 (7/18) in the stage III patients, and 25.0% (1/4) in the stage IV patients. Along with the increase of TNM staging, the positive rate of TSH receptor expression was decreased gradually, with a significant difference between them (χ(2) = 8.93, P < 0.05). The positive rate of TSH receptor expression was 53.8% (14/26) in the lymph node metastasis positive group and 56.3% (27/48) in the lymph node metastasis negative groups, with a non-significant difference between them (χ(2) = 0.04, P > 0.05).

CONCLUSIONSExpression of TSH receptors in the patients with differentiated thyroid carcinoma is quite low, and along with the increase of TNM staging, its positive rate is decreasing gradually. Testing the expression of TSH receptor may provide a basis for TSH suppression therapy after thyroid cancer surgery. This TSH suppression therapy should be personalized in order to reduce the side effects and improve their quality of life.

Adenocarcinoma, Follicular ; metabolism ; pathology ; Adult ; Carcinoma, Papillary ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Receptors, Thyrotropin ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology

Thyroid follicular adenoma and hyperplastic adenomatoid nodule may show overlapping cytologic pattern with thyroid follicular carcinoma and follicular variant of thyroid papillary carcinoma. Fine-needle aspiration cytology (FNAC) has limited role in differential diagnosis of those lesions showing high cellularity and absence of colloid. Those lesions are conventionally termed 'follicular neoplasm'. As diagnostic hallmarks of follicular carcinoma (vascular- and capsular invasion) cannot be detected by cytology, verification by histology after surgery is mandatory. However, only 20% of patients with thyroid nodules diagnosed cytologically as 'follicular neoplasm' are finally diagnosed as carcinoma after surgery. Therefore, there have been many trials to differentiate follicular adenoma (FA) from follicular carcinoma (FTC) in preoperative setting. Among those trials are 1) cell morphometry analysis by computer graphics, analysis of telomerase expression level, quantitation of specific protein markers, or intensive cytological analysis using FNAC specimens, 2) ultrasonographic evaluation, dynamic MRI, or MR spectroscopy for thyroid nodules and 3) gene expression profile analysis for thyroid nodules by microarray technique, all showing limited success or limitations hampering clinical application. Similarly, intra-operative frozen section analysis of thyroid nodule had been known to be of no diagnostic utility in a prospective, randomized trial. Current management strategy for 'follicular neoplasm' is initial surgery for diagnostic purpose to get pathologic diagnosis. If the nodule is diagnosed finally as FTC, completion thyroidectomy with or without radioactive iodine therapy is recommended in most cases. Minimally invasive FTC (without vascular invasion) is known to have excellent prognosis in most cases, so traditionally those patients had undergone unilateral operation without completion thyroidectomy. But, there had been reported cases showing distant metastasis and/or recurrence in patients with 'minimally invasive FTC'. One of problems in diagnosis of 'minimally invasive FTC' is lack of international standardization for pathologic diagnosis. Optimal surgical extent for cases with FTC is not known yet. It might have been due to lack of risk stratification of patients which is unique to FTC (not well differentiated thyroid cancer as a whole), lack of biomarker predicting prognosis of FTC, and lack of controlled trial for management of patients with FTC. In near future, application of molecular diagnostic markers is expected to improve our management strategy for thyroid nodules diagnosed as 'follicular neoplasm', if molecular pathogenesis of FA and of FTC are comprehensively understood.
Adenocarcinoma, Follicular ; Adenoma ; Biopsy, Fine-Needle ; Carcinoma, Papillary ; Colloids ; Computer Graphics ; Diagnosis, Differential ; Frozen Sections ; Humans ; Iodine ; Magnetic Resonance Spectroscopy ; Neoplasm Metastasis ; Pathology, Molecular ; Prognosis ; Recurrence ; Telomerase ; Thyroid Gland ; Thyroid Neoplasms ; Thyroid Nodule ; Thyroidectomy ; Transcriptome