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

OBJECTIVEThe aim of this study was to evaluate the number of central cervical lymph node metastasis (CCLNM) in predicting lateral cervical lymph node metastasis (LCLNM) in patients with papillary thyroid carcinoma (PTC).

METHODSFrom January 2005 to October 2010, a total of 133 patients diagnosed as PTC underwent central and lateral cervical lymph node dissection were enrolled in this study. Quantitative analysis was performed to explore the correlation between the number of CCLNM and LCLNM.

RESULTSThe sensitivity of central cervical node metastasis to predict lateral cervical node metastasis was 84.7%(61/72), and the positive predictive value (PPV) was 66.3% (61/92). The incidence of lateral cervical LNM was correlated with the number of CCLNM (r=0.911, P=0.004). The LCLNM rates in patients with number of CCLNM <2 and ≥ 2 were 54.5% (12/22) and 70.0% (49/70), respectively, with a non-significant difference (P=0.181). The LCLNM rates in patients with number of CCLNM < 3 and ≥ 3 were 50.0% (19/38) and 77.8% (42/54), showing a significant difference (P=0.006). The LCLNM rates in patients with number of CCLNM <4 and ≥ 4 were 55.1% (27/49) and 79.1% (34/43), with a significant difference (P=0.015). The LCLNM rates in patients with number of CCLNM <5 and ≥ 5 with the LLNM rate were 57.6% (34/59) and 81.8% (27/33), showing a significant difference (P=0.019). The LCLNM rates in patients with number of CCLNM <6 and ≥ 6 were 60.0% (39/65) and 81.5% (22/27), showing a significant difference (P=0.047).

CONCLUSIONSCCLNM has a significant association with LCLNM in patients with papillary thyroid carcinoma. LCLNM is mainly observed in patients with ≥ 3 CCLNM. Therefore, the number of CLNM ≥ 3 may be a valuable predictor of lateral cervical lymph node metastasis, and lateral cervical lymph node dissection should be considered.

Axilla ; Carcinoma, Papillary ; secondary ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Neck ; Neck Dissection ; Sensitivity and Specificity ; Thyroid Neoplasms ; pathology

Carcinoma ; secondary ; Carcinoma, Papillary ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Thyroid Neoplasms ; secondary

OBJECTIVETo study the expression of EpCAM and E-cadherin in papillary thyroid carcinoma and to analyze its correlation with various clinicopathologic parameters.

METHODSImmunohistochemical study for EpCAM and E-cadherin was carried out in 91 cases of papillary thyroid carcinoma. Twenty-four cases of papillary hyperplasia of thyroid were used as controls.

RESULTSIn all of the 24 cases of papillary hyperplasia, EpCAM was located on the cell membrane, while in the 91 cases of papillary thyroid carcinoma studied, EpCAM was located within the cytoplasm, with 36.3% (33/91) showing nuclear localization as well. In all the papillary hyperplasia cases studied, E-cadherin showed membranous expression. E-cadherin expression was reduced in 84.6% (77/91) of papillary thyroid carcinoma, as compared with the surrounding native thyroid parenchyma. Amongst the 33 cases of papillary thyroid carcinoma which showed nuclear localization of EpCAM, 30 cases also showed reduced E-cadherin expression. There was a positive correlation between nuclear expression of EpCAM and loss of E-cadherin expression (P = 0.000; Spearman correlation coefficient = 0.857). Nuclear expression of EpCAM correlated with follicular variant of papillary thyroid carcinoma and presence of extrathyroidal extension ( P = 0.037 and 0.033, respectively). Loss of E-cadherin expression correlated with age of patients and presence of lymph node metastasis (P = 0.018 and 0.010, respectively).

CONCLUSIONSE-cadherin expression is reduced in papillary thyroid carcinoma, as compared with native thyroid parenchyma and papillary hyperplasia. Papillary thyroid carcinoma shows loss of EpCAM membranous expression and increased cytoplasmic/nuclear accumulation. Detection of these two markers may provide a valuable reference in defining the biologic behaviors of papillary thyroid carcinoma, including extrathyroidal extension and lymph node metastasis.

Antigens, Neoplasm ; metabolism ; Cadherins ; metabolism ; Carcinoma, Papillary ; metabolism ; secondary ; Cell Adhesion Molecules ; metabolism ; Cell Membrane ; metabolism ; Cytoplasm ; metabolism ; Epithelial Cell Adhesion Molecule ; Humans ; Lymphatic Metastasis ; Neoplasm Proteins ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology

PURPOSE: The BRAF(V600E) mutation represents a novel indicator of the progression and aggressiveness of papillary thyroid carcinoma (PTC). The purpose of this study was to determine the clinical significance of free circulating mutant BRAF(V600E) in predicting the advanced disease of PTC. MATERIALS AND METHODS: Seventy seven matched tumor and plasma samples obtained from patients with both benign and PTC were analyzed for BRAF(V600E) mutation using a peptide nucleic acid (PNA) clamp real-time polymerase chain reaction (PCR). RESULTS: The BRAF(V600E) mutation was absent in tumor DNA samples obtained from patients with benign follicular adenomas or adenomatous goiter. In contrast, 49 of 72 (68.1%) PTC tumors were positive for the BRAF(V600E) mutation. Among them, 3 (6.1%) patients with PTC were positive for BRAF(V600E) mutation in plasma and tumor. However, all 3 patients (100%) had lateral lymph node and lung metastasis. CONCLUSION: These findings suggest that the BRAF(V600E) mutation can be detected using a PNA clamp real-time PCR in the blood of PTC patients with lung metastasis. Future studies are warranted to determine clinical significance of serum BRAF(V600E) mutation in large prospective studies.
Adenocarcinoma, Papillary/*genetics/secondary ; Adult ; Aged ; Carcinoma/*genetics/pathology ; DNA Mutational Analysis ; DNA, Neoplasm/*genetics ; Female ; Humans ; Lung Neoplasms/*genetics ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Neoplasm Staging ; *Peptide Nucleic Acids ; Prospective Studies ; Proto-Oncogene Proteins B-raf/*genetics ; Real-Time Polymerase Chain Reaction ; Thyroid Neoplasms/*genetics/pathology

PURPOSE: Although guidelines indicate that routine dissection of the central lymph nodes in patients with thyroid carcinoma should include the right para-oesophageal lymph nodes (RPELNs), located between the right recurrent laryngeal nerve and the cervical oesophagus and posterior to the former, RPELN dissection is often omitted due to high risk of injuries to the recurrent laryngeal nerve and the right inferior parathyroid gland. MATERIALS AND METHODS: We retrospectively identified all patients diagnosed with papillary thyroid carcinoma who underwent total thyroidectomy with central lymph node dissection, including the RPELNs, between January 1, 2009 and December 31, 2013 at the Thyroid Cancer Center of Yonsei University College of Medicine, Seoul, Korea. RESULTS: Of 5556 patients, 148 were positive for RPELN metastasis; of the latter, 91 had primary tumours greater than 1 cm (p<0.001). Extrathyroidal extension by the primary tumour (81.8%; p<0.001), bilaterality, and multifocality were more common in patients with than without RPELN metastasis; however, there were no significant differences in age and sex between groups. A total of 95.9% of patients with RPELN metastasis had central node (except right para-oesophageal lymph node) metastasis, and the incidence of lateral neck node metastasis was significantly higher in patients with than without RPELN metastasis (63.5% vs. 14.3%, p<0.001). Forty-one patients underwent mediastinal dissection, with 11 patients confirmed as having mediastinal lymph node metastasis with RPELN metastasis on pathological examination. CONCLUSION: RPELN metastasis is significantly associated with lateral neck and mediastinal lymph node metastasis.
Adult ; Aged ; Carcinoma/pathology/*surgery ; Carcinoma, Papillary/pathology/*surgery ; Esophageal Neoplasms/*secondary/surgery ; Female ; Humans ; Incidence ; *Lymph Node Excision ; Lymph Nodes/pathology/*surgery ; Lymphatic Metastasis/pathology ; Male ; Middle Aged ; Recurrent Laryngeal Nerve/pathology ; Republic of Korea/epidemiology ; Retrospective Studies ; Thyroid Neoplasms/pathology/*surgery ; *Thyroidectomy ; Treatment Outcome ; Young Adult

OBJECTIVE: The purpose of this study was to evaluate the patterns of failure, overall survival (OS), disease-free survival (DFS) and factors influencing outcome in endometrial cancer patients who presented with metastatic lymph nodes and were treated with curative intent. METHODS: One hundred and twenty-six patients treated between January 1996 to December 2008 with surgery and adjuvant radiotherapy were identified from our service's prospective database. Radiotherapy consisted of 45 Gy in 1.8 Gy fractions to the whole pelvis. The involved nodal sites were boosted to a total dose of 50.4 to 54 Gy. RESULTS: The 5-year OS rate was 61% and the 5-year DFS rate was 59%. Grade 3 endometrioid, serous, and clear cell histologies and involvement of upper para-aortic nodes had lower OS and DFS. The number of positive nodes did not influence survival. Among the histological groups, serous histology had the worst survival. Among the 54 patients relapsed, only three (6%) failed exclusively in the pelvis and the rest of the 94% failed in extrapelvic nodal or distant sites. Patients with grade 3 endometrioid, serous and clear cell histologies did not influence pelvic failure but had significant extrapelvic failures (p<0.001). CONCLUSION: Majority of node positive endometrial cancer patients fail at extrapelvic sites. The most important factors influencing survival and extrapelvic failure are grade 3 endometrioid, clear cell and serous histologies and involvement of upper para-aortic nodes.
Adenocarcinoma, Clear Cell/pathology/radiotherapy/*secondary/surgery ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Endometrioid/pathology/radiotherapy/*secondary/surgery ; Cystadenocarcinoma, Papillary/pathology/radiotherapy/*secondary/surgery ; Endometrial Neoplasms/pathology/radiotherapy/*surgery ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Radiotherapy, Adjuvant ; Salvage Therapy/methods ; Survival Analysis ; Treatment Failure ; Treatment Outcome

Carcinoma ; classification ; pathology ; Carcinoma, Papillary ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Thyroid Neoplasms ; classification ; pathology ; Tracheal Neoplasms ; secondary

No abstract available.
Aged, 80 and over ; Biopsy ; Carcinoma, Papillary/chemistry/*secondary ; Female ; Humans ; Immunohistochemistry ; Liver Neoplasms/chemistry/*secondary ; Pancreatic Neoplasms/chemistry/*pathology ; Tumor Markers, Biological/analysis

A solid-pseudopapillary tumor (SPT) of the pancreas is known as a low grade malignant tumor with a good prognosis; therefore, surgical intervention is necessary. A 14-year-old boy presented with a large pancreatic SPT and three hepatic metastases. The patient and his family refused surgery. Two serial follow-up CT scans over a period of 13 years demonstrated almost complete disappearance of the pancreatic tumor and three hepatic metastases without relevant treatment. Although there have been a few reports of spontaneous healing of SPT, there has been no report regarding spontaneous disappearance of SPT and distant metastasis. Herein, we report on the spontaneous regression of a large SPT and the disappearance of three hepatic metastases.
Adolescent ; Carcinoma, Papillary/radiography/*secondary ; Humans ; Liver Neoplasms/radiography/*secondary ; Male ; Pancreatic Neoplasms/*pathology/radiography ; Remission, Spontaneous ; Tomography, X-Ray Computed