PURPOSE: Ultrasound (US) and US-guided fine needle aspiration biopsies (FNAB) are considered the modalities of choice for assessing lymph nodes suspected of containing metastases, but the sensitivity of FNAB varies and is specific to the operator. We analyzed the risk of FNAB providing false negative results of lateral neck node metastasis, and evaluated diagnostic accuracy of FNAB, in patients with papillary thyroid cancer. MATERIALS AND METHODS: FNAB was performed in 242 patients suspected of having lateral neck node metastasis on preoperative imaging. Thyroglobulin in the fine-needle aspirate washout (FNA wash-out Tg) and computed tomography enhancement (Hounsfield units) were measured. Patients with negative results on FNAB were examined by intraoperative frozen section. The false negative and true negative groups were compared. RESULTS: Of the 242 patients, 130 were confirmed as having lateral neck node metastases. In 74 patients, the metastasis was identified by FNAB. False positive results were observed in 2 patients (0.8%) and false negatives in 58 (44.6%). Risk analysis showed that patient age <45 years (p=0.006), tumor size >1 cm (p=0.008) and elevated FNA wash-out Tg (p=0.004) were significantly associated with false negative results on FNAB. The accuracy of FNAB increased significantly when combined with FNA wash-out Tg (p=0.003). CONCLUSION: To reduce the false negative rate of FNAB, patient age (<45 years), tumor size (>1 cm) and FNA wash-out Tg (>34.8 ng/mL) should be considered in preoperative planning. Accuracy may be improved by combining the results of FNAB and FNA wash-out Tg.
Adolescent ; Adult ; Aged ; Biopsy, Fine-Needle ; Carcinoma/*diagnosis/*pathology/radiography/surgery ; False Negative Reactions ; Female ; Humans ; Lymph Nodes/*pathology/radiography ; Lymphatic Metastasis/*pathology/radiography ; Male ; Middle Aged ; Multivariate Analysis ; Preoperative Care ; Risk Factors ; Sensitivity and Specificity ; Thyroglobulin/metabolism ; Thyroid Gland/*pathology ; Thyroid Neoplasms/*diagnosis/*pathology/radiography/surgery ; Tomography, X-Ray Computed ; Young Adult

Direct tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization and time-of-flight (MALDI-TOF) mass spectrometry has become increasingly important in biology and medicine, because this technology can detect the relative abundance and spatial distribution of interesting proteins in tissues. Five thyroid cancer samples, along with normal tissue, were sliced and transferred onto conductive glass slides. After laser scanning by MALDI-TOF equipped with a smart beam laser, images were created for individual masses and proteins were classified at 200-microm spatial resolution. Based on the spatial distribution, region-specific proteins on a tumor lesion could be identified by protein extraction from tumor tissue and analysis using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using all the spectral data at each spot, various intensities of a specific peak were detected in the tumor and normal regions of the thyroid. Differences in the molecular weights of expressed proteins between tumor and normal regions were analyzed using unsupervised and supervised clustering. To verify the presence of discovered proteins through IMS, we identified ribosomal protein P2, which is specific for cancer. We have demonstrated the feasibility of IMS as a useful tool for the analysis of tissue sections, and identified the tumor-specific protein ribosomal protein P2.
Aged ; Amino Acid Sequence ; Biological Markers/*analysis ; Carcinoma/*diagnosis/metabolism/pathology ; Chromatography, High Pressure Liquid ; Cluster Analysis ; Female ; Humans ; Image Processing, Computer-Assisted ; Male ; Middle Aged ; Molecular Sequence Data ; Molecular Weight ; Phosphoproteins/analysis/metabolism ; Proteome/analysis ; Proteomics ; Reproducibility of Results ; Ribosomal Proteins/analysis/metabolism ; *Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; *Tandem Mass Spectrometry ; Thyroid Gland/metabolism/pathology ; Thyroid Neoplasms/*diagnosis/metabolism/pathology

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 ; metabolism ; pathology ; Adenocarcinoma, Follicular ; metabolism ; pathology ; surgery ; Bronchial Neoplasms ; metabolism ; secondary ; surgery ; Carcinoid Tumor ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Thyroglobulin ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology ; surgery ; Transcription Factors

OBJECTIVETo study the clinicopathologic characteristics of parathyroid carcinoma (PTC).

METHODSEleven cases of PTC encountered during the period from 1994 to 2012 were enrolled into the study. Forty cases of parathyroid adenoma (PA) were also retrieved for comparison. The clinical manifestations, laboratory results and pathologic features were analyzed, with literature review.

RESULTSThe main clinical manifestations of PTC included neck mass (11/11), hypercalcemia (11/11) and hyperparathyroidism (11/11). Most patients also had osteoporosis (10/11). In contrast, PA often manifested as hypercalcemia (40/40) and hyperparathyroidism (40/40). Histologic examination of PTC showed that the tumor cells contained clear to eosinophilic cytoplasm and separated by dense bands of fibrosis. The tumor mass was surrounded by thick fibrous capsule. Foci of capsular invasion and vascular permeation were identified at the tumor periphery in all cases. Cellular atypia was not conspicuous but mitotic figures and coagulative necrosis were easily identified. On the other hand, PA were composed of tumor cells with clear to eosinophilic cytoplasm, forming glands, trabeculae or nests. Most of them (35/40) had intact fibrous capsule. Mitotic figures were rarely encountered and tumor necrosis was absent. Immunohistochemical study showed that the tumor cells in PTC were positive for CK19 (11/11), chromogranin A (9/11), synaptophysin (7/11) and parathyroid hormone (11/11). They were negative for thyroglobulin, TTF-1 and calcitonin. The Ki-67 index was less than 10% (range = 2% to 9%). In contrast, the tumor cells in PA were positive (40/40) for CK19, chromogranin A, synaptophysin and parathyroid hormone. They were negative for thyroglobulin, TTF-1 and calcitonin. The Ki-67 index was less than 3%. Follow up-data were available in 9 cases of PTC (duration of follow up = 11 months to 224 months) and 7 of the patients were still alive. Follow up of all PA cases showed no evidence of recurrence.

CONCLUSIONSPTC is a rare malignant endocrine tumor presenting as neck mass. Histologic features suggestive of malignant behavior include presence of coagulative tumor necrosis and capsular/vascular invasion. It needs to be distinguished from other entities such as parathyroid adenoma, papillary thyroid carcinoma and medullary thyroid carcinoma.

Adenoma ; metabolism ; pathology ; Adult ; Carcinoma ; metabolism ; pathology ; Carcinoma, Neuroendocrine ; Carcinoma, Papillary ; Chromogranin A ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Hypercalcemia ; etiology ; Hyperparathyroidism ; etiology ; Immunohistochemistry ; Keratin-19 ; metabolism ; Male ; Middle Aged ; Osteoporosis ; etiology ; Parathyroid Hormone ; metabolism ; Parathyroid Neoplasms ; complications ; metabolism ; pathology ; surgery ; Synaptophysin ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology

Adult ; CD56 Antigen ; metabolism ; Carcinoma ; metabolism ; pathology ; surgery ; Carcinoma, Medullary ; pathology ; Carcinoma, Papillary ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Paraganglioma ; metabolism ; pathology ; Thyroid Neoplasms ; metabolism ; pathology ; surgery ; Thyroidectomy ; methods ; Transcription Factors ; Triglycerides ; metabolism

PURPOSE: We investigated the merit of ultrasound (US) features and BRAF(V600E) mutation as an additional study of cytology and compared the diagnostic performances of cytology alone, cytology with US correlation, cytology with BRAF(V600E) mutation, and a combination of cytology, US, and BRAF(V600E) mutation all together. MATERIALS AND METHODS: This study included 185 patients (mean age, 48.4 years; range 20-77 years) with 191 thyroid nodules who underwent US-guided fine-needle aspiration (FNA) with an additional BRAF(V600E) mutation test. Three radiologists highly experienced in thyroid imaging retrospectively reviewed US images and classified each nodule into two categories (positive for malignancy or negative for malignancy). Interobserver variability (IOV) of US assessment between the three readers was estimated using the generalized kappa statistic of Landis and Koch. We also calculated the diagnostic performances of these studies. RESULTS: There were 131 cases of malignancy (131/191, 68.6%) and 60 cases of benign nodules (60/191, 31.4%). In terms of IOV of US assessment, the generalized kappa value was 0.242, indicating fair agreement was reached. The combination of cytology with BRAF(V600E) showed higher specificity (100%) and positive predictive value (PPV) (100%) compared to the combination of cytology, BRAF(V600E), and US (specificity 28.3%, 66.7%, 68.3%; PPV 74.6%, 86.6%, 86.8%, respectively; p<0.001). However, cytology with BRAF(V600E) showed lower sensitivity (84.7%) than cytology with BRAF(V600E) and US (96.2%, 98.5%, 95.4%, respectively; p<0.001). CONCLUSION: Considering the diagnostic performance and low reproducibility of US, the combination of FNA with BRAF(V600E) is the most reliable and objective method for diagnosing thyroid malignancy.
Adult ; Aged ; Biological Markers ; Biopsy, Fine-Needle ; Carcinoma/*diagnosis/genetics/*ultrasonography ; Cytodiagnosis ; Female ; Humans ; Male ; Middle Aged ; Proto-Oncogene Proteins B-raf/*genetics ; Retrospective Studies ; Thyroid Gland/metabolism/pathology ; Thyroid Neoplasms/*diagnosis/genetics/*ultrasonography ; Thyroid Nodule/metabolism/pathology ; Young Adult

PURPOSE: We investigated the merit of ultrasound (US) features and BRAF(V600E) mutation as an additional study of cytology and compared the diagnostic performances of cytology alone, cytology with US correlation, cytology with BRAF(V600E) mutation, and a combination of cytology, US, and BRAF(V600E) mutation all together. MATERIALS AND METHODS: This study included 185 patients (mean age, 48.4 years; range 20-77 years) with 191 thyroid nodules who underwent US-guided fine-needle aspiration (FNA) with an additional BRAF(V600E) mutation test. Three radiologists highly experienced in thyroid imaging retrospectively reviewed US images and classified each nodule into two categories (positive for malignancy or negative for malignancy). Interobserver variability (IOV) of US assessment between the three readers was estimated using the generalized kappa statistic of Landis and Koch. We also calculated the diagnostic performances of these studies. RESULTS: There were 131 cases of malignancy (131/191, 68.6%) and 60 cases of benign nodules (60/191, 31.4%). In terms of IOV of US assessment, the generalized kappa value was 0.242, indicating fair agreement was reached. The combination of cytology with BRAF(V600E) showed higher specificity (100%) and positive predictive value (PPV) (100%) compared to the combination of cytology, BRAF(V600E), and US (specificity 28.3%, 66.7%, 68.3%; PPV 74.6%, 86.6%, 86.8%, respectively; p<0.001). However, cytology with BRAF(V600E) showed lower sensitivity (84.7%) than cytology with BRAF(V600E) and US (96.2%, 98.5%, 95.4%, respectively; p<0.001). CONCLUSION: Considering the diagnostic performance and low reproducibility of US, the combination of FNA with BRAF(V600E) is the most reliable and objective method for diagnosing thyroid malignancy.
Adult ; Aged ; Biological Markers ; Biopsy, Fine-Needle ; Carcinoma/*diagnosis/genetics/*ultrasonography ; Cytodiagnosis ; Female ; Humans ; Male ; Middle Aged ; Proto-Oncogene Proteins B-raf/*genetics ; Retrospective Studies ; Thyroid Gland/metabolism/pathology ; Thyroid Neoplasms/*diagnosis/genetics/*ultrasonography ; Thyroid Nodule/metabolism/pathology ; Young Adult

OBJECTIVETo study the clinicopathological features, immunophenotype, differential diagnosis and prognosis of low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA).

METHODSThe histopathological features and clinical and pathological data of nine cases of LGNPPA were retrospectively analyzed. Immunohistochemistry (Two-step EnVision methods) was used to evaluate the expression of CKpan, vimentin, CK7, CK19, TTF-1 and TG; in situ hybridization was used to detect Epstein-Barr virus mRNA (EBER); and flow-through hybridization was used to evaluate the presence of human papilloma virus (HPV).

RESULTSThe mean age for the nine patients (eight males, one female) was 45.3 years (range 23 to 62 years). Microscopically the tumors were characterized by lobulated, papillary and glandular structures with patchy distribution of spindle cells. The papillary interstitial tissue was edematous, myxoid or hyalinized. The tumors were unencapsulated and infiltrated into the surrounding stroma. Four cases displayed transition between normal nasopharyngeal epithelium to neoplastic cells; and one case contained psammoma bodies. Five cases were strongly positive for CKpan, vimentin, CK7, CK19, TTF-1, and were focally positive for EMA and CD117. These five cases were all negative for TG, CK5/6, CK20, S-100 protein, p63, Calponin and SMA. In situ hybridization for EBER and flow-through hybridization for HPV were negative in all five cases. Follow-up data showed no post-operative recurrence of the LGNPPA.

CONCLUSIONSLGNPPA is a rare low-grade neoplasm with distinct morphological characteristics. Its diagnosis is primarily based on the site of lesions and the histological features. The diagnosis and differential diagnosis of LGNPPA could be aided by immunohistochemical staining. LGNPPA may originate from nasopharyngeal epithelium; and the prognosis is good with simple and complete resection.

Adenocarcinoma, Papillary ; metabolism ; pathology ; Adult ; Carcinoma ; Diagnosis, Differential ; Female ; Herpesvirus 4, Human ; genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Proteins ; metabolism ; Nuclear Proteins ; metabolism ; Prognosis ; RNA, Messenger ; metabolism ; Retrospective Studies ; S100 Proteins ; metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism ; Vimentin ; metabolism

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