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

OBJECTIVETo analyze the clinical and biological features of familial nonmedullary thyroid carcinoma (FNMTC).

METHODSClinical data of 66 FNMTC cases of 32 pedigrees was retrospectively analyzed, compared with that of 182 control cases taken randomly from the patients with sporadic papillary thyroid carcinoma (SPTC), who were diagnosed and treated in Tianjin Cancer Hospital between January 2008 and November 2012. The features of FNMTC of the first and second generations were objectively analyzed. Some data quoted from the literature were also used for the analysis.

RESULTSThe median age at diagnosis of all the 66 FNMTC patients was 44 years, and 57 (86.4%) were females. Moreover, 71.2% (47 patients, 23 pedigrees) of the FNMTC patients exhibited a sibling relationship, and 28.8% (19 patients, 9 pedigrees) of the FNMTC patients exhibited a parent-offspring relationship, and 9 cases in the first generation and 10 cases in the second generation. There were significant differences between the FNMTC group and SPTC group in terms of tumor multicentricity, tumor bilaterality, lymph node metastasis, central lymph node metastasis, concomitant chronic thyroiditis and recurrence (P < 0.05). Compared with SPTC, sibling FNMTC presented a higher rate of central lymph node metastasis, while parent-offspring FNMTC showed frequent tumor bilaterality and a higher rate of recurrence (P < 0.05). Besides, patients in the second generation were diagnosed at an earlier age and had a higher male rate, the tumors were more frequently multifocal and bilateral, and had a higher rate of lymph node metastasis.

CONCLUSIONSFNMTC may be more aggressive than SPTC and patients in the second generation may exhibit the "anticipation" phenomenon. It's necessary to make sufficient detailed interrogation and long-term follow-up of the patients and their family for providing individual recommendations for clinical management.

Adolescent ; Adult ; Aged ; Carcinoma ; complications ; genetics ; metabolism ; pathology ; Carcinoma, Papillary ; genetics ; metabolism ; Female ; Follow-Up Studies ; Genetic Predisposition to Disease ; Hashimoto Disease ; complications ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Sex Factors ; Thyroid Neoplasms ; complications ; genetics ; metabolism ; pathology ; Thyroidectomy ; Thyrotropin ; metabolism ; Young Adult

OBJECTIVETo investigate the aberrant promoter methylation of hMLH1 gene promoter and its clinical significance in papillary thyroid cancer (PTC).

METHODSmethylation of hMLH1 gene promoter in the cancer tissue and matched tumor-adjacent normal tissue of 152 PTC patients were detected by real-time methylation specific PCR (qMSP). The relationship between the methylation of hMLH1 gene promoter and clinicopathological features was analyzed.

RESULTSThe methylation rate of hMLH1 gene promoter in cancer tissues was 37.5% (57/152), of which 33 cases were totally methylated and 24 cases were partially methylated. The methylation rate of adjacent normal tissues was 5.3% (8/152)(all were partially methylated). The methylation rate of PTC tissues was significantly higher than that in the tumor-adjacent normal tissue (P < 0.01). The promoter methylation of hMLH1 gene in PTC was significantly correlated with age, size and number of the primary lesion, local invasion, T stage and lymph node metastasis (P < 0.05) , but not correlated with gender and clinical stage (P > 0.05).

CONCLUSIONPromoter methylation of hMLH1 gene is a common molecular event in PTC tissue, and it is significantly correlated with the progression of PTC.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Adolescent ; Adult ; Age Factors ; Aged ; Carcinoma ; genetics ; metabolism ; pathology ; Carcinoma, Papillary ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; MutL Protein Homolog 1 ; Neoplasm Invasiveness ; Neoplasm Staging ; Nuclear Proteins ; genetics ; metabolism ; Promoter Regions, Genetic ; genetics ; Thyroid Neoplasms ; genetics ; metabolism ; pathology ; Tumor Burden ; Young Adult

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

OBJECTIVETo study the pathologic features, diagnosis, differential diagnosis and molecular characteristics of intraductal tubulopapillary neoplasm of the pancreas (ITPN).

METHODSThe clinical findings, morphologic features, immunophenotype (by EnVision method) and KRAS gene alterations (by reverse transcriptase-polymerase chain reaction) of 6 cases of ITPN encountered during the period from January, 2001 to June, 2010 were analyzed.

RESULTSThere were altogether 2 males and 4 females. The mean age of the patients was 64 years. Gross examination showed that the tumors were located in large pancreatic ducts and appeared as polypoid nodules with ductal obstruction. Solid tumor nodules associated with adjoining dilated ducts were identified in one case. Histologically, the tumors were characterized by tubulopapillary growth pattern without luminal mucin. The tumor cells showed high-grade nuclear atypia with scanty intracytoplasmic mucin. Intraductal necrotic foci were frequently observed. Immunohistochemical study showed that the tumor cells expressed CK7 and CK19. Focal positivity for MUC5AC was demonstrated. Two cases expressed MUC1. The staining for MUC2 was negative. KRAS gene mutations were identified in 2 cases, with a single-amino-acid substitution in codon 12 (35G > A and 35G > T/34G > A).

CONCLUSIONSITPN is a newly described pancreatic intraductal neoplasm and different from intraductal papillary mucinous neoplasm. ITPN is characterized by intraductal tubulopapillary growth pattern, severe cytologic atypia and scanty mucin secretion.

Aged ; Amino Acid Substitution ; Carcinoma, Pancreatic Ductal ; genetics ; metabolism ; pathology ; surgery ; Carcinoma, Papillary ; genetics ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Keratin-19 ; metabolism ; Keratin-7 ; metabolism ; Ki-67 Antigen ; metabolism ; Male ; Middle Aged ; Mucin 5AC ; metabolism ; Mucin-1 ; metabolism ; Pancreatectomy ; Pancreatic Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Treatment Outcome

Several pathologic characteristics are associated with an adverse clinical outcome in papillary thyroid carcinoma (PTC), including the histological variant. This study aimed to investigate immunohistochemical expression and BRAF mutation status based on the histological variant and evaluated potential markers of aggressive behavior of PTC in Korean patients. In all, 407 PTC cases were classified to each histological variant, and the 94 representative cases were subjected to immunohistochemistry and BRAF mutation analysis. The classic type, follicular variant (FV) and tall cell variant (TCV) represented 76.9%, 14.2% and 6%, respectively. TCV showed a larger tumor size (P = 0.009), frequent extrathyroidal extension (P = 0.022) and cervical lymph node (LN) metastasis (P = 0.018). TCV and FV showed the reduced expression of galectin-3 (P = 0.003) and HBME1 (P = 0.114). Regardless of histology, PTEN loss and diffuse S100A4 expression were associated with LN metastasis (P = 0.007, P = 0.013). All TCVs harbored BRAF V600E mutation, and FV harbored less BRAF V600E mutation (P = 0.043). Immunohistochemical evaluation showed characteristic patterns in histological variants. PTEN and S100A4 expression are suggested as indicators of regional lymph node metastasis.
Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/*genetics ; Carcinoma, Papillary/genetics/metabolism/*pathology ; DNA Mutational Analysis ; Exons ; Female ; Galectin 3/metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; PTEN Phosphohydrolase/metabolism ; Proto-Oncogene Proteins B-raf/*genetics/metabolism ; Republic of Korea ; S100 Proteins/metabolism ; Thyroid Neoplasms/genetics/metabolism/*pathology ; Tumor Markers, Biological/metabolism ; Young Adult

OBJECTIVE: To relatively detect the Runx2 mRNA expression in papillary thyroid carcinoma (PTC) and thyroid adenoma, then to investigate the role of Runx2 in the development and progression in PTC and the relationship with the micro calcification in PTC. METHOD: The expression of Runx2 mRNA in 14 samples of PTC and 14 samples of thyroid adenoma was examined by relatively real-time RT-PCR. RESULT: The deltaCT value of the carcinoma group and adenoma group was 2.395 +/- 0.302 and 5.028 +/- 1.179 respectively (P<0.01). The 2(-deltadeltaCT) value of the carcinoma group and adenoma group was 7.826 +/- 5.004 and 1 respectively (P<0.01). The carcinoma group was divided into two groups by calcification and there was no statistical difference (P>0.05), and the adenoma group as well. The carcinoma group was divided into two groups by the size of carcinoma (<1 cm and > or = 1 cm). The deltaCT value was 2.629 +/- 0.300 and 2.212 +/- 0.124 respectively (P<0.05) and the 2(-deltadeltaCT) value was 167.33 +/- 33. 823 and 221.69 +/- 18.843 respectively (P<0.01). The TSH level in carcinoma group and adenoma group had no statistical significance (P>0.05). CONCLUSION The expression of Runx2 mRNA was high in PTC, and was related to the size of carcinoma which was higher in bigger size carcinoma. The role of Runx2 may contribute to the formation of the micro-calcification and the development and progression in PTC and other malignant tumors, such as breast cancer, prostatic carcinoma and osteosarcoma.
Carcinoma ; metabolism ; pathology ; Carcinoma, Papillary ; Core Binding Factor Alpha 1 Subunit ; metabolism ; Female ; Humans ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Thyroid Cancer, Papillary ; Thyroid Neoplasms ; metabolism ; pathology

Adenoma ; genetics ; metabolism ; pathology ; surgery ; Adult ; Carcinoma, Papillary ; genetics ; metabolism ; pathology ; Diagnosis, Differential ; Exons ; Female ; Follow-Up Studies ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Mutation ; Nuclear Proteins ; metabolism ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroglobulin ; metabolism ; Thyroid Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism

OBJECTIVE: To determine the association between activity of BRAF and mitogen-activated protein/ extracellular signal-regulated kinase kinase (MEK) / extracellular signal-regulated kinase (ERK) signal pathway in papillary thyroid cancer and its mechanism. METHODS: We collected the clinical data and blood samples from 73 cases of papillary thyroid cancer and another 16 cases of benign thyroid gland tumor, and detected the expression of rat sarcoma (RAS), BRAF, MEK1/2, and ERK1/2 in all tumor specimens and benign thyroid tissues with immunohistochemistry and Western blot. RESULTS: The expression of RAS, BRAF, pMEK1/2, and pERK1/2 protein in papillary thyroid cancer tissues was higher than those in the benign thyroid tissues(P<0.05 or P<0.01). The expression of RAS, BRAF, MEK1/2, and ERK1/2 was associated with the tumor size, the lymph node metastasis, and the clinical stage of papillary thyroid cancer(P<0.05 or P<0.01). CONCLUSION The expression of RAS, BRAF, pMEK1/2, and pERK1/2 is associated with the pathogenesis, the lymph node metastasis, and the clinical stage of papillary thyroid cancer. The MEK/ERK signaling pathway may be activated by BRAF in papillary thyroid cancer.
Adult ; Aged ; Carcinoma, Papillary ; genetics ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; MAP Kinase Signaling System ; Male ; Middle Aged ; Mitogen-Activated Protein Kinase 1 ; genetics ; metabolism ; Mitogen-Activated Protein Kinase 3 ; genetics ; metabolism ; Proto-Oncogene Proteins B-raf ; genetics ; metabolism ; Thyroid Neoplasms ; genetics ; metabolism ; pathology ; Young Adult ; ras Proteins ; genetics ; metabolism

Adenocarcinoma, Follicular ; epidemiology ; genetics ; metabolism ; pathology ; Carcinoma, Papillary ; pathology ; DNA-Binding Proteins ; metabolism ; Diagnosis, Differential ; Genes, ras ; genetics ; Humans ; Point Mutation ; Prognosis ; Thyroglobulin ; metabolism ; Thyroid Neoplasms ; epidemiology ; genetics ; metabolism ; pathology ; Transcription Factors