OBJECTIVETo study the clinicopathologic features of intraductal papillary mucinous neoplasm (IPMN) and its distinction from mucinous cystic neoplasm of pancreas.

METHODSThe clinical, radiologic and histologic features of 17 cases of IPMN and 13 cases of mucinous cystic neoplasm (MCN) were reviewed. Mucin profiles (MUC1, MUC2 and MUC5AC) were studied by histology (HE) and immunohistochemistry (EnVision).

RESULTS10 of the 17 cases of IPMN were males. 13 cases of the IPMN were located in head of pancreas. Communication with the main pancreatic duct was demonstrated in 15 cases. Histologically, there were mild to severe papillary ingrowths of dysplastic epithelial cells, associated with intervening normal or atrophic pancreatic parenchyma. Ovarian-like stroma was not seen. Ancillary investigations showed that MUC2 and MUC5AC were detected in tumor cells of 9 and 4 cases respectively. The 4 cases with invasive component showed MUC1 positivity. On the other hand, 11 of the 13 cases of MCN occurred in middle-aged to elderly females and were located in the body and tail of pancreas. Ovarian-like stroma was commonly seen and there was no connection with the main pancreatic duct. All non-invasive MCN, regardless of the degree of cytologic atypia, were positive for MUC5AC (but not MUC2). In the 2 cases with invasive component, MUC1 expression was observed, as in IPMN.

CONCLUSIONSThe age and sex of patients, tumor location, absence of ovarian-like stroma, communication with main pancreatic duct and characteristic mucin profiles represent useful parameters in distinguishing IPMN from MCN of pancreas. The tumor cells of IPMN express mainly MUC2, while those of MCN express MUC5AC. MUC1 may also be a useful marker in demonstration of stromal invasion in these tumors.

Adult ; Age Factors ; Aged ; Antigens, Neoplasm ; metabolism ; Biomarkers, Tumor ; metabolism ; Carcinoma, Pancreatic Ductal ; diagnosis ; metabolism ; pathology ; Carcinoma, Papillary ; diagnosis ; metabolism ; pathology ; Cystadenocarcinoma, Mucinous ; diagnosis ; metabolism ; pathology ; Cystadenoma, Mucinous ; diagnosis ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Mucin 5AC ; Mucin-1 ; Mucin-2 ; Mucins ; metabolism ; Pancreas ; metabolism ; Pancreatic Neoplasms ; diagnosis ; metabolism ; pathology ; Precancerous Conditions ; diagnosis ; metabolism ; pathology ; Sex Factors

OBJECTIVETo study the clinicopathologic and immunohistochemical features of cystic neoplasms of the pancreas.

METHODSNinety-two cases of cystic neoplasm of pancreas were retrieved from the Department archival file during the period from 1999 to 2005. Histologic features were studied and the tumors were typed according to WHO classification. Immunohistochemistry was also carried out using paraffin-embedded tissues.

RESULTSThe age of patients ranged from 16 to 80 years. The patients included 33 males and 59 females. The tumors varied from 2 cm to 21 cm in diameter. They consisted of intraductal papillary mucinous neoplasm (36/92), serous cystic neoplasm (18/92), solid pseudopapillary tumor (18/92), mucinous cystic neoplasm (14/92), cystic pancreatic ductal adenocarcinoma (4/92) and cystic pancreatic endocrine neoplasm (2/92). Immunohistochemical study revealed variable staining patterns, with frequent overlaps between different tumor types. In general, serous cystic neoplasm expressed MUC1, while mucinous cystic neoplasm was positive for MUC-5AC, intraductal papillary mucinous neoplasm for MUC-2 and cystic pancreatic ductal adenocarcinoma for MUC-1. On the other hand, solid pseudopapillary tumor expressed alpha-antitrypsin, alpha-antichymotrypsin, vimentin and progesterone receptor.

CONCLUSIONSAccurate diagnosis of pancreatic cystic neoplasms requires correlation of clinical findings, radiologic examination, histologic features and immunostaining results. Pathologic distinction is important because of different prognostic significance. Two-thirds of pancreatic cystic neoplasms are premalignant or malignant and warrant surgical resection, whereas the remaining one-third (including pseudocyst and serous cystadenoma) are benign and can be treated conservatively.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Papillary ; metabolism ; pathology ; Cystadenocarcinoma, Mucinous ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Cystadenoma, Mucinous ; metabolism ; pathology ; Cystadenoma, Serous ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Mucin 5AC ; metabolism ; Mucin-1 ; metabolism ; Neoplasms, Cystic, Mucinous, and Serous ; metabolism ; pathology ; Pancreatic Neoplasms ; metabolism ; pathology ; Young Adult

OBJECTIVETo investigate the clinicopathologic feature, immunophenotype and differential diagnosis of cutaneous Rosai-Dorfman disease (CRDD).

METHODSClinical manifestation, morphologic features and immunohistochemical staining were studied in 8 cases of CRDD.

RESULTSAll 8 patients presented with multiple papules, nodules and/or coalescent patches or plaques distributing over the extremities or trunk, without lymphadenopathy or other systemic abnormalities. Microscopically, the lesions were located intradermally and/or subcutaneously. CRDD was characterized by the presence of S-100 positive histiocytic cells exhibiting emperipolesis, accompanying with infiltration of mixed inflammatory cells. Fibrosis, somewhere in vague storiform pattern due to stromal responses, with distribution of individual neutrophil microabscess was seen in cases with a long course of illness. Dilated vascular spaces in dermis containing numerous large typical histiocytes were seen in 2 cases.

CONCLUSIONSCRDD is a benign, persistent proliferative disease of histiocytes. Systemic involvement is rare, outcome favorable. It should be differentiated from other types of histiocytosis, dermatofibrosarcoma protuberans, xanthoma and lymphoproliferative disorders. Immunohistochemical staining for S-100 protein and CD68 is helpful in making a correct diagnosis.

Aged ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Diagnosis, Differential ; Female ; Histiocytosis, Sinus ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prognosis ; S100 Proteins ; metabolism ; Skin Diseases ; metabolism ; pathology ; surgery

OBJECTIVETo investigate the feasibility of detecting cyclin D1 protein expression and t(11;14) chromosomal translocation in paraffin-embedded tissues and its diagnostic and differential diagnostic significance for mantle cell lymphoma (MCL).

METHODSParaffin-embedded samples of 36 cases of MCL and a control group of 71 cases of small B-cell lymphomas were retrieved from archive materials. Immunohistochemical staining for cyclin D1 and semi-nested PCR for t(11;14) were detected in all samples. House-keeping gene beta-actin was used to detect the quality of DNA.

RESULTS(1) Cyclin D1 was expressed in 26 of the 36 MCL (72.2%). There was no cyclin D1 expression in the control group. (2) beta-actin DNA was detected in 101 of the 107 tumor cases (94.4%). t(11;14) was detected in 22 of the 36 MCL. Translocation was not found in control group. The positive rate for t(11;14) was 64.7% in MCL after exclusion of 2 cases which were negative for both t(11;14) and beta-actin. (3) 29 cases were positive for cyclin D1 and/or t(11;14), the positive rate reached 80.5%.

CONCLUSIONThe combined detection of cyclin D1 and t(11;14) in paraffin-embedded tissues is found to be a specific and feasible method for diagnosis and differential diagnosis of mantle cell lymphoma.

Adult ; Aged ; Aged, 80 and over ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 14 ; Cyclin D1 ; analysis ; Female ; Humans ; Immunohistochemistry ; Lymphoma, Mantle-Cell ; chemistry ; diagnosis ; genetics ; Male ; Middle Aged ; Paraffin Embedding ; Polymerase Chain Reaction ; Translocation, Genetic

BACKGROUNDExposure to cigarette smoke stimulates the proliferation of human pulmonary artery smooth muscle cells (HPASMCs) in vivo and in vitro. However, the molecular mechanism remains unclear. This study aimed at investigating the role of signaling pathways involving protein kinase C alpha (PKCα) and cyclin D1 in the cigarette smoke extract (CSE)-induced HPASMCs proliferation.

METHODSSynchronized HPASMCs were treated with different concentrations of CSE. Cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell counting. Cell cycle was analyzed by flow cytometry with propidium iodide staining. Activation of PKCα was measured by detecting the expression of PKCα protein in the cytosolic and membrane fractions using Western blotting analysis. Small interfering RNA (siRNA) was used to knockdown PKCα and cyclin D1. The cyclin D1 mRNA was assessed by real-time RT-PCR. The PKCα and cyclin D1 protein levels were detected by Western blotting.

RESULTSLow concentrations of CSE (1% - 10%) stimulated proliferation of HPASMCs, with its maximal effect at 5%. CSE (5%) led to PKCα activation. Inhibition of PKCα activity using Gö 6976 or siRNA-mediated knockdown of PKCα significantly attenuated CSE-induced cell proliferation and G1/S transition. Cyclin D1, one of key regulators of G1/S transition, was found to be upregulated by 5% CSE at both the mRNA and protein levels. CSE-stimulated cell proliferation and G1/S transition was abolished by cyclin D1 siRNA. Moreover, Gö 6976 or PKCα siRNA significantly suppressed CSE-induced upregulation of cyclin D1 at both the mRNA and protein levels.

CONCLUSIONPKCα-cyclin D1 pathway at least partially mediates the CSE-induced proliferation in HPASMCs.

Cell Proliferation ; Cells, Cultured ; Cyclin D1 ; physiology ; G1 Phase ; Humans ; Muscle, Smooth, Vascular ; pathology ; Myocytes, Smooth Muscle ; pathology ; Protein Kinase C-alpha ; physiology ; Pulmonary Artery ; pathology ; S Phase ; Signal Transduction ; Smoke ; adverse effects ; Tobacco ; adverse effects

The present study was aimed to investigate the role of cyclin D1 in human pulmonary artery smooth muscle cells (HPASMCs) proliferation and migration induced by cigarette smoke extract (CSE). The eukaryotic expression vector of antisense cyclin D1 gene (pIRES2-EGFP-ascyclin D1) was recombinated. The recombinant and empty vector were separately transfected into normal HPASMCs using liposome. Then the cells were treated with or without 5% CSE. The cells were randomly divided into six groups: control group, vector group, antisense cyclin D1 group, 5% CSE group, vector+5% CSE group and antisense cyclin D1+5% CSE group. The expressions of cyclin D1 mRNA and protein were detected by real-time fluorescence RT-PCR and Western blot, respectively. The proliferation of HPASMCs was examined by cell cycle analysis, MTT assay and proliferation cell nuclear antigen (PCNA) immunocytochemical staining. The migration of HPASMCs was measured by Transwell cell test. The results showed that the eukaryotic expression vector of antisense cyclin D1 gene was constructed and transfected into HPASMCs successfully. The cyclin D1 mRNA and protein levels in antisense cyclin D1 group were significantly lower than those in control group (P<0.05). In 5% CSE group, the cyclin D1 mRNA and protein levels were elevated significantly compared with those in control group (P<0.05), and the indicators of cell and migration in antisense cyclin D1+5% CSE group were remarkably lower than those in 5% CSE group (P<0.05). These results suggest that CSE could promote HPASMCs proliferation and migration through up-regulation of cyclin D1 expression. PIRES2-EGFP-ascyclin D1 could attenuate CSE-induced proliferation and migration of HPASMCs by suppressing the expression of cyclin D1, which implicates that cyclin D1 might be involved in the process of HPASMCs proliferation and migration stimulated by CSE.
Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cyclin D1 ; physiology ; Humans ; Muscle, Smooth, Vascular ; cytology ; pathology ; Myocytes, Smooth Muscle ; cytology ; pathology ; Pulmonary Artery ; cytology ; pathology ; Smoke ; adverse effects ; Tobacco ; adverse effects

The present study aimed to examine the effect of interleukin (IL)-4 on neutrophil chemotaxis in airway inflammation in asthmatic rats and the possible mechanism. Male Wistar rats were intranasally instilled with recombinant rat (rr) IL-4 (rrIL-4) at different doses [2, 4 or 8 μg/animal, dissolved in 200 μL normal saline (NS)] or rrIL-4 at 4 μg/animal (dissolved in 200 μL NS). NS (200 μL) and LPS (6 mg/kg/animal, dissolved in 200 μL NS) were intranasally given respectively in the negative and positive control groups. Moreover, the asthmatic lung inflammation was induced in rats which were then intranasally treated with rrIL-4 (4 μg/animal) or LPS (6 mg/kg/animal). The normal rats treated with different doses of rrIL-4 and those asthmatic rats were sacrificed 6 h later. And animals instilled with rrIL-4 at 4 μg were sacrificed 6, 12 or 24 h later. The bronchoalveolar lavage fluid (BALF) and lungs were harvested for detection of leukocyte counts by Wright-Giemsa staining and lung histopathology by haematoxylin-eosin (HE) staining. The levels of cytokine-induced neutrophil chemoattractant (CINC)-1 and intercellular adhesion molecule (ICAM)-1 in BALF were determined by ELISA. Real-time PCR was used to measure the mRNA expression of CINCs (CINC-1, CINC-2α, CINC-2β, CINC-3) and ICAM-1 in lung tissues. The results showed that the intranasal instillation of IL-4 did not induce a recruitment of neutrophils in BALF in rats. However, IL-4 could increase the CINC-1 level in BALF in a dose-dependent manner at 6 h. But the mRNA expression levels of CINC-1, CINC-2α, CINC-2β, CINC-3 were not significantly increased in lungs of IL-4-treated rats relative to NS negative control group. Moreover, IL-4 was found to augment the mRNA expression of ICAM-1 in lungs and the ICAM-1 level in BALF at 6 h. However, the increase in CINC-1 and ICAM-1 levels in BALF of IL-4-treated asthmatic rats was not significantly different from that in untreated asthmatic rats. These findings indicate that IL-4 does not directly recruit neutrophils in the rat lungs, but it may contribute to airway neutrophilia through up-regulation of CINC-1 and ICAM-1.
Animals ; Asthma ; immunology ; Chemotactic Factors ; immunology ; Intercellular Adhesion Molecule-1 ; immunology ; Interleukin-4 ; immunology ; Lung ; immunology ; Male ; Neutrophils ; immunology ; Rats ; Rats, Wistar

OBJECTIVETo explore the origin and differentiation of gastrointestinal stromal tumors (GISTs).

METHODSImmunohistochemistry staining and electron microscopy were adopted.

RESULTSIn 212 cases of primary GISTs, the positive rates of CD117, CD34, alpha-SMA, MSA, desmin, S-100, PGP9.5 were 96.7%, 77.3%, 19.3%, 15.6%, 1.9%, 16.3%, and 12.3% respectively. Among them, GISTs showed a diffuse and strong positivity for CD117. Electron microscopy of tumor cells demonstrated numerous mitochondria, prominent perinuclear Golgi complex, smooth and rough endoplasmical reticulum and intermediate filaments. Irregular caveolae, dense plaque, incontinuous basal lamina were observed occasionally. Cytoplasmic processes were often observed accompanying with local adhesion present between the processes or between the processes and the cell membrane.

CONCLUSIONSData from both immunophenotype and electron microscopy suggest that GIST might originate from the mesenchymal cells, differentiating to be ICC afterwards, and possessing myoid characteristics in various extent.

Cell Differentiation ; Gastrointestinal Stromal Tumors ; chemistry ; ultrastructure ; Golgi Apparatus ; ultrastructure ; Humans ; Immunohistochemistry ; Microscopy, Electron ; Proto-Oncogene Proteins c-kit ; analysis ; S100 Proteins ; analysis ; Stromal Cells ; chemistry ; ultrastructure ; Ubiquitin Thiolesterase ; analysis

OBJECTIVETo detect over-expression of AChR-gamma mRNA in rhabdomyosarcoma tissues by duplex RT-PCR and discuss its potential in diagnosis of rhabdomyosarcoma.

METHODSDuplex RT-PCR was applied to the simultaneous detection of AChR-alpha and gamma subunit messenger RNA in 17 cases of rhabdomyosarcoma (9 ERMS, 6 ARMS, 2 PRMS). 20 cases of non-rhabdomyosarcomous small round cell tumors (6 poorly differentiated synovial sarcomas, 6 ES/PNET, 6 lymphomas, 2 neuroblastomas) and three normal muscle samples were also detected for AChR-alpha and gamma mRNA by the same method.

RESULTSAChR-alpha and AChR-gamma mRNA were expressed in all the cases of rhabdomyosarcoma. The rate of quantity in both transcripts was AChR-gamma/AChR-alpha >or= 1, but the rate for three normal muscle samples was < 1. Cases of non-rhabdomyosarcomous small round cell tumors were all negative for AChR-gamma.

CONCLUSIONAChR-gamma mRNA expression detected by molecular genetic methods is useful in diagnosis and differential diagnosis of rhabdomyosarcoma.

Diagnosis, Differential ; Humans ; Protein Subunits ; RNA, Messenger ; analysis ; Receptors, Cholinergic ; genetics ; Receptors, Nicotinic ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Rhabdomyosarcoma ; diagnosis

OBJECTIVETo investigate the feasibility of detecting cyclin D1 mRNA in paraffin-embedded tissues by reverse transcriptase polymerase chain reaction (RT-PCR) and competitive RT-PCR and its diagnostic and differential diagnostic significance for mantle cell lymphoma (MCL).

METHODSParaffin-embedded samples of 36 cases of MCL, 71 cases of other small B-cell lymphomas and 20 cases of lymphoid reactive hyperplasia as control group were retrieved from archival materials. Cyclin D1 protein and its mRNA was detected by EnVision and RT-PCR and competitive RT-PCR in all samples. House-keeping gene PGK was choosen as internal control.

RESULTS(1) Cyclin D1 protein was expressed in 27 of the 38 MCL (71.1%). No cyclin D1 expression was found in the control group. (2) PGK was detected in 103 of the 116 cases (88.8%) and also detected in 34 of 36 MCL cases (94.7%). (3) cyclin D1 mRNA was detected in 34 nodal mantle cell lymphoma cases by RT-PCR in paraffin-embedded tissues. The positive rate of cyclin D1 mRNA was 94.4% in mantle cell lymphomas after exclusion of the 2 cases which were negative for both cyclin D1 mRNA and PGK. cyclin D1 mRNA was not detected in other nodal small B-cell lymphomas or lymphoid reactive hyperplasia, except 1 case of B-SLL. Sequencing analysis showed that sequences were identical to cyclin D1. (4) Cyclin D1 mRNA overexpression was detected in 27 cases of nodal mantle cell lymphoma by competitive RT-PCR in paraffin-embedded tissues. The positive rate of cyclin D1 mRNA overexpression was 75.0% in mantle cell lymphomas after exclusion of 2 cases which were negative for both cyclin D1 mRNA and PGK. cyclin D1 mRNA overexpression was not detected in other nodal small B-cell lymphomas or lymphoid reactive hyperplasia.

CONCLUSIONRT-PCR and competitive RT-PCR detection of cyclin D1 mRNA overexpression could be used for the diagnosis and differential diagnosis of mantle cell lymphoma in paraffin-embedded blocks.

Cyclin D1 ; biosynthesis ; genetics ; Diagnosis, Differential ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; metabolism ; pathology ; Lymphoma, Follicular ; genetics ; metabolism ; Lymphoma, Mantle-Cell ; genetics ; metabolism ; pathology ; Paraffin Embedding ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods