Clinical value of radial endorectal ultrasound in the assessment of preoperative staging of rectal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the clinical value of radial endorectal ultrasound (ERUS) in the assessment of preoperative staging of rectal carcinoma.</p><p><b>METHODS</b>One hundred and ten patients with rectal cancer underwent preoperative endorectal ultrasound (ERUS) examination in our hospital from February 2010 to September 2011. ERUS was performed using a Hitachi 900, Hitachi HI Vision Preirus US scanner, with a 5 - 10 MHz rigid rotating radial transducer and a focal length of 2 - 5 cm. The size, shape, echo pattern, infiltration depth, degree of circumferential involvement, extra-rectal invasion of the lesions and lymph node involvement were observed. The results of ERUS staging were compared with histopathological findings of the surgical specimens.</p><p><b>RESULTS</b>The accuracy of ERUS for T staging was 91.4%. The accuracy of ERUS in diagnosing stage T1, T2, T3, T4 cancers was 92.7%, 88.2%, 88.2% and 96.4%, respectively. The sensitivity of ERUS in diagnosing stage T1, T2, T3, T4 cancers was 92.3%, 72.7%, 85.4% and 71.4%, respectively. The specificity of ERUS in diagnosing stage T1, T2, T3, T4 cancer was 92.9%, 92.0%, 90.3% and 100.0%, respectively. Comparing the consistency of preoperative T-staging and postoperative pathological results, the Kappa value was 0.75, with a considerable consistency. The sensitivity, specificity, and accuracy of ERUS in the assessment of lymph node metastasis were 74.2%, 89.9% and 85.5%, respectively. Comparing the consistency of preoperative N-staging and postoperative pathological results, the Kappa value was 0.64, with a considerable consistency.</p><p><b>CONCLUSIONS</b>ERUS is a practical and accurate tool in assessment of preoperative staging of rectal tumors in regard to tumor invasion depth (T) and regional lymph node status (N), with advantages of simple operation, less pain, and high accuracy.</p>

Microcystic/reticular schwannoma occurring in cervical spine: report of a case with literature review / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the morphologic characteristics, immunophenotype and differential diagnosis of a case of microcystic/reticular schwannoma occurring in cervical spine.</p><p><b>METHODS</b>The pathologic features and immunophenotypic profile of a case of microcystic/reticular schwannoma were studied. Immunohistochemistry was performed using EnVision two-step method.</p><p><b>RESULTS</b>The patient was a 35-year-old male and presented with a bump over the fifth cervical spine on radiologic check up. Grossly, the bump was gray-white in color, soft, well-circumscribed but non-encapsulated. The tumor measured 3.5 cm × 3.0 cm × 1.8 cm in size. Histologically, it was composed of two distinctive components. One component resembled the conventional schwannoma but showed focally nuclear pleomorphism, reminiscent of changes in degenerating schwannoma. The other component consisted of epithelial-like cells arranged in a reticular or lace-like pattern, amongst a myxoid matrix. Immunohistochemical study showed that the tumor cells were strongly positive for vimentin, S-100 protein, glial fibrillary acidic protein and neuron-specific enolase, focally positive for CD68, CD10 and Ki-67, and negative for pan-cytokeratin, epithelial membrane antigen, neurofilament, carcinoembryonic antigen, smooth muscle actin, estrogen receptor, progesterone receptor and p53.</p><p><b>CONCLUSIONS</b>Microcystic/reticular schwannoma is a novel variant of schwannoma, arising mainly in internal viscera but seldom in bone. Awareness of this entity is helpful in distinction from chordoma, other mucoid tumors or sarcomas.</p>

Clinicopathologic characteristics and chromosomal abnormalities in salivary mucosa associated lymphoid tissue lymphomas / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the morphological and genetic characteristics in salivary gland marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT) lymphomas.</p><p><b>METHODS</b>Twenty-eight cases of MALT lymphomas of salivary gland were collected from Department of Pathology, Cancer Hospital of Fudan University. Morphological review based on HE sections, and specific chromosomal abnormalities were detected by two-color interphase fluorescent in situ hybridization (FISH). Four different probes were available to detect for API2-MALT1 fusion gene, bcl-10, IgH and MALT1 gene, respectively.</p><p><b>RESULTS</b>There were 16 females and 12 males, median age was 52. In those cases, 18 originated from parotid gland, 6 from submandibular and 4 from sublingual gland. Ten were localized mass and 18 were masses diffusely involved the glands. According to the clinical information, only 8 cases showed symptoms of dry mouth, dry nose or dry eye. Pathological findings showed that all cases had a dense lymphoid infiltration and obliteration and atrophy of acini and ducts. Twenty-two (78.6%) showed prominent monocytoid B cells and more often formed broad halos around epithelial islands. Eighteen (64.3%) showed clusters of lymphoblastic cells or plasma cells, Russel' and Dutcher' body were easily seen. Ten (35.7%) showed nerve or blood vessel infiltration. Interphase FISH showed that 3 cases harbored t(11;18) and 2 cases harbored trisomy 18, but none of all found IgH and bcl-10 translocations. After operation, 22 patients' follow-up information was available. One case died on 15 months later after operation, the rest of 21 cases were alive. Except surgical resection, patients did not get systematic radio-or chemotherapy. Eight to fifteen months after operation, 8 cases found recurred nodules on the original resected sites or cervical lymph nodes, but did not get repeated biopsy. All follow-up time was from 23 to 54 months.</p><p><b>CONCLUSIONS</b>Most salivary MALT lymphomas are arising from parotid glands. Most patients do not have the symptoms of the Sjogren's syndrome. The final diagnosis depends on the pathological findings, the number and distribution of monocytoid B cells and clusters of plasmacytoid cells are hints for diagnosis of salivary MALT lymphomas, invasion of blood vessels or nerve also help for malignant diagnosis. t(11;18) and trisomy 18 may be the main chromosomal abnormalities in salivary gland MALT lymphomas, but with low morbidity. This genetic characteristic may connect with the low malignancy and slow progression in biological behavior.</p>

Prevalence of API2-MALT1 fusion gene in gastrointestinal mucosa-associated lymphoid tissue lymphomas and diffuse large B cell lymphomas / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the difference of the prevalence of t(11;18)(q21;q21)/API2-MALT1 fusion gene between gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B cell lymphoma (DLBCL).</p><p><b>METHODS</b>A total of 57 cases gastrointestinal MALT lymphomas (38 gastric and 19 intestinal lymphomas), 32 DLBCL (28 gastric and 4 intestinal lymphomas) and 7 cases gastric DLBCL accompanied MALT lymphoma were collected from the Cancer Hospital of Fudan University. API2-MALT1 fusion gene was detected by fluorescent in situ hybridization (FISH) using both dual fusion translocation and break apart probes.</p><p><b>RESULTS</b>Among gastrointestinal MALT lymphomas, API2-MALT1 fusion gene was found in 12 of 57 cases (21.1%, 10 gastric and 2 intestinal lymphomas). In contrast, the fusion gene was not found in all 32 DLBCL and 7 gastric DLBCL with MALT lymphoma component. There was statistical significant difference between two groups (chi(2) = 9.383, P = 0.001).</p><p><b>CONCLUSIONS</b>API2-MALT1 fusion gene is a distinctive genetic aberration in MALT lymphomas, and is not present in DLBCL. The findings suggest that gastrointestinal tract MALT lymphomas with API2-MALT1 fusion gene may not transform into DLBCL, which may represent primary lymphoma or transformed API2-MALT1 negative MALT lymphomas.</p>

Frequency of genetic aberrations in mucosa-associated lymphoid tissue lymphoma of different sites / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the frequency of certain specific genetic aberrations, including t (11; 18)/API2-MALT1, t (1; 14)/IgH-bcl-10 and t (14; 18)/IgH-MALT1, in mucosa-associated lymphoid tissue (MALT) lymphoma of different sites.</p><p><b>METHODS</b>One hundred and ninety-six cases of MALT lymphoma from Cancer Hospital of Fudan University were enrolled into the study. The samples consisted of MALT lymphomas from stomach (53 cases, including 44 cases of low-grade MALT lymphoma and 9 cases of MALT lymphoma with diffuse large B-cell lymphoma component), ocular adnexa (50 cases), salivary gland (20 cases), lung (20 cases), intestine (17 cases), skin (17 cases), liver (8 cases), thyroid (5 cases) and other sites (2 cases from tongue, 1 case from pancreas, 1 case from larynx, 1 case from vocal cords and 1 case from kidney). Fluorescence in-situ hybridization for API2-MALT1 fusion gene, bcl-10, MALT1 and IgH genes was performed on paraffin sections.</p><p><b>RESULTS</b>Among the 196 cases of MALT lymphoma, 25 cases (12.8%) possessed API2-MALT1 fusion gene. The positive rates in various sites were significantly different (P = 0.002), as follows: 45.0% (9/20) in lung, 22.7% (10/44) in stomach (without large cell component), 15.0% (3/20) in salivary gland, 2 of 17 cases in intestine and 2.0% (1/50) in ocular adnexa. The fusion gene was not detected in the 9 cases of gastric MALT lymphoma with large cell transformation. It was also negative in the MALT lymphomas from skin, thyroid and other sites. One of the pulmonary MALT lymphoma cases showed simultaneous aberrations of IgH and MALT1 genes, such as t (14; 18)/IgH-MALT1. Two of the gastric MALT lymphoma cases without large cell transformation and one of the pulmonary MALT lymphoma cases showed aberrations in both IgH and bcl-10 genes, such as t (1; 14)/IgH-bcl-10. Six cases of MALT lymphoma, including 2 cases from salivary gland, 2 cases from liver, 1 case from thyroid and 1 case from stomach (large cell transformation), showed trisomy 18. On the other hand, 3 cases, including 2 cases from stomach and 1 case from intestine, showed MALT1 gene amplification.</p><p><b>CONCLUSIONS</b>In general, specific genetic aberrations have a relatively low frequency of occurrence in MALT lymphomas. The positive rates however show a remarkable difference in tumors of different anatomic sites. This phenomenon may suggest that MALT lymphomas in different sites, though sharing similar morphologic features, may have a divergent tumorgenesis.</p>

Chronic hepatitis B virus infection and the methylation status of p16INK4A promoter / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the relationship among HBV-associated histopathological indexes, x gene mutations and the methylation status of p16INK4A promoter in liver with chronic hepatitis B virus infection, in order to illustrate their role in p16INK4A hypermethylation and HCC progression.</p><p><b>METHODS</b>Twenty-three cases of surgically resected HBV-associated hepatocellular carcinoma and twenty-five fine needle aspiration biopsy cases of chronic hepatitis B were chosen for this study. The methylation status of the p16INK4A promoter in tumors, their corresponding peritumoral samples and chronic hepatitis B cases was determined by methylation-specific polymerase chain reaction (MSP). EnVision two-step immunohistochemical staining showed the expression of viral antigens in situ. Tissue HBV DNA levels were determined by real-time fluorescence quantitative PCR. Polymerase chain reaction and the direct sequencing method was used for mutation analysis of HBV x gene.</p><p><b>RESULTS</b>In peritumoral samples (P = 0. 025) and chronic hepatitis B cases (P = 0.029), the expression of HBx protein in methylated groups was all significantly higher than that in unmethylated groups of p16INK4A gene. But in tumors, there was no such significant difference. Other HBV antigens including HBsAg and HBcAg, tissue HBV DNA levels and point mutations of HBV x gene did not show a relationship with the methylation status of p16INK4A gene.</p><p><b>CONCLUSION</b>The data suggest that p16INK4A hypermethylation correlated closely with higher HBx expression in precancerous lesions. HBx may play an important role in the early stage of HBV-associated hepatocarcinogenesis via induction of hepermethylation of p16INK4A promoter.</p>

Abnormal expression of bcl-10 protein in extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue lymphoma type / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the diagnostic role of nuclear expression of bcl-10 protein in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.</p><p><b>METHODS</b>One hundred and forty cases of MALT lymphoma were collected from Cancer Hospital of Fudan University (including 38 cases from stomach, 35 cases from ocular adnexa, 16 cases from intestine, 15 cases from skin, 15 cases from salivary gland, 14 cases from lung, 3 cases from thyroid and 4 cases from other sites). Ten cases of reactive follicular hyperplasia of tonsil, 5 cases of reactive lymphoid hyperplasia of orbit and 143 cases of non-Hodgkin's lymphoma other than MALT lymphoma (including 20 cases of NK/T cell lymphoma, 20 cases of follicular lymphomas, 20 cases of anaplastic large cell lymphomas, 20 cases of nodal diffuse large cell B-cell lymphoma (DLBCL), 10 cases of gastric diffuse large B-cell lymphoma, 13 cases of nodal marginal zone B-cell lymphoma, 12 cases of mantle cell lymphoma, 11 cases of splenic marginal zone B-cell lymphoma, 6 cases of angioimmunoblastic T-cell lymphoma, 6 cases of peripheral T-cell lymphoma, not otherwise specified, 3 cases of small lymphocytic lymphoma, 1 case of lymphoplasmacytic lymphoma and 1 case of plasmacytoma were used as controls. Immunohistochemical study for bcl-10, as well as dual staining with CD20, was performed by EnVision method in paraffin sections.</p><p><b>RESULTS</b>In reactive follicular hyperplasia of tonsil, bcl-10 was moderately or strongly expressed in the cytoplasm of germinal center B cells, while the mantle cells were negative and the marginal zone cells and paracortical T cells showed weak staining. In the 5 cases of reactive lymphoid hyperplasia of orbit, 2 were bcl-10-negative and the remaining 3 expressed bcl-10 in the cytoplasm of germinal center B cells. As for non-MALT lymphomas, 3 gastric DLBCL showed nuclear expression. The remaining cases showed variable cytoplasmic staining. In some cases of lymphoma, bcl-10 was expressed in tumor cells but not in reactive lymphoid cells. On the other hand, 92.1% (129/140) of MALT lymphoma were bcl-10 positive. Among those cases, 54.3% (76/140) showed cytoplasmic positivity and 37.9% (53/140) showed nuclear positivity. The nuclear positivity rate of bcl-10 in different anatomic sites was different. The staining was most intense in MALT lymphoma of ocular adnexa. Dual staining with CD20 showed that the bcl-10-positive cells were also CD20-positive, though the number of bcl-10-positive cells were less than that of CD20-positive cells.</p><p><b>CONCLUSIONS</b>Bcl-10 expression in lymphoid hyperplasia is a universal phenomenon. Cytoplasmic expression of bcl-10 is seen in many different kinds of non-Hodgkin's lymphoma and reactive lymphoid conditions. In some cases of lymphoma, bcl-10 is expressed in tumor cells but not in reactive lymphoid cells, suggesting a possible role of abnormal bcl-10 expression in tumorgenesis. Nuclear expression of bcl-10 is seen mainly in MALT lymphoma, especially when occurring in ocular adnexa and lung. This is in contrast to loss of bcl-10 expression in residual germinal center cells.</p>

Anti-nasopharyngeal carcinoma effect in vivo and in vitro of cytotoxicity T lymphocyte induced by Ad5-latent membrane protein 2A / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the biological characteristics of cytotoxicity T lymphocyte (CTL) induced by dendritic cell (DC) transfected with the Epstein-Barr virus latent membrane protein 2A (EBV-LMP2A) recombinant adenovirus. To establish nasopharyngeal carcinoma (NPC) animal models expressing LMP2A and investigate the anti-tumor effect of LMP2A specific CTL in vivo.</p><p><b>METHODS</b>The mononuclear cells were isolated from human peripheral blood mononuclear cells (PBMC) and cultured with the cytokines [granulocyto-monocyte colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor-alpha TNF-alpha]. The expression of surface markers on mature DC was detected by fluorescence activated cell sorter FACS. Mature DC were transfected with LMP2A recombinant adenovirus. Under the help of interleukin-2 (IL-2), LMP2A specific CTL were induced by coculturing LMP2A-transfected DC with autologous PBMC. The population of CTL was detected by FACS. NPC animal models were constructed by implanting CNE cells expressing LMP2A subcutaneously into BALB/c nude mice. After intra-tumoral injection of LMP2A specific CTL, the size of tumor was measured. The tumors were removed after 30 d and subjected to histological examination.</p><p><b>RESULTS</b>Mature DC displaying typical characteristics of morphology and phenotype were obtained from monocytes cultured in the medium containing GM-CSF, IL-4 and TNF-alpha. The LMP2A specific CTL induced by transfected DC were composed of mainly CD4+ and CD8+ T cells. The NPC animal models were constructed three weeks after implanting CNE cells. The study in vivo indicated that the tumors treated with LMP2A specific CTL grew slowly compared with control. Tumor volume of treated groups was significantly smaller than that of controls. The histological sections showed local necrosis and infiltration of lymphocyte in tumor tissue.</p><p><b>CONCLUSIONS</b>Typically mature DC could be generated in vitro by culturing monocytes with the cytokines. LMP2A-specific CTL could be induced by LMP2A transfected DC in vitro. NPC mice models could be constructed by implanting CNE cells. LMP2A specific CTL could inhibit the growth of implanted tumor and produce an anti-tumor effect in vivo.</p>

Effects of iptkalim, a novel ATP-sensitive potassium channel opener, on hypoxia-induced pulmonary vascular remodeling in rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate whether pulmonary vascular remodeling in hypoxic pulmonary hypertensive rats could be prevented by treatment with a selective K(ATP)CO, iptkalim (Ipt).</p><p><b>METHODS</b>Rats were fed in hypoxic and normobaric environment (10% +/- 0.5% O2, 8 h/day and 6 day/week) and divided into control group, hypoxia group (hypoxic rat treated with ig NS 5.0 ml x kg(-1) x d(-1)), treated group I (hypoxic rat treated with ig Ipt 0.75 mg x kg(-1) x d(-1)), treated group II (hypoxic rat treated with ig Ipt 1.5 mg x kg(-1) x d(-1)). After 4 wk, the mean pulmonary arterial pressure (mPAP), right ventricle/left ventricle and septum [RV/(LV + S)] were measured, and the small pulmonary arterial morphologic changes were observed with morphometric analysis under microscopes in four groups.</p><p><b>RESULTS</b>The level of mPAP and RV/(LV+ S) was significantly higher in the hypoxic group than those in control group (P < 0.01). Morphometric analysis revealed that the ratio of vascular medial wall thickness to external diameter (MT%) and the ratio of vascular medial cross-sectional area to total arterial cross-sectional area (MA%) were also significantly increased in the hypoxic group than those in control group (P < 0.01) and the ratio of vessel lumen cross-sectional area to total arterial cross-sectional area (VA%) was significantly lower in the hypoxic group than those in control group (P < 0.01). Ipt 0.75 mg x kg(-1) x d(-1) or 1.5 mg x kg(-1) x d(-1) decreased the level of mPAP(mmHg), RV/(LV+ S), and inhibited the small pulmonary arterial remodeling significantly. Ipt 1.5 mg x kg(-1) x d(-1) reversed all pathological indices.</p><p><b>CONCLUSION</b>K(ATP)CO iptkalim can be a very promising candidate for the treatment of hypoxic pulmonary hypertension.</p>