Primary cutaneous Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified, in a nonimmunocompromised young man: A case report.

Primary cutaneous EBV (Epstein-Barr virus)-positive diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), is an extremely rare disease. The clinical and pathological features of DLBCL, NOS have not been clearly illustrated. We report a case of primary cutaneous EBV-positive DLBCL, NOS in a 35-year-old Chinese male with multiple ulcerated and nodular lesions on his trunk and arms for 6 months. No other organs, except the skin, were involved. The lesions were localized in the dermis with focal necrosis. The tumor cells were immunoblastic- or centroblastic-like cells and diffusely distributed. There were numerous inflammatory cells in the background. The tumor cells were positive for CD20, PAX-5, MUM1, LMP1, CD30, and Epstein-Barr virus encodedsmall RNA, but negative for EBNA2. Polymerase chain reaction showed a monoclonal IG gene rearrangement. The patient received 6 cycles of CHOP (cyclophosphamide, hydroxydaunorubicin, Oncovin®, prednisone) chemotherapy and went into complete remission. There was no evidence of relapse after 35 months of follow-up.

COX-2/PGE2 Axis Regulates HIF2α Activity to Promote Hepatocellular Carcinoma Hypoxic Response and Reduce the Sensitivity of Sorafenib Treatment.

Purpose: Hypoxia-inducible factor-2α (HIF2α) is regarded as a preferential target for individualized hepatocellular carcinoma (HCC) treatment and sorafenib resistance. Our study aimed to identify the regulatory mechanisms of HIF2α activity under hypoxic conditions. We sought to determine whether the COX-2/PGE2 axis is involved in the regulatory mechanisms of HIF2α activity and of sorafenib resistance in hypoxic HCC cells.Experimental Design: The cell viability, migration, and invasion abilities were measured to analyze the effects of HIF2α on hypoxic HCC cells. Both in vitro and in vivo HCC models were used to determine whether the COX-2/PGE2 axis is a driver of HIF2α level and activity, which then reduces the sensitivity of sorafenib treatment in hypoxic HCC cells.Results: Under hypoxic conditions, the COX-2/PGE2 axis effectively stabilized HIF2α and increased its level and activity via decreasing von Hippel-Lindau protein (p-VHL) level, and also enhanced HIF2α activity by promoting HIF2α nuclear translocation via MAPK pathway. The activation of HIF2α then led to the enhanced activation of VEGF, cyclin D1, and TGFα/EGFR pathway to mediate HCC development and reduce the sensitivity of sorafenib. More importantly, COX-2-specific inhibitors synergistically enhanced the antitumor activity of sorafenib treatment.Conclusions: Our data obtained demonstrate that the COX/PGE2 axis acts as a regulator of HIF2α expression and activity to promote HCC development and reduce sorafenib sensitivity by constitutively activating the TGFα/EGFR pathway. This study highlights the potential of COX-2-specific inhibitors for HCC treatment and particularly for enhancing the response to sorafenib treatment. Clin Cancer Res; 24(13); 3204-16. ©2018 AACR.

[Villous adenoma of the urinary tract: a clinicopathological study].

OBJECTIVE: To explore the clinicopathological features, immunophenotype, differential diagnosis, pathogenesis and prognosis of villous adenoma with poorly differentiated adenocarcinoma of the urinary tract. METHODS: Clinical and pathologic findings of 3 cases of villous adenoma with poorly differentiated adenocarcinoma of the urinary tract were analyzed by gross examination, microscopic investigation and immunohistochemical staining. The related literatures were reviewed. RESULTS: All of the three cases were middle-aged or elderly patients. Three cases all presented with hematuria and mucusuria. Endoscopic examination identified that case 1 had a polyp with broad attachment in the dome of bladder, case 2 had a solid mass in the ureter, and case 3 had a exophytic fungating tumor in the renal pelvis. Microscopically, case 1 revealed a papillary lesion with finger-like processes lined by pseudostratified columnar epithelium with abundant goblet cells. The cells demonstrated moderate degree dysplasia. In case 2 and case 3, both villous adenomas and poorly differentiated adenocarcinoma were observed, the adenoma cells arranged in a cribriform pattern, and the tumor cells showed severe atypia, mitotic activity, and transition with invasive poorly differentiated adenocarcinoma. Immunohistochemically, the tumor cells in three cases were positive for CK20, CEA,EMA and MUC-1; none of them expressed cdx-2 and PSA; In case 2 and 3, the same immunophenotype of villous adenomas and their associated adenocarcinomas was observed, but the number of the positive cells of p53 and Ki-67 staining were significantly increased in the area of adenocarcinomas than in that of the villous adenomas. CONCLUSIONS: Villous adenoma of the urinary tract is rare. It can occur in the urinary bladder, urachus, renal pelvis, ureter and urethra. These lesions may have malignant potential and frequently coexist with other malignant tumors. So, villous adenoma of the urinary tract should be removed completely and sampled thoroughly to avoid missing a more aggressive component.

Molecular pathological study of the human nasopharyngeal carcinoma CNE3 cell line.

The present study aimed to identify the molecular pathological changes of the nasopharyngeal carcinoma (NPC) epithelial CNE3 cell line, which has been used in experimental studies for 20 years in a culture environment. The pathological type of NPC and the presence of the Epstein-Barr virus (EBV) were identified. CNE3 short tandem repeats (STRs) were amplified, analyzed and compared using metastatic carcinoma tissue from primary NPC. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to identify the immunophenotype and EBV-encoded small RNA (EBER) expression in nude mice transplanted CNE3 tumor cells. Polymerase chain reaction (PCR) and DNA sequencing were used to identify the EBV oncogene, BamH1-A right frame 1 (BARF1) and electron microscopy was used to analyze the organization of the ultrastructure. CNE3 was not cross-contaminated by other human cell lines and the EBV was no longer present in the CNE3 cells. The pathological type of CNE3 was transformed from an undifferentiated non-keratinizing carcinoma with focal adenocarcinoma differentiation into a poorly-differentiated adenocarcinoma. In conclusion, this knowledge on the molecular pathological changes of CNE3 may aid in the development of new research approaches for NPC.

[Study on genetic aberrations of ocular mucosa-associated lymphoid tissue lymphomas occurring in southern China].

OBJECTIVE: To study the genetic aberrations of ocular extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type occurring in patients from southern China. METHODS: Fifty seven paraffin-embedded ocular MALT lymphoma specimens from patients in southern China were studied by interphase fluorescence-in-situ hybridization (FISH) for genetic aberrations including t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/IgH-bcl-10, t(14;18) (q32;q21)/IgH-MALT1 and bcl-6/FOXP1 gene translocations. RESULTS: Amongst the 57 cases studied, 9 cases (15.8%) showed chromosome translocations, including 4 cases (7.0%) of t(11;18)(q21;q21)/API2-MALT1, 1 case (1.8%) of t(14;18) (q32;q21)/IgH-MALT1, 1 case (1.8%) of bcl-6 gene-related chromosome translocation and 3 cases (5.3%) of IgH-unknown translocation partner. FISH revealed 17 cases (29.8%) with 3 copies of bcl-6 gene, 21 cases (36.8%) with 3 copies of MALT1 gene and 12 cases (21.1%) with 3 copies of both genes. CONCLUSIONS: The MALT lymphoma-associated chromosome translocations t(11;18)(q21;q21)/API2-MALT1 and t(14;18) (q32;q21)/IgH-MALT1 are demonstrated in ocular MALT lymphomas of southern Chinese patients. The prevalence is significantly different from that reported in northern Chinese and northern American patients, indicating a geographic heterogeneity in the MALT lymphoma-associated genetic aberrations. The presence of 3 copies of bcl-6 and MALT1 genes is the commonest genetic abnormalities observed in ocular MALT lymphomas, suggesting a possible role in MALT lymphomagenesis.

[A clinical study of chromosome translocations in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in Chinese patients].

OBJECTIVE: To investigate the genetic aberrations in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphomas from different sites of the body in Chinese patients. METHODS: Two hundred and seventeen paraffin-embedded MALT lymphoma specimens from 11 major sites were studied with interphase fluorescence in situ hybridization (FISH) to detect t (11; 18) (q21; q21)/API2-MALT1, t (1; 14) (p22; q32)/IGH-BCL10, (14; 18) (q32; q21)/IGH-MALT1 and BCL6 gene involved chromosome translocations. RESULTS: These translocations were mutually exclusive and detected in 21% (46/217) of the cases, including t (11; 18) (q21; q21) API2-MALT1 13% (29/217), t (1; 14) (p22; q32) IGH-BCL10 in 1% (3/217), t (14; 18) (q32; q21) IGH-MALT1 1% (2/217), BCL6 involved translocation in 2% (4/217) and IGH-unknown translocation partner in 4% (8/217). t (11; 18) (q21; q21) API2-MALT1 was found with the highest frequency in MALT lymphoma from lungs (47%, 8/17) and small intestine (29%, 4/14), followed by salivary gland (17%, 1/6), stomach (14%, 12/84) and ocular adnexae (6%, 4/68). t (1; 14) (p22; q32) was only detected in lungs (12%, 2/17) and stomach (1%, 1/84). t (14; 18) (q32; q21) was mainly detected in lungs (6%, 1/17) and ocular adnexae (2%, 1/68). BCL6 gene involved translocation was detected in salivary gland (17%, 1/6) and stomach (4%, 3/84). CONCLUSIONS: It is demonstrated that the four translocations occur with markedly variable frequencies in MALT lymphoma of different sites in Chinese patients. The distributions of these chromosome translocations in Chinese patients are slightly different from those reported in western patients.

[Expressions of matrix metalloproteinase 9 in mucosal natural killer/T cell and mature T cell lymphomas and its relation to Epstein-Barr virus infection].

OBJECTIVE: To investigate the expression of matrix metalloproteinase 9 (MMP9) in mucosal natural killer/T cell and mature T cell lymphomas and its relation to Epstein-Barr virus (EBV) infection. METHODS: The expression of MMP9 and EBV-encoded RNA (EBER) were detected by immunohistochemistry and in situ hybridization in 59 cases of mucosal natural killer/T cell and mature T cell lymphomas. RESULTS: The positivity rates of MMP9 and EBERs were 83.05% and 72.88% respectively. The positivity rate of EBERs was correlated with histopathological subtype (P<0.05), but not with clinical stage, vascular invasion or the patients' survival time (P>0.05). The expression level of MMP9 was not correlated with the clinical stage, vascular invasion or survival time (P>0.05). No significant correlation was found between MMP9 expression and EBV infection. CONCLUSION: EBV may play an important role in the development of mucosal natural killer/T cell and mature T cell lymphomas and promote disease progression by up-regulating MMP9 expression indirectly. Elimination of EBV infection may be helpful to prevent the development of lymphoma.

[Effect of puerarin on the expression of Hsp70 in the rats with cerebral injury induced by acute local ischemia].

OBJECTIVE: To study the effect of puerarin on the expression of Hsp (heat shock protein) 70 in the rats with cerebral injury induced by acute local ischemia. METHOD: Rat model of acute local cerebral ischemia was made by ligating middle cerebral artery. The Hsp70 expression in brain tissue was detected by SP method of immunohistochemistry. RESULT: The expression of Hsp70 was significantly higher in puerarintreated rats than those in the rats with cerebral ischemia. CONCLUSION: Puerarin can enhance the level of Hsp70 expression in the rats with cerebral injury induced by acute local ischemia.

[Protection of puerarin on the cerebral injury in the rats with acute local ischemia].

OBJECTIVE: To study the protection of puerarin on the cerebral injury in the rats with acute local ischemia. METHOD: Rat was evaluated model of acute local cerebral ischemia was made by ligating middle cerebral artery. The cerebral damage toxylin and eosin((HE). RESULT: The number of died neurons were significantly less in puerarin-treated rats than in the rats with cerebral ischemia (P < 0. 05). Similarly, the cerebral edema were significantly attenuated in the puerarin-treated rats as compared with cerebrally ischemic rats. CONCLUSION: Puerarin can prevent the neuron from damage induced by acute cerebral ischemia.