Hepatocellular carcinoma (HCC) has been known as one of the most lethal human malignancies, due to the difficulty of early detection, chemoresistance, and radioresistance, and is characterized by active angiogenesis and metastasis, which account for rapid recurrence and poor survival. Its development has been closely associated with multiple risk factors, including hepatitis B and C virus infection, alcohol consumption, obesity, and diet contamination. Genetic alterations and genomic instability, probably resulted from unrepaired DNA lesions, are increasingly recognized as a common feature of human HCC. Dysregulation of DNA damage repair and signaling to cell cycle checkpoints, known as the DNA damage response (DDR), is associated with a predisposition to cancer and affects responses to DNA-damaging anticancer therapy. It has been demonstrated that various HCC-associated risk factors are able to promote DNA damages, formation of DNA adducts, and chromosomal aberrations. Hence, alterations in the DDR pathways may accumulate these lesions to trigger hepatocarcinogenesis and also to facilitate advanced HCC progression. This review collects some of the most known information about the link between HCC-associated risk factors and DDR pathways in HCC. Hopefully, the review will remind the researchers and clinicians of further characterizing and validating the roles of these DDR pathways in HCC.

Primary cutaneous, extranodal natural killer/T-cell lymphoma, nasal type (PC-ENKTL), is a rare Epstein-Barr virus (EBV)-associated neoplasm with poorly defined clinicopathologic features. We performed a multinational retrospective study of PC-ENKTL and CD56-positive EBV-negative peripheral T-cell lymphoma (PC-CD56+PTCL) in Asia in an attempt to elucidate their clinicopathologic features. Using immunohistochemistry for T-cell receptors (TCRs), in situ hybridization for EBV, and TCR gene rearrangement, we classified 60 tumors into 51 with PC-ENKTL (20 of NK-cell, 17 T-cell, and 14 indeterminate lineages) and 9 with PC-CD56+PTCL. Tumors of T-cell origin accounted for 46% of PC-ENKTLs with half of these cases being TCR-silent. As compared with T-lineage tumors, PC-ENKTLs of NK-cell lineage had more frequent involvement of regional lymph nodes and more frequently CD8-negative and CD56-positive. Cases of PC-ENKTL showed more frequent tumor necrosis, younger age, and a higher frequency of CD16 and CD30 expression than cases of PC-CD56+PTCL. CD56-positive T-lineage PC-ENKTL tumors (n=8) had more localized disease in the TNM (tumor-node-metastasis) staging and were more often of γδ T-cell origin compared with cases of PC-CD56+PTCL (n=9). PC-ENKTLs and PC-CD56+PTCLs were equally aggressive, with a 5-year overall survival rate of 25%. Tumor necrosis and CD16 expression may serve as useful surrogates for differentiating PC-ENKTL from PC-CD56+PTCL. A single lesion, an elevated lactate dehydrogenase level, and the presence of B symptoms were independent poor prognostic factors for PC-ENKTL in multivariate analysis. Further studies with more cases are warranted to delineate the clinicopathologic features and significance of EBV in these rare lymphomas.

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The implication of LVI on prognosis, particularly in ureteral tumors but not in pyelocaliceal tumors, may imply diverse disease characteristics between different tumor locations among UTUC. LVI is essential to identify patients at high risk for metastasis/mortality and can facilitate treatment planning and surveillance strategies, especially in patients with ureteral tumors.

Apart from the phenotypical difference, our HHV8-positive neoplasms were not distinct from the HHV8-negative group. Literature review of 256 cases, including our cases, revealed that HHV8-positive cases were associated more frequently with HIV and EBV infection, with rare MYC rearrangement, and a poorer prognosis than HHV8-negative cases. We propose to name the HHV8-positive cases as 'classical' or 'type I PEL' and the HHV8-negative cases as 'type II PEL', stressing the similarities and the distinctive features between these two groups.

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The study's purposes are to identify patient characteristics, treatment response and survival rate, and to describe the important prognostic factors for our patients with extranodal head and neck lymphoma. Furthermore, no study has systemically discussed the overall figure of this disease in Taiwan and we analyzed our data on this topic. A retrospective review was performed for 86 patients with extranodal head and neck lymphoma, diagnosed in Kaohsiung Medical University Hospital, between 1990 and 2007. We evaluated the medical records and analyzed the possible factors affecting treatment outcomes, survival rate, and free-from-disease (FFD) survival rate. Forty-nine male and 37 female patients were included with a male:female ratio of 1.32:1. The most frequent histologic type was diffuse large B cell lymphoma, accounting for 41.9% of the total. The most common primary site involved with extranodal head and neck non-Hodgkin's lymphoma was a tonsil with 27 cases (31.4%). Stage, international prognostic index (IPI) score, B symptoms, lactate dehydrogenase (LDH) level, and lymph node status significantly affected treatment response. The overall 5- and 10-year survival rates were 68.0% and 57.8%, respectively. The FFD survival rate was 53.6% and 49.3% at 5 and 10 years, respectively. Factors including stage, lymph node status, LDH level, and IPI score produced significant differences in both overall survival and FFD survival. Our analyzed information is similar to other previously presented studies. Stage, IPI score, B symptoms, LDH level, and neck nodal status can be used to evaluate the treatment outcomes. Neck nodal status and stage are the two significant prognostic factors for overall survival.

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