Validation of the Marginal Zone Lymphoma International Prognostic Index.

The Marginal Zone Lymphoma International Prognostic Index (MALT-IPI) was recently developed for use in patients with mucosa-associated lymphoid tissue (MALT) lymphoma based on age, serum lactate dehydrogenase level, and Ann Arbor stage. In this study, we aimed to validate the MALT-IPI. A total of 455 MALT lymphoma patients were included in this study from between January 2005 and February 2017. Event-free survival (EFS), progression-free survival (PFS), cause-specific survival (CSS), and overall survival (OS) were the primary outcomes. Of the 455 patients, MALT-IPI low-, intermediate-, and high-risk groups included 309 (67.9%), 126 (27.7%), and 20 (4.4%) individuals, respectively. When comparing the low-risk group (L MALT-IPI) with the intermediate-high-risk group (I-H MALT-IPI), EFS, PFS, CSS, and OS were significantly different (p = 0.000, p = 0.000, p = 0.027, and p = 0.037). The International Prognostic Index and the Follicular Lymphoma International Prognostic Index failed to predict the prognosis of MALT lymphoma. Use of the MALT-IPI significantly differentiated L MALT-IPI from I-H MALT-IPI with respect to EFS, PFS, CSS, and OS. MALT-IPI is a valuable tool for the prediction of MALT lymphoma prognosis.

Intravascular lymphomatosis presenting as acute hemispheric dysfunction.

Intravascular lymphomatosis (IVL) is known to affect both hemispheres of the brain and manifests clinically as seizures or dementia. To our knowledge, there have been no cases in which acute hemispheric dysfunction is manifested in IVL. We present a 54-year-old man who showed steroid responsive acute hemispheric dysfunction. A technetium 99m-ethyl cysteinate dimer single-photon emission computed tomographic scan of the brain revealed hypoperfusion in the right hemisphere. The bone marrow biopsy specimen confirmed malignant lymphoid cells in vessels, which suggested IVL. Our case signifies the diversity of clinical manifestations in IVL.

Expression of heat shock protein 27 in human atherosclerotic plaques and increased plasma level of heat shock protein 27 in patients with acute coronary syndrome.

BACKGROUND: We intended to identify proteins that are differentially expressed in human atherosclerotic plaques. METHODS AND RESULTS: Comparative 2-dimensional electrophoretic analysis on carotid atherosclerotic endarterectomy specimens (n = 10) revealed that heat shock protein 27 (Hsp27) expression was significantly increased in the nearby normal-appearing area compared with the plaque core area from the same vessel specimen, which was further confirmed by Western blot analysis. The Hsp27 expression in the adjacent normal-appearing vessel areas was much higher than that in nonatherosclerotic reference arteries. The phosphorylation of Hsp27 showed a gradation in the degree of phosphorylation: greatest in the reference arteries, intermediate in the adjacent normal-appearing area, and lowest in plaque core area. Immunohistochemical analysis showed that the phosphorylation of Hsp27 of smooth muscle cells in the carotid endarterectomy specimens was decreased compared with that in the reference artery specimen. The mean plasma level of Hsp27 was significantly higher in patients with acute coronary syndrome (ACS) (n = 27; 106.1 +/- 74.1 ng/mL) than in the normal reference subjects (n = 29; 45.8 +/- 29.5 ng/mL; P < 0.005). The plasma levels of Hsp27 were significantly correlated with those of heat shock protein 70 (Hsp70) (r = 0.422, P < 0.0005), with adjustment for ACS/reference status. CONCLUSIONS: In the atherosclerotic lesion, Hsp27 expression is increased in the normal-appearing vessel adjacent to atherosclerotic plaque, whereas levels in the plaque itself are significantly decreased. Both plaque and adjacent artery show decreased Hsp27 phosphorylation compared with reference vessel. In ACS, plasma Hsp27 and Hsp70 are increased, and levels of Hsp27 correlate with Hsp70, C-reactive protein, and CD40L levels.

Nongastric marginal zone B-cell lymphoma: a prognostic model from a retrospective multicenter study.

The International Prognostic Index (IPI) and Follicular Lymphoma Prognostic Index (FLIPI) are used as prognostic indices for NHL and indolent lymphoma. However, marginal zone B-cell lymphoma (MZL) evidences a distinctive clinical presentation and a natural course; thus, in this study, we attempted to devise an adequate prognostic index for MZL. Two-hundred and five patients diagnosed with MZL were retrospectively reviewed. After analysis of the prognostic factors, progression-free survival (PFS), and overall survival (OS), we constructed a prognostic index of MZL (MZLPI) via the summation of each factor. We then compared PFS and OS with IPI, FLIPI, and MZLPI. According to our multivariate analysis, nodal MZL, ECOG performance > or = 2, and advanced stage were composed of MZLPI. MZLPI was grouped as follows: score 0 as a low-risk group, score 1 as an intermediate risk group, and score 2 as a high-risk group. The PFS curve, according to MZLPI results, evidenced a more discriminated pattern than IPI and FLIPI, and this was especially true in the intermediate risk group. In OS, MZLPI (P=0.0007) evidenced a more discriminated pattern than IPI (P=NS) or FLIPI (P=0.0044). MZLPI, which is constructed of relatively simple factors, may represent a useful prognostic index for the prediction of PFS and OS in MZL, and may also be used as a substitute for IPI or FLIPI.

HMCO5, herbal extract, inhibits NF-kappaB expression in lipopolysaccharide treated macrophages and reduces atherosclerotic lesions in cholesterol fed mice.

HMCO5 is a herbal extract which comprises of eight different herbs. We studied whether this extract has anti-atherosclerotic effects. In lipopolysaccharide (LPS) stimulated RAW264.7 cells, HMCO5 inhibited NF-kappaB activation as well as iNOS promoter activity, inhibited the secretion of TNF-alpha and IL-1beta, and directly inhibited the intracellular accumulation of reactive oxygen species. ApoE knock-out mice fed a high-fat high-cholesterol diet with HMCO5 for 10 weeks showed a significant reduction in atherosclerotic lesions. A notable finding was the preservation of the smooth muscle cell layer in the media of aorta in the HMCO5 co-treated mice. HMCO5 treated mice did not show significant decrease in serum level of cholesterol. These results suggest that HMCO5 has anti-atherosclerotic effects which in part may be attributable to the inhibition of production of NF-kappaB dependent pro-inflammatory cytokines.

Lymphoma Involving Skin and Subcutaneous Fat of the Breast: Two Cases.

Breast lymphoma is uncommon, and it usually involves breast parenchyma and ipsilateral axillary lymph nodes. We report rare cases of cutaneous T-cell lymphoma involving the skin and subcutaneous fat layers mimicking panniculitis of the breasts in a 33-year-old male patient who presented with a growing palpable mass and pain in both breasts and in 17-year-old female patient who presented with an indolent palpable breast mass for 1 year. Extranodal natural killer/T-cell nasal-type and subcutaneous panniculitis-like T-cell lymphomas were diagnosed after skin punch biopsies. Here we report the clinical manifestations, mammographic and ultrasound findings, and the difficulties in histological diagnosis of the cases.

A subset of CD45+/CD19 - cells in bone marrow may be associated with clinical outcomes of patients with mantle cell lymphoma.

Mantle cell lymphoma has features of both indolent and aggressive non-Hodgkin lymphomas. Repeated relapses leading to treatment failure in patients with mantle cell lymphoma might suggest the presence of cancer stem cells. A small cell population with CD45+/CD19 - was previously reported to represent cancer stem cells. We evaluated the clinical relevance of CD45+/CD19 - cells in bone marrow of patients with mantle cell lymphoma (n = 20). A CD45+/CD19 - cell population was observed in newly diagnosed mantle cell lymphoma, and its percentage correlated with tumor cells in bone marrow (r = 0.832, p = 0.001) and score on the simplified mantle cell lymphoma prognostic index (r = 0.675, p = 0.016). After treatment, CD45+/CD19 - cells decreased (mean: 0.012%), and CD45+/CD19 - cells (0.276%) were higher at relapse or progression than at diagnosis. In conclusion, a CD45+/CD19 - cell population in bone marrow aspirates correlated with the clinical outcome of patients with mantle cell lymphoma.

Primary CD56+ T/NK cell lymphoma of the colon.

Primary T/natural killer (NK) cell lymphoma of the colon is extremely rare. Despite the advances in histological and immunophenotypic studies, the diagnosis of primary T/NK cell lymphoma of the colon can be delayed because the early symptoms and colonoscopic findings may be very similar to those of inflammatory bowel diseases such an Crohn's colitis, and most physicians have little available information on this group of neoplasms. Moreover, florid nonspecific inflammatory infiltrates would not allow characterization of the tumor cells in such an inflammatory background. Herein, we describe a patient who initially presented with features that were clinically and colonoscopically similar to Crohn's colitis. Three months later, he had cecal bleeding and perforation, and primary T/NK cell lymphoma of the colon was diagnosed through immunophenotypic and genotypic studies of surgical specimens.

Extranodal natural killer/T-cell lymphoma with long-term survival and repeated relapses: does it indicate the presence of indolent subtype?

BACKGROUND: Extranodal natural killer (NK)/T-cell lymphoma is a subtype of lymphoma that is derived from NK cells. It is considered as an aggressive form of non-Hodgkin's lymphoma because of frequent relapses and resistance to treatment. Relapsed NK/T-cell lymphoma often follows a fulminant course that is refractory to conventional chemotherapy treatment. METHODS: Several patients with extranodal NK/T-cell lymphoma showed long-term survival in spite of frequent relapses. Thus, the medical records of patients diagnosed with extranodal NK/T-cell lymphoma from 1995 to 2007 were reviewed and assessed. RESULTS: Of the 140 cases reviewed, 6 were selected (4.29%). Each of these patients had a minimum of 3 relapses or disease progression during the follow-up period, and their median overall survival was 66 months (range, 42-89 months). They were grouped according to the atypical clinical behavior observed: (1) repeated relapses or progression (≥3 times) during follow-up; and (2) long-term survival of more than 40 months, as the longest overall survival median was previously considered at approximately 40 months. The clinicopathological and laboratory characteristics of these patients were similar to those of other extranodal NK/T-cell lymphoma patients. However, 5 of the studied cases involved relatively lower expression of the proliferation-related antigen Ki-67 (<40-50%), indicating less proliferative activity. Clinically, they showed delayed relapse for at least 20 months after the initial complete remission. CONCLUSION: Our observations suggest that the clinical behavior of some extranodal NK/T-cell lymphoma patients differs from the typical clinical course.

Intravascular large B-cell lymphoma of the cutaneous variant in Korea.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. It is characterized by proliferation of malignant lymphoid cells within the small vessels of various organs. The skin and central nervous system are commonly involved although it occurs in other organs such as the kidneys, adrenals, lung and liver. In Western patients, there is a cutaneous variant of IVLBCL, which involves only the skin. However, the Asian variant, which rarely involves the skin, is associated with hemophagocytosis. It was reported in the majority of Japanese patients. Here, we report a case of the cutaneous variant of IVLBCL in a Korean individual.

Human immunodeficiency virus-negative plasmablastic lymphoma in Korea.

Plasmablastic lymphoma (PBL) is very rare, and predominantly occurs in Human immunodeficiency virus (HIV)-positive individuals. It shows a strong affinity for the oral cavity and for the Epstein-Barr virus (EBV) positive. We investigated the clinicopathologic characteristics of six cases of PBL in Koreans. All patients were HIV-negative and without underlying immunodeficiency. The age distribution was bimodal, and four patients were older than 60 years. Male predominance was observed with male to female ratio of 5:1. The organs primarily involved were the terminal ileum, stomach, oral cavity, tonsil, nasal cavity and meninges. The tumors were histologically typical of PBL. Three of them were composed of monomorphic large immunoblastic or plasmablastic cells, and classified as PBL of the oral mucosa type. Another three cases were classified as PBL with plasmacytic differentiation. Five cases revealed loss of B-cell antigens with CD138 or MUM1 substitution. CD10 was positive in two cases (PBLs of the oral mucosa type), and one of them unexpectedly expressed cytokeratin. EBV was detected in one case (PBL with plasmacytic differentiation). Four patients succumbed to PBL in a relatively short period of time. We suggest that PBL is not strongly associated HIV or EBV in Koreans, and that it shows a variable organ distribution without an oro-nasal predilection.

Nongastric marginal zone B-cell lymphoma: analysis of 247 cases.

Nongastric marginal zone B-cell lymphoma (NG-MZL) is a relatively uncommon indolent lymphoma. From 1990 to 2005, a total of 247 patients with histologically confirmed NG-MZL were analyzed. Ann Arbor stage I/II disease was present in 78% (167 out of 215). One hundred eighty-six patients out of two hundred eight were categorized into the low/low-intermediate risk group (89%) according to International Prognostic Index (IPI). Eighty percent (172/215) were in low risk group according to Follicular Lymphoma International Prognostic Index (FLIPI). Complete and partial remissions (CR and PR) were achieved in 140 (92.7%) and 8 (5.3%) of the 151 stage I/II patients. Especially, radiation containing treatment achieved 96% CR rate (108 out of 113). In 38 patients with stage III/IV, CR and PR were achieved in 17 (44.7%) and 11 (26.3%), respectively. The estimated five-year overall survival (OS) and progression-free survival (PFS) were 93.8% and 70.1%, respectively. Although anthracycline-containing regimen could achieve higher CR rate, it did not improve PFS. Stage III/IV, low hemoglobin, poor performance status, high/high-intermediate IPI, poor risk FLIPI, and nodal MZL were poor prognostic factors for PFS. NG-MZL is an indolent disease. FLIPI has strong power to predict the prognosis of NG-MZL.

Nodal marginal zone B-cell lymphoma: Analysis of 36 cases. Clinical presentation and treatment outcomes of nodal marginal zone B-cell lymphoma.

Nodal marginal zone B-cell lymphoma (NMZL) is a relatively uncommon type of lymphoma. Because of the rarity, the natural history and the optimal treatment modality have not been well defined. Therefore, we performed a retrospective analysis of the clinical features and treatment outcomes of NMZL. Thirty-six patients who were histologically diagnosed as NMZL were included in the analysis. Fifty-three percent of the patients had localized disease (stages I and II), and 21.2% (7/33) had bone marrow involvement at presentation. B symptom was present in only three patients (8.3%). Most patients were categorized as low or low-intermediate risk group by international prognostic index (IPI) (77.1%). Majority (94.4%) of the patients with localized disease achieved complete remission (CR) after the initial treatment. Of the seven patients with disseminated disease, who were treated with anthracycline-based chemotherapy, four patients achieved CR. Of the seven patients who received nonanthracycline-based chemotherapy, no patient achieved CR. After the median follow-up duration of 36 months, the median progression-free survival (PFS) was 3.9 (95% CI; 2.9-5.6) years, and the estimated 5-year PFS and overall survival rates were 47.2 and 82.7%, respectively. The significant predictive factors for PFS were performance status, advanced stage, and follicular lymphoma IPI (FLIPI) in this study. This clinical feature is similar to FL rather than to MZL-MALT type.