Cauda equina lymphoma mimicking non-neoplastic hypertrophic neuropathy of the cauda equina: A case report.

Spinal cauda equina lymphoma (CEL) is very rare, with only about 14 cases reported in the English medical literature. Magnetic resonance image findings and the gross appearance of CEL at surgery are similar to those of non-neoplastic hypertrophic neuropathy of the cauda equina (HNCE); however, their prognosis and treatment are very different. We report a case of CEL and discuss the differences from non-neoplastic HNCE.

Immunohistochemical analysis of CD123, CD56 and CD4 for the diagnosis of minimal bone marrow involvement by blastic plasmacytoid dendritic cell neoplasm.

AIMS: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive haematological malignancy derived from plasmacytoid dendritic cell precursors. Almost all patients show cutaneous manifestations, and >60% show bone marrow (BM) involvement at initial presentation. In cases where there is BM involvement by only a small number of tumour cells, such involvement is difficult to ascertain solely on morphological examination. In such situations, immunohistochemistry (IHC) may be useful in revealing minimal BM involvement by BPDCN. METHODS AND RESULTS: We investigated six patients with BPDCN. Initial morphological diagnosis disclosed BM involvement in only one of the six patients. To confirm BM involvement, IHC for CD4, CD56 and CD123 was performed on BM biopsies or clot sections. IHC revealed minimal BM involvement (CD123, 3/3; CD56, 2/3; CD4, 2/3) in three patients with BM that appeared morphologically normal. CONCLUSIONS: Our data clearly support the utility of IHC in diagnosing minimal BM involvement by BPDCN. Accordingly, we highly recommend immunohistochemical analyses for CD123, CD56 and CD4 in BPDCN patients, particularly in cases where the initial BM study indicates normal morphology.

Clinicopathological characteristics of primary central nervous system lymphoma with low 18F-fludeoxyglucose uptake on brain positron emission tomography.

Primary central nervous system lymphoma (PCNSL) typically shows a strong uptake of F-fludeoxyglucose (FDG) imaged by positron emission tomography (PET). Uncommonly, PCNSL demonstrates a low uptake on FDG PET. We investigated the clinicopathological characteristics of the unusual cases of PCNSL with low FDG uptake.We retrospectively enrolled 104 consecutive patients with newly diagnosed PCNSL who underwent baseline brain FDG PET. The degree of FDG uptake of PCNSL was visually scored by 4 grades (0, ≤contralateral white matter; 1, >contralateral white matter and contralateral gray matter). Grades 0-2 were considered as PCNSL with low uptake. We investigated association of low uptake of PCNSL with the following clinicopathological factors: age, sex, steroid treatment, lactate dehydrogenase level, cerebrospinal fluid protein level, condition of PET scanning, immunohistochemical markers (cluster of differentiation 10 [CD10], B-cell lymphoma 6 [BCL-6], B-cell lymphoma 2 [BCL-2], multiple myeloma oncogene 1 [MUM1], Epstein-Barr virus [EBV] protein, and Ki67), location of lesions, tumor size, multiplicity of lesions, involvement of deep brain structures, and cystic or necrotic appearance of lesions.Of the 104 patients with PCNSL, 14 patients (13.5%) showed PCNSL with low FDG uptake on PET. Among various clinicopathological factors, MUM1 negativity was the only factor associated with low FDG uptake PCNSL by univariate (P = .002) and multivariate analysis (P = .007).This study suggests that the different clinicopathological characteristics between patients with high uptake and low uptake of PCNSL on FDG PET is closely associated with lack of MUM1, a protein known to be a crucial regulator of B-cell development and tumorigenesis.

Spa-1 regulates the maintenance and differentiation of human embryonic stem cells.

Human embryonic stem cells (hESCs) are pluripotent, whereby they can proliferate endlessly and differentiate into many different cell types. At the molecular level, little is known of the mechanisms underlying their capability for self-renewal and differentiation. In the present study, we established two new hESC lines (AMC-hES1 and AMC-hES2) and demonstrated the existence of a regulator that may be a key molecule in hESC dynamics. Spa-1 is a principal Ras-proximate 1 (Rap1) GTPase-activating protein in hematopoietic progenitor cells that regulates Rap1-related signal transduction and is expressed restrictively in human adult tissues (bone marrow, thymus, and spleen). To investigate its functions in hESCs, we examined spa-1 expression profiles during hESC differentiation and used RNA interference (RNAi) to downregulate spa-1 in these cells. Our results show that Spa-1 is expressed in undifferentiated hESCs and is downregulated during hESC differentiation. In addition, the process of passing from the mode of self-renewal to that of differentiation in hESCs was regulated by spa-1 via Rap1/Raf/mitogen-activated protein kinase kinase/extracellular signal-related kinase signaling. An RNAi expression vector against spa-1 (pSUPER.retro.puro) was transfected into hESCs, which were seen to differentiate into three germ layers in spite of being in the undifferentiated condition. Based on our findings, therefore, it appears that spa-1 may be involved in hESC dynamics, and our results provide fundamental information regarding the self-renewal and differentiation of hESCs.

Endoscopic ultrasonography-guided trucut biopsy for the preoperative diagnosis of peripancreatic Castleman's disease: a case report.

Castleman's disease (CD) of the pancreas/peripancreas is extremely rare. The recently introduced, endoscopic ultrasonography (EUS)-guided trucut biopsy (TCB) is a useful diagnostic modality for obtaining tissue samples from peripancreatic lesions. However, its role in diagnosing CD remains unknown. We report a case of localized, peripancreatic, hyaline-vascular CD biopsied using EUS. The pathology results were initially interpreted as an extranodal, marginal-zone B-cell lymphoma. However, polymerase chain reaction (PCR) study for the IgH gene rearrangement revealed a polyclonal pattern. We also reviewed the relevant literature. To our knowledge, this is the first illustrated report on EUS-TCB findings of CD with its pathology results of EUS-TCB mimicked a B-cell lymphoma.

Significantly better prognosis for patients with primary plasma cell leukemia than for patients with secondary plasma cell leukemia.

Plasma cell leukemia (PCL) is a rare variant of multiple myeloma (MM). Patients may either present de novo (primary PCL), or PCL may occur during the course of MM (secondary PCL). We compared the laboratory and clinical findings of both primary and secondary PCL and MM to elucidate their natural history and the relationship among these entities. Ten cases of PCL (7 cases of primary PCL and 3 cases of secondary PCL) and 20 sex- and age-matched cases of MM were compared. The patients with primary PCL showed significantly lower platelet and neutrophil counts in peripheral blood and higher cellularity in bone marrow than patients with MM (p = 0.002, < 0.001 and 0.027, respectively). Immunophenotypic studies showed a different expression of HLA-DR and CD117 antigens among the 3 groups. There was a significant difference in survival between the 3 groups (median survival of primary PCL, secondary PCL and MM = 22.2, 1.3 and 36.4 months, respectively; p = 0.048). The patients with primary PCL showed better prognosis than those with secondary PCL. Primary PCL might be a differently developed disease from MM. In diagnosing PCL, it is important to differentiate primary PCL from secondary PCL for the prediction of prognosis.

Prognostic relevance of the Ki-67 proliferation index in patients with mantle cell lymphoma.

BACKGROUND: A high Ki-67 proliferation index (PI) in neoplastic cells is associated with poor survival in mantle cell lymphoma (MCL). We aimed to determine the cut-off values for the Ki-67 PI as a prognostic factor in MCL according to bone marrow findings. METHODS: Immunohistochemical (IHC) staining for Ki-67 was performed on formalin-fixed paraffin-embedded biopsy tissues from 56 patients with MCL. Patients were grouped based on their Ki-67 PI values. Survival analyses were carried out and the cut-off value for the Ki-67 PI was determined. RESULTS: Of the 56 patients, 39 (69.6%) showed bone marrow involvement of MCL; 21 of these patients had leukemic manifestations at the time of diagnosis. The results of the Ki-67 IHC staining were as follows: ≤10% in 22 patients, 11-20% in 14 patients, 21-30% in 3 patients, 31-40% in 4 patients, 41-50% in 4 patients, and >50% in 9 patients. A cut-off value of 20% revealed significantly different survival rates with mean survival times of 69.8 months (Ki-67 PI≤20%) and 47.9 months (Ki-67 PI>20%), irrespective of bone marrow findings (P=0.034). Clinical outcomes did not differ, regardless of bone marrow findings. However, in cases with bone marrow involvement, the Ki-67 cut-off value of 30% for overall survival was required to yield statistical significance (P=0.033). CONCLUSION: The 20% cut-off value for the Ki-67 PI was clinically meaningful, regardless of bone marrow involvement of MCL. For patients with bone marrow involvement, the statistically significant cut-off value increased to 30%.

Lymphocytic gastritis in Helicobacter pylori-positive gastric MALT lymphoma--report of two cases.

Both lymphocytic gastritis and gastric mucosa associated lymphoid tissue (MALT) lymphoma are associated with Helicobacter pylori (H. pylori) infection. However, this association has not been fully elucidated. We report two cases of lymphocytic gastritis in 57-year-old male and 47-year-old female patients which were diagnosed after the H. pylori eradication to treat gastric MALT lymphoma. MALT lymphoma was successfully treated in case 1, but residual MALT lymphoma remained in case 2. During the follow-up endoscopic examinations, several elevated erosions in case 1 and irregular mucosal atrophy in case 2 were newly detected. Biopsy specimens showed marked infiltration of lymphocytes in the surface epithelium (56.6+/-15.9 intraepithelial lymphocytes (IELs)/100 epithelial cells in case 1 and 40.5+/-9.3 IELs/100 epithelial cells in case 2), which were exclusively CD8-positive T lymphocytes. These findings suggest that H. pylori infection may cause a monoclonal proliferation of B lymphocytes, leading to MALT lymphoma as well as polyclonal proliferation of T lymphocytes which subsequently infiltrated into the surface epithelium as a host immune reaction, resulting in lymphocytic gastritis.

Enhanced expression of neuronal nitric oxide synthase and phospholipase C-gamma1 in regenerating murine neuronal cells by pulsed electromagnetic field.

Pulsed electromagnetic field (PEMF) has been shown to improve the rate of peripheral nerve regeneration. In the present study we investigated the expression of neuronal nitric oxide synthase (nNOS) and phospholipase C-gamma1 (PLC-gamma1) in regenerating rat laryngeal nerves during the exposure to PEMF after surgical transection and reanastomosis. Axons were found to regenerate into the distal stump nearly twice faster in PEMF-exposed animals than in the control. Consistently, motor function was better recovered in PEMF-treated rats. The expression of nNOS and PLC-gamma1 was highly enhanced in the regenerated nerves.

Langerhans cell histiocytosis followed by Hodgkin's lymphoma.

A 22-year-old man was referred to our institution due to lower back pain and was diagnosed with Langerhans cell histiocytosis of the thoracic and lumbar spine. The patient achieved complete remission with radiotherapy and chemotherapy. One year later, right cervical lymphadenopathy was observed and Hodgkin's lymphoma was confirmed on biopsy. The patient was treated with chemotherapy and autologous stem cell transplantation, and experienced no further symptoms. Further, no evidence of recurrence was observed on follow-up imaging. This report discusses the association between Langerhans cell histiocytosis and Hodgkin's lymphoma.

Expression of JL1 in Burkitt lymphoma is associated with improved overall survival.

JL1 is a novel molecule expressed in the surface of hematopoietic precursor cells, but not on any other mature human tissue. Accordingly, JL1 is expressed in acute lymphoblastic leukemia (ALL) cells and can be used both for specific diagnosis and as a target for treatment. However, expression of JL1 by lymphomas has not been thoroughly assessed. Burkitt lymphoma is a potentially curable aggressive lymphoma, but prognostic markers that stratify risk have not been established. We therefore assayed JL1 expression in Burkitt lymphoma patients to assess its value as a prognostic marker for this disease. Tissue microarray blocks of formalin-fixed paraffin-embedded tissue samples from patients with Burkitt lymphoma and other B-cell lymphomas, at the Asan Medical Center and Seoul National University Hospital from January 1998 to December 2008 were immunohistochemically assayed using a mouse monoclonal antibody against JL1. We found that 30.2% of Burkitt lymphoma samples, but no other lymphoma samples, were positive for JL1. JL-1 expression was significantly correlated with patient survival (P = 0.022), but not with other clinical manifestations of the disease, with 91.6% of JL1-positive patients achieving complete remission in response to chemotherapy and 6.25% experiencing disease recurrence. JL1 positivity was significantly correlated with prolonged overall survival by both Kaplan-Meier survival (P = 0.035) and Cox proportional hazard model (P = 0.043) analysis. JL1 expression in Burkitt lymphoma was positively correlated with overall survival and better response to chemotherapy, suggesting that JL1 may be a prognostic marker for risk stratification in these patients.

[Prognostic impact of Helicobacter pylori infection and eradication therapy in gastric mucosa-associated lymphoid tissue lymphoma].

BACKGROUND: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is associated with Helicobacter pylori infection and H. pylori eradication is used as its first-line therapy. However, controversies exist about the prognostic value of H. pylori infection in these patients. We evaluated the prognostic impact of H. pylori infection and eradication therapy in gastric MALT lymphoma. METHODS: A total of 292 patients diagnosed with MALT lymphoma since 2000 were analysed. MALT lymphoma was diagnosed with tissue biopsy and H. pylori infection was diagnosed with hematoxylin-eosin and additional Warthin-Starry stains on tissue sections. Clinical variables such as bone marrow (BM) involvement, multiorgan involvement, tumor stage at diagnosis, and remission were obtained with retrospective review of electronic medical records. RESULTS: Non-gastric MALT lymphoma patients showed higher multiorgan involvement rates (26.6% vs. 9.6%, P<0.001) and higher proportion of stage ≥ 3 (27.7% vs. 16.7%, P=0.029) than gastric cases. Regarding gastric MALT lymphoma, patients with H. pylori infection at diagnosis showed significantly less BM (2.1% vs. 21.8%, P<0.001) and multiorgan involvement rates (6.3% vs. 18.2%, P=0.011) than those without infection. But there was no significant difference in remission rates between them. In contrast, those with successful H. pylori eradication therapy showed significantly higher remission rates (81.0% vs. 30.8%, P<0.001) than those with failure. CONCLUSIONS: Non-gastric MALT lymphoma patients showed worse prognosis compared to gastric cases. As for remission rates in patients with gastric MALT lymphoma, successful H. pylori eradication therapy could be a good prognostic factor even if H. pylori infection was present at diagnosis.

Expression of JL1 is an effective adjunctive marker of leukemia cutis.

CONTEXT: Specific differentiation of leukemia cutis (LC) from nonleukemic dermatoses is crucial to ensure proper treatment for the disease. Because of the exceptionally variable histologic features of LC and the frequent nonleukemic dermatoses in leukemia patients, identification of leukemic cells that infiltrate skin lesions is important. Here, we introduce JL1, a novel leukemia-associated surface antigen, which is not expressed in mature human tissue but in cortical thymocytes and small subpopulations of bone marrow hematopoietic precursors. OBJECTIVES: To assess the expression pattern of JL1 in LC and compare it with other commonly used markers. Also, to evaluate the expression of JL1 in other cutaneous lesions that need differential diagnoses. DESIGN: Immunohistochemical staining with anti-JL1 and other commonly used markers for LC was performed on paraffin-embedded skin biopsies from 32 cases of LC with acute lymphoblastic leukemia/lymphoma and acute myelogenous leukemia. Immunohistochemical staining score was evaluated in each case according to the proportion of positive tumor cells found. JL1 staining was also done on 96 reactive or neoplastic cutaneous lesions. RESULTS: JL1 was detected in 7 of 11 acute lymphoblastic leukemia/lymphoma LC (63.6%) and 7 of 21 acute myelogenous leukemia LC (33.3%), with invariably high-staining scores. None of the other cutaneous lesions or normal tissues expressed JL1. The expression pattern of JL1 was not altered in 2 patients with follow-up biopsies. CONCLUSIONS: Our finding that JL1 is expressed exclusively and stably by leukemic cells suggests that it can be used as a useful adjunctive marker for initial diagnosis and follow-up biopsy of LC, particularly in cases of scarce infiltrates.

A novel mutation of the succinate dehydrogenase B gene in a Korean family with pheochromocytoma.

Pheochromocytoma is a tumor that originates from the adrenal cortex and sympathetic chains. Most pheochromocytomas are sporadic, whereas others occur as hereditary syndromes. Familial pheochromocytoma has been frequently found in association with various mutations in genes of the succinate dehydrogenase family. A 21-year-old Korean male presented with recurrent chest tightness, severe headache, and hypertension. He was diagnosed as pheochromocytoma based on a 24-hour urine test, abdominal computed tomography, and (131)I-MIBG scintigraphy. Genomic DNA was extracted from the patient's whole blood. Primers covering all the coding regions and flanking introns of succinate dehydrogenase (SDH) B, C and D genes were designed and synthesized, and a DNA sequence analysis was performed using the polymerase chain reaction. Direct sequencing of the SDHB gene revealed a deletion of nucleotide 757 (thymidine) in exon 7. This thymidine deletion caused a shift in the reading frame that created a downstream stop codon and a truncated product (p.Cys253ValfsX5). Although the patient had no family history of pheochromocytoma, his father had the same mutation. We report a novel SDHB gene mutation from a Korean family with pheochromocytoma. This is the first report of pheochromocytoma with a confirmed SDHB germline mutation in Korea.

Role of CD4CD25FOXP3 Regulatory T Cells in Psoriasis.

BACKGROUND: CD4(+)CD25(high+)regulatory T cells (Tregs) are considered to be of vital importance for maintaining immunologic self-tolerance and preventing autoimmune diseases. These cells have been found to be deficient in skin lesions and in the peripheral blood of patients with psoriasis. OBJECTIVE: To investigate the role of Tregs in the pathogenesis of psoriasis and to evaluate the changes in Tregs in relation to the severity and the clinical course of psoriasis. METHODS: Immunohistochemistry (CD3, 4, 8, 79 and FOXP3) was performed in 22 psoriatic patients compared to 5 normal controls. Flow cytometry (CD3, 4, 8, 25 and FOXP3) was performed in 18 psoriatic patients and 8 normal volunteers and reverse transcriptase polymerase chain reaction (foxp3 mRNA) was performed in 8 psoriasis patients. RESULTS: An increase in the FOXP3(+) cell fraction was detected in the lesional psoriatic skin irrespective of the severity of psoriasis as compared with the normal skin. However, a decrease in FOXP3(+) cells was observed in the samples obtained from psoriasis of 'acute course'. FOXP3(+) Treg populations in the blood of the 'acute course' psoriasis was not different compared to that of 'chronic course' psoriasis and normal controls. CONCLUSION: The deficiency of FOXP3(+) Tregs in the lesional psoriatic skin might be responsible for the exacerbation of psoriasis.

Clinicopathological features of eight Korean cases of primary hepatic lymphoma.

Primary hepatic lymphoma is very rare, accounting for less than 0.4% of extranodal lymphomas. Furthermore, hepatic lymphoma, either primary or metastatic, is infrequently confirmed histopathologically in needle biopsy specimens. The aim of the current study is to assess the clinicopathological characteristics of primary hepatic lymphomas in Korea, which is an endemic area of chronic B viral hepatitis. In total, 17 cases with liver needle biopsy specimens with involvement of malignant lymphoma, from whom eight cases met the criteria for primary hepatic lymphoma, were selected. The clinicopathological features were reviewed. Five of eight (62.5%) cases were T cell lymphoma, including three cases (37.5%) of hepatosplenic T cell lymphoma. Three cases (37.5%) were diffuse large B cell lymphomas. Seven patients had follow-up data from 25 days to 50 months that was available for evaluation. The partial remission was present in two of seven patients (28.6%) and five patients (71%) died of disease 25 days to 7 months after the diagnosis. The data indicate that the relatively high incidence of T-cell type in Korean cases of primary hepatic lymphoma may be related to its aggressive behavior and poor prognosis despite combination chemotherapy.

Bfl-1 gene expression in breast cancer: its relationship with other prognostic factors.

The Bfl-1 gene, which was isolated from human fetal liver and only recently described, is a member of the Bcl-2 gene family. Reverse transcriptase-polymerase chain reaction was performed on RNA drawn from 30 breast cancer tissues to compare the expression of the Bfl-1 gene with other prognostic factors. The median relative ratio was 3.0 (range, 0.12-26.83) and the Bfl-1 gene expression rate was 36.7% (11/30). There was no statistically significant relationship between the clinicopathologic parameters of patients and the expression value of Bfl-1 gene. The level of Bfl-1 gene expression was higher in more advanced breast cancers than in early cancers. There was no significant relationship between the expression values and currently acknowledged prognostic factors, but a higher expression pattern was noticed in the groups of positive hormone receptors and negative p53 and negative c-erbB2, albeit statistically not significant. It seems that the increased expression of the Bfl-1 gene serves as a contributory factor in breast cancer, in the same way that another group of genes, the Bcl-2 family, contributes to apoptosis.