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1.  Primary Follicular Lymphoma in a Male Breast: A Case Report 
Primary breast lymphoma (PBL) is a rare disease, particularly in males. Diffuse large B cell lymphoma is the most common PBL, while follicular lymphoma is less common. Furthermore, primary follicular lymphoma of a male breast is rarely reported. We report a male patient with primary follicular lymphoma of the breast and hepatocellular carcinoma (HCC). A 46-year-old man was diagnosed with liver cirrhosis secondary to chronic hepatitis B infection. Ten years later, he underwent segmentectomy of the liver due to HCC. Another 5 months later, he presented with a painless mass in the right chest wall. The mass was diagnosed as follicular lymphoma of the breast. The stage was IEA and he did not receive adjuvant therapy. Although only a few cases have been reported, lymphoma should be considered as a possible cause of breast mass, even in male patients.
PMCID: PMC3918521  PMID: 24520230
Breast; Follicular lymphoma; Hepatocellular carcinoma; Liver cirrhosis; Male
2.  Unusual Manifestation of Intravascular Large B-Cell Lymphoma: Severe Hypercalcemia with Parathyroid Hormone-Related Protein 
Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It usually presents with nonspecific symptoms, such as fever, rather than with overt lymphadenopathy. Reports of hypercalcemia, as the initial presentation of IVLBCL, are limited in the literature, despite it being a well-known complication of various solid cancers. We present a 68-year-old male with severe hypercalcemia and increased levels of serum parathyroid hormone-related protein. He was diagnosed with IVLBCL, involving the bone marrow and spleen, and was successfully treated with rituximab-containing chemotherapy. A few previous case reports have shown hypercalcemia in patients with IVLBCL. Much like our case, previous cases with hypercalcemia had advanced diseases, including bone marrow invasion. Although it was an extremely rare manifestation of IVLBCL, we suggest that IVLBCL should be a part of the differential diagnosis in patients with unexplained hypercalcemia. Therefore, an active work-up might be recommended, including positron emission tomography/ computed tomography scan and bone marrow examination, which may be useful for early diagnosis.
PMCID: PMC4132453  PMID: 25038766
Intravascular lymphoma; Hypercalcemia; Parathyroid hormone-related protein
3.  Clinical outcomes of radiation therapy for early-stage gastric mucosa-associated lymphoid tissue lymphoma 
AIM: To evaluate the clinical outcomes of radiation therapy (RT) for early-stage gastric mucosa-associated lymphoid tissue lymphoma (MALToma).
METHODS: The records of 64 patients treated between 1998 and 2011 were analyzed retrospectively. For Helicobacter pylori (H. pylori)-positive patients (n = 31), chemotherapy or H. pylori eradication therapy was the initial treatment. In patients with failure after H. pylori eradication, RT was performed. For H. pylori-negative patients (n = 33), chemotherapy or RT was the first-line treatment. The median RT dose was 36 Gy. The target volume included the entire stomach and the perigastric lymph node area.
RESULTS: All of the patients completed RT without interruption and showed complete remission on endoscopic biopsy after treatment. Over a median follow-up period of 39 mo, the 5-year local control rate was 89%. Salvage therapy was successful in all relapsed patients. Secondary malignancies developed in three patients. The 5-year overall survival rate was 94%. No patient presented symptoms of moderate-to-severe treatment-related toxicities during or after RT.
CONCLUSION: Radiotherapy results in favorable clinical outcomes in patients with early-stage gastric MALToma who experience failure of H. pylori eradication therapy and those who are H. pylori negative.
PMCID: PMC3785628  PMID: 24106407
Gastric mucosa-associated lymphoid tissue lymphoma; Radiation therapy; Treatment response
4.  Sudden Atelectasis and Respiratory Failure in a Neutropenic Patient: Atypical Presentation of Pseudomembranous Necrotizing Bronchial Aspergillosis 
Pseudomembranous necrotizing bronchial aspergillosis (PNBA) is a rare form of invasive aspergillosis with a very poor prognosis. The symptoms are non-specific, and the necrotizing plugs cause airway obstruction. Atelectasis and respiratory failure can be the initial manifestations. Recently, we treated an immunocompromised patient with PNBA, who presented with a sudden onset of atelectasis and acute respiratory failure. There were no preceding signs except for a mild cough and one febrile episode. Bronchoscopy revealed PNBA, and Aspergillus nidulans was cultured from the bronchial wash.
PMCID: PMC3529248  PMID: 23269890
Aspergillosis; Pneumonia; Neutropenia
6.  Bortezomib and melphalan as a conditioning regimen for autologous stem cell transplantation in multiple myeloma 
The Korean Journal of Hematology  2010;45(3):183-187.
High-dose melphalan (200 mg/m2) with autologous stem cell transplantation (ASCT) is the standard treatment for young patients with multiple myeloma (MM). However, the response rates after ASCT are often unsatisfactory. We performed a pilot study by using bortezomib-melphalan as conditioning regimen for ASCT in Korean patients with MM.
The conditioning regimen consisted of administration of intravenous infusion of bortezomib 1.0 mg/m2 on days -4 and -1 and melphalan 50 mg/m2 (day -4) and 150 mg/m2 (day -1). In this study, we enrolled 6 newly diagnosed patients and 2 patients with relapse.
The disease status of the 6 newly diagnosed patients at ASCT was as follows: 1 complete remission (CR), 1 very good partial remission (VGPR), and 4 partial remissions (PRs). The disease status of the 2 relapsed patients at ASCT was PR. All patients except 1 showed adequate hematologic recovery after ASCT. The median time for the absolute neutrophil counts to increase over 500/mm3 was 13 days (range, 10-19 days). Six patients with VGPR or PR at the time of transplantation showed an improvement in response to CR after ASCT. The patients were followed up without any maintenance treatment after ASCT except 1 patient who died during ASCT. During the follow-up period, CR was maintained in 3 newly diagnosed patients, but the other 4 patients, including 2 newly diagnosed patients, relapsed.
Conditioning regimen consisting of bortezomib and melphalan may be effective for ASCT in MM; however, the feasibility of this regimen should be further evaluated in large study populations.
PMCID: PMC2983035  PMID: 21120207
Multiple myeloma; Bortezomib; Melphalan
7.  Complete Remission in a Patient with Human Herpes Virus-8 Negative Multicentric Castleman Disease Using CHOP Chemotherapy 
Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder. Although MCD pathogenesis is unclear, studies have suggested that human herpesvirus 8 (HHV-8) may be associated with the disorder. Recent reports have identified MCD cases without viral infection. A 43-year-old woman presented to our hospital for fever and myalgia of 6 months' duration. The complete blood count revealed an elevated leukocyte count (15.1×103/µL) and a decreased hemoglobin level of 10.0 g/dL. The C-reactive protein level was elevated at 276.5 mg/L. Thoracic computed tomography (CT) scans revealed bilateral axillary lymphadenopathy. There was no evidence of HHV-8, human immunodeficiency virus (HIV), or Mycobacterium infection. Histologic evaluation of a lymph node biopsy from the left axilla yielded a diagnosis of MCD. Cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) were administered for a total of 4 cycles. The patient's fever and lymphadenopathy resolved after the course of chemotherapy. She has been in complete remission for 24 months at this writing. As previously reported, this case report suggests that MCD can develop without viral infection. CHOP chemotherapy may be an effective treatment option for newly diagnosed MCD patients.
PMCID: PMC2731214  PMID: 19707509
Chemotherapy; Human herpes virus 8; Multicentric Castleman disease
8.  High-dose Immunoglobulin Infusion for Thrombotic Thrombocytopenic Purpura Refractory to Plasma Exchange and Steroid Therapy 
The outcomes of the treatment of thrombotic thrombocytopenic purpura (TTP) have been shown to be improved by the administration of plasma exchange. However, treatment options are currently limited for cases refractory to plasma exchange. The autoantibodies that block the activity of ADAMTS13 have been demonstrated to play a role in the pathogenesis of TTP; therefore, high-dose immunoglobulin, which can neutralize these autoantibodies, may be useful for refractory TTP. However, successful treatment with high-dose immunoglobulin for TTP refractory to plasma exchange and corticosteroids has yet to be reported in Korea. Herein, we describe a refractory case which was treated successfully with high-dose immunoglobulin. A 29-year-old male diagnosed with TTP failed to improve after plasma exchange coupled with additional high-dose corticosteroid therapy. As a salvage treatment, we initiated a 7-day regimen of high-dose immunoglobulin (400 mg/kg) infusions, which resulted in a complete remission, lasting up to the last follow-up at 18 months. High-dose immunoglobulin may prove to be a useful treatment for patients refractory to plasma exchange; it may also facilitate recovery and reduce the need for plasma exchange.
PMCID: PMC2686967  PMID: 18787371
Thrombotic Thrombocytopenic Purpura; Plasma Exchange; Glucocorticoids; Immunoglobulin
9.  Hepatitis B Virus Reactivation in a Surface Antigen-negative and Antibody-positive Patient after Rituximab Plus CHOP Chemotherapy 
Rituximab is a monoclonal antibody that targets B-lymphocytes, and it is widely used to treat non-Hodgkin's lymphoma. However, its use has been implicated in HBV reactivation that's related with the immunosuppressive effects of rituximab. Although the majority of reactivations occur in hepatitis B carriers, a few cases of reactivation have been reported in HBsAg negative patients. However, reactivation in an HBsAg negative/HBsAb positive patient after rituximab treatment has never been reported in Korea. We present here an HBsAg-negative/HBsAb-positive 66-year-old female who displayed reactivation following rituximab plus CHOP chemotherapy for diffuse large B-cell lymphoma. While she was negative for HBsAg at diagnosis, her viral status was changed at the time of relapse as follows: HBsAg positive, HBsAb negative, HBeAg positive, HBeAb negative and an HBV DNA level of 1165 pg/ml. Our observation suggests that we should monitor for HBV reactivation during rituximab treatment when prior HBV infection or occult infection is suspected, and even in the HBsAg negative/HBsAb positive cases.
PMCID: PMC2699087  PMID: 19688064
Rituximab; Hepatitis B virus; Lymphoma
10.  Persistent Anemia in a Patient with Diffuse Large B Cell Lymphoma: Pure Red Cell Aplasia Associated with Latent Epstein-Barr Virus Infection in Bone Marrow 
Journal of Korean Medical Science  2007;22(Suppl):S167-S170.
We report a case of pure red cell aplasia (PRCA), which was initially suspected as a result of bone marrow involvement of diffuse large B cell lymphoma. Persistent anemia without an obvious cause was observed in a 47-yr-old man diagnosed with relapsed diffuse large B cell lymphoma. The bone marrow study showed only erythroid hypoplasia without the evidence of bone marrow involvement with lymphoma cells, thus PRCA was suggested. However, parvovirus infection was excluded as a potential cause of PRCA because of negative IgM anti-parvovirus B19 antibody and negative parvovirus PCR in the serum. Latent Epstein-Barr virus (EBV) infection of bone marrow was suggested by in situ hybridization with EBV-encoded small RNA (EBER) that showed a strong positive expression in bone marrow cells. Thus, PRCA was thought to be associated with latent EBV infection in bone marrow cells. Although the finding of unexplained anemia is a possible predictor of bone marrow involvement with lymphoma cells, PRCA as a result of a viral infection including EBV should be considered in lymphoma patients. This is the first report of the occurrence of PRCA associated with latent EBV infection in a patient with non-Hodgkin's lymphoma.
PMCID: PMC2694371  PMID: 17923747
Red-Cell Aplasia; Epstein-Barr Virus; Lymphoma
11.  Glucose Transporter-1 Expression in Squamous Cell Carcinoma of the Tongue 
Tumor cells are known to express hypoxia-related proteins such as glucose transporter-1 (Glut-1). These hypoxia-induced changes may allow tumor cells to survive under sustained hypoxic microenvironments, and the surviving tumor cell under hypoxia may develop a more aggressive phenotype and so result in a poor prognosis.
Materials and Methods
The Glut-1 expression was analyzed by immunohistochemistry, and its association with the prognosis was assessed in 60 patients with squamous cell carcinoma of the tongue.
The Glut-1 expression was diffuse with a membranous pattern, and the median percentage of Glut-1 positive tumor cells was 60% (range: 0.0~90.0%). A high Glut-1 expression (the percentage of positive tumor cells ≥ the median value, 60%) was associated with the location of primary lesion, lymph node metastasis status and disease stage (p<0.05). The expression of Glut-1 was correlated with the Ki-67 expression (r=0.406, p=0.001). Microvessel density, as represented by CD31 staining, was also correlated with the Glut-1 expression although its significance is weak (r=0.267, p=0.039). On the univariate analysis, the group with a high Glut-1 expression showed poorer overall survival than the group with a low Glut-1 expression (p<0.05). However, the Glut-1 expression failed to show any independent prognostic significance on the multivariate analysis.
The expression of Glut-1 may be useful for predicting the prognosis and determining the treatment strategy for the management of squamous cell carcinoma of the tongue.
PMCID: PMC2739325  PMID: 19746220
Tumor hypoxia; Glucose transporter-1; Squamous cell carcinoma; Tongue
12.  Continuous Improvements of a Clinical Pathway Increased Its Feasibility and Improved Care Providers' Perception in TKA 
Knee Surgery & Related Research  2014;26(4):199-206.
We aimed to determine 1) whether dropout rate decreased and 2) whether health care providers' perceptions were changed with continued improvements of contents of clinical pathway (CP) for total knee arthroplasty (TKA).
Materials and Methods
This retrospective study included two separate analyses of patients and health care providers. In the analysis of patients, dropout rates and reasons were evaluated in two cohorts of patients who underwent TKA with CP applied at two different time periods (384 patients from 2009 to 2010 and 242 patients from 2012 to 2013). Contents of CP were continuously improved during the 3-year interval. Self-administered questionnaire surveys targeted to health care providers were carried out twice (2010 and 2013) and compared.
Dropout rate decreased from 19.1% in the first time period to 10.4% in the second time period. Although overall satisfaction of care providers was high at both time-points, doctors had more favorable perceptions than nurses; most positive changes of perception were noted in nurses. The health care providers' perceptions for potential concerns of CP were improved while the perceptions for potential benefits and satisfaction were maintained.
Continuously improved CP has increased feasibility for TKA patients and reduced health care providers' concern about its value. We propose that CP can be implemented and actively used to improve the outcomes and efficacy of patient care for TKA, regardless of the rotation of care providers.
PMCID: PMC4258486  PMID: 25505701
Knee; Arthroplasty; Clinical pathways; Health care providers
13.  Brentuximab vedotin for relapsed or refractory CD30+ Hodgkin lymphoma: a multicenter analysis from Asia 
OncoTargets and therapy  2014;7:1717-1722.
Brentuximab vedotin (SGN-35), an anti-cluster of differentiation (CD)-30 antibody conjugated to the anti-tubulin agent monomethyl auristatin E, has demonstrated promising efficacy and tolerability in relapsed and heavily treated Hodgkin lymphoma (HL). In this study, we report the Asian experience with brentuximab vedotin in patients with relapsed or refractory CD30-positive (CD30+) HL.
This is an observational, multicenter, retrospective study. Between October 2011 and June 2013, a total of 22 patients were treated with brentuximab vedotin under a named patient program in Asia. Patients received a 30 min infusion of brentuximab vedotin at a dose of 1.8 mg/kg of body weight every 3 weeks.
Four patients (18.2%) showed a complete response, and the overall response rate was 72.7%. The median duration of response was 4.4 months (range 1.0–17.4). The median progression-free survival was 5.7 months, and the median overall survival has not yet been reached. The 1-year expected survival rate was 67.2%. The most common grade 3/4 adverse events were neutropenia (n=7; 31.8%). No patients experienced grade 3/4 sensory neuropathy.
These results confirm that brentuximab vedotin as a single agent is also effective and well tolerated when used in Asian patients with relapsed and refractory CD30+ HL.
PMCID: PMC4196794  PMID: 25328405
Asian; efficacy; safety
14.  Comparison of the Freiburg and Charlson Comorbidity Indices in Predicting Overall Survival in Elderly Patients with Newly Diagnosed Multiple Myeloma 
BioMed Research International  2014;2014:437852.
Multiple myeloma occurs primarily in elderly patients. Considering the high prevalence of comorbidities, comorbidity is an important issue for the management of myeloma. However, the impact of comorbidity on clinical outcomes has not been fully investigated. We retrospectively analyzed patients with newly diagnosed myeloma. Comorbidities were assessed based on the Charlson comorbidity index (CCI) and the Freiburg comorbidity index (FCI). The CCI is a summary measure of 19 comorbid conditions. FCI is determined by performance status, renal impairment, and lung disease. This study included 127 patients with a median age of 71 years. Approximately half of the patients had additional disorders at the time of diagnosis, and diabetes mellitus was the most frequent diagnosis (18.9%). The most significant factors for prognosis among patient-related conditions were a history of solid cancer and performance status (ECOG ≥ 2). The FCI score was divided into 3 groups (0, 1, and 2-3), and the CCI score was divided into 2 groups (2-3 and ≥4). FCI was a strong prognostic tool for OS (P > 0.001) and predicted clinical outcome better than CCI (P = 0.059). In conclusion, FCI was more useful than CCI in predicting overall survival in elderly patients with myeloma.
PMCID: PMC4119725  PMID: 25114902
15.  Changes in Osteoblastic Activity in Patient Who Received Bortezomib as Second Line Treatment for Plasma Cell Myeloma: A Prospective Multicenter Study 
BioMed Research International  2014;2014:245247.
We conducted a prospective multicenter study identifying the role of bortezomib in patients with relapsed or refractory plasma cell myeloma (PCM) in bone resorption and formation via bone turnover markers. A total of 104 patients received at least 1 cycle of bortezomib. Most of them had advanced disease (n = 89). Among them, 75 patients completed 4 cycles of treatment. Most of the patients (81.7%) were treated in combination with steroid. After the 4th cycle treatment, 47 of 75 patients achieved CR, nCR, VGPR, and PR (64.4%), while 26 patients achieved less than PR (35.6%). The proportion of patients who achieved ≥ PR increased as patients received more treatment cycles, reaching 90% after the 8th cycle. DKK-1 levels decreased significantly posttreatment. Bone formation markers (bALP and OC) and osteoclast regulator such as sRANKL also decreased significantly. These findings were observed primarily in patients who received steroid and who had a longer disease duration. While sRANKL demonstrated significant reduction posttreatment, osteoprotegerin (OPG) level did not significantly change posttreatment, resulting in a decreased sRANKL/OPG ratio (P = 0.037). In conclusion, our clinical data suggest that treatment with bortezomib and steroid may rearrange the metabolic balance between osteoblast and osteoclast activities in PCM.
PMCID: PMC4094867  PMID: 25050331
16.  R-CHOP chemoimmunotherapy followed by autologous transplantation for the treatment of diffuse large B-cell lymphoma 
Blood research  2014;49(2):107-114.
We investigated factors that influence outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab combined with the CHOP regimen (R-CHOP) followed by upfront autologous stem cell transplantation (Auto-SCT).
We retrospectively evaluated survival differences between subgroups based on the age-adjusted International Prognostic Index (aaIPI) and revised-IPI (R-IPI) at diagnosis, disease status, and positron emission tomographic/computerized tomographic (PET/CT) status at transplantation in 51 CD20-positive DLBCL patients treated with R-CHOP followed by upfront Auto-SCT.
Patients had either stage I/II bulky disease (5.9%) or stage III/IV disease (94.1%). The median patient age at diagnosis was 47 years (range, 22-66 years); 53.3% and 26.7% had high-intermediate and high risks according to aaIPI, respectively. At the time of Auto-SCT, 72.5% and 27.5% experienced complete (CR) and partial remission (PR) after R-CHOP, respectively. The median time from diagnosis to Auto-SCT was 7.27 months (range, 3.4-13.4 months). The 5-year overall (OS) and progression-free survival (PFS) were 77.3% and 72.4%, respectively. The 5-year OS and PFS rates according to aaIPI, R-IPI, and PET/CT status did not differ between the subgroups. More importantly, the 5-year OS and PFS rates of the patients who achieved PR at the time of Auto-SCT were not inferior to those of the patients who achieved CR (P=0.223 and 0.292, respectively).
Survival was not influenced by the aaIPI and R-IPI at diagnosis, disease status, or PET/CT status at transplantation, suggesting that upfront Auto-SCT might overcome unfavorable outcomes attributed to PR after induction chemoimmunotherapy.
PMCID: PMC4090331  PMID: 25025012
Diffuse large B-cell lymphoma; Hematopoietic stem cell transplantation; Autologous transplantation; Rituximab; Survival analysis
17.  Mantle cell lymphoma: a model for risk-adapted treatment approach 
Blood research  2014;49(1):1-2.
PMCID: PMC3974950  PMID: 24724057
18.  Delayed plastic responses to anodal tDCS in older adults 
Despite the abundance of research reporting the neurophysiological and behavioral effects of transcranial direct current stimulation (tDCS) in healthy young adults and clinical populations, the extent of potential neuroplastic changes induced by tDCS in healthy older adults is not well understood. The present study compared the extent and time course of anodal tDCS-induced plastic changes in primary motor cortex (M1) in young and older adults. Furthermore, as it has been suggested that neuroplasticity and associated learning depends on the brain-derived neurotrophic factor (BDNF) gene polymorphisms, we also assessed the impact of BDNF polymorphism on these effects. Corticospinal excitability was examined using transcranial magnetic stimulation before and following (0, 10, 20, 30 min) anodal tDCS (30 min, 1 mA) or sham in young and older adults. While the overall extent of increases in corticospinal excitability induced by anodal tDCS did not vary reliably between young and older adults, older adults exhibited a delayed response; the largest increase in corticospinal excitability occurred 30 min following stimulation for older adults, but immediately post-stimulation for the young group. BDNF genotype did not result in significant differences in the observed excitability increases for either age group. The present study suggests that tDCS-induced plastic changes are delayed as a result of healthy aging, but that the overall efficacy of the plasticity mechanism remains unaffected.
PMCID: PMC4047559  PMID: 24936185
aging; plasticity; transcranial direct current stimulation; transcranial magnetic stimulation; brain-derived neurotrophic factor
19.  Extranodal natural killer/T-cell lymphoma involving the gastrointestinal tract: analysis of clinical features and outcomes from the Asia Lymphoma study group 
The gastrointestinal (GI) tract is one of the most common extranasal sites in extranodal NK/T-cell lymphoma (ENKTL). However, data regarding ENKTL involving the GI tract are relatively scarce. Thus, we performed a multicenter, multinational retrospective study to analyze clinical features and treatment outcomes of ENKTL involving the GI tract.
Patients and methods
Patients with ENKTL involving the GI tract diagnosed in twelve participating centers between 1991 and 2012 were retrospectively analyzed from five Asian countries.
The analysis of 81 patients with ENKTL involving the GI tract revealed that more than 60% of patients presented as advanced disease with B symptoms. 55 patients (68%) had GI manifestations including abdominal pain (n = 26, 32%), GI tract bleeding (n = 17, 21%) and bowel perforation (n = 12, 15%). The most common GI site was the small intestine, including the jejunum and ileum (n = 57, 70.3%). There were 34 patients (42%) who received systemic chemotherapy while 33 patients (41%) underwent surgery plus chemotherapy. However, 35 patients (43%) died due to disease progression, and treatment-related mortality including sepsis occurred in 17 patients (21%). Thus, the median overall survival was 7.8 months (95% Confidence interval: 3.9 – 11.7 months). Patients who could undergo surgery plus chemotherapy showed a trend of better survival than those treated with chemotherapy alone.
Overall, the data indicated that ENKTL involving the GI tract has a dismal prognosis despite active treatment including chemotherapy and surgery. Thus, more effective treatment strategies are required for this disease entity.
PMCID: PMC4225665  PMID: 24238138
Extranodal NK/T-cell lymphoma; Gastrointestinal tract; Prognosis
21.  Cervical Lymphadenitis Caused by Group D Non-typhoidal Salmonella Associated with Concomitant Lymphoma 
Infection & Chemotherapy  2013;45(2):234-238.
Non-typhoidal Salmonella species are important foodborne pathogens that can cause gastroenteritis, bacteremia, and subsequent focal infections. Non-typhoidal salmonellosis is problematic, particularly in immunocompromised hosts. Any anatomical site can be affected by this pathogen via hematogenous seeding and may develop local infections. However, cervical lymphadenitis caused by non-typhoidal Salmonella species is rarely reported. Herein, we have reported a case of cervical lymphadenitis caused by group D non-typhoidal Salmonella associated with lymphoma.
PMCID: PMC3780951  PMID: 24265973
Lymphadenitis; Salmonella; Lymphoma
23.  EBV-Positive T/NK-Cell Lymphoproliferative Disease of Childhood 
Korean Journal of Pathology  2013;47(2):137-147.
Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH), EBV-positive systemic T-cell lymphoproliferative disease (STLPD) of childhood, and chronic active EBV (CAEBV) infection may develop after primary EBV infection. This study reviewed the clinicopathological spectrum of EBV-associated T- and natural killer (NK)-cell LPD, including STLPD and CAEBV infection, with an analysis of T-cell clonality.
Clinicopathological features of seven patients with EBV-associated HLH or STLPD and 12 patients with CAEBV infection were reviewed. Immunohistochemical staining and a T-cell receptor (TCR) gene rearrangement study were performed.
STLPD and EBV-positive HLH showed significantly overlapping clinicopathological findings. One patient with STLPD and one patient with EBV-positive HLH demonstrated moderate to severe atypia of the infiltrating lymphocytes, whereas the remaining patients lacked significant atypia. Twelve patients had CAEBV infection, four of whom suffered mosquito-bite hypersensitivity, five showed NK lymphocytosis, and one suffered hydroa vacciniforme. Infiltrating lymphocytes were predominantly small and devoid of atypia. Hemophagocytic histiocytosis was found in seven of 11 patients. Monoclonality was detected in three (50%) of the six patients with successful TCR gene analysis.
EBV-positive HLH and STLPD share similar clinicopathological findings and may constitute a continuous spectrum of acute EBV-associated T- or NK-cell proliferative disorders. The distinction of EBV-positive T-cell LPD from EBV-positive HLH may be difficult during routine diagnoses because of the technical limitations of clonality assessment.
PMCID: PMC3647126  PMID: 23667373
Epstein-Barr virus infections; Lymphoma, T-cell; Killer cells, natural; Lymphoproliferative disorders; Clonality
24.  Activated Epidermal Growth Factor Receptor is Associated with Cyclooxygenase-2 and Clinical Outcome in Smoking-Related Non-Small Cell Lung Cancer 
EGFR dysregulation occurs in both smoking-related and non-smoking-related NSCLC. In non-smoking-related NSCLC, dysregulation results primarily from mutation of EGFR while in smoking-related NSCLC the molecular mechanisms are incompletely understood. Activation of EGFR is associated with auto-phosphorylation of the receptor (p-EGFR) and has been shown in vitro to result in upregulation of cyclo-oxygenase 2 (COX-2). We sought to determine the relationship between activated EGFR (p-EGFR) and COX-2 in vivo and whether these are associated with clinical outcome in smoking-related NSCLC.
The expression of p-EGFR, EGFR, and COX-2 was studied by immunohistochemistry in 77 surgically-resected stage I/II non-small cell lung cancers (NSCLCs) from smokers. EGFR mutational status was determined by sequencing exons 18–21. Correlation of expression with clinical outcome and other biomarkers, including Ki-67 and microvessel density (MVD), was also examined.
One tumor sample had EGFR mutation (L858R). EGFR overexpression, defined as membranous staining in more than 10% of cancer cells, was found in 37 patients (48.1%). Cytoplasmic staining of p-EGFR in at least 5% of cancer cells was found in 22 of 77 (28.6%) of tumor samples. Forty-five patients (58.4%) showed COX-2 overexpression (cytoplasmic granular staining in more than 10% of cancer cells). Expression of p-EGFR was significantly associated with COX-2 overexpression (p = 0.047), and showed a modest relationship with EGFR overexpression and high Ki-67 (p = 0.087, and 0.092, respectively). COX-2 overexpression also had a significant association with high Ki-67 expression (p = 0.011). No other significant associations were found with Ki-67 or MVD. Expression of p-EGFR was significantly related with a short disease free survival (p = 0.045) but not overall survival. However, neither EGFR nor COX-2 overexpression was associated with prognosis (p > 0.05).
In smoking-related NSCLC, activation of EGFR as reflected by receptor autophosphorylation is significantly associated with COX-2 overexpression and high proliferative activity in lung cancer cells. p-EGFR may better predict increased malignant potential and worse prognosis of early stage NSCLC than EGFR overexpression alone. Therapeutic strategies targeting both EGFR and COX-2 may be needed in smoking-related NSCLC.
PMCID: PMC3608693  PMID: 19235531
lung cancer; epidermal growth factor receptor; cyclo-oxygenase; survival
25.  Extranodal natural killer/T-cell lymphoma with long-term survival and repeated relapses: does it indicate the presence of indolent subtype? 
The Korean Journal of Hematology  2012;47(3):202-206.
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.
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.
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.
Our observations suggest that the clinical behavior of some extranodal NK/T-cell lymphoma patients differs from the typical clinical course.
PMCID: PMC3464337  PMID: 23071475
Extranodal NK/T-cell lymphoma; Relapse; Survival; Indolent

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