Clinical study of chemotherapy-related cognitive impairment in patients with non-Hodgkin lymphoma

BACKGROUND Chemotherapy for malignant tumors can cause brain changes and cognitive impairment,leading to chemotherapy-induced cognitive impairment(CICI).Current research on CICI has focused on breast cancer and Hodgkin’s lymphoma.Whether patients with non-Hodgkin’s lymphoma(NHL)undergoing chemo-therapy have cognitive impairment has not been fully investigated.therapy have cognitive impairment has not been fully investigated.AIM To investigate whether NHL patients undergoing chemotherapy had cognitive impairments.METHODS The study included 100 NHL patients who were required to complete a compre-hensive psychological scale including the Brief Psychiatric Examination Scale(MMSE)at two time points:before chemotherapy and within 2 wk of two chemo-therapy courses.A language proficiency test(VFT),Symbol Number Pattern Test(SDMT),Clock Drawing Test(CDT),Abbreviated Daily Cognition Scale(ECog-12),Prospective and Retrospective Memory Questionnaire,and Karnofsky Perfor-mance Status were used to assess cognitive changes before and after chemo-therapy.RESULTS The VFT scores for before treatment(BT)and after treatment(AT)groups were 45.20±15.62,and 42.30±17.53,respectively(t-2.16,P<0.05).The CDT scores were 8(3.5-9.25)for BT and 7(2.5-9)for AT groups(Z-2.1,P<0.05).Retrospective memory scores were 13.5(9-17)for BT and 15(13-18)for AT(Z-3.7,P<0.01).The prospective memory scores were 12.63±3.61 for BT and 14.43±4.32 for AT groups(t-4.97,P<0.01).The ECog-12 scores were 1.71(1.25-2.08)for BT and 1.79(1.42-2.08)for AT groups(Z-2.84,P<0.01).The SDMT and MMSE values did not show a significant difference between BT and AT groups.CONCLUSION Compared to the AT group,the BT group showed impaired language,memory,and subjective cognition,but objec-tive cognition and execution were not significantly affected.

Primary Non-Hodgkin’s Malignant Lymphoma of the Uterus at the Reference Hospital of Maradi/Niger: A Case Report

Malignant non-Hodgkins lymphoma (MHNL) of the uterus is uncommon. We report a case diagnosed on the basis of histologic and immunohistochemical studies of a hysterectomy specimen induced by a very painful pelvic mass in a 50-year-old patient with no previous history of the disease. It was classified as Ann Arbor IV Bb after imaging, given the medullary infiltration and signs of clinical and biological evolutivity: the patient had received two courses of chemotherapy, CHOP protocol. She died 23 days after the second treatment due to a hypertensive crisis.

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

The role of radiotherapy in patients with refractory Hodgkin’s lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors

Background:Approximately 10%–30%of patients with Hodgkin’s lymphoma(HL)experience relapse or refractory(R/R)disease after first-line standard therapy.Brentuximab vedotin(BV)and immune checkpoint inhibitors(ICIs)have important roles in the salvage treatment of R/R HL.However,subsequent treatment for HL refractory to BV and/or ICI treatment is challenging.Methods:We retrospectively analyzed patients in two institutions who had R/R HL,experienced BV or ICI treatment failure,and received radiotherapy(RT)thereafter.The overall response rate(ORR),duration of response(DOR),progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Overall,19 patients were enrolled.First-line systemic therapy comprised doxorubicin,bleomycin,vinblastine,and dacarbazine(ABVD,84.2%);AVD plus ICIs(10.5%);and bleomycin,etoposide,doxorubicin,cyclophosphamide,vincristine,procarbazine,and prednisone(BEACOPP,5.3%).After first-line therapy,15(78.9%)and four patients(21.1%)had refractory disease and relapsed,respectively.After R/R HL diagnosis,six(31.6%),two(10.5%),and 11(57.9%)patients received BV and ICIs concurrently,BV monotherapy,and ICI monotherapy,respectively.All patients received intensity-modulated RT(n=12,63.2%)or volumetric modulated arc therapy(VMAT;n=7,36.8%).The ORR as well as the complete response(CR)rate was 100%;the median DOR to RT was 17.2 months(range,7.9–46.7 months).Two patients showed progression outside the radiation field;one patient had extensive in-field,out-of-field,nodal,and extranodal relapse.With a median follow-up time of 16.2 months(range,9.2–23.2 months),the 1-year PFS and OS were 84.4%and 100%,respectively.PFS was associated with extranodal involvement(P=0.019)and gross tumor volume(P=0.044).All patients tolerated RT well without adverse events of grade≥3.Conclusion:RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Endoscopic features and prognoses of mantle cell lymphoma with gastrointestinal involvement

AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival (EFS), and overall survival (OS) of those patients.RESULTS: Of the 35 patients, GI involvement in the esophagus, stomach, and duodenum was found in 2 (5.7%), 26 (74.3%), and 12 (34.3%) patients, respectively. Twenty-one of the 35 patients underwent colonoscopy; among them, GI involvement in the ileum, cecum, colon, and rectum was found in 10 (47.6%), 3 (14.3%), 12 (57.1%), and 10 (47.6%), respectively. Various lesions, such as superficial, protruded, fold thickening, or ulcerative, were found in the stomach, whereas multiple lymphomatous polyposis (MLP) was dominant from the duodenum to the rectum. Twelve patients were treated with a hyper-CVAD/MA regimen, and they had better OS (3-year rate, 88.3% vs 46.4%, P < 0.01) and better EFS (3-year rate, 66.7% vs 33.8%, P < 0.05) than the remaining 23 patients who were not treated with this regimen. CONCLUSION: MLP was a representative form of intestinal involvement, whereas a variety of lesions were found in the stomach. The hyper-CVAD/MA regimen may improve survival in these patients.

Composite diffuse large B-cell lymphoma and classical Hodgkin's lymphoma of the stomach:Case report and literature review

The combination of classical Hodgkin’s lymphoma(cHL)and non-Hodgkin lymphoma coexisting in the same patient is not common,especially in one extranodal location.Here we present a rare case of composite diffuse large B-cell lymphoma(DLBCL)and cHL occurring simultaneously in the stomach of a 53-year-old female who presented with upper abdominal discomfort and gas pain.Surgery was performed and the disease was diagnosed pathologically as composite lymphoma of DLBCL and cHL using hematoxylin-eosin and immunohistochemical staining.Epstein-Barr virus(EBV)infection was not detected by in situ hybridization for EBV-encoded RNA or immunohistochemistry for EBV latent membrane protein-1.Polymerase chain reaction analysis from the two distinct components of the tumor demonstrated clonal immunoglobulinκlight chain gene rearrangements.The patient died approximately 11 mo after diagnosis in spite of receiving eight courses of the CHOP and two courses of the rituximab-CHOP(RCHOP) chemotherapy regimen.This case report showed that the two distinct components,DLBCL and cHL,appeared to originate from the same clonal progenitor cell,and that EBV infection was not essential for transformation during the course of tumorigenesis.

Primary pancreatic lymphoma: Report of six cases

AIM： To heighten recognition of primary pancreatic lymphoma （PPL） in clinical practice. METHODS： A retrospective review of the clinical presentation, imaging characteristics and pathological features of PPL patients were presented, as well as their diagnosis and treatment, in combination with literature review. RESULTS： Histological diagnosis was made in four patients by surgery and in two patients by EUS-FNA. The six PPL patients （5 males and 1 female; age range, 16-65 years; mean age, 46 years） had the duration of symptoms for two weeks to three months. The primary presenting symptoms, though not characteristic, were abdominal pain, abdominal masses, weight loss, jaundice, nausea and vomiting. One of the patients developed acute pancreatitis. In one patient, the level of serum CA19-9 was 76.3 μg/L. Abdominal CT scan showed that three of the six tumors were located in the head of pancreas, two in the body and tail, and one throughout the pancreas. Diameter of the tumors in the pancreas in four cases was more than 6 cm, with homogeneous density and unclear borders. Enhanced CT scan showed that only the tumor edges were slightly enhanced. The pancreatic duct was irregularly narrowed in two cases whose tumors were located in the pancreatic head and body, in which endoscopic retrograde cholangiopancreatography （ERCP） showed that the proximal segment was slightly dilated. Two patients underwent Whipple operation, one patient underwent pancreatectomy, and another patient underwent operative biliary decompression. PPL was in stage Ⅰ E in 2 patients and in stage Ⅱ E in 4 patients according to the Ann Arbor classification system. The diagnosis of B-cell non-Hodgkin＇s lymphoma was made in all patients histopathologically. All six patients underwent systemic chemotherapy, one of whom was also treated with gamma radiometry. One patient died two weeks after diagnosis, two patients lost follow-up, two patients who received chemotherapy survived 49 and 37 mo, and the remaining patient is still alive 21 mo, after diagnosis and treatment. CONCLUSION： PPL is a rare form of extranodal lymphoma originating from the pancreatic parenchyma. Clinical and imaging findings are otherwise not specific in the differentiation of pancreatic lymphoma and pancreatic cancer, which deserves attention. EUS-guided fine-needle aspiration （EUS-FNA） of the pancreas requires experienced cytopathologists as well as advanced immunohistochemical assays to obtain a final diagnosis on a small amount of tissue. Surgery and adjuvant chemotherapy or radiotherapy can produce fairly good outcomes.

A case of primary isolated non-Hodgkin’s lymphoma of the esophagus in an immunocompetent patient

Primary non-Hodgkin’s lymphoma of the esophagus is a rare disease.A case of primary isolated nonHodgkin’s lymphoma of the esophagus in a 77-yearold man without acquired immunodeficiency syndrome is presented.We describe the clinical features and the imaging findings(barium swallow,endoscopic ultrasonography and CT)of a biopsy proven B-cell lymphoma with diffuse transmural involvement of the esophagus wall,which was discovered incidentally.We also briefly review the literature.

Primary gastric non-Hodgkin lymphomas:Recent advances regarding disease pathogenesis and treatment

Primary gastric lymphomas(PGLs)are distinct lymphoproliferative neoplasms described as heterogeneous entities clinically and molecularly.Their main histological types are diffuse large B-cell lymphoma(DLBCL)or mucosaassociated lymphoma tissue.PGL has been one of the main fields of clinical research of our group in recent years.Although gastric DLBCLs are frequent,sufficient data to guide optimal care are scarce.Until today,a multidisciplinary approach has been applied,including chemotherapy,surgery,radiotherapy or a combination of these treatments.In this minireview article,we provide an overview of the clinical manifestations,diagnosis and staging of these diseases,along with their molecular pathogenesis and the most important related clinical published series.We then discuss the scientific gaps,perils and pitfalls that exist regarding the aforementioned studies,in parallel with the unmet need for future research and comment on the proper methodology for such retrospective studies.Aiming to fill this gap,we retrospectively evaluated the trends in clinical presentation,management and outcome among 165 patients with DLBCL PGL who were seen in our institutions in 1980-2014.The study cohort was divided into two subgroups,comparing the main 2 therapeutic options[cyclophosphamide doxorubicin vincristine prednisone(CHOP)vs rituximab-CHOP(R-CHOP)].A better outcome with immunochemotherapy(R-CHOP)was observed.In the next 2 mo,we will present the update of our study with the same basic conclusion.

Positron emission tomography/computerized tomography in the evaluation of primary non-Hodgkin's lymphoma of prostate

Primary malignant lymphoma of the prostate is exceedingly rare.Here we report a case of a 65-year-old man who presented with increased urinary frequency,urinary urgency,and urinary incontinence for two years.Benign prostatic hypertrophy was suspected at primary impression.Ultrasound revealed a hypoechoic lesion of the prostate.The total serum prostate-specific antigen was within normal range.Positron emission tomography/computerized tomography(PET/CT)showed a hypermetabolic prostatic lesion.Prostate biopsy was consistent with a non-germinal center diffuse large B cell lymphoma.There was complete remission of the prostatic lesion following six cycles of chemotherapy as shown on the second PET/CT imaging.18F-fluoro-deoxy glucose PET/CT is not only a complement to conventional imaging,but also plays a significant role in the diagnosis and evaluation of treatment response of prostatic lymphoma.

Primary early-stage intestinal and colonic non-Hodgkin's lymphoma: Clinical features, management, and outcome of 37 patients

AIM： To analyze the clinical features, management, and outcome of treatment of patients with primary intestinal and colonic non-Hodgkin＇s lymphoma （PICL）. METHODS： A retrospective study was performed in 37 patients with early-stage PICL who were treated in our hospital from 1958 to 1998. Their clinical features, management, and outcome were assessed. Prognostic factors for survival were analyzed by univariate analysis using the Kaplan-Meier product-limit method and log-rank test. RESULTS： Twenty-five patients presented with Ann Arbor stage Ⅰ PICL and 12 with Ann Arbor stage Ⅱ PICL. Thirty-five patients underwent surgery （including 31 with complete resection）, 22 received postoperative chemotherapy or radiotherapy or both. Two patients with rectal tumors underwent biopsy and chemotherapy with or without radiotherapy. The 5- and 10-year overall survival （OS） rates were 51.9% and 44.5%. The corresponding diseasefree survival （DIS） rates were 42.4% and 37.7%. In univariate analysis, multiple-modality treatment was associated with a better DFS rate compared to single treatment （P= 0.001）. While age, tumor size, tumor site, stage, histology, or extent of surgery were not associated with OS and DFS, use of adjuvant chemotherapy significantly improved DFS （P = 0.031） for the 31 patients who underwent complete resection. Additional radiotherapy combined with chemotherapy led to a longer survival than chemotherapy alone in six patients with gross residual disease after surgery or biopsy.CONCLUSION： Combined surgery and chemotherapy is recommended for treatment of patients with PICL, Additional radiotherapy is needed to improve the outcome of patients who have gross residual disease after surgery.

Potential model for differential diagnosis between Crohn's disease and primary intestinal lymphoma

AIM To evaluate the usefulness of different parameters to differentiate Crohn's disease(CD) from primary intestinal lymphoma(PIL).METHODS The medical records of 85 patients with CD and 56 patients with PIL were reviewed retrospectively. Demographic, clinical, laboratory, endoscopic, and computed tomographic enterography(CTE) parameters were collected. The univariate value of each parameter was analyzed. A differentiation model was established by pooling all the valuable parameters. Diagnostic efficacy was analyzed, and a receiver operating characteristic(ROC) curve was plotted.RESULTS The demographic and clinical parameters that showed significant values for differentiating CD from PIL included age of onset, symptom duration, presence of diarrhea, abdominal mass, and perianal lesions(P < 0.05). Elevated lactate dehydrogenase and serum β2-microglobulin levels suggested a PIL diagnosis(P < 0.05). The endoscopic parameters that showed significant values for differentiating CD from PIL included multiple-site lesions, longitudinal ulcer, irregular ulcer,and intraluminal proliferative mass(P < 0.05). The CTE parameters that were useful in the identification of the two conditions included involvement of ≤ 3 segments, circular thickening of the bowel wall, wall thickness > 8 mm, aneurysmal dilation, stricture with proximal dilation, "comb sign", mass showing the "sandwich sign", and intussusceptions(P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the differentiation model were 91.8%, 96.4%, 93.6%, 97.5%, and 88.5%, respectively. The cutoff value was 0.5. The area under the ROC curve was 0.989.CONCLUSION The differentiation model that integrated the various parameters together may yield a high diagnostic efficacy in the differential diagnosis between CD and PIL.

Secondary pancreatic involvement by a diffuse large B-cell lymphoma presenting as acute pancreatitis

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. More than 50% of patients have some site of extra-nodal involvement at diagnosis, including the gastrointestinal tract and bone marrow. However, a diffuse large B-cell lymphoma presenting as acute pancreatitis is rare. A 57-year-old female presented with abdominal pain and matted lymph nodes in her axilla. She was admitted with a diagnosis of acute pancreatitis. Abdominal computed tomography (CT) scan showed diffusely enlarged pancreas due to infiltrative neoplasm and peripancreatic lymphadenopathy. Biopsy of the axillary mass revealed a large B-cell lymphoma. The patient was classified as stage Ⅳ, based on the Ann Arbor Classification, and as having a high-risk lymphoma, based on the International Prognostic Index. She was started on chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). Within a week after chemotherapy, the patient’s abdominal pain resolved. Follow-up CT scan of the abdomen revealed a marked decrease in the size of the pancreas and peripancreatic lymphadenopathy. A literature search revealed only seven cases of primary involvement of the pancreas in B-cell lymphoma presenting as acute pancreatitis. However, only one case of secondary pancreatic involvement by B-cell lymphoma presenting as acute pancreatitis has been published. Our case appears to be the second report of such a manifestation. Both cases responded well to chemotherapy.

Diagnosis of the jejunoileal lymphoma by double-balloon endoscopy

AIM:To investigate the feasibility of double-balloon endoscopy(DBE) to detect jejunoileal lymphoma,compared with fluorodeoxyglucose positron emission tomography(FDG-PET).METHODS:Between March 2004 and January 2011,we histologically confirmed involvement of malignant lymphoma of the jejunoileum in 31 patients by DBE and biopsy.In 20 patients of them,we performed with FDGPET.We retrospectively reviewed the records of these 20 patients.Their median age was 64 years(range 50-81).In the 20 patients,the pathological diagnosis of underlying non-Hodgkin's lymphoma(NHL) comprised follicular lymphoma(FL,n = 12),diffuse large B cell lymphoma(DLBCL,n = 4),mantle cell lymphoma(MCL,n = 2),enteropathy associated T cell lymphoma(ETL,n = 1) and anaplastic large cell lymphoma(ALCL,n = 1).RESULTS:Ten cases showed accumulation by FDGPET(50%).FDG-PET was positive in 3 of 12 FL cases(25%) while in 7 of 8 non-FL cases(88%,P < 0.05).Intestinal FL showed a significantly lower rate of positive FDG-PET,in comparison with other types of lymphoma.Cases with endoscopically elevated lesions(n = 10) showed positive FDG-PET in 2(20%),but those with other type NHL did in 8 of 10(80%,P < 0.05).When the cases having elevated type was compared with those not having elevated type lesion,the number of cases that showed accumulation of FDG was significantly smaller in the former than in the latter.CONCLUSION:In a significant proportion,small intestinal involvement cannot be pointed out by FDG-PET.Especially,FL is difficult to evaluate by FDG-PET but essentially requires DBE.

Lymphomatous involvement of gastrointestinal tract: Evaluation by positron emission tomography with ^(18)F-fluorodeoxyglucose

AIM： To demonstrate the ^18F-fluorodeoxyglucose positron emission tomography （18F-FDG PET） findings in patients with non-Hodgkin＇s lymphoma （NHL） involving the gastrointestinal （GI） tract and the clinical utility of modality despite of the known normal uptake of FDG in the GI tract. METHODS： Thirty-three patients with biopsy-proven gastrointestinal NHL who had undergone FDG-PET scan were induded. All the patients were injected with 10-15 mCJ FDG and scanned approximately 60 min later with a CTI/ Siemens HR （＋） PET scanner. PET scans were reviewed and the maximum standard uptake value （SUVmax） of the lesions was measured before and after the treatment, if data were available and compared with histologic diagnoses. RESULTS： Twenty-five patients had a high-grade lymphoma and eight had a low-grade lymphoma. The stomach was the most common site of the involvement （20 patients）. In high-grade lymphoma, PET showed focal nodular or diffuse hypermetabolic activity. The average SUVmax＋SD was 11.58±5.83. After the therapy, the patients whose biopsies showed no evidence of lymphoma had a lower uptake without focal lesions. The SUVmax＋SD decreased from 11.58±5.83 to 2.21± 0.78. in patients whose post-treatment biopsies showed lymphoma, the SUVmax＋SD was 9.42±6.27. Low-grade follicular lymphomas of the colon and stomach showed diffuse hypermetabolic activity in the bowel wall （SUVmax= 8.2 and 10.3, respectively）. The SUVmax was 2.02-3.8 （mean 3.02） in the stomach lesions of patients with MALT lymphoma. CONCLUSION： ^18F-FDG PET contributes to the diagnosis of high-grade gastrointestinal non-Hodgldn＇s lymphoma, even when there is the normal background FDG activity. Furthermore, the SUV plays a role in evaluating treatment response. Low-grade NHL demonstrates FDG uptake but at a lesser intensity than seen in high-grade NHL.

AIDS-associated plasmablastic lymphoma presenting as a poorly differentiated esophageal tumor: A diagnostic dilemma

Plasmablastic lymphoma (PBL) is a rare form of diffuse large B-cell lymphoma characterized by weak/absent expression of conventional B-cell markers and strong expression of plasma cell markers. It is strongly associated with human immunodeficiency virus (HIV) and Epstein Barr virus infection, and shows an unusual tropism to the oral cavity. Herein we describe a patient with AIDS who presented with weight loss and dysphagia owing to a large gastroesophageal mass. His radiographic and endoscopic findings and long history of cigarette consumption suggested carcinoma. Biopsy demonstrated a poorly differentiated tumor stained negatively to routine lymphoid markers including CD20. However, gene rearrangement studies confirmed a B-cell process and a more detailed immunohistochemical analysis revealed the cells stained positively for CD138 (plasma cell antigen). These findings were diagnostic of PBL. Our report reviews the wide differential diagnosis of PBL and underscores the importance of a broad array of viral and molecular studies needed to establish this diagnosis.

Molecular markers(PECAM-1,ICAM-3,HLA-DR)determine prognosis in primary non-Hodgkin's gastric lymphoma patients

AIM： To investigate the prognostic significance of PECAM-1, ICAM-3 and HLA-DR antigens in patients with primary non-Hodgkin＇s gastric lymphoma. METHODS： We immunohistochemically studied PECAM-1, ICAM-3 and HLA-DR antigen expression in 36 B-cell MALT-type primary gastric lymphoma patients. Ten non-malignant and ten healthy gastric tissue specimens were used as controls. Clinicopathological and survival data were correlated with the staining results. RESULTS： HLA-DR antigen expression was detected in 33 gastric lymphoma patients （91.7%） and 6 nonmalignant patients （54.5%）. PECAM-1 stained tumor cells of 10 patients （27.8%）, endothelial cells of 9 patients （25%） and inflammatory infiltrate of 4 patients （40%） with benign gastric disease. ICAM-3 expression was observed on the tumor cells of 17 patients （47.2%）, while 5 non-malignant patients （50%） were stained positive as well. None of the healthy controls was stained for any of the genes studied. In the multivariate analysis, HLA-DR antigen and PECAM-1 were proved to be statistically significant independent prognostic factors associated with a favourable and an unfavourable prognosis respectively （P= 0.009 and P= 0.003）. In the univariate analysis, PECAM-1（＋）/ICAM-3（-） and HLA-DR（-）/ICAM-3（-） patients exhibited a significantly decreased overall survival compared to those with the exactly opposite gene expression patterns （P=0.0041 and P= 0.0091, respectively）. Those patients who were HLA-DR（＋ ）/ICAM-3（＋ ）/PECAM-I（-） （n = 8） had a significantly higher survival rate compared to the rest of the group （n = 24） （P= 0.0289）. CONCLUSION： PECAM-1, ICAM-3 and HLA-DR are representative markers of tumor expansion potential and host immune surveillance respectively. Their combined use may help us to identify high-risk patients who could benefit from more aggressive therapeutic protocols.

Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin＇s lymphoma

Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.

Simultaneous occurrence of a hepatocellular carcinoma and a hepatic non-Hodgkin's lymphoma infi ltration

To investigate the simultaneous occurrence of hepatocellular carcinoma and non-Hodgkin's lymphoma, we report the case of a 70 year old patient with a primary diagnosis of non-Hodgkin's lymphoma in 2002. In a routine follow up investigation of his chronic lymphocytic leukemia a newly detected mass in the Couinaud's segments 2 and 3 was found. No hepatitis C virus or hepatitis B virus infection or cirrhosis was evident. After laparoscopic segmentectomy the histological examination revealed a hepatocellular carcinoma. While the relation between liver parenchyma damages and hepatocellular carcinoma or non-Hodgkin's lymphoma is well known, only a few publications have focused on the coexistence of hepatocellular carcinoma and non-Hodgkin's lymphoma. With this case we demonstrate the coexistence of these diseases without having a pre- damaged liver parenchyma.

Progressively Enlarging Goiter:Case Reports of Primary Thyroid Lymphoma and Literature Review

Primary thyroid lymphoma(PTL)is an exceptionally rare and highly aggressive potentially curable malignant disease.We report three typical cases of PTL referred to our hospital.All three cases had long history of Hashimoto’s thyroiditis,and presented with progressively enlarging neck mass.The first two cases were confirmed by surgical biopsy to be diffuse large B cell lymphoma,and received radiotherapy combined with chemotherapy,or received only chemotherapy.The third case was confirmed by core needle biopsy to be mucosa-associated lymphoid tissue lymphoma,and received radiotherapy.In summary,confirmation of PTL diagnosis is essential for further clinical decisions.Core biopsy should be one of the most important methods to make the diagnosis of PTL,while the use of fine needle aspiration cytology alone is still limited in diagnosing PTL.