Trisomy 3 may predict a poor response of gastric MALT lymphoma to Helicobacter pylori eradication therapy

AIM: To investigate the relation of the response to Helicobacter pylori eradication therapy to the depth of tumor invasion and chromosome abnormalities in patients with mucosaassociated lymphoid tissue (MALT) lymphoma and to determine the clinical value of aneuploidy.METHODS: We studied 13 patients with localized gastric MALT lymphoma of stage E1. Before eradication therapy,the depth of tumor invasion was assessed by endoscopic ultrasonography in 8 patients and by endoscopic examination and gastrointestinal series in the remaining patients. To detect chromosomal abnormalities, paraffin-embedded tissue sections of diagnostic biopsy specimens underwent tissuefluorescence in situ hybridization (FISH), using chromosomespecific α-satellite DNA probes for chromosomes 3,7,12,and 18 and YAC clones for t(11;18)(q21;q21).RESULTS: Seven of the 13 patients had complete regression(CR) in response to H pylori eradication therapy. No patient with CR had submucosal tumor invasion. Trisomy 18 was seen in 1 patient with CR, and both trisomies 12 and 18 were present in another patient with CR. All patients with no response or progressive disease had deep submucosal tumor invasion and showed t(11;18)(q21;q21) or trisomy 3. Trisomy 7 was not detected in this series of patients.CONCLUSION: The depth of tumor invasion is an accurate predictor of the response of stage E1 MALT lymphoma to H pylori eradication therapy and is closely associated with the presence of chromosomal abnormalities. Trisomy 3 may predict the aggressive development of MALT lymphoma.

Pseudomembranous colitis presenting as acute colonic obstruction without diarrhea in a patient with gastric Burkitt lymphoma

Pseudomembranous colitis (PMC) usually manifests asfever and diarrhea in hospitalized patients treated withsystemic antibiotics. We described a case of PMC withintestinal obstruction but without diarrhea. A 60-yearold man was hospitalized for chemotherapy for the treatment of Burkitt lymphoma of the stomach. The patient became febrile and complained of crampy abdominal pain during the post-chemotherapy nadir. Plain abdominal radiography showed some intestinal gas and niveau. Because stool cytotoxin assay for clostridium difficile was positive and colon fiberscopic examination showed a pseudomembrane at the left side of the colon,and a diagnosis of PMC was made. Treatment with intracolonic vancomycin administration by colonoscopy and nasoileus tube was successful. Physicians should take into account the possibility of bowel obstruction due to PMC occurring in patients undergoing chemotherapy and perform emergency colonoscopy examination of suspected cases.

Recurrent chromosomal rearrangements at bands 8q24 and 11q13 in gastric cancer as detected by multicolor spectral karyotyping

AIM: To identify chromosomal translocations specific to gastric cancer (GC), spectral karyotyping (SKY) analysis was performed on established cell lines and cancerous ascitic fluids.METHODS: SKY analysis of 10 established cell lines and seven cancerous ascitic fluid samples identified recurrent chromosomal breakpoints and translocations in GC,several of which involved chromosomal loci of oncogenes or tumor suppressor genes.RESULTS: A total of 630 chromosomal breaks were identified. Chromosome no.8 was the most frequently involved in rearrangements (65 breaks), followed by chromosomes no. 11 (53), no. 1 (49), no. 7 (46), no. 13 (37), no. 3 (36), no. 17 (33), and no. 20 (29). Frequent breakpoints were detected in 8q24.1 (30 breaks), 11q13 (29), 13q14 (16), 20q11.2 (14), 7q32 (13), 17q11.2 (13),18q21 (12), 17q23 (9), 18q11.2 (9). SKY analysis identified a total of 242 chromosomal rearrangements including 190 reciprocal and non-reciprocal translocations. The recurrent combinations of chromosomal bands involved in translocations were 8q24.1 and 13q14 (3 cases), 8q24.1 and 11q13 (3), 11q13 and 17q11.2 (2), and 18q11.2 and 20q11.2 (2). Our study validated the ability of SKY to characterize in detail the chromosomal rearrangements in solid tumors and derived cell lines. Moreover,fluorescence in situ hybridization helped to identify the insertions, translocations, and homogeneously staining regions of MYCand CCND1 gene loci.CONCLUSION: The non-random co-localization of certain cytogenetic bands suggests the importance of chromosomal translocations in gastric carcinogenesis, by serving as landmarks for the cloning of GC causing genes.

Detection of BCL2-IGHrearrangement on paraffin-embedded tissue sections obtained from a small submucosal tumor of the rectum in a patient with recurrent follicular lymphoma

A 59-year-old woman was admitted to our hospital because of recurrent follicular lymphorna (FL). Colonoscopic examination revealed a rectal submucosal tumor (SMT) without any erosions and ulcers. In this patient, it was difficult to distinguish non-Hodgkin's lymphoma (NHL) invasion from other disorders of the colon including carcinoid tumor merely based on endoscopic findings. Histopathologic and immunohistochemical studies on biopsy specimens showed an infiltration of atypical lymphocytes that were positive for CD20 and BCL2 but negative for UCHL-1. Fluorescence in situ hybridization on paraffin-embedded tissue sections (T-FISH) identified a translocation of BCL2 with IGHgene.Based on these findings, the tumor was defined as an invasion of FL. T-FISH method is useful for the detection of a monoclonality of atypical lymphocytes in an SMT of the gastrointestinal tract, and particularly for the detection of chromosomal translocations specific to lymphoma subtypes.

Lack of evidence for leukocyte maternal microchimerism in primary biliary cirrhosis

It is reasonable to assume that microchimerism could also be involved in the induction of primary biliary cirrhosis (PBC). However, previous reports investigated only fetus-microchimerism in women patients. Maternal microchimerism has not been investigated until now.The current study aimed to clear either maternal microchimerism was involved in the pathogenesis of PBC or not.METHODS: We used fluorescence in situ hybridization on paraffin-embedded tissue (We called 'Tissue-FiSH'.) to determine whether maternal cells infiltrated in male patients who were diagnosed as having PBC. Tissue-FiSH was performed by using both X and Y specific probes on the biopsy liver sample of 3 male PBC patients.RESULTS: Infiltrating lymphocytes demonstrated both X and Y signals in all 3 male patients.CONCLUSION: Maternal microchimerism dose not play asignificant role in PBC. PBC may not relate to fetus and maternal microchimerism.

Hepatitis B virus reactivation in a patient undergoing steroid-free chemotherapy

A 62-year-old Japanese man who was positive for hepatitis B surface antigen (HBsAg) and anti-HBe antibody, underwent chemotherapy for non-Hodgkin's lymphoma (NHL). Mutations were detected in the precore region (nt1896) of HBV. Because steroid-containing regimen may cause reactivation of hepatitis B virus (HBV) and hepatitis may progress to be fulminant afcer its withdrawal, we administered CHO (CPA, DOX and VCR) therapy and the patient obtained complete response. However, he developed acute exacerbation of hepatitis due to HBV reactivation. Recovery was achieved with lamivudine (100 mg/d) and plasma exchange. The present case suggests that acute exacerbation of hepatitis can occur with steroid-free regimen. Because the efficacy of the prophylactic use of lamivudine has been reported and the steroid enhances curability of malignant lymphoma,the steroid containing regimen with prophylaxis of lamivudine should be evaluated further.

Successful treatment with rifampin for fulminant antibiotics-associated colitis in a patient with non-Hodgkin's lymphoma

A 74-year-old man was admitted to the hospital because of chemotherapy for relapsed non-Hodgkin's lymphoma (NHL).The patient became febrile and experienced diarrhea after chemotherapy. Although ceftazidime and amikacin sulfate were administered as empiric therapy, diarrhea was continued.After several days, stool cytotoxin assay for clostridium difficile (C. difficile) was positive and he was diagnosed as having antibiotics-associated colitis (AAC). Although antibiotics were discontinued and both oral vancomycin and metronidazole were administrated, disease was not improved. To rule out the presence of an additional cause of diarrhea, colon fiberoscopic examination was performed. It revealed multiple deep ulcerative lesions at right side colon, surface erosive and minute erosive lesions in all continuous colon.Pseudomembranes were not seen. These findings are compatible with AAC without pseudomembranes. There are no reports that the rifampin is effective on refractory AAC.However, we administered oral rifampin for the current patient.The reasons are 1) conventional antibiotics were not effective,2) rifampin has excellent in vitro activity against C. difficile,and 3) the efficacy of rifampin on relapsing colitis due to C.difficile is established. After administration of rifampin, fever alleviated and diarrhea was improved. Because AAC may result in significant mortality, patients with refractory or fulminant AAC should be treated with oral rifampin from outset.

Successful endoscopic hemostasis for gastric arterial bleeding due to invasion of malignant lymphoma

A 75-year-old male with malignant lymphoma (ML) accompanied with gastric lesion was treated with combination chemotherapy. The patient produced tarry stool on the 4th d, and emergency gastroscopy showed arterial bleeding from the lesion. Hemostasis was achieved by injecting pure ethanol and using hemostatic clips. There is only one previous report on endoscopic hemostasis being effective for bleeding due to lymphoma. Since gastric bleeding causes significant mortality, endoscopic hemostasis should be considered as first-line treatment for ML patients who were treated with chemotherapy.