Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Detected by Clonotypic Polymerase Chain Reaction Despite Continuous Pathologic Remission Induced by Involved-Field Radiotherapy

2005 ◽  
Vol 23 (16) ◽  
pp. 3768-3772 ◽  
Author(s):  
Ariela Noy ◽  
Joachim Yahalom ◽  
Leah Zaretsky ◽  
Ian Brett ◽  
Andrew D. Zelenetz

Purpose Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is indolent and often associated with Helicobacter pylori bacterial infection. H pylori–independent MALT develops either in the absence of the bacteria or persists after bacterial eradication. We have previously demonstrated long-term pathologic remission after involved-field radiotherapy therapy (IFRT). We determined molecular remission status by clonotypic polymerase chain reaction (PCR). Patients and Methods Twenty-four consecutive patients with stage I to IIE gastric MALT lymphoma who obtained a pathologic remission after IFRT alone were evaluated. All had at least two follow-up endoscopic gastroduodenal biopsies at Memorial Sloan-Kettering Cancer Center. IFRT median dose was 30 Gy (range, 28.5 to 43.5 Gy). Post-treatment biopsies were subjected to semi-nested clonotypic PCR. Results All patients obtained a complete response based on routine immunohistochemical pathologic analysis of random post-treatment gastric biopsies. Median follow-up from completion of IFRT was 63 months (range, 19 to 117 months). Event-free survival was 96%; 23 of 34 patients remained in clinical and pathologic complete remission. Baseline DNA extraction yielded 17 clone-specific primer pairs. At the first follow-up test, 14 of 17 pairs were PCR positive. Eight remained persistently positive; and one was persistently negative. Others were intermittently positive. Conclusion Despite sustained biopsy-proven remissions for as long as 117 months after radiation, the vast majority of patients remain positive by clonotypic PCR. This suggests that the malignant clone is present but missing either an internal or external signal essential to the cancer phenotype. One possibility is that radiation eradicates the polyclonal H pylori–specific T cells eliminating critical local factors necessary for proliferation of the monoclonal B cells.

1997 ◽  
Vol 15 (3) ◽  
pp. 1104-1109 ◽  
Author(s):  
B Rudolph ◽  
E Bayerdörffer ◽  
M Ritter ◽  
S Müller ◽  
C Thiede ◽  
...  

PURPOSE The differential diagnosis of early gastric mucosa-associated lymphatic tissue (MALT) lymphoma based on Helicobacter pylori gastritis may be difficult when lymphoepithelial lesions are not detected. The aim of the present study was to investigate the question whether the polymerase chain reaction (PCR) or cure of H pylori infection may be of help in this respect. PATIENTS AND METHODS Twenty patients with suspected low-grade gastric MALT lymphomas were treated in a double-blinded, randomized, crossover trial with 2,250 mg of either amoxicillin or placebo, both in combination with omeprazole, for 14 days with the aim to cure H pylori infection. PCR was performed using primers specific for the CDR3 region to detect monoclonal B cells. RESULTS In five of 20 patients, MALT lymphomas were finally diagnosed. Three of these five patients went into complete remission, while two were referred to surgery. In the 15 patients with gastritis, complete regression was observed in all cases. With respect to PCR, monoclonal bands were detected in all four of the analyzed lymphoma patients before histology showed lymphoma. In addition, monoclonal bands were found in three patients with gastritis. In the patients with gastritis and monoclonal PCR, complete regression took longer as compared with the remaining 12 patients with polyclonal PCR and gastritis (P = .0209). Successful H pylori eradication was associated with earlier diagnosis of the MALT lymphoma (P = .0237). CONCLUSION CDR3-PCR may be of help in the differential diagnosis of early gastric MALT lymphoma. Furthermore, H pylori eradication may lead to earlier diagnosis.


Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 1182-1187 ◽  
Author(s):  
Hongxiang Liu ◽  
Hongtao Ye ◽  
Ahmet Dogan ◽  
Renzo Ranaldi ◽  
Rifat A. Hamoudi ◽  
...  

The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a multistep process and can be clinico-pathologically divided into Helicobacter pylori-associated gastritis, low-grade tumors, and high-grade tumors. The molecular events underlying this progression are largely unknown. However, identification of the genes involved in MALT lymphoma-specific t(11;18)(q21;q21) and t(1;14)(p22;q32) has provided fresh insights into the pathogenesis of this disease. T(11;18)(q21;q21) results in a chimeric transcript between the API2 and theMALT1 genes, whereas t(1;14) (p22;q32) causes aberrant nuclear BCL10 expression. Significantly, nuclear BCL10 expression also occurs frequently in MALT lymphomas without t(1;14)(p22;q32), suggesting an important role for BCL10 in lymphoma development. Thirty-three cases of H pylori gastritis, 72 MALT lymphomas, and 11 mucosal diffuse large B-cell lymphomas (DLBCL) were screened for t(11;18)(q21;q21) by reverse transcription–polymerase chain reaction followed by sequencing. BCL10 expression in lymphoma cases was examined by immunohistochemistry. The API2–MALT1 fusion transcript was not detected in H pylorigastritis and mucosal DLBCL but was found in 25 of 72 (35%) MALT lymphomas of various sites. Nuclear BCL10 expression was seen in 28 of 53 (53%) of MALT lymphomas. Of the gastric cases, the largest group studied, the frequency of both t(11;18)(q21;q21) and nuclear BCL10 expression was significantly higher in tumors that showed dissemination to local lymph nodes or distal sites (14 of 18 = 78% and 14 of 15 = 93%, respectively) than those confined to the stomach (3 of 29 = 10% and 10 of 26 = 38%). Furthermore, t(11;18)(q21;q21) closely correlated with BCL10 nuclear expression. These results indicate that both t(11;18)(q21;q21) and BCL10 nuclear expression are associated with advanced MALT lymphoma and that their oncogenic activities may be related to each other.


2019 ◽  
Vol 12 (10) ◽  
pp. e230878
Author(s):  
Karim Nashed ◽  
Keith Lai ◽  
Tyler Stevens ◽  
Gareth Morris-Stiff

A 79-year-old woman presented to the emergency department following a motor vehicle collision. As part of her workup she underwent a CT scan which identified a large mass containing calcifications centred around the gastric antrum, and while being assessed she produced 500 mL of haematemesis. An endoscopy revealed an area of friable mucosa the nature of which was uncertain, and multiple biopsies revealed amyloid deposition and active Helicobacter pylori gastritis. Following review of imaging and pathology, a diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma was established. She was treated with quadruple therapy for the H. pylori and at 6-month follow-up she is asymptomatic with repeat endoscopy revealing healing of the ulceration and no biopsy evidence of H. pylori or MALT.


Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1255-1260 ◽  
Author(s):  
A Savio ◽  
G Franzin ◽  
AC Wotherspoon ◽  
G Zamboni ◽  
R Negrini ◽  
...  

The differential diagnosis between Helicobacter pylori (H pylori- associated chronic gastritis and low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT) and the assessment of endoscopic biopsy specimens after treatment of lymphoma can be problematic. Although immunocytochemistry can be used to identify clonal B-cell populations, which are characteristic of MALT lymphoma, its application to small biopsy specimens and the subsequent interpretation can be difficult. The polymerase chain reaction (PCR) can detect clonal B-cell populations by analysis of the Ig heavy chain gene in routinely fixed paraffin-embedded material and might provide a useful tool in the assessment of these specimens. We have investigated the value of histology and PCR in the diagnosis of lymphoma and its followup in formalin-fixed paraffin-embedded gastric endoscopy biopsy specimens from 69 sequential patients selected on the basis of a dense mucosal lymphoid infiltrate associated with H pylori infection. Histologic evidence of MALT lymphoma was identified in 13 cases, 9 of which showed PCR-detected monoclonality. In 12 of 13 cases, H pylori was eradicated, and in 11 of 12 cases, histologic regression of the lymphoma followed. PCR evidence of monoclonality disappeared in 6 of 9 originally monoclonal cases. This was synchronous with histologic remission in 1 case, but lagged in the remaining 5 cases by up to 28 months. Two of the 3 of the 9 cases originally monoclonal by PCR that have not shown molecular regression have monoclonal-amplified products 17 and 24 months after negative histology. In 3 cases, the histology of the biopsies was considered indeterminate or discordant. In 1 of these cases, the histologic features were obscured by crush artefact. In a second case, there was molecular evidence of monoclonality in the absence of histologic features suggestive of lymphoma; this persisted after H pylori eradication. An additional single case originally diagnosed as reactive developed a PCR detectable clonal population 29 months after original evaluation in the absence of histologic features of lymphoma but in the presence of persistent H pylori infection. These findings suggest that the histologic assessment of gastric biopsies remains the method of choice for the diagnosis of lymphoma in gastric endoscopic biopsies with a dense mucosal lymphoid infiltrate. PCR provides a useful technique to support the diagnosis if clonal amplification products are found. The significance of PCR detected clonality in the absence of histologic evidence of lymphoma in uncertain but may represent a stage of tumor progression/regression when the clonal population is insufficient to be detected by conventional histology. This is supported by the evidence that PCR- detectable monoclonality can persist after treatment and the disappearance of histologically detectable lymphoma.


Blood ◽  
2021 ◽  
Author(s):  
Marius Mayerhoefer ◽  
Markus Raderer ◽  
Wolfgang Lamm ◽  
Michael Weber ◽  
Barbara Kiesewetter ◽  
...  

Post-treatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G-protein-coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate PET with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow-up biopsies for assessment of residual disease (non-complete remission (CR)) after first-line H. pylori (HP) eradication. Forty-six post-HP eradication [68Ga]Pentixafor-PET/MRI examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor-PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard, and showed CR in six cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive value of [68Ga]Pentixafor-PET for detection of residual gastric MALT lymphoma at follow-up, were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r=0.51 and r=0.52 (P=0.008 and P=0.006). In conclusion, CXCR4 imaging with [68Ga]Pentixafor-PET may represent a promising test for assessment of residual gastric MALT lymphomas after HP eradication.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2993
Author(s):  
Barbara Kiesewetter ◽  
Christiane Copie-Bergman ◽  
Michael Levy ◽  
Fangtian Wu ◽  
Jehan Dupuis ◽  
...  

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, H. pylori negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of 57 cases of H. pylori negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes. Results: MALT1 translocation, most likely t(11;18)(q21;q21)/BIRC3-MALT1, was detected in 39% (22/57) cases, and IGH translocation was further seen in 12 MALT1-negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways (TNFAIP3 = 23%, CARD11 = 9%, MAP3K14 = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from MALT1, albeit not IGH translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy (p = 0.004). Conclusion: H. pylori negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways.


Author(s):  
Laura Renard ◽  
Adrien Lemaignen ◽  
Guillaume Desoubeaux ◽  
David Bakhos

Laryngeal leishmaniasis is an unusual form of the disease. We report the case of a patient who consulted for dysphonia and dysphagia in a context of asthenia and weight loss. The patient had lesions that were suggestive of laryngeal cancer but were revealed to be leishmaniasis by histopathology examination and polymerase chain reaction. Treatment with amphotericin B and miltefosine permitted complete resolution of the lesions and no recurrence during the 18-month follow-up period.


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