it is well established , that more than 90% of low - grade malt lymphomas are associated with h. pylori infection1 ) .
indeed , the eradication of h. pylori infection has been associated with the regression of gastric malt lymphoma in 70% to 80% of patients2 , 3 ) .
additional factors contribute to the development of malt lymphoma such as : environmental , microbial , immune and genetic factors .
transformation of malt lymphoma has been described ; there is genetic evidence for a clonal link between low- and high - grade components4 ) . here
, we report a case of high - grade hepatic malt lymphoma that occurred six years after achieving complete remission of a low - grade gastric malt lymphoma with h. pylori eradication therapy .
although we were unable to obtain cytogenetic evidence , the radiological and pathologic findings suggested that the low - grade malt was transformed to a high - grade hepatic malt lymphoma .
a 67-year - old woman visited our hospital with complaints of abdominal discomfort , indigestion and constipation for five days . physical examination and laboratory findings were not specific , and her performance was excellent .
gastroscopic examination showed an ulcero - infiltrative lesion at the greater curvature side of the antrum ( figure 1 ) .
diffuse and nodular aggregates of lymphoid cells were composed of monotonous small to medium - sized lymphocytes with round to cleaved nuclei and clear cytoplasm . in some areas ,
relatively large atypical lymphoid cells were also present in less than 10% of tumor cells .
immunohistochemical stains were positive for cd20 and cd79a , but negative for cd45ro , cd3 , cd5 , cd23 , bcl-2 and cyclin d1
an abdominal ct scan revealed focal wall thickening on the greater curvature side of antrum without any lymph node enlargement .
unfortunately , a bone marrow biopsy was not performed , thus staging work - up of the lymphoma was not fully performed .
the patient was diagnosed with a low - grade gastric malt lymphoma and treated for h. pylori infection for 14 days with omeprazole 20 mg bid , clarithromycin 500 mg bid and amoxicillin 1,000 mg bid .
follow - up gastroscopic examinations , one and three months after h. pylori eradication , showed marked improvement of gastric lesions .
h. pylori infection was absent by rapid urease testing and histology , but malt lymphoma was still present on histology evaluation . thereafter the patient was lost to follow - up .
four years later , the patient visited our hospital again with complaints of indigestion and constipation .
gastroscopy showed diffuse erythematous changes of the antral mucosa with an irregular surface at the site of the previous malt lymphoma that appeared to be a scar .
gastric mucosal biopsy showed well preserved foveolar epithelium , and sparsely scattered inflammatory cells in the lamina propria devoid of residual lymphoma .
abdominal ct scan showed neither gastric wall thickening nor lymph node enlargement ( figure 3 ) .
about two years later , the patient returned to our hospital with complaints of general weakness and epigastric discomfort .
blood tests on admission showed a hematocrit of 36.1% , a white blood cell count of 4,200/mm , a platelet count of 77,000/mm , a protein of 4.6 g / dl , an albumin of 2.4 g / dl , a total bilirubin of 3.0 mg / dl ( 0.2 - 1.0 mg / dl ) , a direct bilirubin of 2.5 mg / dl ( 0.0 - 0.2 mg / dl ) , an alkaline phosphatase of 588 u / l ( 32 - 104
u / l ) , an alanine aminotransferase of 196 u / l ( 10 - 36
u / l ) , an aspartate aminotransferase of 357 u / l ( 10 - 30
u / l ) , a lactate dehydrogenase of 1,871 u / l ( 211 - 423
u / l ) , and a prothrombin time of 11.8 sec ( 10 - 14 sec ) .
histological examination revealed only chronic inflammation and intestinal metaplasia with the absence of h. pylori infection and malt lymphoma ( figure 4 ) .
abdominal sonography and liver mri showed multiple hepatic nodules with multiple celiac and para - aortic lymphadenopathy ( figure 5 ) .
ultrasonography - guided percutaneous core needle biopsy was performed on the hepatic nodules ; histological examination revealed a patchy infiltration , of atypical lymphoid cells , replacing the liver parenchyma .
the composition of the large lymphoid cells , found in the liver biopsy , was significantly increased when compared to the previous gastric malt lymphoma .
immunohistochemical stains were positive for cd20 , but negative for : cd45ro , cd3 , cd5 , cd23 , bcl-2 and cyclin d1 ( figure 6 ) .
immunohistochemical stains for ki-67 were performed both on the biopsy from the previous low - grade gastric malt lymphoma and the liver core biopsy .
the ki-67 labeling index , from the liver biopsy sample , was much higher ( 70% ) than in the previous gastric biopsy ( 20% ) ( figure 7 ) .
these pathological findings suggested a hepatic malt lymphoma that represented a transformation from the previously treated low - grade gastric malt lymphoma to a high - grade malt lymphoma .
the patient , and her family , refused further treatment and her clinical status deteriorated rapidly ; she died from sepsis one month later .
the malt lymphoma was first described as a distinct pathologic entity in 1983.5 ) in 1988 , it became apparent that the gastric malt lymphoma is caused by chronic h. pylori infection ; this triggers lymphoid infiltration and formation of organized lymphoid tissue6 , 7 ) .
perhaps the strongest evidence is that in approximately two thirds of cases , the lymphoma regresses after treatment of the h. pylori infection2 , 3 ) .
it is assumed that the initial proliferation of lymphoma cells occurs in an antigen - dependent fashion ; this explains the tendency for these lymphomas to remain anatomically localized and to respond to antibacterial therapy .
given that most patients with h. pylori gastritis do not develop malt lymphoma , additional events such as environmental , microbial , immune and genetic factors must play an important role8 ) .
our patient was positive for h. pylori infection ; the initial original gastric malt lymphoma completely disappeared after eradication of h. pylori infection .
however , the occurrence of transformation to a high - grade lymphoma without evidence of h. pylori re - infection strongly suggests that some other pathological mechanisms , besides h. pylori infection , played a role in disease progression .
the understanding of the biology of the gastric malt lymphoma has improved over the past few years .
there is a common structural cytogenetic abnormality associated with this disorder , t(11;18)(q21;q21 ) , detected in 21% to 60% of cases8 - 11 )
. this translocation acts to fuse the inhibitors of apoptosis ( iap ) family api2 with the novel gene malt1 .
the characterization of another , albeit less frequent recurrent translocation , t(1;14)(p22;q23 ) has led to the identification of bcl1012 , 13 ) .
both translocations are known to result in activation of the central transcription factor nf-b14 ) .
nf-b induction appears to drive antigen independent growth of the lymphoma cells , promoting disease dissemination and unresponsiveness to h. pylori eradication therapy8 ) .
transformation of malt lymphoma has been described , and there is a genetic evidence for a clonal link between low- and high - grade components4 ) .
deletion of the p16 , mutations of the p53 gene , translocation breakpoint involved in t(6;14)(p21;q32 ) , and bcl-6 have been described to be associated with transformation of the malt lymphoma15 - 17 ) . moreover , numerous investigators have sequenced immunoglobulin heavy chain ( igh ) genes , and have found frequent somatic mutations that can be ongoing18 ) .
somatic hypermutations , together with isotype switch recombination , contributes to b - cell maturation .
unfortunately , we could not perform cytogenetic evaluations or igh gene rearrangement analysis in our patient .
however , in the pathological findings , the composition of the large lymphoid cells and the expression of the proliferation marker ki-67 were significantly increased in the hepatic nodules compared to the previous gastric malt lymphoma ; these results suggested that the hepatic nodules represented a transformation to a higher grade malignant lymphoma from the prior low - grade gastric malt lymphoma .
in addition , the occurrence of high - grade transformation , even after complete remission of the original gastric lesion , its aggressive nature may suggest that our patient had one or more underlying cytogenetic abnormalities .
however , the possibility that the hepatic malt lymphoma might be a newly developed and separate lesion , with no relationship to the initial low - grade gastric malt lymphoma , can not be completely excluded . in summary
, we report a case of high - grade hepatic malt lymphoma that occurred six years after achieving complete remission of a low - grade gastric malt lymphoma .
although we did not perform cytogenetic evaluation , the hepatic malt lymphoma was considered to represent a transformation from the gastric malt lymphoma on the basis of radiological and pathological findings . in addition
, these findings suggest that the determination of a complete cure for malt lymphoma based on gastroscopic and histological findings might not be adequate .
regular follow - up , even after complete remission of the original lesion , is mandatory , and cytogenetic studies should be considered in certain cases if available .
 the mucosa - associated lymphoid tissue ( malt ) lymphoma , which was first described in 1983 , is known to be caused by chronic helicobacter pylori ( hp ) infection , which triggers lymphoid infiltration and formation of organized lymphoid tissue . in approximately two thirds of cases of malt , 
 the lymphoma has been observed to regress after treatment of h. pylori infection ; this provides strong evidence of a causative role of hp in the etiology of malt . 
 we report a case of a 67-year - old female patient with a high - grade malt lymphoma of the liver ; this occurred six years after complete remission of a low - grade gastric malt lymphoma and after complete eradication of h. pylori . 
 there was no recurrence of the previous low - grade gastric malt lymphoma . based on radiological and pathologic findings , 
 the high - grade malt was considered to result from transformation of the low - grade gastric malt lymphoma . 
INTRODUCTION
CASE REPORT
DISCUSSION