B-cell monoclonality precedes the development of gastric MALT lymphoma in Helicobacter pylori-associated chronic gastritis.

Little is known about the temporal changes in Helicobacter pylori density and B-cell clonality during the evolution from chronic gastritis to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Biopsied specimens from 28 patients with chronic gastritis who developed gastric MALT lymphoma (group A) and from 24 similar patients who did not (group B) during an equivalent follow-up period (mean, 42 months) were retrospectively scored for histological features of MALT lymphoma (0 to 5) and H. pylori density (0 to 3). B-cell clonality was analyzed by polymerase chain reaction (PCR). During the observation period, the H. pylori density in group A decreased significantly in comparison with group B; the mean change in H. pylori density (final minus initial density) per 1000 days was -1.4 for group A and +0.2 for group B (P < 0.005). Monoclonality was detected more frequently in group A (79%) than in group B (21%; P < 0.005), and it preceded the histological evidence of malignant transformation in 64% of those patients who showed monoclonality in group A. These results suggest that H. pylori is thus more closely associated with the precursor or initial phase in the genesis of gastric MALT lymphoma than with the later phase, as its density decreases as the tumor progresses. The detection of B-cell monoclonality by PCR is thus of possible use for predicting the histological genesis of gastric lymphoma.     

Marginal zone B-cell lymphoma of MALT in small intestine associated with amyloidosis: a rare association

A 62-yr-old man presented with a 5-yr history of intermittent abdominal distention and pain. These symptoms persisted for several months and subsided without treatment. A diagnosis of suspected small bowel lymphoma was made based on plain radiograph and computerized tomogram findings, and he was referred to our institution for further evaluation. Segmental resection of the small intestine was performed and the diagnosis of marginal zone B-cell lymphoma associated with amyloidosis was made. This is the first case of marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) in the small intestine associated with amyloidosis in Korea.     

Expression of CD10, CD75 and CD43 in MALT lymphoma and their usefulness in discriminating MALT lymphoma from follicular lymphoma and chronic gastritis.

AIMS: While it may be difficult to discriminate between chronic gastritis, MALT lymphoma and a gastric location of a nodal lymphoma using histology of small endoscopic biopsies alone, additional markers like CD10, CD75 and CD43 and proliferative activity may be of value. We assessed the expression of these antigens in MALT lymphoma and their usefulness in discriminating MALT lymphoma from follicular lymphoma and from gastritis. METHODS AND RESULTS: Tissue samples of 38 patients with gastric MALT lymphoma were immunohistochemically stained for expression of CD10, CD75 and/or CD43. Proliferation index was scored using MIB-1 staining. Ten cases of nodal follicle centre B-cell lymphomas (n = 11) and 18 cases of high-grade MALT lymphoma (n = 22) showed moderate to high CD75 expression (25-100% positive cells). All tested low-grade MALT lymphomas (n = 9) and chronic gastritis (n = 6) were negative (0-25%) for CD75. All MALT lymphomas (n = 25) were negative for CD10. High-grade lymphomas show significantly higher proliferation indices (67% vs. 16%) than low-grade lymphomas. Only four of 26 MALT lymphomas were slightly positive for CD43. All gastritis biopsies (n = 4) were negative for CD43. CONCLUSIONS: These data suggest that combining both CD10 and CD75 may be useful in discriminating between low-grade MALT, high-grade MALT lymphoma and extranodal location of follicular lymphoma. However, CD43 expression cannot in the majority of cases be used to distinguish between low-grade MALT lymphoma and gastritis.     

Discordant lymphoma: MALT lymphoma of the stomach and follicular lymphoma of the parotid gland

More than one histological type of malignant lymphoma can occur simultaneously in an individual. The entity is classified as either composite or discordant lymphoma. Both types of lymphoma, particularly discordant lymphoma comprised of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue lymphoma (MALT-L) and follicular lymphoma (FL), are rare. We report a case of discordant lymphoma comprising MALT-L in the stomach and FL in the parotid gland. The patient was a 50-year-old Japanese woman who visited the University Hospital of Showa (Tokyo, Japan) because a barium study showed erosive gastric lesions. A gastro-intestinal endoscopy was performed 2 months after the barium study, which showed irregular erosions throughout the stomach body. A gastric biopsy showed MALT-L, and Helicobacter pylori (H. pylori) infection was confirmed. The patient had noticed a painless and elastic hard tumor mass of about 2 cm in diameter in the area of the left parotid gland 6 months before the barium study. We removed the parotid gland tumor and diagnosed it as FL 6 months after the barium study. We were able to diagnose the MALT-L and FL by morphological, immunohistochemical and molecular analyses of paraffin-embedded sections. This appears to be the first reported case of MALT-L and FL occurring together as a discordant lymphoma.     

Composite lymphoma: association of a follicular lymphoma and a chronic lymphocytic leukemia

We report the case of a 71-year-old woman presenting with composite lymphoma (CL) composed of a follicular lymphoma and a B-cell chronic lymphocytic leukemia. CL is a rare lymphoproliferative disorder, characterized by two distinct morphological and immunophenotypical patterns in the same anatomical site, most frequently of biclonal origin. This entity must be distinguished from transformation of low-grade lymphoma into high-grade lymphoma and from lymphoma with differentiation such as follicular lymphoma with marginal differentiation. In this context, molecular analysis including immunoglobulin rearrangement, sequencing and FISH analyses is determinant and can be improved by tissue microdissection. Routinely, CL must not be misdiagnosed because of its prognosis and treatment implication.     

Genetic evidence for a clonal link between low and high-grade components in gastric MALT B-cell lymphoma

High-grade MALT lymphomas often contain low-grade tumour components; both cell populations have been shown to express the same immunoglobulin light chain previously. However, the clonal link between the low and high-grade components has not been established at the genetic level. To investigate this link, we have examined low- and high-grade components microdissected from tissue sections of four high-grade gastric MALT lymphomas. PCR and sequence analyses were performed to identify clone-specific rearranged immunoglobulin heavy chain gene sequences. In each of these cases, the PCR products from the two components were identical in size by electrophoresis. Direct sequencing revealed common clone-specific immunoglobulin heavy chain gene rearrangements in both lesions of each case, providing genetic evidence for a clonal link. These results support the proposal that high-grade MALT lymphomas generally evolve from low-grade clones.     

Detection of monoclonality of gastric MALT lymphoma using PCR method and its clinicopathological application

Twenty cases of H. pylori-related gastric lymphoproliferative disorders including 12 cases of MALT lymphoma (Grade 5 after Wotherspoon, et al), 6 of suspicious of MALT lymphoma (Grade 4), and 2 of active chronic gastritis (Grade 3) were studied. Using the nested PCR method, paraffin-embedded gastric biopsy specimens of these 20 cases were investigated whether or not monoclonal IgH rearrangement could be demonstrated in infiltrating lymphoid cells. Monoclonal IgH rearrangement was recognized in 6 of 12 MALT lymphomas, but in other 14 cases including 6 of MALT lymphomas the monoclonality was not recognized. The result showed the sensitivity was 50% and the specificity was 100% with this method. Follow-up study after eradication of H. pylori was performed on 6 cases of MALT lymphoma which had showed the monoclonality before, using the same method. The monoclonality disappeared in 5 of 6 and histology showed a complete remission. In the remaining one case the monoclonality was yet demonstrated and lymphoma cells were histologically recognized. Thus, this method is very useful to assess not only the histological diagnosis of MALT lymphoma but also the effectiveness after treatment.     

滤泡性淋巴瘤与黏膜相关淋巴组织淋巴瘤的滤泡网免疫表达的差异

目的探讨滤泡性淋巴瘤(follicular lymphoma,FL)与黏膜相关淋巴组织淋巴瘤(mucosa-associated lymphoid tissue lym-phoma,MALToma)免疫标记表达的差异及意义。方法对26例FL和12例MALToma做C4d、CD21、CD35、CD10和bcl-6的免疫组化SP法染色,并做CD35/C4d和CD21/C4d免疫组化双标染色,观察瘤性滤泡和植入滤泡中上述免疫标记物分布区域及阳性率。结果 26例FL中的瘤性滤泡和12例MALToma中的植入滤泡均出现扩大的、表达CD35和CD21的滤泡树突网,26例FL中有19例瘤性滤泡中央滤泡树突状细胞周围出现C4d沉积;12例MALToma中有6例植入滤泡的生发中心边缘有C4d沉积。FL的瘤性滤泡内的细胞可见CD10和bcl-6的表达而MALToma中植入滤泡CD10和bcl-6表达阴性。结论 FL的瘤性滤泡与MALToma植入滤泡中滤泡网免疫组化表达尤其C4d表达的差异,可以用于两者的鉴别诊断。     

B细胞淋巴瘤与EB病毒关系的观察

为了了解我国非免疫缺陷相关B淋巴瘤是否与EBV有关，我们采用EBVencodedsmallRNA（EBER－1）原位杂交对127例非免疫缺陷相关B淋巴瘤进行了研究。结果显示，其中8例瘤细胞核内有EBER－1的表达（中心母细胞型4例；淋巴浆细胞样型、浆细胞型、免疫母细胞型和不能分型的高度恶性B细胞淋巴瘤各1例），检出率为6．3％。这一结果与欧美的情况一致（5％左右）．但明显低于我国何杰金病（82％）及T淋巴细胞（62％）的检出率，因此提示EBV在非免疫缺陷B淋巴瘤发病中的作用是有限的，主要致病因素还有待进一步研究。     

Significance of C4d deposition in the follicular lymphoma and MALT lymphoma and their relationship with follicular dendritic cells

We evaluated the deposition of C4d in follicular lymphomas (FL) and extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma). Deposition of C4d was detected in 118 lymphoma tissues from patients with lymphoma and in 20 reactive hyperplasia lymphadens (RHL) using immunohistochemistical methods. FL, MALT lymphoma, and RHL were studied using double staining for CD35/C4d and Bcl-2/C4d. We studied 26 FL tissues, 19 of which showed C4d deposition. C4d deposition was detected around the follicular dendritic cells (FDCs) in the neoplastic follicles. There was no significant difference between the positive ratio of C4d and the grades of FL. We studied 12 MALT lymphoma tissues, six of which displayed C4d deposition. In these tissues, C4d deposition was detected in the peripheral region of partially colonized follicles in the form of an irregular ring, but was not found in the central region. C4d deposition was negative in completely colonized follicles. There was no C4d deposition in diffuse large B-cell lymphomas, mantle cell lymphomas, B-small lymphocytic lymphomas, T-lymphoblastic lymphomas, peripheral T-cell lymphomas, and anaplastic large cell lymphomas. C4d around the FDCs in the neoplastic follicles was a specific indicator for FL. C4d deposition in partially colonized follicles of MALT lymphoma was completely different from that in neoplastic follicles of FL, forming a key point for differential diagnosis.     

One patient with double lymphomas: simultaneous gastric MALT lymphoma and ileal diffuse large B-cell lymphoma

Multiple different lymphomas in a single person are very rare. The author herein reports the case of a 69- year-old Japanese woman with double gastrointestinal lymphoma. The patient presented with epigastralgia. Endoscopic examination revealed erosions and elevation of the gastric body and a large ulcerated tumor of the terminal ileum. Biopsies were obtained from these lesions. The gastric lesion was MALT lymphoma with monocytoid B-cell proliferation and lymphoepithelial lesions. Light chain restriction was present. Helicobacter pylori were present on Giemsa stain. The gastric lesions did not regress despite of therapy, which were confirmed by follow-up biopsy. The ileal lesion was obvious diffuse large B-cell lymphoma. The lesion regressed by chemotherapy. The patient is now alive 3 years after the first presentation.     

Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): a multifocal disease

Gastrectomy specimens from five patients following gastroscopic biopsies which showed low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) were examined by serially sectioning and paraffin wax embedding using a 'swiss roll' technique. This procedure allowed the construction of a map of the specimen on which the distribution of the lymphoma could be plotted. In each case confluent lymphoma was identified. In addition small foci of lymphoma consisting of 1-4 lymphoid follicles surrounded by neoplastic centrocyte-like cells were seen. The positions of these 'micro-lymphomas' were plotted on the gastrectomy maps, showing multiple foci distributed throughout the gastric mucosa. The identification of these microscopic lesions may explain the development of local relapse, often after a long disease-free interval, in patients with gastric MALT lymphoma treated by partial gastrectomy where excision appears to have been complete. Patients treated in this way should, therefore, be followed-up indefinitely, with regular endoscopy and gastric biopsy, in order to identify early local disease relapse.     

Follicular lymphoma with monocytoid B-cell proliferation: molecular assessment of the clonal relationship between the follicular and monocytoid B-cell components

Although a number of studies have recognized that follicular lymphomas may be accompanied by a prominent proliferation of monocytoid B-cells, the clonal relationship between these components has not been adequately assessed. Using laser capture microdissection, we isolated the follicular and monocytoid B-cell components from four well-characterized cases of follicular lymphoma with prominent monocytoid B-cells. DNA from each component was analyzed using polymerase chain reaction (PCR)-based methods to assess for clonal rearrangements of the immunoglobulin heavy chain gene (IgH) and for the presence of the bcl-2 gene major breakpoint region/joining region (MBR/JH) DNA fusion products by conventional PCR and fluorescence melting curve analysis. Evidence of clonal identity was established in the follicular and monocytoid B-cell components of three cases by demonstration of IgH gene rearrangements of identical size using IgH PCR, by comparison of complementarity determining region III (CDRIII) DNA sequences, or by detection of bcl-2 MBR/JH fusion products of identical size and/or melting temperature. Molecular analysis of the fourth case revealed a monoclonal and MBR/JH-positive follicular component accompanied by a polyclonal and MBR/JH-negative monocytoid B-cell proliferation. We conclude that the follicular and monocytoid B-cell components of this variant of follicular lymphoma are clonally identical in the majority of cases. However, in a minority of these cases, the monocytoid B-cell component is reactive. Larger studies that assess the prognostic significance of follicular lymphoma with monocytoid B-cells will benefit from molecular studies that assess the clonal relationship of both components.     

Autoantibody activity of the immunoglobulin secreted by a follicular B-cell lymphoma

In patients with B-cell lymphoma, only in rare cases a secreted paraprotein is found, and in very few of them an associated autoantibody activity has been demonstrated. Here we report the case of a patient with a low-grade B-cell lymphoma with a serum biclonal paraprotein (G,M)lambda and severe erythroblastopenia. Indirect immunofluorescence studies of total serum revealed cytoplasmic (Hep-2 cells) and extracellular matrix (rat tissue sections) staining, suggestive of a new specificity. After gel filtration of serum samples, only the IgM-containing fraction showed the same pattern of staining. Tumor-derived hybridomas expressed an unmutated V3-11 gene identical to that found in tumor samples and secreted an IgM immunoglobulin endowed with the same reactivity, which confirms the tumoral origin of the tissue-reactive protein. The results suggest a link between the autoimmune condition in this patient and the novel specificity displayed by the tumor-derived immunoglobulin.     

Prognostic significance of B-cell differentiation genes encoding proteins in diffuse large B-cell lymphoma and follicular lymphoma grade 3

Aim

To define prognostic significance of B-cell differentiation genes encoding proteins and BCL2 and BCL6 gene abnormalities in diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern.

Methods

In 53 patients with diffuse large B-cell lymphoma and 20 patients with follicular lymphoma grade 3 with >75% follicular growth pattern the following was performed: 1) determination of protein expression of BCL6, CD10, MUM1/IRF4, CD138, and BCL2 by immunohistochemistry; 2) subclassification into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) groups according to the results of protein expression; 3) detection of t(14;18)(q32;q21)/IgH-BCL2 and BCL6 abnormalities by fluorescent in situ hybridization in diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern as well as in GCB and ABC groups; and 4) assessment of the influence of the analyzed characteristics and clinical prognostic factors on overall survival.

Results

Isolated BCL6 expression was more frequently found in follicular lymphoma grade 3 with >75% follicular growth pattern than in diffuse large B-cell lymphoma (P = 0.030). There were no differences in BCL2 and BCL6 gene abnormalities between diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern. Diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern patients were equally distributed in GCB and ABC groups. t(14;18)(q32;q21) was more frequently recorded in GCB group, and t(14;18)(q32;q21) with BCL2 additional signals or only BCL2 and IgH additional signals in ABC group (P = 0.004). The GCB and ABC groups showed no difference in BCL6 gene abnormalities. There was no overall survival difference between the patients with diffuse large B-cell lymphoma or follicular lymphoma grade 3 with >75% follicular growth pattern, however, GCB group had longer overall survival than ABC group (P = 0.047). Multivariate analysis showed that BCL6, CD10, and BCL2 expression, BCL2 and BCL6 abnormalities, and International Prognostic Index were not significantly related to overall survival.

Conclusion

Patients with diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern have very similar characteristics and their prognosis is more influenced by protein expression of B-cell differentiation stage genes than by tumor cells growth pattern, BCL2 and BCL6 abnormalities, and International Prognostic Index.The World Health Organization (WHO) classification defines diffuse large B-cell lymphoma as a specific type of mature B-cell neoplasm (1). However, diffuse large B-cell lymphoma types show clinical, morphological, immunophenotypic, and cytogenetic heterogeneity (2-7). Clinical heterogeneity of diffuse large B-cell lymphoma is a consequence of the expression of B-cell differentiation stage genes. The gene expression analysis has identified three prognostically significant molecular subtypes of diffuse large B-cell lymphoma as follows: germinal center B-cell-like (GCB), activated B-cell-like (ABC), and type 3 diffuse large B-cell lymphoma, which express neither genes of normal GCB-cells nor genes that are normally induced during in vitro activation of peripheral blood B-cells (8-10).Immunohistochemical subclassification of diffuse large B-cell lymphoma showed that GCB and ABC groups greatly differ (11-19). Immunohistochemical GCB and ABC groups are not always considered to be prognostically significant predictors (16-19).Cytogenetic analysis showed t(14;18)(q32;q21)/IgH-BCL2 to be more common in GCB than in ABC (20-24).Follicular lymphoma is the second most common non-Hodgkin B-cell lymphoma (B NHL) (1,25). Follicular lymphoma grade 3, in contrast to indolent follicular lymphoma grade 1 and follicular lymphoma grade 2, is clinically aggressive and has more in common with diffuse large B-cell lymphoma (5).The morphological subtypes of follicular lymphoma grade 3, follicular lymphoma grade 3A, and follicular lymphoma grade 3B show morphological, immunohistochemical, and cytogenetic characteristics of variable clinical importance (1). Clinicopathologic evaluation revealed no differences in survival between follicular lymphoma grade 3A and follicular lymphoma grade 3B patients, yet follicular lymphoma grade 3 cases with a predominant diffuse component (>50%) had a significantly worse survival (25-27).Follicular lymphoma grade 3 is characterized by variable CD10 and BCL2 protein expression and cytogenetic abnormalities, ie, rearrangements of BCL6 gene, BCL2 gene amplification, and less common t(14;18)(q32;q21) (28). Both t(14;18)(q32;q21) and BCL2 protein expression are more common in follicular lymphoma grade 3A, while BCL6 gene rearrangements are more common in follicular lymphoma grade 3B (29-32).Therapy and prognosis of patients with diffuse large B-cell lymphoma and follicular lymphoma are defined according to their morphological characteristics, clinical stage, and clinical prognostic factors included in the International Prognostic Index (IPI) (33,34).The aim of this study was to determine whether follicular lymphoma grade 3 with >75% follicular growth pattern is part of the morphological, immunophenotypic, and cytogenetic spectrum of diffuse large B-cell lymphoma. For that purpose, we determined the following parameters: 1) protein expression of B-cell differentiation stage genes BCL6, CD10, MUM1/IRF4, CD138, and BCL2 expression in patients with diffuse large B-cell lymphoma and lymphoma grade 3; 2) subclassification into GCB and ABC groups according to the results of protein expression profile; 3) t(14;18)(q32;q21)/IgH-BCL2 and abnormalities of BCL6 gene in diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern, as well as in GCB and ABC groups; and 4) the influence of protein expression, cytogenetic abnormalities, and clinical prognostic factors of age, sex, Ann Arbor clinical stage, and IPI risk group on overall survival (35,36).     

Focal follicular features in tonsillar diffuse large B-cell lymphomas: follicular lymphoma with diffuse areas or follicular colonization

Focal follicular features in diffuse large B-cell lymphomas (DLBCLs) are bound to raise the question of follicular lymphoma (FL) with diffuse areas, because the diagnosis of FL is based on the presence of follicular areas, even though focal. We report 7 cases of primary tonsillar DLBCLs with focal follicular features that presented with morphologic, immunohistochemical, and biological features distinct from those of FL. Histologically, these tumors were characterized by involvement of pericryptal follicles with adjacent dominant diffuse areas. Monomorphous large tumor cells were evenly spaced with abundant, often clear cytoplasm, and blastoid nuclei often with a delicate nuclear membrane. Importantly, residual germinal centers (GCs) were present in the form of either an intrafollicular GC remnant or an isolated GC in the midst of diffuse tumor. An extrafollicular and/or parafollicular growth pattern was also observed. Bcl-6 staining revealed a predominantly sporadic occurrence of Bcl-6(+) cells, comprising <50% of tumor cells, and none displayed diffusely dense collections (>75%) of Bcl-6(+) tumor cells characteristic of the GC or FL. Staining for CD10 was negative in 6 cases. Five of 7 patients were younger than 60, the median age of other patients with primary tonsillar DLBCL. No extratonsillar involvement was seen at 18 months after diagnosis. After chemotherapy or radiotherapy, complete remission was achieved with ease in all patients, but 2 patients who were treated with chemotherapy alone relapsed at 24 and 30 months. In conclusion, tonsillar DLBCL includes a small (10%) but distinct subgroup that warrants distinction from FL with predominant diffuse areas or de novo DLBCL. It appears that the focal follicular features in tonsillar DLBCL likely represent follicular colonization of marginal zone B-cell lymphoma, probably high-grade, if the possibility of FL is excluded.     

Lambert-Eaton myaesthenic syndrome: a possible association with Hodgkin's lymphoma

Lambert-Eaton myasthenic syndrome is a presynaptic neuromuscular junction disorder typically associated with small cell lung carcinoma. The characterstic electrophysiological abnormality is a low amplitude compound muscle action potential that shows a marked increment after maximal voluntary contraction or brief tetanic nerve stimulation. We describe a patient who had LEMS in association with Hodgkin's disease. A 61 year old woman presented with proximal muscle weakness 6 years following successful treatment of Hodgkin's disease. Her symptoms responded well to treatment with diaminopyridine. 9 additional patients have been described with LEMS in association with lymphoproliferative diseases. A systemic malignancy is usually found within 2 years of LEMS diagnosis but may present later. LEMS should be considered in patients with Hodgkin's disease presenting with muscle weakness.     

Follicular colonization of nodal marginal-zone B-cell lymphoma resembling follicular lymphoma: report of 6 cases

The formation of neoplastic B-cell follicles is accepted as a diagnostic criterion of follicular lymphoma. However, extranodal marginal-zone B-cell lymphomas (MZBLs) of mucosa-associated lymphoid tissue (MALT) type also sometimes contain numerous lymphoid follicles and may even have a predominantly follicular growth pattern. However, morphologic, immunohistochemical, and genotypic findings suggest that lymphoid follicles in extranodal MZBLs are neoplastic follicles formed as the result of colonization of previously reactive follicles by tumor cells (centrocyte-like cells). We present here 6 cases of nodal MZBL demonstrating a follicular growth pattern. Immunohistochemical study demonstrated that the tumor cells were CD10-, CD20+, CD79a+,CD138-, Bcl-2+, Bcl-6- and IRF4+. Residual nonneoplastic follicular center cells were CD10+, CD20+, CD79a+, Bcl-2-, and Bcl-6+. CD21/CD23 immunostain demonstrated a disrupted follicular dendritic cell pattern characteristic of follicular colonization in extranodal MZBL of MALT type. Taken in conjunction with the morphologic findings, nodal MZBL may also show a follicular growth pattern similar to extranodal MZBL of MALT type. The marginal-zone nature is most recognizable on immunohistochemistry, although the histologic appearance alone may cause some diagnostic problems. It is important for pathologists to consider this type of lesion in diagnostic practice.     

A duodenal follicular lymphoma associated with the lesion mimicking MALT lymphoma in terminal ileum and Bauhin valve

This is a case report of a 66-year-old woman who consulted us with a 1-week history of postprandial epigastric discomfort and dyspepsia. Upper and lower gastrointestinal endoscopy and double-balloon enteroscopy revealed lesions in three parts: a swelling with a shallow depression in the ampulla of Vater, flat and rough nodules in the jejunum, and a mixture of lymphoid polyposis and rough surface of follicular lymphoma of the terminal ileum and Bauhin valve. The histological, immunophenotypic, and molecular findings of the duodenal lesion confirmed the diagnosis of follicular lymphoma. We initially diagnosed the ileal lesion as MALT lymphoma immunohistochemically. However, Southern blot hybridization analysis for immunoglobulin heavy chain gene rearrangement showed identical monoclonal bands in both the duodenal and ileal lesions. The molecular cytogenetic studies were also positive for the 14;18 translocation in both lesions. Therefore, the true diagnosis of this ileal lesion should be a follicular lymphoma with marginal zone differentiation. Primary follicular lymphomas of gastrointestinal tract were suggested to have intermediate features between nodal follicular lymphoma and MALT lymphoma. This case is an important clue to prove the similarity of follicular lymphoma of gastrointestinal tract to MALT lymphoma and will be crucial in considering the therapeutic strategy.