Low-grade Malignant Lymphoma Research Articles

Expression of integrins and CD44 isoforms in non-Hodgkin's lymphomas: CD44 variant isoforms are preferentially expressed in high-grade malignant lymphomas.

Low- and high-grade malignant non-Hodgkin's lymphomas have been investigated by immunohistochemistry for their expression of various integrins and CD44 isoforms. Comparison with the expression patterns obtained in non-malignant adult lymph nodes revealed the following differences: alpha 6 and beta 4 integrins were expressed in several high-grade malignant lymphomas to a lower degree than in both the low-grade malignant lymphomas and the normal lymph nodes; all other integrins (alpha 2, alpha 4, alpha 5, alpha v, beta 1, beta 2, beta 3, and beta 7) did not exhibit significant differences in the expression levels between malignant and non-malignant tissues. The standard isoform of CD44 (CD44s) was highly expressed in all lymphoid tissues. Using CD44 exons-specific monoclonal antibodies, CD44 variant isoforms were not detected in non-malignant lymph nodes and were detected only rarely in low-grade malignant lymphomas. In contrast, high-grade malignant lymphomas expressed several CD44 variant isoforms, which included the products from the variant exons 3v, 6v, and 9v, but not 4v. Specifically, detection of exon 3v and 6v products indicates a more aggressive phenotype.

Helicobacter pylori gastritis and primary gastric non-Hodgkin's lymphomas.

To evaluate further the relation between gastric malignant lymphoma of the mucosa associated lymphoid tissue (MALT) and Helicobacter pylori. One hundred and sixty two surgical specimens of MALT lymphoma were retrospectively investigated to determine tumour type and inflammatory patterns. In 121 cases biopsy specimens obtained before surgery were available and stained with haematoxylin and eosin, periodic acid Schiff, Giemsa and Warthin-Starry stains. Residual lymphoid follicles were found less often in high grade malignant than in low grade malignant MALT lymphomas. Chronic active gastritis was shown within the mucosa at some distance from the tumours in 143 of 146 specimens. In all the cases for which biopsy specimens could be evaluated, colonisation of the mucosa by H pylori had occurred. Lymphoid follicles and lymphoid aggregates were detected in 82.7% of the antral, and in 85% of the body mucosa specimens. These data support the hypothesis that H pylori has an important role in the development of MALT lymphomas. Furthermore, the chronic inflammation preceding malignant transformation might enhance the probability of malignant transformation via chronic stimulation of the lymphoid tissue. This might in part indicate why MALT lymphomas occur most often in the stomach.

Zystische lymphoepitheliale Läsionen im Kopf-Hals-Bereich bei HIV-infizierten Patienten

Benign lymphoepithelial cysts (BLC) are rare disorders of salivary glands (0.6%). In patients infected by HIV, they are seen more often. In comparison to sporadic BLC, the patients are younger, the diameter of the cysts is up to 5 cm and they are often located bilaterally. At the Department of ENT, Head and Neck Surgery of the Ludwig-Maximilians-University, Munich, ten HIV-infected patients (two females) showed lymphoepithelial cysts (six times bilaterally). One of these revealed a metastasis of a small cell neoplasma near the cysts, another patient showed a non-Hodgkin's lymphoma of low grade malignancy (MALT-type), and one patient additionally had bilateral Warthin's tumours. The BLCs were mostly located in the parotid tail. In three cases, the cysts were found on the inferior border of the parotid and once at the submandibular gland. The age ranged from 27 to 71 years (medium 45.7 years). The mode of HIV infection was homosexuality five times, drug abuse twice, heterosexuality once, and blood products once. In two cases, the channel of transmission was unknown. The majority of the patients showed minor HIV illness (CDC II [n = 2]/CDC III [n = 4]); the rest had advanced immunodeficiency (CDC IV [n = 4]). All the cysts were examined by ultrasonography and NMR. According to the clinical findings and the general stage of health, BLCs were either enucleated (n = 8) or a superficial parotidectomy (n = 5) and selective biopsy of lymph nodes (n = 3) suspected to be malignant were performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-grade non-hodgkin's lymphoma after high-grade non-hodgkin's lymphoma in a child with ataxia teleangiectasia

Non-Hodgkin lymphomas (NHL) account for approximately 50% of neoplasms in patients with ataxia telangiectasia (AT). Prognosis is poor. Published data regarding the treatment of NHL in patients with AT suggested that these children respond poorly to therapy. The authors report on an infant with AT with mediastinal high-grade T-NHL who remained in continuous complete remission after chemotherapy. Diagnosis of AT was established after tumor diagnosis. The 7-month-old boy was treated according to the acute lymphoblastic leukemia-Berlin, Frankfurt, Münster 86 protocol. The therapeutic response was prompt, but therapy had to be stopped because of severe side effects. Surprisingly, the boy remained in a stable complete remission for 3 1/2 years. Then tumors in both kidneys occurred and the child died a few months later. Postmortem examination demonstrated large tumors in both kidneys caused by a low-grade malignant lymphoma of B-cell lineage. Congenital immune deficiency should be ruled out at diagnosis of rare malignancies in respect to age. NHL in patients with AT can be cured, but poor tolerance to chemotherapy has to be considered. Patients whose disease has been cured may be at high risk for development of a second independent malignancy.

Extensive small intestinal T-cell lymphoma of low-grade malignancy associated with a new chromosomal translocation

Primary T-cell lymphoma of the small intestine is rare, and most cases have proved rapidly fatal. We describe a case of lymphoma involving the small intestine uniformly and extensively in a 28-year-old man on initial examination seen with long-standing diarrhea, malabsorption, and recurrent episodes of intestinal obstruction. Clinical remission was obtained with pentostatin (2'-deoxycoformycin, supplied by Professor Catovsky, London UK) after the patient had failed to improve under conventional chemotherapy. Tumor specimens as well as mesenteric lymph node, liver, and bone marrow specimens were studied with conventional pathology and immunochemistry. Additionally, mesenteric lymph nodes and peripheral blood cells were studied for T-cell receptor (TCR) gene rearrangement and karyotype. Lymphoma cells were small T-lymphocytes with irregular pleomorphic nuclei, bearing the CD3, CD4 and TCR alpha-beta phenotype. Peripheral-blood cytology and bone marrow biopsy were normal. Southern blot analysis of the TCR beta-chain gene revealed the same monoclonal rearrangement in the mesenteric lymph nodes and peripheral blood lymphocytes. An as yet undescribed t(4;16)(q26;p13) translocation, involving the region where the interleukin-2 (IL-2) gene has been mapped, was present in the mesenteric lymph nodes and peripheral blood lymphocytes. We believe this is the first description of an extensive, small intestinal lymphoma of low-grade malignancy made up of monoclonal T-cells with a TCR alpha-beta and helper/inducer phenotype, associated with a novel chromosomal translocation.

２３年経過した胃原発悪性リンパ腫の一剖検例

We report herein a rare autopsy case of malignant lymphoma arising in the stomach, which recurred in the superficial lymph nodes and the skin 21 years after gastrectomy.The patient, a 46-year-old man, had a history of gastrectomy under the clinical diagnosis of gastric cancer 23 years ago. At that time, on histological examination, the resected stomach was diagnosed as peptic ulcer. About 10 years after gastrectomy, superficial lymph node swellings and therapy-resistant eruptions in the skin appeared. Twenty-one years after gastrectomy, malignant lymphoma of the submandibular lymph node was diagnosed. Reevaluation of the resected stomach and regional lymph nodes revealed the presence of atypical small lymphocytes with irregular nuclei throughout the gastric wall and in the lymph nodes, indicating neoplastic proliferation rather than inflammatory infiltrates. Seventeen months after the diagnosis of malignant lymphoma, the patient died due to disseminated intravascular coagulation and multiple organ failure.An autopsy disclosed hepatomegaly, splenomegaly and enlargement of the systemic lymph nodes. Histologically small to medium-sized atypical lymphoid cells infiltrated in the liver, spleen, systemic lymph nodes, kidneys, lungs, pericardium, pancreas, gallbladder and adrenal glands. The most interesting finding was the presence of Hodgkin-like cells admixed with small to medium-sized atypical lymphoid cells, especially in the liver, spleen, and lymph nodes.An immunohistochemical examination on formalin-fixed and paraffin-embedded sections revealed that atypical lymphoid cells were reacted for T-cell markers (MT-1, UCHL-1, OPD4) but Hodgkin-like cells were not reacted for those antibodies.In conclusion, the present case is interpreted that low-grade malignant lymphoma arising in the stomach transformed into a more aggressive type after 23 years.

High-Grade Transformation of Chronic Lymphocytic Leukemia and Low-Grade Non-Hodgkin’s Lymphoma:Genotypic Confirmation of Clonal Identity

The abrupt appearance of a high-grade tumor in patients with low-grade malignant lymphoma usually is associated with an accelerated clinical disease course. The high-grade lymphoma may take a variety of histologic forms and often, but not always, represents evolution of the original low-grade disease, as shown by immunophenotypic or immunogenotypic studies. The authors describe the transformation of a variety of low-grade B-cell neoplasms to high-grade tumors in four patients. The initial diagnoses included chronic lymphocytic leukemia and mantle cell lymphoma in one patient each and low-grade follicular lymphoma in two patients. The high-grade tumors were classified as lymphoblastic lymphoma in one patient and small noncleaved cell lymphoma in two patients. The high-grade component manifests primarily in the peripheral blood as circulating blast-like cells consistent with large-cell lymphoma in the remaining patient. In each case, immunophenotypic studies showed identical monoclonal surface immunoglobulin expression on the low- and high-grade tumors. Immunoglobulin heavy chain gene and kappa light chain gene studies showed identical clonally rearranged bands in paired samples from three of the four patients, a finding indicative of clonal identity. Unexpectedly, dissimilar immunoglobulin light and heavy chain gene rearrangements were detected in the paired samples from one patient with previously diagnosed follicular lymphoma, making the relationship of the two tumors from this patient uncertain; however, additional Southern blot analysis of the bcl-2 gene showed identical rearrangements in both lesions. Furthermore, polymerase chain reaction across the t(14;18) major breakpoint region in both tumors amplified nucleotide fragments of identical size, confirming the clonal identity of the low- and high-grade lymphomas despite the divergent immunoglobulin gene studies. These studies show that low-grade malignant lymphomas of small lymphocytic, mantle cell, or follicular small cleaved cell types may assume high-grade morphologic characteristics, that this change is the result of transformation of the preexisting low-grade malignant neoplasm, and that this progression, like typical Richter's syndrome, is associated with a dramatically accelerated clinical course. In addition, these studies confirm previous reports that disparate immunoglobulin light and heavy chain gene rearrangements are not necessarily an indicator of different cellular origins, and additional genotypic studies occasionally may be required to show the clonal identity of the cell population involved in these morphologic transformations.(ABSTRACT TRUNCATED AT 400 WORDS)

Cutaneous T cell lymphoma of signet ring cell type: a specific clinico/pathologic entity.

We describe a new case of signet ring cell peripheral T cell lymphoma in a 45-year-old man. This lymphoma had a very indolent course, since--without treatment--the clinical staging has shown no evidence of disease progression 11 years after initial symptoms. Immunophenotype indicated pan T antigens (Leu 4 CD3, Leu 1 CD5) and T suppressor cytotoxic antigen (IOT8 CD8) expression. Several T antigens (Leu 5b CD2, Leu 9 CD7, Leu 3a CD4) were not expressed. The proliferation index was less than 5% with Ki 67 monoclonal antibodies. The ultrastructural study showed characteristic cytoplasmic vacuoles containing microvesicles. Five cases of signet ring T cell lymphoma, which were very similar to our case, have been previously described. Their characteristics were primary cutaneous presentation, indolent course, good response to current therapies and a long survival period. The indolent course of these signet ring cell lymphomas may indicate that this type of lymphoma is a low grade malignant lymphoma and not only a morphological pattern.

G2M arrest and apoptosis in murine T lymphoma cells following exposure to 212Bi alpha particle irradiation

Asynchronous exponentially growing EL4 murine T lymphoma cells were exposed either to high LET α-radiation from 212Bi-DTPA or to γ-radiation from a 137Cs source. Radiation-induced cell cycle perturbation was studied by flow cytometry. Alpha irradiation, like γ, transiently arrested cells in the G2M phase in a dose-dependent manner. The maximum percentages of cells accumulated in G2M 18 h after α- and γ-irradiation were comparable, though the dose-response relationships differed. The “RBE” value for G2M block for α- versus γ-radiation was approx. 4. Electron microscopic studies of the cell samples where a large proportion of cells were arrested in G2M showed subcellular changes in nuclear membrane and the presence of morphologically apoptotic cells. Biochemical analysis of DNA from irradiated cells by agarose gel electrophoresis revealed more extensive DNA fragmentation for α- vs γ-irradiation, even at relatively low total doses. We conclude that the high LET radiation is more efficient in inducing G2M block and apoptosis in EL4 lymphoma cells. The overall radiosensitivity of some high and low grade malignant lymphoma cells to radiation may correlate with these processes. The clinical implications of 212Bi-induced G2M delay may be particularly important for biologically targeted high LET radiopharmaceutical therapy.

Severe immunodeficiency in patients treated with fludarabine monophosphate.

Fludarabine monophosphate (FAMP) has been shown to be highly effective against low-grade malignant B-cell lymphoproliferative diseases. Because some opportunistic infections were observed in patients treated with FAMP, we investigated the influence of this drug on several parameters of immunocompetence. For 17 consecutive patients treated with FAMP for CLL or low-grade malignant lymphoma we studied T-cell subpopulations during and after therapy by flow cytometry and our findings were correlated with the clinical course of their disease. A pronounced decrease in the various T-cell subpopulations was seen in all cases, that for CD4+ cells was still present 11-13 months after the end of the therapy. In 7 patients a severe opportunistic infection developed; the outcome was fatal in 2 cases. Only 5 patients did not experience any serious infection. These results show that FAMP therapy in a dose of 25 mg/m2/day for 5 d every 4 weeks might be too toxic for patients with very advanced disease. However, in view of the efficacy of FAMP, the possibility of less intensive schedules for these advanced cases should be explored.

Long-term follow-up of patients with low-grade malignant lymphomas treated with doxorubicin-based chemotherapy or chemoimmunotherapy.

We reviewed survival data of patients with low-grade lymphoma entered on Southwest Oncology Group (SWOG) lymphoma trials in 1972 to 1983 to determine the utility of doxorubicin-containing therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]) in such patients. We identified all patients with low-grade lymphoma, no prior therapy, and stage III or IV disease who were treated with full-dose CHOP induction therapy on any arm of SWOG studies 7204, 7426, or 7713. Survival data for this group of patients were correlated with pretreatment prognostic factors, including histology, patient age, sex, symptom status, performance status, bone marrow or extranodal involvement, and the number of disease sites. The effect of maintenance treatment was also assessed. Four hundred fifteen patients met criteria for inclusion in the study group. With median follow-up periods of 12.8 years (maximum, 19.8 years), the median survival duration was 6.9 years. Survival was significantly shorter in patients with follicular mixed or small lymphocytic histology, age greater than 40 years, male sex, B-symptom status, and SWOG performance status greater than 1. Multivariate regression analysis showed histology, age, and sex to be independent predictors of survival. There was no definite survival plateau of cured patients in any subgroup, although the survival curve for follicular mixed histology patients showed long-term survival of approximately 25%. Maintenance therapy did not prolong survival. Doxorubicin-containing treatment did not prolong the overall median survival of low-grade lymphoma patients compared with results with less-aggressive programs.

The role of interferon alfa 2b (IFN) as maintenance therapy in patients with low-grade malignant lymphoma

The role of interferon alfa 2b (IFN) as maintenance therapy in patients with low-grade malignant lymphoma

On the influence of alpha-2 interferon (roferon-a) on remission duration in patients with stages III and IV low grade malignant non-Hodgkin's lymphoma

On the influence of alpha-2 interferon (roferon-a) on remission duration in patients with stages III and IV low grade malignant non-Hodgkin's lymphoma

左えきかに限局した悪性リンパ腫に対して外科的治療を加えた１例

A case of low grade malignant lymphoma in the axillary region of a 49-year-old man is described. The patient presented with an asymptomatic thumb-tip sized and elastic-soft tumor of the left axillary region in the Summer of 1988. The tumor gradually increased to become first-sized in June 1992. The pathological diagnosis from a biopsy specimen was non-Hodgkin's malignant lymphoma. Lymph nodes in other regions did not increase in size, and therefore the axillary tumor was dissected. The period of Postoperative follow-up is short, but at present there has been no relapse. Although stage 1 non-Hodgkin's lymphoma, such as this case, is generally treated with radiation therapy, surgery was performed in this case. The authors consider that low grade lymphoma may be dissected, thereby avoiding any possible post radiotherapy disorders.

Bone marrow histopathology and prognosis in malignant lymphomas.

Bone marrow trephine biopsies of patients with non-Hodgkin's malignant lymphomas (ML), followed for at least 4 years, were investigated using univariate and multivariate survival analyses to detect which anagraphic data and histomorphologic medullary patterns before therapy were related to the prognosis. In 234 ML (146 low grade, 88 high grade), univariate analysis showed that survival was reduced by bone marrow involvement, absence of reactive lymphoid nodules, and low marrow cellularity. Moreover, in low-grade ML, patients 50 years or older and showing absence of myeloid hyperplasia, excess of hemosiderin and mast cell hyperplasia had significantly lower-survival rates. The prognostic relevance of these parameters did not change when cases without marrow involvement were separately analyzed. Multivariate analysis showed that, besides marrow involvement, age and myeloid hyperplasia had significant prognostic importance in low-grade ML, and lymphoid nodules in high-grade ML. Our data confirm the value of bone marrow histopathology in ML and indicate that the prognosis is related not only to medullary involvement but also to the morphology of the uninvolved marrow.

Comparative quantitative study of Ki-67 Antibody Staining in 78 B and T cell malignant lymphoma (ML) using two image analyser systems

Total Ki-67 stained area percentage was studied in 32 B and 46 T malignant lymphomas (ML) using two different image analyser systems (TAS, Leitz; SAMBA TM 2005, TITN) respectively. The total Ki-67 area percentage was highly correlated to the number of Ki-67 positive cellular profiles (B-ML, r = 0.93; T-ML, r = 0.88), indicating that area percentage is a reliable alternative method to the manual cell counting. Image analysis allows quicker measurements, appropriate to large and strictly lymphomatous regions. The cell image processor (SAMBA TM 2005, TITN) linked to a color video camera was more suitable for immunohistochemical sections and allowed more automated and faster measurements than the texture analyser (TAS, Leitz) linked with a black and white camera. Alkaline phosphatase technique with fast red as chromogen was more suitable for the detection of Ki-67 stained area by thresholding than peroxidase technique with aminoethylcarbazol or with diaminobenzidine as chromogens. Significant differences were found between low and high grade in B and T ML according to the Kiel classification (mean values +/- SD of 7.7 +/- 3.8% and 16.6 +/- 6.2% in B-ML and of 10.2 +/- 7.9% and 25.6 +/- 16.3% in T-ML respectively). In follicular B-ML, considering follicular areas only, values were comparable to high grade ML; angioimmunoblastic-lymphadenopathy-like (AILD-type) T-ML belonging to low grade ML showed similar values to pleomorphic T-ML with medium and/or large cells belonging to high grade ML.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular Kinetics, Dosimetry, and Radiobiology of α-Particle Radioimmunotherapy: Induction of Apoptosis

Though clinical results for radioimmunoconjugate therapy of most common epithelial tumors have been disappointing, dramatic responses have been observed repeatedly in the treatment of high- and low-grade malignant lymphomas. This high clinical responsiveness after radioimmunoconjugate therapy sometimes appears to be out of proportion to the calculated radiation dose absorbed by the lymphoma tissue. Here we describe some key aspects of the kinetics, dosimetry, and cellular radiobiology of murine lymphoma cells exposed to 212Bi-radiolabeled alpha-particle-emitting immunoconjugates specific for the differentiation antigen Thy 1.2. Approximately 25 cell-bound alpha-particle-emitting immunoconjugates per target cell were required to reduce clonogenic survival by 90% (the radiobiological D10). Serial kinetic analyses of the antibody and radioisotope components of the immunoconjugates revealed significant levels of dechelation and up to 7.5% cellular internalization of the isotope. Cellular radiation dosimetry performed by Monte Carlo computer simulation of alpha-particle energy deposition patterns based on the observed radiopharmacokinetics showed that the D10 resulted from approximately four alpha-particle traversals through the nucleus, corresponding to an absorbed radiation dose of approximately 0.95 Gy to the cell nucleus. Electron micrographs and DNA gel studies of murine lymphoma cells undergoing radioimmunoconjugate therapy in vivo and in vitro demonstrated bizarre blebbing patterns, condensation of chromosomal material, and internucleosomal DNA fragmentation patterns characteristic of programmed cell death (apoptosis). We conjecture that the efficacy of radioimmunoconjugates against responsive cell types may be the result of passive DNA damage by ionizing radiation and the initiation of apoptosis in response to radioimmunotherapy.

Prednimustine and mitoxantrone (PmM) in patients with low-grade malignant non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), and prolymphocytic leukemia (PLL)

Thirty-five patients with a mean age of 60.6 years (44-78 years, 22 male, 13 female) with advanced low-grade non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), or prolymphocytic leukemia (PLL) were treated every 4 weeks with prednimustine 100 mg/m2 p.o. d 1-d 5 and mitoxantrone 8 mg/m2 i.v. d 1 and d 2. Seven patients had CLL, one lymphocytic NHL, two PLL, 13 immunocytoma, nine centroblastic/centrocytic NHL, and three centrocytic NHL. Twenty-five patients were pretreated. The subjective toxicity of the treatment was mild, with no WHO grade-3 alopecia, polyneuropathy, cardiotoxicity, mucositis, nausea, or vomiting. Hematologic side effects with WHO grade-4 granulopenia and thrombopenia were experienced by 26% and 23% of the patients, respectively. The overall response rate (CR+PR) was 72% for lymphoma patients and 37% for CLL patients, with a median remission duration of 14.6 months. The maximum response was achieved after a median of two treatment courses. Prednimustine with mitoxantrone is a subjectively well tolerated treatment for low-grade malignant NHL, to be further evaluated in phase-III studies. The regimen may shorten the duration of treatment, saving time-consuming out-patient visits and costs.

Reactivity of the Endothelial Cell Marker EN4 With Malignant B-Cells in Low-Grade Malignant Lymphomas and with Subpopulations of B- and T-Cells in Blood and Reactive Lymphoid Tissue

Expression of the endothelial cell marker EN4 was studied by immunohistochemical staining in 56 biopsies of malignant Non-Hodgkin lymphomas (NHL), Hodgkin's disease, reactive lymphatic tissue and in non-lymphatic organs and by flow-cytofluorometry in blood and tonsil cell suspensions.In addition to positivity in endothelial cells, MAb EN4 reacted with numerous leukocytes localized in perivascular zones, mostly T lymphocytes and monocytes/macrophages. Neoplastic B cells of low-grade lymphocytic and centrocytic NHL, immunocytomas and neoplastic T (CD3+/CD4+) cells from one lymphoblastic lymphoma were also positive. In contrast, however, centroblastic/centrocytic NHL, high grade malignant B-cell lymphomas and Reed-Sternberg cells in Hodgkin's disease were negative.The majority of B-cells and CD8 positive T-cells both in blood and tonsil cell suspensions were EN4 positive. CD4+ cells were EN4 positive but to a lesser extent. All CD14 positive monocytes, all granulocytes and the majority of CD56 positive cells...

節外性の低悪性度リンパ腫 ＭＡＬＴリンパ腫を含む

Malignant lymphoma (ML) of low grade malignancy includes small lymphocytic lymphoma and follicular lymphoma other than large cell type. Recent study revealed intermediate lymphocytic lymphoma (ILL) and monocytoid B-cell lymphoma (MBCL) to be new types of ML of low grade malignancy. These two types of ML are fundamental elements of ML developing in so-called mucosa associated lymphoid tissue (MALT). In this report, results of our study on ILL and MBCL of extranodal organs were described.ILL is composed of small lymphoid cells with morphologic features between those of well-differentiated lymphocytic lymphoma and poorly differentiated lymphocytic lymphoma of follicular center cell origin. The frequency of ILL in nodal and extranodal non-Hodgkin's lymphoma was almost same. The frequency was high in salivary gland and thyroid lymphoma. Histologic features of chronic lymphocytic thyroiditis (CLTH) are constantly observed in cases with thyroid lymphoma. Histologic findings suggestive of Sjogren's syndrome such as formation of lymphoid follicles and myoepithelial islands were observed in one third of cases with salivary lymphoma. These findings suggested that autoimmune diseases such as CLTH and Sjogren's syndrome played an important role in the etiology of thyroid and salivary lymphoma.MBCL shows the proliferation of the atypical lymphoid cells with abundant and pale cytoplasm and reniform nucleus. The high incidence of Sjogren's syndrome in cases with MBCL was evident suggesting the etiologic role of Sjogern's syndrome for development of MBCL. Six cases of MBCL developing in extranodal sites such as thyroid, stomach, and rectum were described below. Two of three patients with thyroid lymphoma presented with positive serum antithyroid antibodies, and one had CLTH. In all three patients with gastric or rectal lymphoma, reactive lymphoid hyperplasia was present near the tumors. These findings suggested the important role of long-standing inflammation for development of MBCL as well as ILL.