Low-grade Marginal Zone B-cell Lymphoma Research Articles

Association of Pulmonary MALT Lymphoma and Sarcoidosis

Introduction Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by the chronic inflammation. Mucosa associated lymphoid tissue (MALT) lymphoma is a low-grade marginal zone B-cell lymphoma of MALT often etiologically associated with chronic inflammation in the underlying organ. A rare association between sarcoidosis and MALT lymphoma has been reported. Case Description We present the case of a 75-year-old woman who presented with chronic cough and dyspnea of several years' duration. She was found to have fluctuating lung infiltrates on serial imaging studies. A bronchial biopsy revealed chronic inflammation, and no evidence of infection. She was then treated with oral steroids with a transient benefit. However, the infiltrate and symptoms recurred, therefore 8 months later, she underwent repeat imaging. This showed a relapse of the infiltrate and enlarged mediastinal lymphadenopathy. The lung infiltrate was biopsied (percutaneously). This demonstrated a MALT lymphoma. Imaging studies done for staging showed a large retroperitoneal lymph node. A biopsy of this node revealed non-caseating granulomas, consistent with sarcoidosis. Chemotherapy with bendamustine and rituximab was initiated for therapy of the MALT lymphoma. Discussion A rare association between pulmonary MALT lymphoma and underlying inflammation caused by sarcoidosis has been previously described. In our patient, sarcoidosis was diagnosed in a biopsy of a retroperitoneal lymph node, but we suspect that there is likely involvement of the mediastinal nodes. Disclosures Rao: Bayer & Daiichi Sankyo:Consultancy.Daniel:GSK:Other: Paid speaker for COPD medications.

Primary Hepatic Marginal Zone B Cell Lymphoma : A Case Report and Review of the Literature

Primary hepatic lymphoma (PHL) is a very rare malignancy, and constitutes about 0.016% of all cases of non-Hodgkin's lymphoma and is often misdiagnosed. The optimal therapy is still unclear and the outcomes are uncertain. Among PHLs, a primary hepatic low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is extremely rare. We present a case of primary hepatic lymphoma (MALT lymphoma) treated with surgical resection and adjuvant chemotherapy. A 38-year-old Korean man, who was diagnosed with chronic hepatitis B 20years ago, was admitted for liver biopsy after liver lesions were detected on follow-up computed tomography scan (CT). Liver biopsy revealed the diagnosis of marginal zone B-cell malignant lymphoma (MALT lymphoma). The preoperative clinical staging was IE, given that no additional foci of lymphoma were found anywhere else in the body. The patient underwent left hemihepatectomy. Subsequently, the patient received two cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) regimen. After 15months of follow-up, the patient is alive and well without any evidence of disease recurrence. Although the prognosis is variable, good response to early surgery combined with postoperative chemotherapy can be achieved in strictly selected patients.

Impact of proliferative indices and tumor suppressor genes on treatment response in marginal zone lymphomas

Firstly, increased Ki67 and MUM-1 staining has been associated with worse prognosis in marginal zone B cell lymphomas (MZL). However, ours is the first study to assess the impact of proliferative indices on chemotherapy response. Secondly, loss of p53 and p16 tumor suppressor genes (TSG) has traditionally been associated with cancer progression. The significance of these markers in MZL was investigated. Thirdly, we explored the role of proliferative indices and tumor suppressor genes in identifying MZLs with significant plasmacytic differentiation (PD). Consecutive MZL cases (2006–2008) were identified. Slides were reviewed to confirm the diagnosis; immunohistochemical stains for Ki67, MUM-1, WT-1, p53, and p16 were subsequently performed and graded for percentage staining. Wilcoxon two-sample test and Pearson correlation coefficient were performed. Twenty-nine cases were analyzed. None of the assayed markers were correlated with treatment response. Ki67 and MUM1 expression, however, were correlated with PD (p = 0.0136 and p = 0.0042). A correlation between MUM1 and p16 staining was also seen (p = 0.0006). IHC assay for TSGs, p53 and p16, and proliferative indices (Ki67, MUM1, WT1) is unlikely to predict treatment response in low-grade MZL. Ki67 and MUM1 staining, however, may serve as a useful adjunct in ascribing PD.

Patchy Left-Sided Colitis: Primary Eosinophilic Colitis or Paraneoplastic Syndrome?

A 46-year-old man, affected by low-grade marginal zone B-cell lymphoma of splenic origin, presented with persistent abdominal pain, diarrhea, and hematochezia. The patient was not taking any medication. Blood analyses revealed augmented eosinophilic count (7.3%). Serological tests and stool tests were negative for parasitic/nonparasitic infections. The screenings for autoimmune disorders, allergies, and celiac disease were also negative. The colonoscopy showed a left-sided, patchy colitis, with zones of erythema, edema, and erosions covered with fibrin, alternated to macroscopically normal areas (Figure A and B).

B-Cell Lymphoma Associated with Sjögren's Syndrome among Japanese Patients : A Clinicopathologic and Immunohistochemical Study of 15 Cases

To clarify the clinicopathological findings of B-cell lymphoma associated with Sjögren's syndrome (SJS) among Japanese Patients, 15 individuals with this disease were studied. The patients, 14 females and one male, ranged in age from 41 to 73 years with a median age of 56 years. These lymphomas arose not only in the salivary gland (n=4) but also in other mucosal extranodal sites (n=5). Histologically, six cases were marginal zone B-cell lymphoma (MZBL) of the mucosa-associated lymphoid tissue (MALT) type, three cases were diffuse large B-cell lymphoma (DLBCL) + MALT type lymphoma, two cases were nodal MZBL and one case each was small lymphocytic lymphoma, Burkitt's lymphoma, CD10(+) DLBCL and DLBCL + nodal MZBL. Using in situ hybridization, numerous Epstein-Barr virus(+) tumor cells were detected only in the case of Burkitt lymphoma. There were no human-herpes type 8(+) tumor cells in any of the 15 cases. There was no API2-MALT1 fusion transcript in any of the eight cases examined. B-cell lymphoma associated with SJS also frequently affected extranodal organs in patients from Japan as well as from patients in Western countries. The majority of B-cell lymphomas in patients with SJS also appear to be low-grade MZBLs or high-grade lymphomas probably derived from MZBL both in Western countries and in Japan.

Marginal Zone B-Cell Lymphoma Among Primary B-Cell Lymphoma of Waldeyer's Ring: Histopathologic and Immunohistochemical Study of 16 Tonsillectomy Specimens

Two subtypes of marginal zone B-cell lymphoma (eg, mucosa-associated lymphoid tissue [MALT] type and splenic type) have been reported in the lymph node. To determine the presence or absence of marginal zone B-cell lymphoma of MALT type and the splenic type among Waldeyer's ring (WR) lymphomas, 16 tonsillectomy specimens were studied. Ten cases (63%) were marginal zone B-cell lymphoma. Among marginal zone B-cell lymphoma, 7 were the MALT type and the remaining 3 cases of marginal zone B-cell lymphoma were the splenic type. Moreover, 4 cases of 7 MALT-type lymphomas contained numerous large cells (diffuse large B-cell lymphoma arising from a low-grade marginal zone B-cell lymphoma of MALT type). The low incidence of primary mucosa-associated lymphoid tissue type lymphoma of WR in previous reports may be because it is difficult to correctly identify the characteristic histologic findings of MALT-type lymphoma because of the small biopsy size.

Dissemination of a Sjögren's syndrome–associated extranodal marginal‐zone B cell lymphoma: Circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy‐ and light‐chain variable‐region gene rearrangements

Both the genesis and outgrowth of extranodal marginal-zone B cell lymphomas (MZLs) of the mucosa-associated lymphoid tissue (MALT) type are generally thought to represent antigen-driven processes. We undertook this study to analyze lymphoma progression and dissemination outside of the MALT-type lesions. Histopathologic and Ig heavy- and light-chain variable-region gene (V(H/L)) analyses were performed in sequential tissue samples from a patient with primary Sjögren's syndrome (SS) with glandular (parotid) manifestations and subsequent nodal dissemination of a low-grade MZL. This MZL expressed a CD20+,CD27+,sIgM/kappa+,IgD-,CD5-,CD10-,Bcl-6-,CD23-,p53-,p21-,MDM2- phenotype and mutated V(H)1-69/D2-21/J(H)4alpha-V(kappa)A27/J(kappa)2 Ig rearrangements. Notably, circulating lymphoma cells from the parotid glands occurred transiently in the patient's blood, as detected by single-cell polymerase chain reaction. In addition, 2 minor B cell clones (clones 2 and 3, with V(H)3-07/D3-22/J(H)3b-V(lambda)3L/J(lambda)2/3 and V(H)3-64/D3-03/J(H)2-V(kappa)A19/J(kappa)2 rearrangements, respectively) were also detected in the parotid glands and blood, and 1 of these (clone 2) was also detected in the lymph nodes. Ig V(H/L) analyses revealed ongoing (antigen-driven) mutations of the glandular lymphoma rearrangements, but an invariant mutation pattern of their nodal counterparts. These data indicate coexpansion and transient (re)circulation of the lymphoma clone and 2 additional glandular B cell clones in a primary SS-associated extranodal MZL. Combined histologic and molecular features of the nodal lymphoma subclone reflect a process of "follicular colonization" that eventually froze the mutation machinery after accumulation of additional (antigen-driven) Ig V(H/L) mutations.

Magenlymphome und Gastrointestinale Stromatumoren (GIST)

Gastric lymphoma and gastrointestinal stromal tumours (GISTs) are rare malignancies of the upper gastrointestinal tract. The most common gastric lymphoma are low-grade marginal zone B-cell lymphoma (MZBCL) of MALT type. They develop as a consequence of chronic Helicobacter pylori infection, the histological hallmark are lymphoepithelial lesions. In early stages of disease, H. pylori eradication alone may lead to complete lymphoma remission in up to 75% of cases. Nonresponder or locally advanced lymphoma should be treated with radiation therapy. Advanced lymphoma may be treated with the nucleoside analogon cladribine within clinical trials. Based on clinical and novel molecular markers a risk stratification and a prediction of response to therapy might be possible in the future. GISTs are mesenchymal tumours that characteristically express CD-117 (c-kit). They are mostly localized in the upper gastrointestinal tract and are frequently diagnosed in an advanced stage. Conventional chemotherapy is ineffective. For resectable non-metastasized tumours surgical therapy is the treatment of choice. Imatinib is the first and so far only effective systemic therapy which is presently indicated in irresectable or metastasized GISTs. More than 80% of patients respond to imatinib therapy either with partial remission or stable disease. FDG-PET plays an important role in the early prediction of response to imatinib therapy. The optimal dosage and duration of treatment and the role of imatinib as adjuvant or neo-adjuvant therapy for GISTs remains to be defined.

Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLTspecific probes

The translocation of chromosome 11, long arm, region 2, band 1, to chromosome 18, long arm, region 2, band 1 (t(11;18)(q21;q21)) represents a recurrent chromosomal abnormality in extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (MALT) type and leads to a fusion of the apoptosis inhibitor-2 (API2) gene on chromosome 11 and the MALT lymphoma-associated translocation (MLT) gene on chromosome 18. A 2-color fluorescence in situ hybridization (FISH) assay, which can be used for the detection of t(11;18) in interphase nuclei and metaphase chromosomes on fresh and archival tumor tissue, was developed. The P1 artificial chromosome (PAC) clone located immediately telomeric to the MLT gene and the PAC clone spanning the API2 gene were differentially labeled and used to visualize the derivative chromosome 11 resulting from t(11;18), as evident by the overlapping or juxtaposed red and green fluorescent signals. The assay was applied to interphase nuclei of 20 cases with nonmalignant conditions and 122 B-cell non-Hodgkin's lymphomas (NHLs). The latter group comprised 20 cases of nodal follicle center cell lymphoma and diffuse large B-cell NHL, 10 cases of gastric diffuse large B-cell lymphoma, 10 cases of hairy cell leukemia, and 82 cases of MZBCL (41 extranodal from various locations, 19 nodal, and 22 splenic MZBCL) including 35 cases with an abnormal karyotype, 2 of which revealed t(11;18). By interphase FISH, t(11;18) was detected in 8 gastrointestinal low-grade MALT-type lymphomas including the 2 cytogenetically t(11;18)+ cases. In the 8 t(11;18)+ cases, the FISH results were confirmed by reverse transcriptase–polymerase chain reaction (RT-PCR) usingAPI2 and MLT specific primers. Our results indicate that t(11;18)(q21;q21) specifically characterizes a subgroup of low-grade MZBCL of the MALT-type and that the FISH assay described here is a highly specific and rapid test for the detection of this translocation.