Background

This is a low grade Non-Hodgkin's lymphoma (NHL), B-cell immunophenotype. Unlike most cases of diffuse small cell lymphomas, this lymphoma tends to occur with localized rather than generalized lymphadenopathy. This lymphoma is the lymph node equivalent of MALT lymphoma, lymphomas arising within mucosal-associated tissues such as the gastrointestinal tract and salivary glands. It is more accurately diagnosed as a marginal zone lymphoma.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Marginal zone lymphoma Monocytoid B-cell lymphoma
INCIDENCE	Less common than other types of diffuse small cell lymphomas
SEX (M:F)	Females are 2-5x more likely

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
Autoimmune disorders	Sjogren's syndrome

 

PATHOGENESIS

CHARACTERIZATION

Primary nodal marginal zone B-cell lymphoma arising from more than one clonal neoplastic population. Finch CN, Nichols M, Shrimpton A, Liu D, Hutchison RE. Department of Pathology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.

Arch Pathol Lab Med 2000 Dec;124(12):1816-9 Abstract quote Primary nodal marginal zone B-cell lymphoma is an uncommon monoclonal B-cell lymphoproliferative disorder. We report a case of a 79-year-old woman who presented with generalized lymphadenopathy. Histologic and immunohistochemical examinations of biopsy sections from an axillary lymph node were consistent with nodal marginal zone B-cell lymphoma. Flow cytometry analysis showed 2 distinct clonal B-cell populations expressing lambda or kappa light chain restriction. Subsequently, genomic deoxyribonucleic acid (DNA) isolated from a paraffin-embedded lymph node section was analyzed for the presence of gene rearrangements. Polymerase chain reaction (PCR) analysis of immunoglobulin heavy chain genes revealed 3 rearranged DNA bands, confirming the presence of more than one clonal B-cell population. These immunophenotypic and genotypic findings have not been previously described in association with this type of lymphoma. To our knowledge, this represents the first reported case of biclonal nodal marginal zone B-cell lymphoma.

 

CLINICAL VARIANTS	CHARACTERIZATION
SPLEEN
EXTRA-NODAL MALT LYMPHOMAS
PEDIATRIC
Marginal zone B-cell lymphoma in children and young adults. Taddesse-Heath L, Pittaluga S, Sorbara L, Bussey M, Raffeld M, Jaffe ES.	Am J Surg Pathol 2003 Apr;27(4):522-31 Abstract quote We describe the clinicopathologic findings of 48 cases of marginal zone B-cell lymphoma (MZL) in children and young adults, a disease that has been recognized previously only rarely in this age group. Patients ranged in age from 2 to 29 years, with pediatric patients (</=18 years) comprising 52% of the cases. As in adults, both primary nodal (N) and extranodal (E) MZL were observed. However, primary NMZL comprised the majority of the cases (67%) and demonstrated distinctive clinical and histologic features. NMZL occurred most commonly in young males (median 16 years, male/female ratio 5.4:1), with no underlying disease, presenting as localized adenopathy (90% stage I), with excellent prognosis and low rate of recurrence. In contrast, EMZL were much less common, and patients were older (median 24.5 years), with only a slight male predominance (male/female ratio 1.2:1). Most patients had localized disease (73% stage I) with excellent prognosis and infrequent recurrences. In addition, an association with autoimmune disease was observed in 19% of the EMZL. Both primary NMZL and EMZL in young patients shared similar morphologic and immunophenotypic findings to those described in adults and were monoclonal B-cell proliferations with monoclonality demonstrated in 94% of the cases. A common morphologic feature in NMZL was disruption of residual follicles resembling progressive transformation of germinal centers (PTGC), observed in 66% of the cases. Although the precise relationship of primary NMZL and the PTGC-like changes is unclear, it is possible that NMZL arises in a background of PTGC, as florid PTGC often occurs in young males. We conclude that EMZL in children and young adults are similar to EMZL of mucosa-associated lymphoma tissue occurring in older patients. However, pediatric NMZL appear to have distinctive clinical and histologic features.
SKIN
Marginal zone lymphoma with a dual cutaneous and leukemic presentation and an aberrant myeloid-monocytic phenotype. Keehn CA, Cualing H. Department of Pathology, University of south Florida college of Medicine, Tampa, FL, USA.	J Cutan Pathol. 2006 Mar;33(3):236-41. Abstract quote   Marginal zone lymphoma (MZL) is an indolent neoplasm of mature B cells, classified by the World Health Organization into three categories: nodal, splenic, and extranodal MZL of mucosa-associated lymphoid tissue (MALT lymphoma). We present an unusual case of MZL with cutaneous, leukemic, and bone marrow involvement at presentation and expression of an aberrant myeloid-monocytic phenotype. This case is best classified as MZL of leukemic subtype.
Primary Cutaneous Marginal Zone B-Cell Lymphoma Clinical and Therapeutic Features in 50 Cases J. J. Hoefnagel, MD; M. H. Vermeer, MD, PhD; P. M. Jansen, MD, PhD; F. Heule, MD, PhD; P. C. van Voorst Vader, MD, PhD; C. J. G. Sanders, MD; M. J. P. Gerritsen, MD, PhD; M. L. Geerts, MD, PhD; C. J. L. M. Meijer, MD, PhD; E. M. Noordijk, MD, PhD; R. Willemze, MD, PhD; for the Dutch Cutaneous Lymphoma Working Group	Arch Dermatol. 2005;141:1139-1145. Abstract quote Background  Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is a low-grade B-cell lymphoma that originates in the skin, with no evidence of extracutaneous disease. Studies focusing on the optimal treatment of PCMZL have not been published thus far. We describe 50 patients with PCMZL to further characterize clinical characteristics and outcome and, in particular, to evaluate our current therapeutic approach. Observations  The majority of the patients (36/50 [72%]) presented with multifocal skin lesions, and 14 patients (28%) presented with solitary or localized lesions. The initial treatment of patients with solitary lesions consisted of radiotherapy or excision, whereas patients with multifocal lesions received a variety of initial treatments, most commonly radiotherapy and chlorambucil therapy. Cutaneous relapses developed in 19 (48%) of 40 patients who had complete remission and were more common in patients with multifocal disease. After a median period of follow-up of 36 months, 2 patients developed extracutaneous disease, but none of the patients died of lymphoma. Conclusions  Patients with PCMZL who have solitary lesions can be treated effectively with radiotherapy or excision. For patients with PCMZL who have multifocal lesions, chlorambucil therapy and radiotherapy are suitable therapeutic options. In case of cutaneous relapses, the beneficial effects of treatment should carefully be weighed against the potential adverse effects.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
BONE MARROW
Comparative Study of Marginal Zone Lymphoma Involving Bone Marrow Sara A. Kent, MD, Daina Variakojis, MD, and LoAnn C. Peterson, MD	Am J Clin Pathol 2002;117:698-708 Abstract quote Few studies have characterized or compared the pathologic features of bone marrow involvement by extranodal (EMZL), splenic (SMZL), and nodal marginal zone lymphoma (NMZL). We evaluated 45 bone marrow biopsy specimens from 39 patients with marginal zone lymphomas. As previously reported, bone marrow involvement was frequent (100%) in patients with SMZL. We also identified lymphoma involving bone marrow in 11 (44%) of 25 patients with EMZL and 1 of 2 patients with NMZL. The patterns of infiltration were mixed in all groups; however, the extent of involvement was greater in SMZL than in EMZL. In addition, germinal centers were present in bone marrow biopsy specimens involved by lymphoma in 4 patients with SMZL. Intrasinusoidal infiltration was common (10/12 [83%]) and prominent in patients with bone marrow involvement by SMZL, but was not invariably present. Intrasinusoidal infiltration of the bone marrow also was not specific for SMZL since similar infiltrates, although subtle, also were found in patients with other small B-cell lymphoproliferative disorders, including 6 (55%) of 11 patients whose bone marrow samples were infiltrated by EMZL.
LYMPH NODE	Prominent sinusoidal pattern Medium to large cells with abundant clear cytoplasm and irregular or folded nuclei Resemble reactive monocytoid cells seen in the sinuses of lymph nodes Frequent presence of PMNs Frequent follicular colonization
Nodal marginal zone lymphoma: a heterogeneous tumor: a comprehensive analysis of a series of 27 cases. Camacho FI, Algara P, Mollejo M, Garcia JF, Montalban C, Martinez N, Sanchez-Beato M, Piris MA.	Am J Surg Pathol. 2003 Jun;27(6):762-71. Abstract quote We have reviewed the clinical, morphologic, immunophenotypical, and molecular features of a series of 27 cases of nodal marginal zone lymphoma with the aim of defining this entity more precisely. The series was characterized by a relatively favorable clinical course, with a low clinical stage at diagnosis (59% patients with clinical stage I-II) and a 5-year overall survival probability of 79%. However, the disease persisted in a relatively large fraction of the patients, thus yielding a 5-year failure-free survival probability of 22%. Molecular and immunohistochemical analyses of the series revealed heterogeneity in the frequency of IgV(H) somatic mutation and in the expression of IgD, CD43, MUM1, and CD38. Apart from the absence of nuclear Bcl10, no clear distinction could be made from the expression profiling of other B-cell lymphomas claimed to be derived from marginal zone B cells. Additionally, the immunophenotype of the tumoral cells in all cases but one differed from that described in monocytoid B cells. It was characterized by a Bcl2-, p21+, cyclin E+ profile. The analysis of apoptosis-regulator proteins disclosed abnormalities in the expression of survivin and active caspase 3, which could partially explain the abnormal regulation of apoptosis observed in these tumors. Molecular and immunohistochemical data obtained in this study strongly imply that there is significant heterogeneity among the cases included in the category termed nodal marginal zone lymphoma.
FLORAL
A "floral" variant of nodal marginal zone lymphoma. Karube K, Ohshima K, Tsuchiya T, Yamaguchi T, Kawano R, Suzumiya J, Harada M, Kikuchi M.	Hum Pathol. 2005 Feb;36(2):202-6. Abstract quote   Summary We describe 6 cases of a specific variant of nodal marginal zone lymphoma with "floral" lymph follicles in patients ranging in age from 18 to 66 years. All 6 patients had lymphadenopathy, either local (n = 5) or systemic (n = 1), and good performance status (0), and none had fever, weight loss, or night sweating. They all underwent excisional biopsy. Histologically, all lesions had a distinctive morphology, with proliferation of medium-sized atypical lymphoid cells in the marginal zone, hyperplastic lymph follicles with enlarged germinal centers, and a thickened mantle zone. In places, folliculolysis was observed. On immunohistochemical staining, the atypical lymphoid cells showed a B-cell phenotype (CD20 + ), IgM positivity in 2 of 5 cases, and negativity for CD5, CD10, CD23, CD43, bcl-6, and IgD. Polymerase chain reaction examination for immunoglobulin heavy chain in 5 cases showed monoclonality in all. Five patients did not receive adjuvant chemotherapy and had no recurrences. The patient with systemic lymphadenopathy received chemotherapy and had a complete response without relapse. This variant should be differentiated from the usual nodal marginal zone lymphoma because of its specific clinical and pathological features.

 

SPECIAL STAINS/ IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
Positive	Surface Ig (mostly IgM) Cytoplasmic Ig in about 40% Pan B (CD19, CD20, CD22, CD 79a) BCL-2 protein
Negative	CD5, CD10, CD23

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
MANTLE CELL LYMPHOMA
Mantle cell lymphoma disguised as marginal zone lymphoma. Jacobson E, Burke P, Tindle BH. Department of Pathology and Fletcher Allen Health Care, University of Vermont College of Medicine, Burlington, VT 05405, USA.	Arch Pathol Lab Med. 2005 Jul;129(7):929-32. Abstract quote   We report a case of mantle cell lymphoma histologically indistinguishable from marginal zone lymphoma. An 83-year-old man presented with a 9.0-cm, slowly enlarging axillary mass. Microscopically, the neoplastic process was largely interfollicular, surrounding residual follicular centers, some of which had discernible small lymphocyte mantles. Overall, the morphologic pattern was highly suggestive of marginal zone lymphoma. However, flow cytometric and immunohistochemical results, including cyclin D1 positivity, revealed an immunophenotype that fit with mantle cell lymphoma. The differential diagnosis of mantle cell lymphoma is broad, and it is well known that mantle cell lymphoma can assume a number of histologic appearances, including, infrequently, that of more indolent B-cell non-Hodgkin lymphomas. Although not pathognomonic, cyclin D1 positivity is highly specific for mantle cell lymphoma and is key in distinguishing these clinically dissimilar malignant lymphomas. In recent years, detection of cyclin D1 has expanded the recognizable histologic spectrum of mantle cell lymphoma.
PERIPERHAL T-CELL LYMPHOMA
Peripheral T-cell lymphoma mimicking marginal zone B-cell lymphoma. Uherova P, Ross CW, Finn WG, Singleton TP, Kansal R, Schnitzer B. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602, USA.	Mod Pathol 2002 Apr;15(4):420-5 Abstract quote Peripheral T-cell lymphoma (PTCL) may assume a variety of histologic and cytologic appearances. We describe eight cases of PTCL morphologically simulating marginal zone B-cell lymphoma. We reviewed PTCL cases diagnosed in our institution between 1990 and 2000 and selected eight cases for study based on the following criteria: small-cell morphology with abundant, clear cytoplasm and either marginal zone involvement by the neoplastic infiltrate in lymph node biopsies or lymphoepithelial lesions in extranodal biopsies. Histologic features and ancillary studies were reviewed. Patients included six women and two men with a median age of 53 years (range, 35 to 74 years). Six patients were diagnosed with primary nodal PTCL, and two presented with primary extranodal disease. The original diagnosis was PTCL in only four cases; three cases were diagnosed as atypical lymphoid infiltrate, and one case as benign lymphoepithelial lesion. Lymph node biopsies revealed partial effacement of the architecture with residual follicles surrounded by the neoplastic small cells. Extranodal sites included hard palate, tongue, tonsil, and submandibular glands; all but one case demonstrated lymphoepithelial lesions. Monoclonality was demonstrated in six of eight cases (rearrangement of T-cell receptor gene), and three of eight had an aberrant T-cell population by flow cytometry. The differential diagnosis of atypical lymphoid infiltrates with morphologic features of marginal zone B-cell lymphoma should include PTCL. This uncommon morphological mimicry should be recognized, because PTCL is an aggressive disease regardless of morphology and should be treated accordingly.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors	Transformation to a large cell lymphoma is a poor prognostic feature

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Extranodal MALToma

Lymphoma

Splenic Marginal Zone Lymphoma

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Last Updated April 10, 2006

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