Lymphoma of the ocular adnexa: A study of 353 cases

We studied the cases of 353 patients with lymphoma involving the ocular adnexa diagnosed at the Massachusetts General Hospital between 1974 and 2005. The patients included 153 males and 200 females, aged 7 to 95 years, with a mean age of 64 years. In 277 cases, there was no known history of lymphoma. Seventy-six patients had a history of lymphoma, with the ocular adnexa being involved at relapse or with progression of the previously diagnosed lymphoma. The patients had marginal zone lymphoma (182 cases), follicular lymphoma (80 cases), mantle cell lymphoma (18 cases), small lymphocytic lymphoma/chronic lymphocytic leukemia (13 cases), lymphoplasmacytic lymphoma (4 cases), splenic marginal zone lymphoma (2 cases), low-grade B cell, not subclassified (19 cases), precursor B lymphoblastic lymphoma (3 cases), diffuse large B-cell lymphoma (26 cases), and 1 case each of high-grade B-cell lymphoma, not subclassified, peripheral T-cell lymphoma, unspecified type, extranodal NK/T-cell lymphoma, nasal type, and Hodgkin lymphoma, nodular sclerosis type. Almost all marginal zone lymphoma patients (168 of 182, 92%) had primary ocular adnexal lymphoma. Fourteen marginal zone lymphoma patients (8%) had a prior history of lymphoma, usually arising in another extranodal site. Twenty-five of 80 (31%) follicular lymphoma patients had a prior history of lymphoma, usually arising in lymph nodes. Patients with mantle cell lymphoma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, and splenic marginal zone lymphoma almost always had a prior history of lymphoma or were known to have widespread disease at the time of diagnosis of ocular adnexal lymphoma. A subset of the diffuse large B-cell lymphomas were associated with large destructive masses involving adjacent structures such as paranasal sinuses, raising the possibility that they may have arisen from one of the adjacent structures and involved the ocular adnexa by direct extension. The relatively high proportion of low-grade lymphoma, not subclassified, highlights the difficulty that may arise in distinguishing different types of low-grade lymphoma, particularly when biopsies are small and artifactually distorted. Ocular adnexal lymphoma is primarily a disease of older adults, with a slight female preponderance. Most lymphomas are low-grade B-cell lymphomas, with marginal zone lymphoma being by far the most common type. Marginal zone lymphoma typically involves the ocular adnexa primarily, whereas other types of low-grade B-cell lymphoma often involve the ocular adnexa secondarily. High-grade B-cell lymphomas only occasionally involve the ocular adnexa, and T-cell lymphoma, NK-cell lymphoma, and Hodgkin lymphoma are only rarely encountered in this site.     

Pulmonary lymphoma of mucosa-associated lymphoid tissue type followed as a long-standing indeterminate lesion in immunoglobulin M-type paraproteinemia

An 82-year-old woman with monoclonal immunoglobulin (Ig) M-type paraproteinemia had a large opacity in the right lung field. The abnormal shadow on roentgenogram had persisted for more than 6 years since the initial diagnosis of paraproteinemia, which had been diagnosed as Waldenstr?m’s macroglobulinemia (WM). Computed tomography revealed the lesion as a pulmonary tumor which was finally diagnosed as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) after surgical removal. MALT lymphoma constitutes the majority of primary pulmonary lymphomas and is often associated with monoclonal IgM-type paraproteinemia as well as WM, a distinctive lymphoproliferative disorder. Pulmonary MALT lymphoma should frequently be suspected in case of an indeterminate pulmonary tumor with IgM-type paraproteinemia.     

Marginal zone lymphoma of the breast—A diminished role for surgery

IntroductionPrimary breast lymphoma by definition is localized to one or both the breasts with or without involvement of regional lymph nodes with no other extra mammary site involvement. Role of surgery in the treatment armamentarium is less well defined.Presentation of caseA 62 year old post-menopausal lady was found to have 1.2 × 1.2 × 0.6 cm mass in the left breast on diagnostic mammography. Core needle biopsy reveals marginal zone lymphoma. Complete staging work-up was performed which was negative for regional spread and metastatic foci. She was diagnosed to have a localized stage IE extra nodal low grade marginal zone lymphoma of the MALT type involving breast. She received radiotherapy to the breast and is in remission at follow up after one year.DiscussionAccurate diagnosis requires adequate tissue biopsy either by a core needle or a surgical biopsy for histopathologic evaluation and immunophenotyping. Immunohistochemically the tumors are positive for pan B-cell markers (CD 19, CD 20, CD22, and CD 79a) and lack T cell markers. For stage IE Marginal zone lymphoma radiotherapy alone and for stage IIE combined chemo-radiation offers the best possible control of the disease. Progression free survival for MZL is better than diffuse large B-cell lymphoma.ConclusionAt present the best evidence support radiotherapy in localized disease and combined chemo-radiation in advanced disease. Role of surgery is minimal and is seen in case of diagnostic dilemma. Rarity of the diagnosis precludes large scale prospective studies making therapeutic decisions difficult and challenging.     

Splenic Marginal Lymphoma and Glomerulonephritis: Case Report and Review of the Literature

Malignant lymphomas can affect kidneys in several ways. They may precipitate acute renal failure by causing ureteral or renal vascular obstruction, or by direct renal parenchymal infiltration. Furthermore, they may insult renal function via paraneoplastic mechanisms such as hypercalcemia. Lymphomas only rarely can cause glomerulonephritis (GN). We report a case of a 72-year-old male who presented with mild renal function impairment, proteinuria, and microscopic hematuria, suggesting active glomerulonephritis, and pancytopenia of immune origin. A bone marrow biopsy led to a diagnosis of splenic marginal zone lymphoma. Although a kidney biopsy was not performed, glomerulonephritis was attributed to the lymphoma and splenic marginal zone lymphoma-related glomerulonephritis was the final diagnosis. The course of splenic marginal zone lymphoma is extremely indolent. The first manifestation in some patients can be immune cytopenia or other autoimmune phenomena. These patients may respond well to corticosteroids. Therefore, our patient was started on prednisolone resulting in a good hematologic response. Renal function also improved and proteinuria and hematuria disappeared, suggesting a lymphoma-related origin of the GN. Two years after full steroids withdrawal, the patient remained stable with a good renal function and daily protein excretion less than 300 mg. Lymphomas rarely are the cause of secondary glomerulonephritis; however, with a lack of an apparent cause, the clinician should be aware of them, particularly in the elderly with autoimmune manifestations.     

Splenic marginal zone lymphoma with micronodular T-cell rich B-cell lymphoma

The types of B-cell lymphoma commonly involving the spleen include splenic marginal zone lymphoma and T-cell/histiocyte-rich large B-cell lymphoma. We describe a unique case of splenic marginal zone lymphoma associated with micronodular T cell/histiocyte-rich large B-cell lymphoma in the red pulp, a combination that has not previously reported in the literature.     

Primary splenic marginal zone lymphoma with bladder metastases mimicking interstitial cystitis

We report the case of a 76-year-old patient with a past medical history of low-grade chronic lymphocytic leukaemia who presented with severe chronic bladder symptoms attributed to interstitial cystitis. She underwent cystectomy and ileal conduit formation after the failure of all conventional treatment. Bladder histopathology revealed primary splenic marginal zone lymphoma. Literature review shows the rarity of such non-hematopoietic visceral metastases. This may represent the first reported splenic marginal zone lymphoma with bladder involvement and highlights the clinical and histological similarities with interstitial cystitis.     

Pathologic and clinical features of primary pulmonary extranodal marginal zone B-cell lymphoma of MALT type

We reviewed pathologic, phenotypic, and clinical features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type primarily involving lung to address unresolved questions regarding behavior and pathologic features of unambiguously diagnosed pulmonary MALT lymphoma. Lung specimens from 50 patients were reviewed. Forty-one had low-grade MALT lymphoma. Nine had low-grade MALT lymphoma and diffuse large B-cell lymphoma. The patients included 32 women and 18 men with a median age of 68 years (range 34-88 years). Half of the patients were asymptomatic at the time lymphoma was diagnosed. Radiographic abnormalities were more commonly unilateral (37 patients) than bilateral (12 patients). Localized masses or nodules occurred in 39 patients. Associated autoimmune disorders (29%) and monoclonal gammopathies (43%) were common. Low-grade lymphomas formed intraparenchymal masses composed of centrocyte-like cells, plasmacytoid lymphocytes, and plasma cells that formed lymphoepithelial lesions and exhibited a lymphangitic growth pattern. Mediastinal lymph nodes were involved histologically in 44% of cases. Lymphoma-specific survival was 71.7% at 10 years, and overall survival was significantly worse than age-and gender-matched control patients. None of the following features predicted those patients who had an adverse outcome: systemic symptoms, presence of autoimmune disorders or paraproteinemia, anatomic distribution and number of pulmonary lesions, lymph node involvement, or presence of anthracycline-treated large B-cell lymphoma.     

Splenic marginal zone cell lymphoma.

We describe four female patients with primary splenic low-grade non-Hodgkin's B-cell lymphomas with the morphology and immunophenotype of splenic marginal zone lymphocytes. The patients presented with splenomegaly, anemia, and weight loss. The bone marrow was involved in all four cases. Liver involvement was found in one patient; and in another, a CT scan revealed lymphadenopathy in the chest and abdomen. The histology of the spleen was characterized by broad concentric strands of monomorphic medium-sized lymphocytes around lymphoid follicles in one case and infiltrating follicles in two cases. Selective replacement of follicles was seen in one case. Tumor in splenic hilar lymph nodes (four cases) and liver (one case) was similar. Three patients remain well 4, 9, and 12 months, respectively, after splenectomy without further treatment. One patient who received chemotherapy died 1 year after splenectomy.     

Management of neurotropic low-grade B-cell lymphoma: report of two cases

BACKGROUND: Low-grade lymphomas do not commonly involve the central or peripheral nervous system. METHODS: Case report and review of the literature of two cases of B-cell lymphoma of the extranodal marginal zone type involving the head and neck region with evidence of extensive neurotropism are detailed in this report. RESULTS: One patient was initially seen with a mass in the temporalis muscle and the other with a masticator space mass. The clinical course was indolent in both cases, although associated imaging studies suggested a more aggressive tumor. Both patients were treated with moderate-dose radiotherapy only. At the time of writing, one patient has no evidence of disease 6.5 years after treatment and the other at 6 months. CONCLUSIONS: This suggests that some marginal zone lymphomas exhibit a low-grade clinical course despite an aggressive radiographic pattern of perineural and neurotropic spread. This type of lymphoma might be effectively treated with moderate-dose radiotherapy.     

Primary Cutaneous B-Cell Lymphomas

B-cell lymphomas occurring in the skin often tend to be of systemic origin with secondary cutaneous involvement. Primary cutaneous B-cell lymphomas tend to be indolent disorders, with the exception of primary cutaneous diffuse large B-cell lymphoma–leg type (PCDLBCL-LT). In indolent conditions, the distinction between cutaneous lymphoma and cutaneous lymphoid hyperplasia can be difficult. Integration of all available information, including the clinical setting, is crucial to arriving at the appropriate diagnosis. In this review, we cover the diagnostic approaches to primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, and PCDLBCL-LT, and discuss their differential diagnosis.     

Mucosa-associated lymphatic tissue lymphoma of the lower lip in a child

Mucosa-associated lymphatic tissue lymphoma of the lip in a child is a very rare clinical entity whose cause is poorly understood. We describe an 11-year-old boy who presented with a 5-month history of an asymptomatic nodule on the lower lip with the clinical appearance of a benign mucocele.After surgical excision of the lower lip lesion, lymphocyte phenotypic analysis and histologic examination of the specimen disclosed an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphatic tissue type of the buccal minor salivary glands.Mucosa-associated lymphatic tissue lymphoma of the lip may clinically resemble a large mucocele. To prevent a delayed detection of lip mucosa-associated lymphatic tissue lymphoma, an incisional biopsy of large mucous cysts of the oral mucosa before marsupialization is recommended.     

BCL-2 is consistently expressed in hyperplastic marginal zones of the spleen,abdominal lymph nodes,and ileal lymphoid tissue

BCL-2 is an antiapoptotic protein overexpressed in follicular lymphomas, principally as a result of the t(14;18)(q32;q21), and useful in distinguishing follicular lymphoma (usually BCL-2 positive) from follicular hyperplasia (BCL-2 negative). BCL-2 is also overexpressed in other lymphoma types without the t(14;18), including marginal zone B-cell lymphoma, because of other, poorly understood mechanisms. It has been suggested that BCL-2 immunoreactivity can distinguish between malignant (BCL-2 positive) and reactive (BCL-2 negative) marginal zone B cells. In this study, we evaluated 26 spleen, 10 abdominal lymph node, and 3 ileum specimens with marginal zone B-cell hyperplasia for BCL-2 expression immunohistochemically. We also analyzed these cases using polymerase chain reaction methods to evaluate for the presence of clonal rearrangements of the immunoglobulin heavy chain gene (IgH) using consensus V FRIII and J region primers, and the t(14;18) involving both the major breakpoint and the minor cluster regions of the bcl-2 gene. All (100%) cases of splenic, abdominal lymph node, and ileal marginal zone hyperplasia displayed strong BCL-2 reactivity in the marginal zone B cells. In all cases analyzed, IgH polymerase chain reaction demonstrated a polyclonal pattern, and bcl-2/JH DNA fusion sequences were not detected. Our results indicate that BCL-2 is consistently expressed by reactive marginal zone B cells of the spleen, abdominal lymph nodes, and ileal lymphoid tissue and should not be used as a criterion for discriminating between benign and malignant marginal zone B-cell proliferations involving these sites.     

Isolated renal intravascular lymphoma: a case report and review of the literature

Intravascular large B-cell lymphoma (IVLBCL) is a very rare subtype of extranodal large B-cell lymphoma. It may involve various organ systems such as skin, liver, lung or kidney. Isolated kidney involvement of IVLBCL is also very rare. Herein we report a very rare case of isolated renal IVLBCL presented with fever of unknown origin, acute kidney injury and nephrotic syndrome. Diagnosis was suspected with isolated high renal ¹⁸F fluorodeoxyglucose uptake in positron emission tomography and confirmed with renal biopsy. Complete remission was obtained with combined chemotherapy including rituximab. We reviewed the English literature in terms of IVLBCL with renal involvement and we could only find 16 such cases. Accordingly, fever, AKI and nephritic syndrome are the most common presenting symptoms in renal intravascular lymphoma.     

Successful treatment of IgA nephropathy in association with low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue type

Kidney and the urogenital tract are among the various mucosal sites involved in mucosa-associated lymphoid tissue (MALT) lymphoma. We report a case with simultaneous onset of crescentic immunoglobulin (Ig) A nephropathy and gastrointestinal low-grade B-cell lymphoma of the MALT type with kidney infiltration. M-component of IgM lambda was detected in the serum, and the renal biopsy specimen showed monotypic lambda light chain staining in the lymphoma cells but not the glomeruli. The heavy proteinuria and impaired creatinine clearance returned to normal, and microscopic hematuria disappeared 20 months after treatment with chlorambucil as single-agent chemotherapy. This coincided with a complete resolution of the gastric and renal lymphoma infiltration. The close association of both the onset and successful outcome of the two entities thus support their possible causal relationship, and we discuss the possibility of an association of the disturbance of the MALT by the lymphoma cells with the pathogenesis of IgA nephropathy.     

An unusual cause of acute renal failure: renal lymphoma

Renal involvement is a common finding in non-Hodgkins lymphoma (NHL). Acute renal failure at initial presentation due to lymphomatous infiltration of the kidneys has been described infrequently. We report a 17-year-old male who presented with acute renal failure due to massive lymphomatous infiltration of the kidneys, which necessitated hemodialysis. The diagnosis of B-cell NHL was established by tru-cut biopsy of the kidneys and the patient had an excellent response to high-dose chemotherapy with no major complication. The presence of extrarenal involvement in the testes and the retroperitoneal lymph nodes made the diagnosis of primary renal lymphoma debatable. However, considering the delay in diagnosis and the high proliferative rate of B-cell NHL, we might postulate that the disease had originated primarily in the kidneys. We recommend that in NHL cases with severe renal involvement, full-dose chemotherapy should be instituted with meticulous clinical and laboratory follow-up in order to improve clinical and renal failure status rapidly and to avoid further dissemination of NHL.     

Fluorescence immunophenotypic and interphase cytogenetic characterization of nodal lymphoplasmacytic lymphoma

Lymphoplasmacytic lymphoma (LPL) is a small B-cell lymphoma with plasmacytic differentiation that does not fulfill the criteria for any other small B-cell lymphoma. Cytogenetic characterization of nodal LPL is limited and the distinction from marginal zone lymphomas with plasmacytic differentiation can be problematic. Thus, 17 cases of lymph node-based LPL were studied with fluorescence immunophenotypic and interphase cytogenetics for the investigation of neoplasia (FICTION) using a CD79a antibody and probes to detect trisomies of chromosomes 3 (15 cases), 12 (16 cases), and 18 (17 cases); rearrangements (R) of IgH (10 cases), BCL6 (6 cases), PAX5 (7 cases), and MALT1 (16 cases); and deletion 6q21 (7 cases). Cases with IgH R were further studied with an IgH/BCL2 probe. In cases without FICTION studies, previously reported fluorescence in situ hybridization results for IgH, PAX5, and deletion 6q21 were available from prior studies. The histopathology, immunophenotype, and available clinical data were also reviewed. Three pathologic categories were recognized: 5 classic LPL, 5 vaguely nodular polymorphous (VN-P), and 7 other. Among the classic LPL, 4/4 had an IgM paraproteinemia, 5/5 had bone marrow involvement (BM+), and 1/5 had +MALT1. One of one VN-P LPL had an IgM paraprotein, 2/4 were IgM+, 2/4 IgG+, 1/3 had BM+, and 1/5 had an IgH R. Among the other cases, 2/3 had a paraprotein, 2/7 were IgM+, 5/7 IgG+, and 0/3 had BM+. Of these cases, 1 showed +12, 1 +18, and 1 IgH/BCL2 rearrangement plus +18. None of the 17 cases had a 6q21 deletion or +3. Therefore, with rare exception, lymph node-based LPL with classic or more varied histopathologic features does not have the cytogenetic abnormalities frequently associated with bone marrow-based LPL/Waldenstrom macroglobulinemia or many of the marginal zone lymphomas. The search for better objective inclusionary criteria for LPL must continue.     

Follicular colonization in B-cell lymphoma of mucosa-associated lymphoid tissue

The formation of neoplastic B-cell follicles is universally accepted as diagnostic of a follicle centre cell (FCC) lymphoma. Low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) are characterized by a diffuse infiltrate of cells of uncertain lineage known as "centrocyte-like" cells because of their resemblance to centrocytes (small cleaved cells). Some MALT lymphomas, however, contain numerous follicles and may even have a predominantly follicular appearance. These follicles may be reactive or show immunoglobulin (Ig) light-chain restriction, indicating their neoplastic nature. We have proposed that these neoplastic follicles are not composed of follicle centre cells but result from colonization of reactive follicles by CCL cells. In this study, the immunophenotype and genotype of 10 primary gastrointestinal lymphomas with a follicular component have been determined. One case exhibited the morphological, immunophenotypic, and genotypic features of FCC lymphoma (Ig light-chain restriction, CD10+, KB61 (CDw32)-, Jh, and bcl-2 gene rearrangement). Neoplastic follicles in the remaining nine cases, which showed the features of MALT lymphoma, were of a different phenotype (Ig light-chain restriction, CD10- KB61(CDw32)+), and these lymphomas showed Jh but not bcl-2 gene rearrangement. Taken in conjunction with the morphological features, these findings suggest that in these cases the neoplastic follicles formed as the result of colonization of previously reactive follicles by neoplastic CCL cells. Thus, not all lymphomas containing neoplastic follicles are of FCC origin. Follicular colonization, as seen in low-grade MALT lymphomas, is likely to be a recapitulation of an as yet undescribed normal immunological phenomenon that may involve marginal zone B cells.     

Gastric lyphoma - still a result of surgery?]

In extranodal non-Hodgkin's lymphoma (NHL), the gastrointestinal tract is by far the most frequent localization. One must differentiate between primary lymphoma, e.g. those arising in the gastrointestinal tract, and secondary lymphoma, which can affect the digestive tract as a disseminations of nodal lymphoma. Analysis of histomorphologic and immunhistochemical characteristics and the concept of mucosa-associated lymphoid tissue (MALT) have led to primary gastrointestinal lymphoma now being viewed as an independent entity. The great majority of gastric lymphoma (>90%) are marginal zone B-cell lymphoma of the MALT type, previously called low grade MALT lymphoma, and diffuse large B-cell lymphoma, previously called high grade gastric lymphoma. This review examines current views on pathogenesis, diagnosis, and therapy of this disorder.