Transformation of indolent mantle cell lymphoma to pleomorphic mantle cell lymphoma: case report and review of clinical and morphologic variants

We report a case of indolent mantle cell lymphoma with progression to pleomorphic mantle cell lymphoma 8 years after initial presentation. The first lymph node biopsy showed expanded mantle zones composed of uniformly small B lymphocytes. A cyclin D1 immunohistochemical stain was negative and the patient was observed. Eight years later, the patient developed symptomatic splenomegaly. Microscopic examination of the spleen revealed expanded mantle zones with an increased number of large cells with irregular nuclear contours. Immunohistochemistry for cyclin D1 was positive. A repeat cyclin D1 immunohistochemical staining performed on the initial lymph node biopsy was positive, indicating an inadequate initial study. Immunoglobulin heavy-chain gene rearrangement studies confirmed clonal identity. A revised diagnosis of indolent mantle cell lymphoma with progression to pleomorphic mantle cell lymphoma was rendered. The differential diagnosis of mantle cell lymphoma, including clinical and morphologic variants, is discussed.     

Mantle cell lymphoma with partial involvement of the mantle zone: an early infiltration pattern of mantle cell lymphoma?

Most patients with mantle cell lymphoma present with a diffuse or nodular infiltration of the involved organs at diagnosis. We present two patients with a rare morphological variant, displaying a partial involvement of the mantle zone. Patient 1 presented with an enlarged inguinal lymph node, which showed marked follicular hyperplasia with singly spread Cyclin D1+ small lymphoid cells in the mantle zones. An additional lymph node biopsy taken 3 months later showed the same pattern. Patient 2 presented with a classical mantle cell lymphoma with lymph node, bone marrow and gastro-intestinal involvement. However, revision of an appendectomy specimen taken 4 years earlier showed pronounced follicular hyperplasia with singly spread Cyclin D1+ small lymphoid cells in the mantle zones. Mantle cell lymphoma with partial involvement of the mantle zone has rarely been reported and many represent an early manifestation of mantle cell lymphoma. Our cases also illustrate that the inclusion of an anti-cyclin D1 antibody in the diagnostic panel of antibodies to study unexplained follicular hyperplasia, might be advised.     

A case report of mantle zone lymphoma progressing into follicular lymphoma

The authors report a case of mantle zone lymphoma (MZL) progressing into follicular lymphoma (FL) with macroglobulinemia (IgM, lambda). At a first lymph node biopsy, a diagnosis of MZL was made on the basis of the presence of vague neoplastic nodules, consisting of small lymphoid cells and small cleaved cells. At a second lymph node biopsy, nodules of follicular lymphoma were observed in the central zones of the vague neoplastic nodules. At a third biopsy, the central zones were found to expand, revealing FL dominant pattern. The progress of FL from MZL also was suggested by sIg, AIPase, anti-CALLA (common acute lymphoblastic leukemia antigen) antibody, and anti-DRC (dendritic reticulum cell) antibody findings. Consequently, this is suggested to be a neoplasm of B-lymphocytes differentiating from small lymphocytes in the primary follicle or the mantle zone of secondary follicle into germinal center cells. The anti-DRC antibody findings suggest the neoplastic cells of FL induce DRC as the neoplastic stroma.     

Marginal zone variant of mantle cell lymphoma: CD5-negative cyclin D1-positive variant posing a diagnostic dilemma

Described herein is an unusual case of mantle cell lymphoma (MCL) histologically mimicking marginal zone lymphoma (MZL). An 83-year-old man presented with multiple adenopathies and a hilar mass encroaching on the right lung. A transbronchial biopsy showed small blue cells suspicious for small cell carcinoma. On further analysis the cells were predominantly small cleaved and CD20 positive, suggesting follicular lymphoma, grade 2. An axillary lymph node biopsy showed germinal centers surrounded by monocytoid B cells. Flow cytometry was negative for CD5 and CD23 and the diagnosis of MZL was considered. Because of the aggressive clinical behavior, including extensive necrosis on imaging studies, immunohistochemistry for cyclin D-1 was performed and was positive. Bone marrow was extensively involved and it showed t(11;14), in addition to other complex cytogenetic abnormalities. Differentiating MCL from MZL has prognostic and therapeutic implications, particularly when considering the potential role of targeted therapy and cell cycle modulators.     

Cyclin D1 and t(11;14)-positive B-cell neoplasms resembling marginal zone B-cell lymphoma: a morphological variant of mantle cell lymphoma

We describe 3 unusual B-cell non-Hodgkin's lymphomas in which the entire tumors histologically mimicked marginal zone B-cell lymphoma. All patients were male (mean age, 65 years). Excisional biopsy from lymph node (2 of 3) and parotid gland (1 of 3) showed proliferation of monocytoid B-cells with plasmacytoid features (2 of 3) and conspicuous absence of large lymphoma cells (3 of 3). By immunohistochemistry, cyclin D1 was positive (3 of 3), CD23 was negative (3 of 3), and aberrant expression of CD5/CD43 was present in 1 case. Ki67 labeling was greater than 50% in 1 case and 10% to 25% in the other 2 cases. Evidence of the t(11;14) was detectable in all by molecular techniques. One patient died within 15 months, and the other 2 patients had widely disseminated diseases at the last follow-up (8 months). Based on these features, we believed that the best classification for these lesions is the marginal zone B-cell lymphoma-like mantle cell lymphoma.     

Clonal cytogenetic abnormalities are predictor in developing non-Hodgkin lymphomas?

Pathological analysis is the cornerstone for diagnosing malignant lymphoma. Status of cytogenetic abnormalities is frequently left unexamined if no evidence of malignancy is found in pathological analysis. In this study, we presented 3 cases in which clonal cytogenetic abnormalities were detected but morphological alterations of the same tissue did not support malignant non Hodgkin lymphoma at the first lymph node biopsy. Case 1 is a 55-year-old female with lymphadenopathy neoplastic process confirmed by flow cytometry and polymerase chain reaction (PCR). Chromosome analysis revealed 47,XX,t(3;22)(q27;q11),+del(9)(p12)[16]/46,XX[4]. The pathological analysis of subsequent lymph node biopsy indicated diffuse large B-cell lymphoma (DLBCL). Case 2, a 74-year-old female, for whom the pathological analysis, molecular studies and flow cytometric analysis of the first lymph node biopsy found no evidence of clonal cell. Cytogenetic analysis demonstrated a terminal deletion of chromosome 7 and 1, and the patient received a second lymph node biopsy and splenectomy. A pathological diagnosis of splenic marginal zone lymphoma (SMZL) was made. In Case 3 who was a 66-year-old female with right cervical and axillary lymph node enlargement. Cytogenetic analysis showed clonal karyotypic abnormalities: 48,XX, t(14;18)(q32;q21) [13]/46, XY [7]. The diagnosis of follicular lymphoma was rendered by the second biopsy of axillary lymph node according to the analysis of morphology and immunohistochemistry. We propose that clonal cytogenetic abnormalities may be a high potential risk for developing non-Hodgkin lymphomas. Follow-up and rebiopsy must be performed in patients who are cytogenetically abnormal but morphologically benign.     

A common clonal origin of nodal marginal zone B-cell lymphoma and plasma cell myeloma demonstrating different immunophenotypes: a case report of composite lymphoma.

We demonstrated an 83-year-old male case of composite lymphoma. Before 18 years, he was diagnosed with nodal marginal zone B-cell lymphoma in the cervical lymph node. Peripheral blood showed anemia and IgA (kappa)-type monoclonal gammopathy (IgA; 3,625 mg/dL). Bone marrow aspiration biopsy exhibited plasma cell myeloma, in which atypical plasma cells were positive for cytoplasmic IgA (kappa) and atypical lymphoid cells intermingled were positive for CD20. In contrast, cervical lymph node biopsy revealed nodal marginal zone B-cell lymphoma, in which lymphoma cells were positive for cytoplasmic IgG (lambda). Southern blotting analysis of the IgH gene showed same clonal rearrangement band in both lymph node and bone marrow samples and additional band in the bone marrow. Sequence analyses of the IgH gene showed an identical sequence of CDR3 in both samples. Thus, we demonstrated a common clonal origin of composite lymphoma comprising nodal marginal zone B-cell lymphoma and plasma cell myeloma. Nodal marginal zone B-cell lymphoma recurred in cervical lymph node and involved into the bone marrow, differentiating into plasma cell myeloma in which Ig isotype switched and monoclonal gammopathy developed. Sequence analysis of the IgH gene was a powerful tool for determination of clonal origin.     

Peripheral T-cell lymphoma with a nodular growth pattern

Peripheral T-cell lymphomas (PTCL) with nodular growth patterns are very rare, with only 17 cases reported previously. Here, we report a case of PTCL with a nodular growth pattern. The patient was an 81-year-old Japanese woman who complained of malaise, fever and generalized lymph node swelling. Cervical lymph node biopsy was performed, and histological examination revealed proliferation of medium- to large-sized atypical lymphoid cells with indented to irregular nuclei, distinct nucleoli and clear cytoplasm. The nodular growth pattern of the lymphoma cells was obvious. On immunohistochemistry, the atypical lymphoid cells proved to be of T-helper cell origin (CD2+CD3CD4+CD5+CD7+ CD8-CD10-CD25-CD30-CD57-). Polymerase chain reaction analysis of the T-cell receptor gamma-chain revealed a monoclonal rearrangement band. This unusual growth pattern should be distinguished among PTCL, as such cases could be confused with reactive nodular hyperplasia, nodular lymphoma, mantle cell lymphoma and marginal zone lymphoma with nodular colonization.     

Primary nodal marginal zone B-cell lymphoma arising from more than one clonal neoplastic population

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.     

Early phase of intestinal mantle cell lymphoma: a report of two cases associated with advanced colonic adenocarcinoma.

Intestinal mantle cell lymphoma characteristically produces multiple polyps, a finding reported as multiple lymphomatous polyposis. The early stages of intestinal mantle cell lymphoma before polyp formation and the pattern of initial lymph node invasion, however, have not been described. We recently encountered two cases of intestinal mantle cell lymphoma in their early development found incidentally associated with advanced colonic adenocarcinoma. We present herein the clinical, histopathological, immunohistochemical, and molecular genetic features of these two cases. In one case, a single polypoid mass was found with invasion limited to mucosa and submucosa of the terminal ileum and without lymph node compromise. In the second case, there were multiple mucosal aggregates of neoplastic cells without formation of polyps. Regional lymph nodes in the latter case showed either partial or complete involvement by lymphoma. In both cases, immunohistochemistry (CD20+, CD5+, cyclin D1+, CD10-, and CD23-), and demonstration of clonal immunoglobulin heavy chain and bcl-1 gene rearrangements by PCR analysis confirmed the diagnosis of mantle cell lymphoma.     

Follicular lymphoma mimicking marginal zone lymphoma in lymph node: a case report

Nodal follicular lymphoma (FL) is typically composed of follicular or nodular proliferation of small cleaved lymphoid cells, presumably derived from germinal center (GC) B cells. The hallmark of FL is t(14;18)(q32;q21) chromosomal translocation, which juxtaposes anti-apoptotic gene BCL2 to immunoglobulin heavy chain (IGH) promoter. Reflecting this background, FL cells are immunohistochemically positive for BCL2 as well as GC B cell markers CD10 and BCL6. It is known that low grade B-cell lymphomas, including FL, chronic lymphocytic leukemia/small lymphocytic lymphoma, and marginal zone lymphoma, are sometimes associated with marginal zone differentiation or plasmacytic differentiation. The marginal zone differentiation obscures the morphological differences among these, providing diagnostic challenges for histopathologists. In this paper, we present a case of FL, originally mimicking marginal zone lymphoma in the axillary lymph node. Subsequent bone marrow biopsy showed paratrabecular infiltration of small to medium-sized lymphoid cells. Immunohistochemical analysis of the bone marrow biopsy together with histopathology and flow cytometry of the axillary lymph node led to a final diagnosis of FL with marginal zone differentiation in the axillary lymph node and its bone marrow infiltration. Our case illustrates and reconfirms the importance of clinicopathological correlation which leads to a correct diagnosis.     

LYMPH NODE INVOLVEMENT IN WALDENSTROM'S MACROGLOBULINEMIA

The pattern of lymph node involvement in Waldenström's macroglöbulinemia (MG) is described according to clinical and histological materials from 2 biopsy and 4 autopsy cases. The histological features of biopsy were well-differentiated, diffuse, lymphocytic lymphoma in one case (case 1) and sinus histiocytosis (SH) with nodular aggregates of lymphoid cells as observed by the first biopsy in the other case (case 2). An immunofluorescent study of lymph nodes revealed monoclonal proliferation of B lymphocytes (IgM, κ) in both cases. In case 2, a majority of circulating lymphoid cells bore membrane-bound monoclonal IgM. The histological features of lymph nodes obtained by the second biopsy in case 2 was comparable with the well-differentiated, lymphocytic lymphoma in some nodes, and diffuse and nodular proliferation with preservation of sinuses in the other nodes. The pattern of lymph node involvement of 4 autopsy cases were also analysed. According to these investigations, It is suggested that lymph node showing SH is a pattern of lymph node involvement of MG.     

Lymph node involvement in Waldenstr?m's macroglobulinemia

The pattern of lymph node involvement in Waldenstr?m's macr?globulinemia (MG) is described according to clinical and histological materials from 2 biopsy and 4 autopsy cases. The histological features of biopsy were well-differentiated, diffuse, lymphocytic lymphoma in one case (case 1) and sinus histiocytosis (SH) with nodular aggregates of lymphoid cells as observed by the first biopsy in the other case (case 2). An immunofluorescent study of lymph nodes revealed monoclonal proliferation of B lymphocytes (IgM, gamma) in both cases. In case 2, a majority of circulating lymphoid cells bore membrane-bound monoclonal IgM. The histological features of lymph nodes obtained by the second biopsy in case 2 was comparable with the well-differentiated, lymphocytic lymphoma in some nodes, and diffuse and nodular proliferation with preservation of sinuses in the other nodes. The pattern of lymph node involvement of 4 autopsy cases were also analysed. According to these investigations. It is suggested that lymph node showing SH is a pattern of lymph node involvement of MG.     

CD1c antigens are present in normal and neoplastic B-cells

The immunohistochemical detection of CD1c antigen is described in mantle zone B-cells of the tonsil, lymph node, and spleen, and also in the marginal zone B-cells of the spleen. CD1c expression was observed in most cases of low-grade, but in only a single case of high-grade, B-cell non-Hodgkin's lymphoma. It was not detected in germinal centre cells, nor in Epstein-Barr virus-transformed or Burkitt's lymphoma B-cell lines. This distribution suggests that CD1c expression may occur preferentially in slowly proliferating B-cell populations and does not support previous suggestions that CD1c is a human equivalent of the mouse thymus leukaemia antigens.     

Transformation of hairy cell leukemia to high-grade lymphoma: a case report and review of the literature

The coexistence of hairy cell leukemia (HCL) and non-Hodgkin's lymphoma is extremely rare. In the few reports demonstrating such coexistence, the relationship between the 2 entities was mostly inconclusive. We report a case of HCL that transformed to large cell lymphoma. This case has been followed for more than 4 years with immunohistochemical, flow cytometric, and molecular genetic studies on multiple bone marrow biopsy specimens, a splenectomy specimen, and a lymph node biopsy. In our case, the immunophenotype and tartrate-resistant acid phosphatase stain confirmed that the large cell lymphoma was of HCL origin. The markedly increased Ki-67 staining (proliferation fraction) in the lymph node biopsy specimen compared to the earlier splenectomy specimen indicated the transformation of a low-grade leukemia to a high-grade lymphoma. The overexpression of p53 in the lymph node implies that p53 mutation was probably involved in the pathogenesis of HCL transformation.     

Hepatic MALT lymphoma disclosing a nodal extension

We report a case of a 50-year-old man with chronic viral hepatitis B presenting with a primary hepatic lymphoma of mucosa-associated lymphoid tissue, revealed clinically by a pedicular nodal mass. The liver biopsy showed an active chronic hepatitis and a dense portal lymphoid infiltrate with centrocyte-like cells inducing typical biliary lympho-epithelial lesions. The lymph-node biopsy revealed a marginal zone lymphoma pattern. A monoclonal rearrangement of the immunoglobulin heavy chain gene was detected in the lymph node by polymerase chain reaction. This case of primary hepatic mucosa-associated lymphoid tissue lymphoma confirms that the liver also contains mucosa-associated lymphoid tissue, in which low grade lymphoma can arise.     

CT-guided needle biopsy in the diagnosis of lung adenocarcinoma accompanied by extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: a rare combination

We represent a rare case of lung adenocarcinoma accompanied by extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). The patient was a 66-year-old male presented with 1 month history of recurrent cough and hemoptysis. Chest CT showed solitary ground-glass opacity (GGO) in the upper lobe of the right lung and mediastinal lymph node enlargement in station 3p. A CT-guided transthoracic needle biopsy was performed. Tissue specimens of the GGO revealed a typical adenocarcinoma. Histopathologic diagnosis of mediastinal lymph node was extranodal marginal zone lymphoma of MALT. Because of its rarity, extranodal marginal zone lymphoma of MALT should be considered in the differential diagnosis when we encounter mediastinal lymphadenopathy in patients with lung adenocarcinoma.     

Hyperplasia of mantle/marginal zone B cells with clear cytoplasm in peripheral lymph nodes. A clinicopathologic study of 35 cases

We describe 35 peripheral lymph nodes classified as mantle cell/marginal zone B-cell hyperplasia with clear cells using morphologic and immunologic findings. For the purpose of this study, we obtained clinical follow-up information and performed immunoglobulin gene rearrangement studies on paraffin sections by polymerase chain reaction. Architecturally, the nodes were suggestive of a benign process: no pericapsular infiltration, sinuses readily identified, scattered reactive follicles present, and paracortical nodular hyperplasia present. No monocytoid B cells were present. Focally, small lymphoid cells with round nuclei and clear cytoplasm (clear cells) formed monomorphic nodular, inverse follicular, and/or marginal zone patterns. Flow cytometry and immunohistochemical analysis revealed neither light chain restriction nor an aberrant B-cell phenotype. Immunoglobulin gene rearrangement studies showed a clonal band in 1 of 26 cases in which DNA was amplified. To ascertain the clinical relevance of this positive case, follow-up information was obtained 30 months after the initial biopsy; the 83-year-old woman was alive without treatment but had splenomegaly and bone marrow involvement by marginal zone B-cell lymphoma. The morphologic and immunologic criteria used for diagnosis of mantle cell/marginal zone B-cell hyperplasia with clear cytoplasm are valid; however, to rule out the possibility of occult lymphoma, immunoglobulin gene rearrangement studies and clinical follow-up are necessary.     

A unique collision tumor in breast: invasive ductal carcinoma and mucosa-associated lymphoid tissue lymphoma

We report an extraordinary case of a collision tumor consisting of invasive ductal carcinoma with adjacent malignant lymphoma presenting as a single mass in the breast. A 79-year-old woman presented with a breast mass. A core biopsy performed at an outside hospital was interpreted as medullary carcinoma. On review of the breast core biopsy, a diagnosis of a synchronous malignant lymphoma and invasive ductal carcinoma was rendered. The patient underwent lumpectomy and axillary dissection. The excised specimen revealed a 2.1-cm, moderately differentiated invasive ductal carcinoma, partially surrounded by malignant lymphoma with areas where both tumors were intermixed. All 27 axillary lymph nodes were extensively involved by lymphoma, and 1 lymph node demonstrated metastatic carcinoma. The morphology and results of immunohistochemistry, flow cytometry, and cytogenetic analysis were consistent with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.     

Histopathology of leukaemic non-Hodgkin's lymphoma in bone marrow

Staging biopsies of the bone marrow in lymphoma patients are among the most important indications and therefore of substantial practical importance. Occasionally it is the only organ infiltrated, and therefore a bone marrow biopsy is the prime diagnostic choice in cases of leukemic lymphomas. A synoptical diagnostic approach relying on immunophenotypic as well as on molecular biological criteria aside from histomorphology (cytomorphology), is of utmost importance for the subtyping of malignant lymphomas. This too can be done reliably on bone marrow biopsies, as comparative studies have yielded a concordance rate of more than 90% with lymphoma typing on corresponding lymph nodes. Cytology and the pattern of infiltrates, (i.e. diffuse, interstitial, nodular peritrabecular and intrasinusoidal), in combination with immunological phenotyping are the mainstays for subtyping, giving clear-cut decisions in most cases of small B-cell lymphoma, mantle zone as well as marginal cell and follicular lymphomas and hairy cell leukemia. Among the blastic variants the most important are the lymphoblastic lymphomas of either B- or T-cell type which have to be discerned from AML and the so-called blastoid mantle cell lymphomas. T-cell lymphomas are rare compared to B-cell lymphomas. Among the rarely seen T-cell neoplasias the lymphoma of large granular lymphocytes is the dominating lymphoma, which in most cases can only be diagnosed reliably by molecular biological means, followed by T-CLL, Sezary's syndrome and hepatosplenic chi delta lymphoma.