A 70-yr-old woman was hospitalized with a history of dry cough. Bronchial endoscopy and transbronchial lung biopsy were performed. However, the findings of histopathology and immunohistochemistry were not sufficient to decide whether the lesion was benign or malignant, because of the presence of crush artifacts in the biopsy specimens. We performed B-cell clonality studies using BIOMED-2 multiplex PCR (InVivoScribe Technologies, USA) to detect clonal rearrangements in the immunoglobulin gene. The results of multiplex PCR showed clonal rearrangements of both kappa and lambda immunoglobulin light chain genes. The findings of immunochemistry revealed that the lesion expressed lambda light chain, but not kappa light chain. Based on the clinical, pathologic, and molecular findings, this case was diagnosed as pulmonary MALT lymphoma. We report the first case in Korea of lambda-expressing MALT lymphoma that is shown to have dual clonal rearrangements of kappa and lambda immunoglobulin light chain gene by multiplex PCR.
Aged ; Female ; *Gene Rearrangement, B-Lymphocyte, Light Chain ; Humans ; Immunoglobulin kappa-Chains/*genetics ; Immunoglobulin lambda-Chains/*genetics ; Lymphoma, B-Cell, Marginal Zone/*diagnosis/genetics/pathology ; Polymerase Chain Reaction

<b>OBJECTIVEb>To evaluate the ancillary diagnostic value of IgH gene rearrangements in those B-cell lymphoproliferative disorder cases whom are difficult in making a final diagnosis.

<b>METHODSb>IgH gene clonal rearrangements were retrospectively analyzed in a total of 77 diagnostically difficult B-cell lympho-proliferative patients. Standardized BIOMED-2 system IgH gene clonality assay kit targeting FR1, FR2, FR3 was used, followed by heteroduplex-polyacrylamide gel electrophoresis (PAGE) and silver nitrate staining.

<b>RESULTSb>The final diagnoses of the 77 cases were: 12 cases of reactive lymphoid hyperplasia, 20 cases of atypical lymphoid hyperplasia or suspicious lymphoma, and 45 cases of B-cell lymphoma. Detection rates of at least one positive reaction were 2/12, 11/20 (55%), 36/45 (80%) in the three groups, respectively. In B-cell lymphomas, the clonality detection rate of FR1, FR2 and FR3 was 60% (27/45), 60% (27/45) and 56% (25/45), respectively. The type distribution were: 20 marginal zone lymphomas, including 18 extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, 7 diffuse large B-cell lymphomas, 7 follicular lymphomas, 1 mantle-cell lymphoma, 1 Burkitt's lymphoma, 4 plasma cell neoplasms and 5 unclassified B-cell lymphomas. Rearrangements of FR1, FR2 or FR3 were not detected in 9 (20%) of the B cell lymphoma cases, nevertheless, one of them had developed liver lesion later, and was confirmed finally to be B cell lymphoma. Fourteen patients of reactive lymphoid hyperplasia with positive IgH gene clonal rearrangements, and atypical lymphoid hyperplasia had follow-up history available. Four of them were diagnosed as lymphoid malignancies upon further biopsy, and in three of them, clonal IgH gene rearrangements were detected.

<b>CONCLUSIONSb>B-cell lymphoproliferative disorder requiring a detection of clonal IgH gene rearrangement for making a final diagnosis. Combined detections of three IgH FR1, FR2 and FR3 rearrangements provide important ancillary diagnostic value in confirming suspected B-cell lympho-proliferative disorders. It is important to take an additional biopsy or to follow-up those patients who that have a detectable IgH gene clonal rearrangement but without apparent morphological evidence of lymphoma. For cases with a negative IgH gene rearrangements, it might be necessary to perform clonality analysis for other forms of gene rearrangements including IgH or IgK and IgL in order to further improve the detection sensitivity.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Follow-Up Studies ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Humans ; Lymphoma, B-Cell ; diagnosis ; genetics ; pathology ; Lymphoma, B-Cell, Marginal Zone ; diagnosis ; genetics ; pathology ; Lymphoma, Follicular ; diagnosis ; genetics ; pathology ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; genetics ; pathology ; Lymphoproliferative Disorders ; diagnosis ; genetics ; pathology ; Male ; Middle Aged ; Neoplasms, Plasma Cell ; diagnosis ; genetics ; pathology ; Pseudolymphoma ; diagnosis ; genetics ; pathology ; Retrospective Studies ; Young Adult

<b>OBJECTIVEb>To study the clinicopathologic features and differential diagnosis of splenic B-cell marginal zone lymphoma (SMZL) involving bone marrow.

<b>METHODSb>The clinical and pathologic features of 22 patients with SMZL were retrospectively studied. Immunophenotypic analysis was carried out by flow cytometry and immunohistochemistry. Immunoglobulin heavy chain rearrangement study was performed using polymerase chain reaction-based method.

<b>RESULTSb>Villous lymphocytes were found in peripheral blood smears of 11/18 of the patients. In bone marrow aspirates, lymphocytosis (> 20%) was demonstrated in 15 cases (15/18) and villous lymphocytes in 6 cases (6/18). Flow cytometry showed CD19(+) CD20(+) FMC7(+) CD22(+) CD10(-) CD2(-) CD3(-) CD7(-) in 18 cases. Bone marrow biopsies of all the 22 patients revealed various degrees and patterns of neoplastic infiltration, as follows: mild (4 cases, 18.2%), moderate (11 cases, 50.0%) or severe (7 cases, 31.8%); intrasinusoidal (16 cases, 72.7%), interstitial (14 cases, 63.6%), nodular (11 cases, 50.0%) or diffuse (1 case, 4.5%). Reactive germinal center formation (CD23(+) bcl-2(-)) was found in 2 cases (91.0%). Immunohistochemical study showed the following results: CD20(+) PAX5(+) CD3(-) CD5(-) CD10(-) cyclin D1(-) CD23(-) CD43(-) Annexin A1(-) CD11C(-) CD25(-) in all the 22 cases, CD38(+) in 2 cases (9.1%) and CD138(+) in 2 cases (9.1%).

<b>CONCLUSIONSb>Different and overlapping patterns of bone marrow involvement are observed in SMZL. As the histologic and immunophenotypic features are not specific to SMZL, distinction from other types of mature B-cell lymphomas is necessary.

Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; Bone Marrow ; pathology ; Diagnosis, Differential ; Female ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; pathology ; Lymphoma, B-Cell, Marginal Zone ; genetics ; metabolism ; pathology ; Lymphoma, Follicular ; metabolism ; pathology ; Lymphoma, Mantle-Cell ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; Splenic Neoplasms ; genetics ; metabolism ; pathology ; Waldenstrom Macroglobulinemia ; metabolism ; pathology

CD5 Antigens ; metabolism ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 18 ; Cyclin D1 ; metabolism ; Diagnosis, Differential ; Humans ; Ki-67 Antigen ; metabolism ; Lymphoma, B-Cell, Marginal Zone ; genetics ; metabolism ; pathology ; Lymphoma, Follicular ; genetics ; metabolism ; pathology ; radiotherapy ; Lymphoma, Mantle-Cell ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Pseudolymphoma ; metabolism ; pathology ; Translocation, Genetic

<b>OBJECTIVEb>To study the clinicopathologic features, immunohistochemical findings, differential diagnosis and prognosis of type II enteropathy-associated T-cell lymphoma (EATL).

<b>METHODSb>Fourteen cases of type II EATL encountered in Department of Pathology, Nanjing General Hospital were retrospectively reviewed. The clinical data, histologic features, immunohistochemical findings and follow-up information were analyzed, with literature review.

<b>RESULTSb>There were altogether 12 males and 2 females. The median age of patient was 49 years. The sites of involvement included jejunum (10 cases) and ileum/colon (4 cases). The patients often presented with an abdominal mass, abdominal pain, diarrhea and constitutional symptoms such as fever, night sweating and cachexia. There was no clinical evidence of gluten-sensitive enteropathy. Histologically, the lymphoma cells showed full-thickness infiltration of the intestinal wall. They contained round hyperchromatic nuclei and pale cytoplasm. The stroma was minimally inflamed, with or without associated coagulative necrosis. A remarkable finding was the presence of villous atrophy, cryptal hyperplasia and intraepithelial lymphocytosis. Immunohistochemical study showed that the tumor cells expressed CD3, CD43 and CD8 (14/14). Some of them were also positive for CD56 (11/14) and CD30 (2/14). The staining for CD4, CD20, CD79a and myeloperoxidase was negative. A high proliferation index was demonstrated by Ki-67 immunostain. In-situ hybridization for EBER was negative. Follow-up data were available in 9 cases. The duration of follow-up ranged from 6 months to 36 months. Seven patients died within 14 months.

<b>CONCLUSIONSb>EATL is a rare type of lymphoma with intestinal involvement. Associated enteropathy is not demonstrated, in contrast to cases encountered in Nordic countries. A correct diagnosis requires evaluation of clinical manifestations, pathologic features and ancillary study results.

Adolescent ; Adult ; Aged ; CD3 Complex ; metabolism ; CD8 Antigens ; metabolism ; Diagnosis, Differential ; Enteropathy-Associated T-Cell Lymphoma ; genetics ; immunology ; pathology ; surgery ; Female ; Follow-Up Studies ; Gene Rearrangement, T-Lymphocyte ; Humans ; Ileal Neoplasms ; genetics ; immunology ; pathology ; surgery ; Jejunal Neoplasms ; genetics ; immunology ; pathology ; surgery ; Leukosialin ; metabolism ; Lymphoma, B-Cell, Marginal Zone ; metabolism ; pathology ; Lymphoma, Extranodal NK-T-Cell ; metabolism ; pathology ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

<b>OBJECTIVEb>To study the clinicopathologic features of primary thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT).

<b>METHODSb>The clinical and pathologic findings were evaluated in 3 cases of biopsy confirmed thymic MALT lymphoma. The clincopathologic features, treatment and prognosis were discussed and literatures reviewed.

<b>RESULTSb>One male and two female patients presented with asymptomatic mediastinal masses with a history of Sjögren syndrome. They were aged 36, 35 and 41 years respectively, and only one patient had B symptoms. Grossly, all three tumors were encapsulated and had multiple variable-sized cysts on cut-surface. Histopathologically, the normal thymic lobular architecture was effaced by abnormal dense lymphoid infiltration. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating and expanding Hassall's corpuscles and epithelial cyst lining. All cases showed apparent plasmacytic differentiation. Immunohistochemically, the tumor cells were positive for CD20, CD79a, bcl-2 and negative for CD3, CD5, cyclin D1, CD43, CD10, bcl-6, and CD23. The plasma cells showed kappa light chain restriction. Immunoglobulin heavy chain rearrangement in three cases was confirmed by PCR. All patients were at early stage and received routine chemotherapy with or without radiotherapy after surgical removal. All patients achieved complete remission with 24, 18 and 3 months follow-up, respectively.

<b>CONCLUSIONSb>Primary thymic MALT lymphoma may be a rare distinctive lymphoma. It can be diagnosed by HE and immunohistochemical study and should be differentiated from reactive lymphoid proliferation, other types of lymphoma and mediastinal thymoma.

Adult ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antigens, CD20 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Diagnosis, Differential ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Keratin-19 ; metabolism ; Lymphoma, B-Cell, Marginal Zone ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Male ; Prednisone ; therapeutic use ; Pseudolymphoma ; pathology ; Thymus Hyperplasia ; pathology ; Thymus Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Vincristine ; therapeutic use