Follicular dendritic cells in bone marrow lymphoproliferative diseases: an immunohistochemical study including a new paraffin-resistant monoclonal antibody, DR53

Two-hundred and twenty-one bone marrow biopsies with lymphoid infiltrates were studied histologically and immunohistochemically, to assess the incidence and the pattern of follicular dendritic cells. Three monoclonal antibodies selective for follicular dendritic cells were used: CD21, CD35 and DR53, all reactive on paraffin-embedded material. Follicular dendritic cells were present in two of 38 benign lymphoid aggregates, 92 of 134 low grade B-cell lymphomas (45 of 62 lymphocytic, 16 of 27 lymphoplasmacytoid, 0 of six hairy cell leukaemias, five of six centrocytic, 19 of 21 centroblastic-centrocytic, seven of 12 low grade NOS), one of 23 high grade B-cell lymphomas, 0 of 10 T-cell lymphomas, 0 of three Hodgkin's disease and four of 13 suspicious infiltrates. Follicular dendritic cells were found in lymphomatous involvement with nodular, patchy and massive growth pattern, but not in interstitial ones. They formed follicle-like networks, whose number and size were directly correlated to the tumour mass. The origin and frequency distribution of follicular dendritic cells in bone marrow biopsy lymphomas is discussed and the diagnostic relevance of follicular dendritic cell immunostaining in routine bone marrow biopsy lymphoid infiltrates is assessed.     

Benign CD10-positive T cells in reactive lymphoid proliferations and B-cell lymphomas.

Recent reports have indicated that the neoplastic T cells of angioimmunoblastic T-cell lymphoma express CD10. It has been suggested that the demonstration of a CD10+ T-cell population may assist in establishing a diagnosis of angioimmunoblastic T-cell lymphoma and in distinguishing angioimmunoblastic T-cell lymphoma from other peripheral T-cell lymphomas. It has been unclear, however, whether this phenotypically unusual T-cell population might be present in other settings as well. In this report, we have retrospectively examined 64 cases of lymph node and solid tissue biopsies for the presence of CD10+ T cells using multicolor flow cytometry. Discrete populations of CD10+ T cells were found in 5 of 28 cases (18%) of reactive lymphoid hyperplasia, 4 of 17 cases (23%) of follicular lymphoma, and 9 of 19 cases (47%) of marginal zone B-cell lymphomas. The CD10+ T cells constituted 1-6% of total cells analyzed and 相似文献   

Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma.

Using immunohistochemical methods, we evaluated zeta-associated protein (ZAP)-70 expression in 341 cases of non-Hodgkin and Hodgkin lymphoma. In B-cell NHL, ZAP-70 was positive in five of six (83%) precursor B-lymphoblastic lymphoma, 11 of 37 (30%) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), five of 39 (13%) mantle cell lymphoma, one of 12 (8%) Burkitt lymphoma, and one of 12 (8%) nodal marginal zone B-cell lymphoma. In 22 cases of CLL/SLL, seven of nine (78%) with unmutated IgVH genes expressed ZAP-70, compared with one of 13 (8%) with mutated IgVH genes (P=0.0015 Fisher's exact test). ZAP-70 expression was not detected in diffuse large B-cell lymphoma (n=26), extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (n=24), follicular lymphoma (n=21), plasma cell myeloma/plasmacytoma (n=10), lymphoplasmacytic lymphoma (n=10), or splenic marginal zone lymphoma (n=6). In T/NK-cell NHL, ZAP-70 was positive in all extranodal natural killer (NK) / T-cell lymphoma, nasal-type (n=6) and enteropathy-type T-cell lymphoma (n=4), four of five (80%) subcutaneous panniculitis-like T-cell lymphoma, six of eight (75%) mycosis fungoides, three of five (60%) precursor T-lymphoblastic lymphoma, 10 of 17 (59%) peripheral T-cell lymphoma, two of four (50%) blastic NK-cell lymphoma, one of three (33%) T-cell prolymphocytic leukemia, 13 of 52 (25%) anaplastic large cell lymphoma, and one of six (17%) angioimmunoblastic T-cell lymphoma. Seven of 12 (58%) cutaneous CD30-positive lymphoproliferative disorders were also ZAP-70-positive. In Hodgkin lymphoma, ZAP-70 was negative in neoplastic cells in all cases tested. ZAP-70 staining in B-cell lymphomas and reactive T cells was predominantly nuclear with variable cytoplasmic staining. By contrast, ZAP-70 staining in T/NK-cell lymphomas was heterogeneous, and a shift from predominantly nuclear to predominantly cytoplasmic staining was observed, particularly in those neoplasms with high-grade morphology. In summary, ZAP-70 is expressed by many lymphoma types, correlates with immunoglobulin heavy-chain variable region gene mutational status in CLL/SLL, and can be detected reliably using immunohistochemical methods.     

Immunohistochemical analysis of B-cell lymphoma using tissue microarrays identifies particular phenotypic profiles of B-cell lymphomas

AIMS: To validate the applicability of tissue microarray (TM) in immunohistochemical profiling of B-cell lymphoma and to identify particular phenotypic profiles of B-cell neoplasms. METHODS AND RESULTS: Eighty-two diffuse large B-cell lymphomas (DLBL), 54 follicular lymphomas (FL) and 74 mantle cell lymphomas (MCL) were arrayed. Immunohistochemical stains of TM were compared with immunostains of conventional, formalin-fixed and frozen material sections. Concordant staining results were obtained in more than 88% of cases for CD20, CD3, CD5, CD10, CD23, Bcl-2, IgD, secretory differentiation, p53 and p21 expression. Prognostically relevant hot-spot expression of Ki67 yielded concordant results in 71%. Applying TM for characterization of p27KIP1 expression, both typical and blastoid MCL only rarely showed p27KIP1 expression (9% and 15%), whereas 32% of nodal DLBL were p27KIP1-positive, irrespective of high proliferative activity. Among 22 B-cell lymphomas investigated genetically, a p53 + p21- immunophenotype in >20% of tumour cells correlated with p53 locus deletion. CONCLUSIONS: Lymphoma TM allows for immunohistochemical profiling of human B-cell lymphoma with a comparable accuracy to immunohistochemical studies performed on conventional tissue sections. Nodal DLBLs showed significantly more frequent expression of IgD and p27KIP1 than extranodal DLBL. MCL and DLBL frequently showed aberrant p27KIP1 expression. A p53 + p21- immunophenotype in >20% of tumour cells in B-cell non-Hodgkin's lymphoma correlates with p53 gene deletion.     

CD10 expression in peripheral T-cell lymphomas complicated by a proliferation of large B-cells.

CD10 expression by the neoplastic T cells in angioimmunoblastic T-cell lymphoma was recently described. As cases of peripheral T-cell lymphoma, unspecified, fail to show similar CD10 expression, this feature helps discriminate between these two entities, particularly in cases exhibiting morphologic overlap. Given these findings, we studied CD10 expression in a subtype of peripheral T-cell lymphoma known as peripheral T-cell lymphoma complicated by a proliferation of large B cells and compared it with angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation. A total of 33 cases were identified including peripheral T-cell lymphoma complicated by a proliferation of large B cells (10), angioimmunoblastic T-cell lymphoma (10) and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (13). Diagnoses were established by hematoxylin and eosin (H&E) stain, immunohistochemistry and/or molecular findings (polymerase chain reaction for T-cell receptor-gamma gene rearrangement). Two of 10 cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells showed aberrant CD10 expression (20%) compared to 9/10 cases of angioimmunoblastic T-cell lymphoma (90%) and 8/13 of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (62%). One case each of angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation showed a rare, but not unequivocal, CD10+ atypical cell. Four cases of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation were CD10 negative. Of the 2 CD10+ peripheral T-cell lymphoma complicated by a proliferation of large B cells, one had no H&E or IHC features of angioimmunoblastic T-cell lymphoma and showed only a rare positive cell. The second case, a lung biopsy, exhibited diffuse CD10 tumor cell positivity. The predominant staining pattern in the CD10+ cases was characterized by scattered, mostly individual, morphologically neoplastic cells. A rare case showed clusters of positive cells. Our data indicate that only 20% of cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells show CD10 expression by the neoplastic T cells in contrast to angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation which exhibit CD10 staining in 90 and 62% of cases, respectively. This finding does not reach statistical significance with a P-value of 0.57 (Fisher's exact test). As these entities appear to be biologically distinct and may portend different overall survivals, CD10 expression may serve as an additional discriminating criterion.     

Diagnostic usefulness of CD23 and FMC-7 antigen expression patterns in B-cell lymphoma classification

CD23 and FMC-7 are normal B-cell antigens used during diagnostic immunophenotyping of suspected lymphoproliferative disorders, but the diagnostic usefulness of antigenic expression patterns of simultaneous 2-color staining and flow cytometric analysis has not been reported. We evaluated the FMC-7 and CD23 expression pattern in 201 cases of B-cell lymphoma from tissue biopsy specimens by multiparameter flow cytometry. The CD23-/FMC-7+ pattern was the most common pattern in large cell, mantle cell, and marginal zone lymphomas. The CD23 and FMC-7 antigen, along with the CD5 coexpression pattern, permitted accurate classification of all 71 cases of small lymphocytic, mantle cell, and marginal zone types of lymphoma. The widest variation of patterns was with follicular cell lymphoma, although most cases expressed the CD23 +/-/FMC-7+ pattern (+/-, partial or minor subset expression). The CD23 and FMC-7 antigen expression pattern was predictive of subtypes in more than 95% of lymphoma cases and could narrow the differential diagnosis in the remaining cases. We conclude the flow cytometric CD23/FMC-7 expression pattern achieved by dual staining facilitates accurate and reproducible classification of B-cell lymphomas and has diagnostic usefulness.     

Immunoreactivity of B-cell markers (CD79a, L26) in rare cases of extranodal cytotoxic peripheral T- (NK/T-) cell lymphomas.

The monoclonal antibodies L26 (CD20) and CD79a are very useful reagents for the immunohistochemical assessment of B-cell lineage in lymphoproliferative disorders. Although very few CD20-positive peripheral T-cell lymphomas (PTL) have been reported, comprehensive analyses of CD79a reactivity in extranodal PTL and NK/T-cell lymphomas have not been performed previously. This study investigated CD79a (clone JCB117) and CD20 reactivity in 94 extranodal non-B-cell lymphomas (enteropathy-type intestinal T-cell lymphoma [n = 52], nasal NK/T-cell lymphoma [n = 11], and primary cutaneous PTL [n = 31]) and in 17 cases of nodal PTL, unspecified. In four cases (enteropathy-type intestinal T-cell lymphoma [n = 3] and nasal NK/T-cell lymphoma [n = 1]), the majority of tumor cells stained for CD79a (all CD20 negative) and one cutaneous PTL, unspecified, was CD20 positive (CD79a negative). Extensive immunophenotyping and polymerase chain reaction-based molecular analyses revealed that all five B-cell marker-positive extranodal lymphomas had a cytotoxic phenotype and did indeed represent monoclonal peripheral T-cell proliferations. To minimize the risk of misinterpretation of lymphoma cell lineage, especially in cases of extranodal, lymphoproliferative disease, we suggest the use of both CD79a and CD20 in combination with a panel of antibodies reactive to T cells, such as betaF1 and CD5, and to T cells and NK cells, such as CD3, CD2, CD56, and TIA-1.     

Lymphoma of the breast. A clinicopathologic study of primary and secondary cases

BACKGROUND: Primary lymphomas of the breast are rare, accounting for 1.7% to 2.2% of extranodal lymphomas and 0.38% to 0.7% of all non-Hodgkin lymphomas. Although secondary breast lymphomas are also rare, they represent the largest group of metastatic tumors of the breast. OBJECTIVES: To investigate the clinicopathologic and immunophenotypic characteristics of breast lymphomas, the relative frequency of primary and secondary mammary lymphomas, and in selected cases, the role of gene rearrangement analysis in diagnosis and staging of these lymphomas. RESULTS: We conducted a retrospective review of 22 cases of breast lymphoma diagnosed at William Beaumont Hospital, Royal Oak, Mich, during a 30-year period (1963-1994). Eleven of the 22 cases fulfilled the criteria for primary breast lymphoma; these cases represented 0.6% of all non-Hodgkin lymphomas seen in our hospital. Of the 11 cases, 5 were diffuse large B-cell lymphomas, 2 were follicle center lymphomas, 2 were marginal zone B-cell lymphomas (mucosa-associated lymphoid tissue type), 1 was a lymphoplasmacytoid lymphoma, and 1 was a peripheral B-cell neoplasm, unclassified. Using a panel of immunohistochemical stains (CD45RO, CD45RA, CD43, CD3, CD20, CD30, CD68, and HLA-DR), 8 cases demonstrated unequivocal B-cell phenotype and 3 cases had equivocal or weak staining patterns for B-cell markers. We identified no cases of T-cell lymphoma. Of 7 cases that had bone marrow biopsies for staging, 3 were positive morphologically for bone marrow involvement. Molecular analysis of B- and T-cell gene rearrangement was used to exclude bone marrow involvement in one case with bone marrow lymphoid aggregates and to confirm negativity in a case that was morphologically negative. Of the 11 secondary breast lymphomas, 5 were diffuse large B-cell lymphomas; 1 was diffuse large B-cell, primary mediastinal subtype; and 5 were follicle center lymphomas. CONCLUSIONS: Breast lymphomas represented 1.2% of all non-Hodgkin lymphomas in this study; the frequency of primary and secondary cases was equal. In both groups, right breast lesions were predominant, and the most frequent morphologic type was diffuse large B-cell lymphoma. Gene rearrangement analysis is helpful in selected cases to rule out bone marrow involvement, especially in older patients, in whom lymphoid aggregates are common.     

Immunohistochemical determination of CD23 expression in Hodgkin's disease using paraffin sections

The leukocyte antigen CD23 is expressed during B-cell development, and functions as an IgE receptor and a lymphocyte growth factor. We studied the expression of CD23 in paraffin sections of lymphoid tissue using the monoclonal antibody BU38. Fifteen cases of Hodgkin's disease, ten reactive lymph nodes, eight B-cell, and seven T-cell non-Hodgkin's lymphomas were analysed immunohistologically. CD23 positivity was seen on follicular dendritic cells and a small number of lymphocytes in reactive nodes. Thirteen of the 15 cases of Hodgkin's disease showed CD23 expression in both neoplastic cells and reactive lymphocytic infiltrate. The antigen was demonstrated in four of the B-cell and one of the T-cell tumours. CD23 may be important in mediating the mixed cellular infiltrate characteristic of Hodgkin's lymphoma.     

Large B-cell lymphoma of thyroid. Two cases with a marginal zone distribution of the neoplastic cells

We report 2 cases of B-cell lymphoma of the thyroid in which although a marginal zone distribution of the neoplastic cells was present, the cytologic features of the cells indicated large cell lymphoma. One of the cases showed an accumulation of crystalline inclusions within the cytoplasm of the neoplastic cells. Many of these inclusion-bearing cells showed plasmacytoid features. By immunohistochemical studies performed on formalin-fixed paraffin-embedded tissue, both of the cases showed a B-cell phenotype as indicated by CD20 expression, and 1 showed kappa light chain restriction. In both cases, Ki-67 staining corroborated the impression of an aggressive neoplasm with staining of 50% and 90% of the tumor cells. Both patients received cyclophosphamide, doxorubicin, vincristine, and prednisone with radiation therapy, and both are without evidence of disease after 17 and 18 months of follow-up. It is important to recognize this pattern of large B-cell lymphoma of the thyroid gland. While the indolent course typical of most low-grade extranodal marginal zone lymphomas is not likely in these cases, the outcome may be favorable if patients are treated aggressively with therapy for large cell lymphoma.     

Usefulness of follicular dendritic cell pattern in classification of peripheral T-cell lymphomas

Classification of peripheral T-cell lymphomas based on morphological criteria can present problems due to overlap in histological features amongst the subtypes. An immunohistochemical study was designed to study the follicular dendritic cell patterns in 21 cases of peripheral T-cell lymphoma which had been classified using the updated Kiel classification. Three patterns of distribution were observed: 1 follicular dendritic cells not detected (3 cases); 2 follicular dendritic cells restricted to remnant follicle centres (7); 3 follicular dendritic cells present as an expanded network of cells exceeding the confines of germinal centres (11). Ten out of 11 angioimmunoblastic lymphomas showed an expanded network of follicular dendritic cells. The only negative case showed features which, on review, were in keeping with a pleomorphic, medium and large cell lymphoma showing an unusual proliferation of small venules. Other than angioimmunoblastic lymphomas, only one other case showed follicular dendritic cell hyperplasia. This was an unclassified peripheral T-cell lymphoma. We conclude that follicular dendritic cell hyperplasia may be used an an aid to diagnosis of the angioimmunoblastic type of peripheral T-cell lymphoma, and we recommend the routine staining of these cells in typing of T-cell lymphomas to facilitate comparison between centres.     

Lymphocyte immunophenotyping of B-cell lymphomas: a flow cytometric analysis of neoplastic and nonneoplastic cells in 271 cases

We have reviewed our experience with 271 B-cell lymphomas to determine the effectiveness of flow cytometry in the characterization of these malignancies. Flow cytometric immunophenotyping of the total lymphocyte and/or large lymphocyte populations confirmed the morphologic diagnosis of B-cell lymphoma in 92% of cases, which included 79% monoclonal and 13% surface immunoglobulin (SIg)-negative lymphomas. Light chain monoclonality was most frequent in low grade and follicular center cell (FCC) lymphomas, while SIg-negative cases were most common in high grade and non-FCC types. Low grade lymphomas of all histologic types had high median percentages of neoplastic cells and low T-cell percentages. Conversely, high grade lymphomas exhibited lower and less uniform median percentages of B-cells, with higher numbers of T-cells and lower CD4/CD8 ratios than low grade lymphomas. Several differences in B- and T-cells were observed between specific high grade histologic types. FCC lymphomas with a diffuse pattern had lower percentages of CD4+ cells and lower CD4/CD8 ratios than cases with a follicular pattern. Thus, immunophenotypic differences were observed between histologic types or groups with known differences in clinical course and prognosis. We conclude that flow cytometry provides reliable information on neoplastic and nonneoplastic cells in lymph nodes involved by B-cell lymphomas.     

CD5+ T-cell/histiocyte-rich large B-cell lymphoma.

CD5 expression in neoplastic large B-cells in T-cell/histiocyte-rich large B-cell lymphoma has not been reported, to the best of our knowledge. Here we describe the first case of CD5+ T-cell/histiocyte-rich large B-cell lymphoma that is well documented by histomorphology, immunohistochemistry, flow cytometry immunophenotyping and sorting, and immunoglobulin heavy-chain gene rearrangement study by polymerase chain reaction. The expression of CD5 in large neoplastic B-cells was demonstrated by immunohistochemistry and multicolor flow cytometry. The clonal nature of the CD5+ neoplastic B-cells was confirmed by rearranged immunoglobulin heavy (IgH) chain with polymerase chain reaction (PCR) of flow cytometry-sorted CD5+/CD19+/kappa+ cells. The CD5+ neoplastic large B-cells expressed bcl-6 and MUM1/IRF4 but not CD138 by immunohistochemistry. This suggests that the neoplastic cells may be of late germinal-center B-cell/ early post-germinal center B-cell origin. The patient responded to chemotherapy, CHOP (Cytoxan, doxorubicin, vincristine, and prednisone), and Rituxan very well and is currently in complete remission clinically. We propose that the current case, CD5+ T-cell/histiocyte-rich large B-cell lymphoma, represents a variant of recently reported de novo CD5+ diffuse large B-cell lymphomas. Our patient has had an excellent response to treatment; however, the clinical and biologic significance of CD5 expression in T-cell/histiocyte-rich large B-cell lymphoma requires further studies. Awareness of the CD5+ T-cell/histiocyte-rich large B-cell lymphoma variant will prompt pathologists to perform CD5 immunohistochemical stain in cases of T-cell/histiocyte-rich large B-cell lymphoma. This will lead to identifying more cases to understand the clinical and biologic characteristics of this variant.     

Follicular dendritic cell immunohistochemical markers in angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma is characterized by a paracortical proliferation of medium to large neoplastic T cells, often with clear cytoplasm, in a background of arborizing high endothelial venules, many surrounded by follicular dendritic cells (FDCs). IHC staining may be applied to highlight these extrafollicular FDCs, traditionally using CD21, or CD23. Several alternative FDC markers have been described, including CNA.42, cystatin A/acid cysteine proteinase inhibitor (ACPI, involved in antigen presentation), and fascin (an actin binding protein). The authors stained a collection of 45 angioimmunoblastic T-cell lymphomas with CD21, CD23, CNA.42, cystatin A, and fascin for direct comparison of FDC staining characteristics in this setting. CD21 highlighted the expected dendritic network of cell processes, within residual follicles and outside of follicles, often adjacent to proliferating vessels. CD23 exhibited similar staining quality but was less sensitive than CD21. CNA.42 showed only diffuse weak labeling of FDCs. Cystatin A stained the cytoplasm of follicular dendritic cells within and outside of follicles; however, staining was often not sharply localized to dendritic cell processes, and scoring was further complicated by reactivity with other cell types in over half of the cases. Likewise, fascin stained a variety of cell types, including strong staining of interdigitating dendritic-like cells, moderate staining of endothelial cells, and only weak staining of follicular dendritic cells within and outside of follicles. Thus, CD21 remains the most reliable marker of follicular dendritic cells in angioimmunoblastic T-cell lymphoma.     

CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms

We evaluated the immunohistochemical profile and specificity of CD138 reactivity in 238 specimens from hematopoietic and nonhematopoietic neoplasms. In 91 bone marrow biopsies, CD138 reactivity was observed for nonneoplastic plasma cells, neoplastic plasma cells in multiple myeloma cases (43/43), and the plasmacytic component in lymphoplasmacytic lymphoma cases (4/4). Stromal reactivity was noted in 7 multiple myeloma cases. Of 9 bone marrow specimens involved by metastatic carcinoma, tumor cells were CD138+ in 5 cases; stromal reactivity was noted in 7 cases. Studies of 76 nodal and extranodal lymphomas (B-cell, 49; T-cell, 8; Hodgkin lymphoma, 19), 1 Langerhans cell histiocytosis, and 14 nonneoplastic lymph nodes revealed CD138 reactivity only for nonneoplastic plasma cells, the neoplastic cells of 2 large B-cell lymphomas (immunoblastic type, plasmacytoid features), and the clonal plasmacytic component of 3 of 3 extranodal and 1 nodal marginal zone lymphoma. Evaluation of 56 epithelial and nonepithelial tumors revealed CD138 positivity for neoplastic cells of carcinomas of various types (30/33), frequently with associated stromal reactivity, and for neoplasms of mesenchymal, melanocytic, and other tumor types (12/23). Within the hematopoietic system, CD138 is an excellent marker of plasmacytic differentiation. Based on its broad staining profile, CD138 reactivity for neoplastic cells is not a definitive marker for plasmacytic derivation, unless a hematolymphoid origin has been established.     

Immunohistochemical detection of BCL-3 in lymphoid neoplasms: a survey of 353 cases.

The bcl-3 gene at chromosome 19q13 encodes a member of the IkappaB family involved in regulating the NFkappaB pathway. Originally identified by its involvement in the rare t(14:19)(q32;q13), BCL-3 expression has never been analyzed in a wide variety of lymphomas. We assessed BCL-3 expression in 353 cases of non-Hodgkin lymphoma and Hodgkin lymphoma using formalin-fixed, paraffin-embedded tissue specimens, a monoclonal antibody specific for BCL-3, and immunohistochemical methods. Of 172 B-cell lymphomas, 10 (6%) were positive for BCL-3, including six of 23 (26%) diffuse large B-cell lymphoma, one of 17 (6%) small lymphocytic lymphoma, one of 26 (4%) follicular lymphoma, and two of 49 (4%) mantle cell lymphoma. All other B-cell neoplasms were negative, including marginal zone lymphoma (n=24, 11 extranodal, nine nodal, four splenic), Burkitt lymphoma (n=10), lymphoplasmacytic lymphoma (n=10), lymphoblastic lymphoma (n=8), and plasmacytoma (n=5). Of 111 T/NK-cell lymphomas, 25 (23%) were positive for BCL-3, including 13 of 40 (32%) anaplastic large-cell lymphoma, three of 10 (30%) angioimmunoblastic T-cell lymphoma, two of eight (25%) extranodal NK/T-cell lymphoma of nasal type, three of 12 (25%) mycosis fungoides, one of five (20%) enteropathy-type T-cell lymphoma, and two of 21 (10%) peripheral T-cell lymphoma unspecified. All other T-cell neoplasms were negative, including lymphoblastic lymphoma (n=6), prolymphocytic leukemia (n=6), and subcutaneous panniculitis-like T-cell lymphoma (n=3). Of 70 Hodgkin lymphomas, of all types, 29 (41%) were positive for BCL-3. The relatively high frequency of BCL-3 expression in some non-Hodgkin and Hodgkin lymphoma types raises the possibility that BCL-3 is involved in the pathogenesis of these tumors, and may be a target of new therapies.     

Peripheral T-cell lymphoma with extensive dendritic cell network mimicking follicular dendritic cell tumor: a case report with pathologic, immunophenotypic, and molecular findings

Peripheral T-cell lymphoma (PTCL) with a nodular pattern of growth is uncommon and may be misdiagnosed initially as a B-cell lymphoma or reactive process. We report a case of a rapidly growing PTCL with a distinctly nodular pattern in an axillary lymph node from an 89-year-old man. Immunohistochemical stains for CD21, CD23, and CD35 highlighted an extensive dendritic cell network that imparted the nodular appearance and, in addition, was associated intimately with the neoplastic cells. The neoplastic cells otherwise had an immunophenotype similar to previously reported cases of PTCL with a nodular pattern and germinal center origin (CD3+, CD4+, CD5+, bcl-6+, CD31+, subset CD10+, subset CXCL13+, and subset CD79a+). Molecular studies confirm a clonal T-cell receptor g gene rearrangement. This case emphasizes unusual morphologic features in a PTCL that may be mistaken for follicular lymphoma or a tumor of follicular dendritic cell origin.     

Analysis of clonality of atypical cutaneous lymphoid infiltrates associated with drug therapy by PCR/DGGE

Atypical lymphocytic infiltrates that mimic cutaneous lymphoma (ie, pseudolymphoma) are often observed in skin biopsy specimens from patients with altered immune function. The latter may reflect systemic immune dysregulatory states such as collagen vascular disease or human immunodeficiency virus infection. Among the iatrogenic causes are drug therapy with agents that abrogate lymphocyte function. These drugs encompass the anticonvulsants, antidepressants, phenothiazines, calcium channel blockers, and angiotensin-converting enzyme inhibitors. The appellation of lymphomatoid hypersensitivity reaction has been applied to cases of drug-associated pseudolymphoma. Pathologically and clinically, the distinction of such cases from cutaneous lymphoma is difficult. We employed the polymerase chain reaction (PCR) on archival material of proven drug-associated lymphomatoid hypersensitivity reactions both to explore its utility as an adjunct in diagnosis and to investigate the genotypic aberrations induced by drug therapy. Formalin-fixed, paraffin-embedded biopsy specimens from seven cutaneous T-cell lymphomas (CTCL), one nodal T-cell lymphoma, two cutaneous B-cell lymphomas, three typical hypersensitivity reactions, one tonsil, and 14 lymphomatoid hypersensitivity reactions were studied. Control cases for which DNA derived from fresh tissue was used include the Jurkat T-cell tumor line, placenta, one nodal B-cell lymphoma, and one case of reactive lymph node hyperplasia. DNA was obtained and purified by standard methods, then amplified with oligonucleotide primers specific for the T-cell receptor gamma locus and the immunoglobulin heavy chain genes. T-cell amplicons were analyzed by denaturing gradient gel electrophoresis (DGGE) and B-cell amplicons by either nondenaturing polyacrylamide or agarose gel electrophoresis. The nodal and Jurkat T-cell lymphomas, six of seven CTCL, one cutaneous B-cell lymphoma, and 2 of 14 lymphomatoid hypersensitivity reactions showed dominant ("monoclonal") T-cell gene rearrangement patterns, and the remainder of cases were polyclonal. A causal relationship between drug therapy and skin eruption was ascertained in the two patients showing T-cell rearrangements, and both experienced complete and sustained lesional resolution on discontinuation of the implicated drug. The only immunoglobulin heavy chain gene rearrangements detected by PCR were in two of the three B-cell lymphomas. We conclude that PCR/DGGE is a powerful method for assaying T-cell clonality in archival tissue and can aid in the discrimination of reactive from malignant cutaneous infiltrates with appropriate clinicopathologic correlation. Recognition that a monoclonal TCRgamma rearrangement can be observed in cases of drug-associated lymphomatoid hypersensitivity may help in avoiding a misdiagnosis of malignant lymphoma.