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Background
These rare lymphomas were only identified by pathologists working with a battery of immunoperoxidase stains and gene rearrangement studies. Through diligent efforts, it was noted that this sub-group of lymphomas, previously classified as T-cell lymphomas, were actually B-cell lymphomas and responded to therapies best tailored for B-cell lymphomas.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS INCIDENCE/
PREVALENCEAGE
Leuk Lymphoma. 2005 Sep;46(9):1295-300. Abstract quote
T-cell rich B-cell lymphoma (TCRBCL) is considered a rare variant of aggressive B-cell lymphoma characterized by few neoplastic cells and a large reactive infiltrate with striking similarities to nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL). In childhood, these tumors occur even less frequently. Biopsy specimens at diagnosis from 16 children (13 boys) with a median age of 12 years (range, 7 to 18) were immunophenotyped. The proliferation rate was assessed with monoclonal antibodies against Ki-67 and repp86 antigens and additional clonality analyses were performed.
Ten patients had localized disease and only two had B symptoms. All patients showed high Ki-67 expression (median: 80%, range 40% to 90%), but low repp86 expression (median: 25%, range 10% to 50%). PCR-based clonality studies of the hypervariable CDR III region of the immunoglobuline heavy chain and the T-cell receptor gamma-chain genes demonstrated predominant clones in nine and five patients, respectively. Three patients had previous or concomitant NLPHL and two of them received initial treatment for Hodgkin's disease. All patients achieved remission after a brief polychemotherapy regimen. Two patients subsequently relapsed and one was rescued by salvage therapy including autologous stem cell transplantation. At a median follow-up of 23 months, 15 patients (94%) are alive.
The striking contrast between the proliferation rates determined by Ki-67 and repp86 expression points to a possible arrest in the G1 cell cycle phase because repp86 expression is restricted to the S, G2 and M cell cycle phases. This G1 arrest may explain the paradoxon of high Ki-67 expression in a paucicellular lymphoma with a favorable prognosis in young patients.SEX GEOGRAPHY EPIDEMIOLOGIC ASSOCIATIONS
DISEASE ASSOCIATIONS CHARACTERIZATION
PATHOGENESIS CHARACTERIZATION
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC LABORATORY MARKERS
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS EYE
- Primary intraocular T-cell-rich large B-cell lymphoma.
Cummings TJ, Stenzel TT, Klintworth G, Jaffe GJ.
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Arch Pathol Lab Med. 2005 Aug;129(8):1050-3. Abstract quote
We report a primary intraocular T-cell-rich large B-cell lymphoma in a 57-year-old woman who underwent 3 diagnostic vitrectomies for a presumed diagnosis of panuveitis. She developed no light perception in the left eye and underwent enucleation.
Histopathologic and immunohistochemical studies on the enucleated globe disclosed a primary intraocular large B-cell lymphoma involving the choroid, vitreous, and retina. A large population of T cells was identified among the neoplastic B-cell population. B-cell immunoglobulin gene rearrangement and T-cell receptor gene rearrangement studies using the polymerase chain reaction method indicated that a monoclonal immunoglobulin kappa light chain population was present and that the T-cell population was not monoclonal.
This case highlights the importance of interpreting cytologic features in vitreous aspirates in the context of the clinical situation.SKIN SPLEEN
Int J Surg Pathol. 2004 Jan;12(1):31-7. Abstract quote
We review the clinical, pathologic, and molecular genetic features of 3 splenic T-cell-rich B-cell lymphomas and discuss their differential diagnosis. All patients presented with symptomatic splenomegaly and underwent diagnostic/therapeutic splenectomy.
Microscopically, the spleen in all cases showed a micronodular proliferation of lymphoid cells. A proportion of the nodules demonstrated central hyalinization or sclerosis. There was also an exuberant extramedullary hematopoiesis.
On immunohistochemical stain, the nodules consisted predominantly of small T cells with scattered large atypical B cells. The clonal nature of the atypical B cells was confirmed by polymerase chain reaction assays for immunoglobulin heavy-chain gene rearrangement. In the H&E sections, the differential diagnoses included Hodgkin's lymphoma, follicular lymphoma, peripheral T-cell lymphoma, and nonneoplastic granulomatous process. The presence of exuberant extramedullary hematopoiesis also raised the possibility of a chronic myeloproliferative disorder.
The combined morphologic, immunohistochemical, and molecular genetic data are essential for a correct diagnosis of splenic T-cell-rich B-cell lymphoma.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL VARIANTS T-CELL/HISTIOCYTE RICH LARGE B-CELL LYMPHOMA
- T-cell/histiocyte-rich large B-cell lymphoma displays a heterogeneity similar to diffuse large B-cell lymphoma: a clinicopathologic, immunohistochemical, and molecular study of 30 cases.
Wang J, Sun NC, Chen YY, Weiss LM.
Department of Pathology and Laboratory Medicine, Loma Linda University Medical Center, Loma Linda, CA 92354, USA .
Appl Immunohistochem Mol Morphol. 2005 Jun;13(2):109-15. Abstract quote
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL), a proliferating peripheral B-cell neoplasm, is a morphologic variant of diffuse large B-cell lymphoma (DLBCL), which may be confused with Hodgkin's lymphoma, non-Hodgkin's lymphoma, and reactive lymphadenopathies. Though more recent studies suggested that it might be a distinct clinicopathologic entity and/or a heterogeneous entity with derivation from germinal center B cells, its histogenetic derivation remains controversial.
The authors analyzed 30 cases of THRLBCL to further characterize the origin of the neoplastic cells using immunohistochemical and molecular studies for expression of Bcl-6, CD10, and CD138, as well as rearrangements of IgH/bcl-2 genes on paraffin-embedded tissue. Half of the cases (15/30) showed Bcl-6 expression and five cases (19%) showed CD10 expression, but none had CD138 expression (0/20). Only three cases showed coexpression of both Bcl-6 and CD10. Molecular studies performed in 21 cases detected rearrangement of immunoglobulin heavy gene in 18 cases, with none having detectable Bcl-2 gene rearrangement.
These data indicate that similar to DLBCL, the cell origin of neoplastic cells in THRLBCL is composed of a heterogeneous group of proliferating peripheral B cells, with only some cases originating from germinal center B cells and others derived from heterogeneous origins. Lack of Bcl-2 gene rearrangements seems to argue against a possible progression from preexisting follicular lymphoma.
Thus, the normal counterpart of the neoplastic cells cannot at this time be the sole basis for the subclassification of THRLBCL.
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE CD20
- CD20-Negative T-Cell-Rich B-Cell Lymphoma as a Progression of a Nodular Lymphocyte-Predominant Hodgkin's Lymphoma Treated With Rituximab: A Molecular Analysis Using Laser Capture Microdissection.
Pijuan L, Vicioso L, Bellosillo B, Ferrer MD, Baro T, Pedro C, Lloreta-Trull J, Munne A, Serrano S.
From *Hospital del Mar-IMAS-IMIM, Autonomous University of Barcelona, and Pompeu Fabra University, Barcelona, Spain; and daggerHospital Clinico Universitario, Virgen de la Victoria, Malaga, Spain. Reprints: Lara Pijuan, MD, Department of Pathology, Hospital del Mar-IMAS-IMIM, Passeig Maritim 25-29, Barcelona, Spain 08003
Am J Surg Pathol. 2005 Oct;29(10):1399-1403. Abstract quote
Rituximab is a chimeric anti-CD20 monoclonal antibody. It has shown efficacy in patients with B-cell non-Hodgkin lymphoma and also in CD20-positive Hodgkin lymphoma. Recently, CD20-negative tumors have been described after Rituximab therapy.
We report a 34-year-old man with a history of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), treated with different chemotherapy regimens, including anthracyclines and Rituximab. After 4 years in complete remission, he developed a CD20-negative T-cell-rich B-cell lymphoma (TCRBCL) presenting as multiple lung lesions. This case shows the difficulties in the diagnosis of CD20-negative lymphomas when the number of tumor cells is low and when they are found in a predominant T-cell context.
Using anti-CD79a as a B-cell marker is mandatory to overcome the difficulties in identifying these tumors. Moreover, this case illustrates the usefulness of laser capture microdissection to obtain purified cell populations for molecular studies in lymphomas with relative paucity of tumor cells, as well as the need to analyze different IgH gene regions to decrease the rate of false-negative results in PCR clonality studies.LSP1
- Leukocyte-specific phosphoprotein-1 and PU.1: two useful markers for distinguishing T-cell-rich B-cell lymphoma from lymphocyte-predominant Hodgkin's disease.
Marafioti T, Mancini C, Ascani S, Sabattini E, Zinzani PL, Pozzobon M, Pulford K, Falini B, Jaffe ES, Muller-Hermelink HK, Mason DY, Pileri SA.
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
Haematologica. 2004 Aug;89(8):957-64. Abstract quote
BACKGROUND AND OBJECTIVES: T-cell-rich B-cell lymphoma is a rare variant of diffuse large B-cell lymphoma. It shows morphologic, phenotypic and molecular similarities to lymphocyte predominant Hodgkin's disease, and in consequence the two diseases may sometimes be difficult to distinguish. In this paper, we have evaluated the usefulness of the pan-leukocyte marker LSP1 and the transcription factor PU.1 for resolving such diagnostic problems.
DESIGN AND METHODS: Immunohistochemical techniques were used to investigate the expression of LSP1 and PU.1 in 34 tumors, comprising typical examples of T-cell-rich B-cell lymphoma (15 cases), lymphocyte-predominant Hodgkin's disease (13 cases), and lymphocyte-rich classical Hodgkin's disease (6 cases).
RESULTS: The neoplastic cells of T-cell-rich B-cell lymphoma were LSP1-positive and PU.1-negative, whereas the lymphocytic and/or histiocytic (L&H) cells of lymphocyte-predominant Hodgkin's disease were mostly LSP1-negative, with variable PU.1 expression. The two markers did not discriminate between T-cell-rich B-cell lymphoma and lymphocyte-rich classical Hodgkin's disease, whilst they concurred to the distinction between lymphocyte-predominant and lymphocyte-rich classical Hodgkin's disease by integrating the already available tools.
INTERPRETATION AND CONCLUSIONS: Antibodies to LSP1 and PU.1 may represent useful reagents for the differential diagnosis between T-cell-rich B-cell lymphoma and lymphocyte-predominant Hodgkin's disease.ELECTRON MICROSCOPY
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES HODGKIN'S DISEASE
- Reed-Sternberg-like cells in T-cell rich B-cell lymphoma: a diagnostic dilemma.
Shahabuddin MD, Raghuveer CV.
Sikkim Manipal Medical College, Gangtok, Sikkim.
Indian J Pathol Microbiol. 2003 Jan;46(1):55-6. Abstract quote
T-cell-rich B-cell lymphoma (TCRBCL) is a recently described variant of diffuse Non-Hodgkin's lymphoma (NHL) which requires immunohistochemical analysis for its recognition. Striking similarities exist between TCRBCL and lymphocyte predominant Hodgkin's Disease (LPHD) due to the presence of Reed-Sternberg (R-S) like cells.
Hence, the need for distinction between the two is of utmost importance from a prognostic and therapeutic stand point.
The present study describes a case of TCRBCL, misdiagnosed as Hodgkin's Disease (HD) on fine needle aspiration (FNA) cytology. However, immunostaining of paraffin embedded sections corrected the cytological diagnosisPERIPHERAL T-CELL LYMPHOMAS
PROGNOSIS CHARACTERIZATION
- T-cell-rich B-cell lymphoma: a clinicopathologic study of 21 cases and comparison with 43 cases of diffuse large B-cell lymphoma.
Aki H, Tuzuner N, Ongoren S, Baslar Z, Soysal T, Ferhanoglu B, Sahinler I, Aydin Y, Ulku B, Aktuglu G.
Division of Hematopathology, Department of Pathology, Cerrahpasa Tip Fakultesi, Istanbul Universitesi, Patoloji Anabilim Dali, Istanbul 34303, Turkey.
Leuk Res. 2004 Mar;28(3):229-36. Abstract quote
Clinicopathologic features of 21 patients with T-cell-rich B-cell lymphoma (TCRBCL) were reviewed and compared to 43 patients with diffuse large B-cell lymphoma (DLBCL) to determine if there were distinguishing clinical characteristics and differences in response or survival to CHOP therapy.
For the diagnosis of TCRBCL, the current WHO criteria was used. In all of our cases, the majority of cells are non-neoplastic T cells and <10% large neoplastic B cells are present. The initial pathologic diagnosis was nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) in two cases. Patients with TCRBCL were significantly younger (median: 46 years) and had a significantly higher incidence of B symptoms (62%), hepatomegaly (33%) and marrow infiltration (33%) at presentation when compared to DLBCL (P<0.03). The CR rate after treatment was 48% for TCRBCL patients versus 79% for the DLBCL (P<0.003). Although the CR rates in between the two groups are significant, the difference in 3 years survival rates in each CR groups was insignificant (80% versus 77%).
The overall survival time in the two groups was 17 months. Event-free survival time in TCRBCL was 12 months, compared with 17 months in the DLBCL (P>0.05). The frequency of patients with TCRBCL achieving CR was 52.6% whereas that of patients with DLBCL was 79% (P<0.003). The TCRBCL 3 years event-free survival 48% and overall survival 64% were 63 and 72% for DLBCL, respectively.
- T-cell rich B-cell lymphoma: clinical distinctiveness and response to treatment in 45 patients.
Ripp JA, Loiue DC, Chan W, Nawaz H, Portlock CS.
Yale University School of Medicine, New Haven, CT USA.
Leuk Lymphoma. 2002 Aug;43(8):1573-80. Abstract quote
T-cell rich B-cell lymphoma (TCR-BCL) is a recently described pathologic diagnosis without a place among traditional lymphoma classification systems. In the past, TCR-BCL has been included among other diagnoses, in particular lymphocyte predominant Hodgkin's disease (LPHD).
The study of TCR-BCL cohorts may elucidate clinical distinctiveness, response to therapy, and the effect of treatment regimen on outcome. Between 1992 and 1997, a hematopathologist at Memorial Sloan-Kettering Cancer Center (MSKCC) diagnosed 45 patients with TCR-BCL according to published criteria. Clinical data was collected through retrospective chart review and communication with other patient providers. Our patients presented most commonly as males in their fourth decade with advanced stage disease. Three-year overall survival (OS) and failure-free survival (FFS) were 73 and 37%, respectively. Conventional combination chemotherapy regimens were utilized for an aggressive non-Hodgkin's lymphoma (NHL) diagnosis in 26 and for a Hodgkin's disease (HD) diagnosis in 10. Disease-free survival (DFS) was significantly better for NHL (36%) vs. HD (10%) directed chemotherapy at 3 years (p = 0.003). Overall survival at 3 years was not statistically different (62 vs. 79%) due to successful salvage therapy in both groups. It is important to distinguish TCR-BCL from LPHD and classical HD. Advanced stage, extranodal disease, involvement of the mediastinum, mesentery and/or spleen are clinical clues to a TCR-BCL diagnosis.
Chemotherapy directed to a NHL diagnosis rather than HD results in a significant improvement in disease-free survival. Initial Hodgkin's disease-directed (HD-directed) chemotherapy should be avoided, although salvage transplantation may result in prolonged survival.
TREATMENT CHARACTERIZATION GENERAL CHEMOTHERAPY
- Rituximab in combination with vinorelbine/gemcitabine chemotherapy in patients with primary refractory or early relapsed T cell rich B cell lymphoma. A pilot study.
Xiros N, Economopoulos T, Valsami S, Rontogianni D, Fountzilas G, Raptis S.
Second Department of Internal Medicine-Propaedeutic, Evangelismos Hospital, University of Athens, Ipsilandou 45-47, 106 76 Athens, Greece.
Leuk Res. 2003 Dec;27(12):1097-9. Abstract quote
Rituximab is a chimeric monoclonal antibody that binds specifically to the CD20 antigen expressed in most B cell lymphomas. As single agent or in combination with chemotherapy rituximab has shown significant activity in patients with relapsing or refractory aggressive lymphomas.
Because T cell rich B cell lymphomas (TCRBCL) also express the CD20 antigen, we decided to evaluate the efficacy and tolerability of the anti-CD20 monoclonal antibody rituximab combined with chemotherapy in four patients with either primary refractory or early relapsed TCRBCL. The chemotherapy regiment consisted of vinorelbin and gemcitabine, a combination with known efficacy in patients with refractory aggressive lymphomas. The patients received 6 cycles of rituximab at the dose of 375 mg/m(2), combined with vinorelbine 25 mg/m(2) and gemcitabine 800 mg/m(2) at 3-week intervals. Three complete responses and one partial response were observed among our four patients with refractory or early relapsed TCRBCL without significant adverse effects, indicating considerable efficacy of this combination.
Therefore, rituximab should be tested in combination with chemotherapy in the front line treatment of patients with TCRBCL.
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