Diagnosis Of Angioimmunoblastic T-cell Lymphoma Research Articles

Expressions of CXCL13, CD10 and bcl-6 in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified

To study the value of immunomarkers CXCL13, CD10, bcl-6 in pathologic diagnosis of angioimmunoblastic T-cell lymphoma (AITL). One hundred and fifteen cases of AITL, 30 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) and 30 cases of reactive lymph nodes with paracortical hyperplasia (RH) encountered during the period from January, 1990 to January, 2008 were retrieved from the archival files of the Department of Pathology, West China Hospital of Sichuan University, China. The morphologic features were reviewed and compared. Immunohistochemical study was performed by SP method for CXCL13, CD10, bcl-6, CD21, CD3epsilon, CD3, CD45RO, CD20 and Ki-67. TCR-gamma gene rearrangement study was also carried out. Regressed follicles were evident in 7.8% (9/115) of AITL cases, 6.7% (2/30) of PTCL, NOS cases and 83.3% (25/30) of RH cases, respectively. A marked increase of number of arborizing venules was shown in 98.3% (113/115) of AITL cases, 63.3% (19/30) of PTCL, NOS cases and 76.7% (23/30) of RH cases, respectively. In lymph nodes with paracortical hyperplasia, the expression of CXCL13, CD10 and bcl-6 were restricted to the germinal centers. In AITL, 96.5% (111/115) of cases showed CXCL13 expression, in contrast to 26.7% (8/30) of PTCL, NOS. Expression of CD10 and bcl-6 were found in the neoplastic cells in 50.4% (58/115) and 78.3% (90/115) of AITL, and 3.3% (1/30) and 3.3% (1/30) of PTCL, NOS, respectively. Irregular meshworks of CD21-positive follicular dendritic cells were found in all the AITL cases. Clonal TCR-gamma rearrangement was detected in 83% (83/100) of the AITL cases. AITL is a type of lymphoma originated from the follicular helper T cells. Detailed morphologic assessment and use of immunohistochemical markers are essential for accurate diagnosis.

Characterization of CXCL13+ Neoplastic T Cells in Cutaneous Lesions of Angioimmunoblastic T-cell Lymphoma (AITL)

Skin manifestations of angioimmunoblastic T-cell lymphoma (AITL) are frequent, sometimes as first manifestations of the disease. In the absence of a specific marker for neoplastic cells, diagnosis of AITL in skin biopsies is often difficult. CD10 and CXCL13 have been recently recognized as characteristic markers of AITL, but have not been yet investigated in the skin. We analyzed 15 skin biopsies from 8 patients with AITL having skin manifestations and compared them to 14 skin biopsies from patients with various cutaneous lymphocytic infiltrates. A few CD10 lymphocytes were found in only 2 samples of the AITL group, the identification of which was hampered by the presence of a dermal CD10 cell population with dendritic features. By contrast, CXCL13 lymphoid cells were identified in most AITL cutaneous biopsies (n=12, 80%), whereas, absent in all samples from control cases. Among 12 biopsies with CXCL13 cells, cutaneous involvement by AITL was suspected in only 5 on the basis of light microscopy and classic immunophenotyping. In another case, a diagnosis of cutaneous marginal zone B-cell lymphoma had been proposed. In conclusion, this study shows that neoplastic AITL CXCL13 T cells localize in the skin and that accurate diagnosis of AITL lesions can be done in skin specimens using CXCL13 immunostaining on paraffin-embedded tissues.

Spectrum of bone marrow findings in patients with angioimmunoblastic T‐cell lymphoma

Bone marrow (BM) biopsy is often performed early in the evaluation of patients with angioimmunoblastic T-cell lymphoma (AITL), and may be the first diagnostic tissue sample; yet the BM histopathology associated with this disease has not been well described. In this study, BM specimens from 13 patients with AITL were reviewed. Seven (54%) were involved by AITL, which was characterised by paratrabecular and interstitial polymorphous infiltrates containing cytologically atypical lymphocytes, histiocytes and eosinophils. The neoplastic cells were positive for CD10 and CXCL13 by immunohistochemistry in a subset of cases. As in lymph nodes, the lymphomatous infiltrate in some BMs contained numerous small or scattered large B cells, resembling either benign lymphoid aggregates or T cell rich large B cell lymphoma, respectively. Secondary haematological changes were frequent and presented independent of BM involvement by AITL; these included trilineage haematopoietic hyperplasia and plasmacytosis. When BM biopsy preceded the diagnosis of AITL, these secondary changes were misinterpreted as chronic myeloproliferative disease (n = 2), or plasma cell dyscrasia (n = 2). In two cases, these changes obscured the presence of BM involvement by AITL. The spectrum of BM findings in AITL patients is important to recognise for early and accurate diagnosis in this disease.

Angioimmunoblastic T-Cell Lymphoma Initially Presenting with Replacement of Bone Marrow and Peripheral Plasmacytosis

A 73-year-old man presented with lymphadenopathy, hepatosplenomegaly, and a variety of hematological and immunological abnormalities. The bone marrow was replaced by polymorphic cellular infiltrates containing aggregates of CD10(+) T-cells. Circulating lymphoplasmacytic/immunoblastic cells showed an early plasma cell immunophenotype on flow cytometric analysis. Combination of these observations indicated that the underlying disorder of this patient was angioimmunoblastic T-cell lymphoma (AITL); postmortem pathology was consistent with progression of peripheral T-cell lymphoma. Even in the absence of definitive lymph node biopsy, the appearance of the bone marrow and the peripheral blood can lead to the diagnosis of AITL.

Angioimmunoblastic T-Cell Lymphoma With Supervening Epstein-Barr Virus–Associated Large B-Cell Lymphoma

Patients with angioimmunoblastic T-cell lymphoma can have profound immune dysfunction and immunodeficiency. Epstein-Barr virus-driven B-cell lymphoid proliferation can occur in angioimmunoblastic T-cell lymphoma, as in other immunodeficiency states. However, few cases of Epstein-Barr virus-positive B-cell lymphoma arising in patients with preexisting angioimmunoblastic T-cell lymphoma have been reported. We report a case of angioimmunoblastic T-cell lymphoma in which diffuse large B-cell lymphoma developed 56 months after the diagnosis of angioimmunoblastic T-cell lymphoma. The patient survived for 9 years after the initial diagnosis of angioimmunoblastic T-cell lymphoma, and molecular studies performed on multiple biopsy specimens during this period revealed the dynamic nature of clonal lymphoid expansion. Epstein-Barr virus latent membrane protein 1 and Epstein-Barr virus-encoded RNA were detected in the diffuse large B-cell lymphoma, suggesting that Epstein-Barr virus may have played a role in the pathogenesis of the diffuse large B-cell lymphoma.

Angioimmunoblastic T-Cell Lymphoma With Supervening Epstein-Barr Virus–Associated Large B-Cell Lymphoma

Abstract Patients with angioimmunoblastic T-cell lymphoma can have profound immune dysfunction and immunodeficiency. Epstein-Barr virus–driven B-cell lymphoid proliferation can occur in angioimmunoblastic T-cell lymphoma, as in other immunodeficiency states. However, few cases of Epstein-Barr virus–positive B-cell lymphoma arising in patients with preexisting angioimmunoblastic T-cell lymphoma have been reported. We report a case of angioimmunoblastic T-cell lymphoma in which diffuse large B-cell lymphoma developed 56 months after the diagnosis of angioimmunoblastic T-cell lymphoma. The patient survived for 9 years after the initial diagnosis of angioimmunoblastic T-cell lymphoma, and molecular studies performed on multiple biopsy specimens during this period revealed the dynamic nature of clonal lymphoid expansion. Epstein-Barr virus latent membrane protein 1 and Epstein-Barr virus– encoded RNA were detected in the diffuse large B-cell lymphoma, suggesting that Epstein-Barr virus may have played a role i...

Expression of CXCL13 by Neoplastic Cells in Angioimmunoblastic T-Cell Lymphoma (AITL)

Angioimmunoblastic T-cell lymphoma (AITL) represents a distinct entity among peripheral T-cell lymphomas (PTCLs). The cellular origin of AITL remains unknown, although a possible derivation from follicular helper T cells (TFH) has been suggested based on the CD4/Bcl-6 phenotype. It has been recently shown that expression of CXCL13, a chemokine critically involved in B-cell migration into germinal centers, is characteristic of TFH cells, as compared with other T helper subsets. We compared CXCL13 expression in 29 AITLs, 20 PTCLs, unspecified, 10 anaplastic large cell lymphomas (ALCL), and 4 other PTCLs. We showed that CXCL13 is expressed by AITL (29 of 29, 100%) and a subset of PTCL, unspecified (6 of 20, 30%), which all showed borderline features with AITL, but in only 1 of 10 (10%) ALCLs, and 0 of 4 other PTCLs. Two-color immunostainings further showed that CXCL13 was found in the cytoplasm of atypical CD5-positive T cells that expressed CD10. We conclude that CXCL13 expression is a common characteristic of AITL, which can help to delineate the morphologic spectrum of the disease, and further supports its derivation from TFH cells. CXCL13 expression may also provide an additional useful tool for the diagnosis of AITL.

Expression of CXCL13, a chemokine highly upregulated in germinal center T-helper cells, distinguishes angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified

The germinal center T-helper cell has been proposed as the cell of origin for angioimmunoblastic T-cell lymphoma. Our recent report of expression of CXCL13, a chemokine critical for germinal center formation and one of the most highly upregulated genes in the germinal center T-helper cell subset, in the majority of angioimmunoblastic T-cell lymphoma cases, provided further support for this theory. To determine the specifity of this marker for angioimmunoblastic T-cell lymphoma, we evaluated CXCL13 expression in 26 nodal-based peripheral T-cell lymphomas and 14 lymph nodes showing paracortical lymphoid hyperplasia. No significant paracortical CXCL13 staining was seen in the reactive lymph nodes. By WHO classification criteria, 20 of the lymphoma cases were considered peripheral T-cell lymphoma, unspecified, and six were reclassified as angioimmunoblastic T-cell lymphoma after immunohistochemical detection of disorganized follicular dendritic cell meshworks. Combining the results of our studies, 31 of 35 angioimmunoblastic T-cell lymphoma cases (89%) showed CXCL13 expression, in contrast to two out of 20 peripheral T-cell lymphoma, unspecified cases (10%). The two peripheral T-cell lymphoma, unspecified cases that were positive for CXCL13 showed a Lennert lymphoma-like histology. While these cases did not meet all histologic criteria for angioimmunoblastic T-cell lymphoma, they did show an increase in EBV-positive B cells, suggesting they may be histologic variants of angioimmunoblastic T-cell lymphoma. In conclusion, CXCL13 expression is a distinctive feature of angioimmunoblastic T-cell lymphoma, providing further support for the germinal center T-helper cell as the cell of origin for this neoplasm. Given its specificity when compared to cases of peripheral T-cell lymphoma, unspecified as well as paracortical lymphoid hyperplasia, it may be a useful marker in the diagnosis of angioimmunoblastic T-cell lymphoma.

Toxic epidermal necrolysis secondary to angioimmunoblastic T‐cell lymphoma

A 67-year-old man presented with a history of lymphadenopathy, fevers and separate skin eruptions of erythrodermic spongiotic dermatitis initially and subsequent toxic epidermal necrolysis. Initial lymph node biopsies showed non-specific granulomatous changes, and skin biopsies and bone marrow aspirate were not diagnostic. His toxic epidermal necrolysis responded well to 3 days of intravenous immunoglobulin. The patient was discharged from hospital and reviewed regularly as an outpatient. Due to persisting lymphadenopathy, further lymph node biopsy led to the diagnosis of angioimmunoblastic T-cell lymphoma, a rare form of peripheral T-cell lymphoma with a poor prognosis. At the time of diagnosis his condition deteriorated rapidly and he died soon after.

CD10 and BCL6 expression in the diagnosis of angioimmunoblastic T-cell lymphoma: utility of detecting CD10 + T cells by flow cytometry

Angioimmunoblastic T-cell lymphoma (AITCL) is a histologically distinct and relatively common subtype of T-cell lymphoma. Although the putative normal cell counterpart is a mature CD4+ T cell, the precise cell of origin remains elusive. We evaluated cases with a diagnosis of AITCL to determine the specificity and utility of CD10 coexpression, particularly by flow cytometry (FCM), in facilitating this diagnosis. Coexpression of BCL6 was also assessed. Eight AITCL cases were evaluated histologically, immunohistochemically, and by 4-color FCM. Four cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), were also analyzed. The lymphoma cells in all 8 AITCL cases were CD4+, CD45RO+ T cells, with classic extrafollicular meshworks of CD21/CD23/CD35+ follicular dendritic cells. Furthermore, all cases of AITCL cases contained interfollicular CD10+ cells by immunohistochemistry, and increased coexpression of CD10 on T cells was also detected in 6 of 8 cases by FCM. CD10 coexpression was not observed in all 4 PTCL-NOS cases. Although not specific for AITCL, increased numbers of BCL6+ cells were seen in AITCL as compared with PTCL-NOS. Double immunohistochemistry performed on an AITCL case with high numbers of BCL6+ cells highlighted coexpression of BCL6 and CD4 on the same cells. The finding suggests that AITCL may be a neoplasm of (possibly intrafollicular) CD10+, BCL6+, and CD4+ memory T cells. Although our series is small, our results suggest that CD10 coexpression may be a useful discriminant, particularly if the differential diagnosis is PTCL-NOS, and demonstrate that this can be determined by FCM.

Usefulness of CD10 Study by Multi-Colour Flow Cytometry in Angioimmunoblastic T-Cell Lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct clinicopathological entity among peripheral T-cell lymphoma in the WHO classification. Whereas antigen “loss” or “deletion” of one or several pan-T cell antigens is a hepful feature of neoplastic lymphocytes in many T-cell lymphomas, no specific immunophenotypic patterns were available to recognize the tumour T-cells of AITL until recently. Indeed, Attygalle et al. reported that in this disorder neoplastic T-cells can be recognized by the aberrant expression of CD10 using immunochemistry in lymph nodes as well as in the involved extranodal sites. Lee et al. has also confirmed this specific phenotypic feature in cell suspension of lymph nodes using flow cytometry (FCM) in 3 cases of AITL. Here, we evaluated the CD10 expression by T cells in patients with AITL using four-colour FCM. The present study included lymph nodes (LN, n=10), peripheral blood (PB, n=5), bone marrow (n=1) and skin (n=1) samples from 13 patients with a diagnosis of AITL and with available cytologic histologic, immunologic and molecular data. Lymph nodes of reactive hyperplasia (n=13), B-cell lymphoma (n=23), other T-cell lymphoma (n=6) and peripheral blood from healthy donors (n=18) were used as control group. According with previous immunohistochemistry results, a fraction of T-cells expressed CD10 (using a level of at least 5% of all CD5+ cells) in 9/10 AITL lymph nodes with a mean number of 18%. Interestingly, among these 9 cases, 5 could be studied in peripheral blood also and all cases showed a fraction of T-cells expressing CD10, whatever be the lymphocytosis (median 1.1 109/l range 0.82 to 11.32 109/l). In three of these cases, tumoral T-cells presented also lack of surface CD3. In two cases of AITL diagnosed in LN, the aberrant CD10 expression by T-cells was found in bone marrow and skin, respectively. In the control group, T-cells were CD10 negative using the cut-off of 5%.In conclusion, we demonstrate that the assessment of CD10 expression by neoplastic T-cells can be achieved by multi-colour FCM in lymph nodes and involved extranodal sites. Our results are concordant with the statement of Attygalle that CD10 expression by T-cells can be used as a marker of both malignancy and AITL type. In addition, this is to our knowledge the first description of circulating CD10 neoplastic T-cells in AITL. Further study with a larger series of patients is required to confirm these data, to standardize the cut-off of positivity and to evaluate the sensibility of FCM versus immunohistochemistry. [Display omitted]

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 ≤14% of the total T-cell population. Using two-color immunohistochemical stains, many of the CD10+ PAX5-negative presumptive T cells were found to be located within germinal centers. These findings indicate that a normal small subset of CD10+ peripheral T cells exists and, at least when present in small numbers, should not be considered an indication of a T-cell neoplasm.

Occurrence of Angioimmunoblastic T Cell Lymphoma in a Patient with Chronic Myelomonocytic Leukemia Features

In a patient with recently diagnosed chronic myelomonocytic leukemia features, the biopsy of a peripheral lymphadenopathy seven months later revealed disorganised lymphoid tissue with a few large EBER (+) LMP1 (+) B-lymphocytes before any treatment was given. At this time, a clonal TCR y rearrangement and very faint clonal IgH rearrangement were demonstrated, and the diagnosis of angioimmunoblastic T-cell lymphoma was made. Treatment with MOPP was started, followed by Hydroxycarbamide and CHOP but the outcome was fatal. During the evolution, there was no blastic transformation of the chronic myelomonocytic leukemia. The T-cell lymphoma extended to abdominal lymph nodes, Waldeyer ring and bone marrow and the percentage of large LMP1 EBER (+) B-cells increased in the lymph nodes. These findings do not support a common stem cell abnormality leading to myelodysplasia in the bone marrow and lymphoma in peripheral lymph nodes. The lack of a clearcut light chain restriction in the EBV infected B-cell is suggestive of a persistant EBV infection in polyclonal or oligoclonal activated B-cells as described in immunodepressed patients. The association of CMML features and an angioimmunoblastic T-cell lymphoma is discussed.