Angioimmunoblastic T cell lymphoma, AILD, AIL-TCL

Definition

A T-cell lymphoma characterised by a systemic polymorphous infiltrate involving lymph nodes and associated with proliferation of high endothelial venules and follicular dendritic cells.

It is thought this lymphoma may arise from the normal population of intrafollicular CD4+, CD10+, bcl-6+ T-cells1. It is possible that the T-cells are not intrinsically CD10 positive, but the acquisition of CD10 positivity is secondary to their follicular localisation2. Alternatively, positivity for PD-1 may indicate that AIL-TCL is derived from germinal centre T-cells

Synonyms; angioimmunoblastic lymphadenopathy with dysproteinaemia, immunoblastic lymphadenopathy.

Epidemiology

Accounts for 1-2% of all non-Hodgkin lymphomas and 15-20% of peripheral T-cell lymphomas. It is a condition of the middle-aged to elderly, most patients being over 60 years of age1. There may be an association with EBV infection5. One case report suggests that AILD arose without EBV infection but that EBV infection was associated with subsequent transformation to a high grade B-cell lymphoma4.

Clinical features

Presentation is usually with an acute onset of generalised lymphadenopathy, usually accompanied by hepatosplenomegaly and often with a skin rash. Nodular skin lesions, plaques, purpura and urticaria are less common1. There is often fever, chills, night sweats, weight loss, pruritus, arthralgia and ascites. Leukocytosis with neutrophilia or eosinophilia and lymphopenia1, a polyclonal hypergammaglobulinaemia, circulating immune complexes, cold agglutinins, haemolytic anaemia, positive rheumatoid factor and anti-smooth muscle antibodies are common. The paraneoplastic effects have been attributed to the expansion of multiple oligoclonal cytokine-producing T-cell subsets and tumour-associated proliferation of B cells and plasma cells2.

90% of patients have disseminated stage II or IV disease.

Histopathology

The pattern of development of AIL-TCL appears to be complex, with early and late stages of lymph node involvement recognised2:

• Early stage: the neoplastic T-cells proliferate with the paracortex. Initially the nodal architecture is partially effaced with a neoplastic paracortical infiltrate which is polymorphous. There are medium-size lymphocytes, with pale to clear cytoplasm and distinct cell membranes. There are admixed small lymphocytes, eosinophils, plasma cells. There may be large basophilic blastic B-lymphocytes and Reed-Sternberg-like cells. The adjacent germinal centres are hyperplastic, with minimal infiltration by tumour cells. Perifollicular sinuses (D2-40+/CD31+) are prominent.

• Late stage: tumour cells extend into germinal centres, which undergo dissolution. Follicular dendritic cells (FDC) persist, in distorted networks, in association with B-cells (bcl-6+), usually in proximity to patent trabecular sinusoids. The FDCs retain positivity for CD21 and CD23, but the cells of the follicle associated stroma also acquires desmin-positivity1. Curvilinear fibrotic tracts may represent residual trabecular sinuses, retaining positivity for CD312. Only at the latest stages, and usually in association with a large cell morphology, are the sinuses and their associated B-cells and FDCs eliminated.

Bcl-6-negative monocytoid B-cells are plasma cells are seen mainly in a perisinusoidal distribution.

Only a few cases of splenic involvement have been described. There may be a nodular infiltration of red and white pulp or a diffuse infiltrate of lymphocytes, plasma cell, immunoblasts and sometimes eosinophils1.

The bone marrow is involved in about two thirds of cases. It is usually hypercellular. Haemolytic anaemia is associated with erythroid hyperplasia. The myeloid series may also be hyperplastic. The lymphomatous infiltrate is usually focal and often paratrabecular.

In patients with cutaneous lesions, there is a variably dense, often perivascular, sometimes periadnexal, dermal infiltrate with vascular hyperplasia or a leukocytoclastic vasculitis. Epidermotropism and a spongiotic reaction are not features. There may be a component of eosinophils. The lymphoid cells in cutaneous lesions have small to medium size somewhat irregular nuclei and are predominantly CD3+/CD5+.

Skin lesions may show large B-cells if undergoing transformation to EBV-associated large B-cell lymphoma.

In some cases, angioimmunoblastic lymphadenopathy may be oligoclonal and might represent a pre-neoplastic condition.

Immunohistochemistry

Loss of T-cell antigens is uncommon1. The positivity for bcl-6 and CD10 is unique among T-cells.

†: fresh frozen tissue only

The immunoblasts and Reed-Sternberg-like cells are positive for B-cell markers and commonly for EBV LMP-11. Rarely, the RS-like cells are positive for CD15 and CD30. Rarely, the T-cells are positive for EBV.

Cytogenetics tend to be distinct:

trisomy 3
trisomy 5
gains of X chromosome

Differential diagnosis

A young age and clinical history of an infection, particularly EBV, or an autoimmune disorder suggest a reactive diagnosis. AIL-TCL is the peripheral T-cell lymphoma most likely to harbour EBV. The conditions in the differential lack extrafollicular proliferation of CD21+ FDCs.

• viral infection. EBV infection is usually associated with a predominance of CD8+ cells, in contrast to AIL-TCL.

• autoimmune disorders

• Castleman's disease of hyaline vascular type show burnt-out follicles, but they have an expanded mantle.

• Atypical T-zone hyperplasia.

• Hodgkin lymphoma; lacks clear cells and burnt-out germinal centres.

• THRLBCL; eosinophils and plasma cells are lacking and the B-cells are EBV-. Lacks clear cells.

• Peripheral T-cell lymphomas, NOS; may be positive for bcl-6 but not for CD101 or CXCL131.

• Follicular lymphoma with diffuse areas; may show co-expression of CD10 and bcl-6; compare the distribution of T and B cells with that of CD10 and bcl-6.

• Adult T-cell lymphoma/leukaemia with angioimmunoblastic T-cell lymphoma (AILT)-like features.

Prognosis

Although more than 50% of patients achieve remission on treatment1, the median survival is less than 3 years7. A few patients run an indolent course or remit spontaneously1. Some patients develop EBV-positive DLBCL4,7, secondary large T-cell lymphoma7or Hodgkin lymphoma7.

References

World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

1 Ferry JA. Angioimmunoblastic T-cell lymphoma. Advances in Anatomic Pathology 2002;9:273-279.

2 Ottaviani, G., C. E. Bueso-Ramos, et al. (2004). "The role of the perifollicular sinus in determining the complex immunoarchitecture of angioimmunoblastic T-cell lymphoma." Am J Surg Pathol 28(12): 1632-40.

3 Grogg KL, Attygale AD, Macon WR, et al. Expression of CXCL13, a chemokine highly upregulated in germinal center T-helper cells, distinguishes angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified. Mod Pathol 2006; 19:1101-7

4 Abruzzo LV, Schmidt K, Weiss LM, et al. B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus. Blood 1993; 82:241-6 FULL TEXT

5 Weiss LM, Jaffe ES, Liu XF, et al. Detection and localization of Epstein-Barr viral genomes in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma. Blood 1992; 79:1789-95 FULL TEXT

6 Ortonne N, Dupuis J, Plonquet A, et al. Characterization of CXCL13+ neoplastic t cells in cutaneous lesions of angioimmunoblastic T-cell lymphoma (AITL). Am J Surg Pathol 2007; 31:1068-76

7 Attygalle AD, Kyriakou C, Dupuis J, et al. Histologic evolution of angioimmunoblastic T-cell lymphoma in consecutive biopsies: clinical correlation and insights into natural history and disease progression. Am J Surg Pathol 2007; 31:1077-88

8 Murakami YI, Yatabe Y, Sakaguchi T, et al. c-Maf expression in angioimmunoblastic T-cell lymphoma. Am J Surg Pathol 2007; 31:1695-702

This page last revised 18.11.2007.

©SMUHT/PW Bishop