Angioimmunoblastic T cell lymphoma, 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 infection.

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, dermal infiltrate with vascular hyperplasia or a vasculitis.

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.

CD1a
CD2†	positive
CD3	positive
CD4	usually positive in the majority neoplastic cells
CD5	positive in almost all cases1
CD7†	variable
CD8	usually positive in reactive cells which form a minority
CD10	positive1, 26/353
CD11b
CD16
CD21	FDCs positive1
CD23	FDCs positive1
CD25
CD30
CD35	FDCs positive1
CD56
CD57
TdT
TIA-1
ALK
bcl-6	a subset of cells positive in most cases1
CXCL13	31/353

†: 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.

Prognosis

Although more than 50% of patients achieve remission on treatment¹, the median survival is less than 3 years. A few patients run an indolent course or remit spontaneously¹. Some patients develop secondary EBV-positive DLBCL.

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

This page last revised 13.8.2006.

©SMUHT/PW Bishop