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:

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.

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