[ Home Page ] [ Site Map ]

Follicle Centre Lymphoma

CLINICAL FEATURES

• Most patients have generalised lymphadenopathy, although a small proportion present with apparent stage I disease
• Bone marrow involvement in over 50%; peripheral blood less frequently involved
• Extranodal disease is rare and is almost never a presenting feature

LABORATORY DIAGNOSIS

A) Morphology

• Forms follicles throughout the node and involves surrounding tissue
• Neoplastic follicles consist of a mixture of centrocytes and centroblasts, but lack the micro-architecture of germinal centres
• Involves para-trabecular zone of bone marrow

A follicular growth pattern	A mixture of centrocytes and centroblasts	Aberrant expression of bcl-2 indicative of the t(14,18)

B) Immunophenotype

• sIgM, sometimes with sIgD, CD19, strong CD20, CD10, CD75, CD45RA, CD38 and bcl-2
• CD23 is sometimes present on a proportion of cells
• sIgG is seen in a few cases
• Phenotypes reflect that of the normal germinal centre.

Three-colour flow cytometric analysis of lymph node cells for a typical case of follicle centre lymphoma. A proportion of cells express CD10 in combination with CD38. There is light chain restriction with almost all the cells expressing sIg-kappa. The other main immunophenotypic features are the presence of either IgM or IgG with CD19, CDw75 and CD20. CD23 is present in some cases. CD45RA is often aberrantly expressed in follicle centre lymphoma.

CYTOGENETICS

• t(14;18) is present in over 90% of cases leading to deregulation of bcl-2
• The presence of bcl-2 or t(14,18) in cells with a germinal centre phenotype is a key diagnostic feature
• A high incidence of non-specific genetic abnormalities are detected by CGH and micro-satellite imbalance ^2,3
• Deletion of the tumour suppressor genes p15 and p16 and over-expression of p53 is associated with transformation ⁴
• The detection of t(14,18) by PCR is used as a test for malignant disease in the bone marrow. This may be of prognostic value in patients receiving high dose chemotherapy.

bcl-2/IgH PCR in a series of bone marrow samples from patients with follicular centre lymphoma. A rearranged band is seen in lanes 2, 3, 4, 5, 8 & 9. Lane 11 is a standard. The varying size of the band illustrates the variation in breakpoints between patients.

TRANSFORMATION AND PROGRESSION

• Transformation is replacement of all or part of node by a diffuse infiltrate of centroblasts and immunoblasts. This may involve a single node or be part of generalised disease
• Some patients present with transformed disease
• In rare cases acute leukaemia develops; this may be related to c-myc deregulation through a further translocation involving chromosome 8
• Disease progression is characterised by increasing disease bulk and refractoriness to alkylating agents.

Transformed follicle centre lymphoma. In this case the patient had clinical features of acute leukaemia with marrow replacement by large lymphoid blast cells with the phenotype sIg-kappa+, CD19+, CD10+, CD23-

OUTCOME AND THERAPY

• Follicle centre lymphoma is an indolent relapsing disease with a median overall survival of 8-10 years ²²
• The front-line treatment is chlorambucil in most patients
• Prolonged complete remission on single agent chemotherapy is predictive of overall survival, however almost all patients will relapse
• The incidence of transformation is 30% at ten years ²⁵. Median survival after transformation is 22 months but is better if the disease is localised ²⁶
• Some patients achieve complete remission on high dose therapy but it is uncertain whether survival is prolonged ²⁷ or which patients are most appropriately treated in this way
• It is currently unclear whether radiotherapy can be curative in the small group of patients who have stage I disease at presentation.

[ Home Page ] [ Site Map ]