Category Archives: Lymphoma

Follicular Lymphoma

Also known as Follicular Center Lymphoma, and Small Cleaved Mixed or Large Cell Lymphoma

Clinical Information

- affects adults (average age 55 years)

- very common non-Hodgkin’s Lymphoma (around 40% of all non-Hodgkin’s Lymphoma)

- presents in a late stage often, with disseminated disease

- prognosis poor as follicular lymphoma is slow growing and does not respond well to treatments and few cells are actively dividing – not curable

- commonly (80%) transforms to an aggressive lymphoma, diffuse large B cell lymphoma

Classification in the working formulation

1.    Follicular small cleaved, mixed, large, or small non-cleaved cells

Classification in WHO/ REAL

1.    Mature B cell neoplasm-Follicular centre B-cell lymphoma

Genetic changes

1.    t(14;18) (q32;q21)

2.    Rearrangements of BCL6 on chromosome 3q27

3.    t(2;18) (p12;q21)

4.    +7

5.    +18

6.    6q23-26

7.    p53 at 17p13

Pathogenesis

1.    Translocation of bcl-2 on chromosome 18 to IgH on chromosome 14 causes overexpression of bcl-2, an anti-apoptotic gene.  Continual production of bcl-2 allows for continued survival of follicular centre cells (prevention of apoptosis) in the germinal centre.  May allow for accumulation of further mutations that allow for progression to high grade lymphoma.

e.    differences between reactive hyperplasia in a lymph node and follicular lymphoma

1.    Follicular lymphoma demonstrates growth of neoplastic follicles through lymph node capsule (with splitting of capsule) and may demonstrate growth into extracapsular adipose tissue. (Follicles of reactive hyperplasia will not demonstrate growth into extracapsular tissue and will not demonstrate capsular splitting).

2.    Follicular lymphoma demonstrates expansion of germinal centre (evident on reticulin stain or CD21/CD23 stain).  (No expansion of germinal centre in reactive hyperplasia).

3.    Germinal centres are devoid of tingible body macrophages in follicular lymphoma.  (Tingible body macrophages present in reactive hyperplasia).

4.    Obliteration of cortical sinuses, with involvement of paracortical, interfollicular and medullary zones by malignant cells with cleaved/convoluted nuclei in follicular lymphoma, which is absent in reactive hyperplasia.

5.    Follicles in follicular lymphoma are not variable in size (as in a reactive lymph node)

6.    Follicles in follicular lymphoma demonstrate a disruption in architecture (lack of eccentricity with pale centre and darker periphery as seen in reactive hyperplasia).

7.    Presence of bcl-2 staining within germinal centres of follicular lymphoma.  (Absent in reactive hyperplasia).

Sites of Involvement

- lymph nodes, bone marrow and spleen are all common

- involvement of blood is uncommon

Microscopy

- follicular pattern, with back-to-back follicles lacking follicle polarization and consisting of small lymphocytes

- there is also a diffuse variant which does not have a follicular pattern

- follicle consists of centrocytes and centroblasts

- no tingle-body macrophages are present (as the cells are immortal to death signals, as they are over-expressing bcl-2)

- low mitotic rate

- stroma is usually scant and compressed between follicles

- mantle zone is scant or compressed

Centrocytes

- small cleaved follicular center cells

Centroblasts

- large noncleaved follicular center cells

Follicular Lymphoma

Follicular lymphoma showing back to back follicles with loss of normal lymph nodes architecture.

Follicular Lymphoma

Higher power view of follicle in follicular lymphoma displaying abnormal lymphocytes and lack of tingle-body macrophages. There is also an irregular mantle zone.

CD20 Immunohistochemistry

CD20 immunohistochemistry in follicular lymphoma is positive, demonstrating that the malignant lymphocytes are B cells.

CD20 Immunohistochemistry

CD20 staining the membranes of the malignant clonal follicular lymphoma B cells, which have overtaken the lymph node forming large areas lacking T cells (which do not stain).

 BCL-2 Immunohistochemistry

BCL-2 immunostaining follicle center cells in follicular lymphoma. Follicle center cells should not express BCL-2 normally, as it is an anti-apoptotsis protein. In follicular lymphoma, the malignant lymphocytes express BCL-2 and escape death. BCL-2 positive follicles are seen in follicular lymphoma.

BCL-2 Follicular Lymphoma

BCL-2 immunohistochemistry highlighting malignant follicle center B cells in a case of follicular lymphoma. Notice the dark nuclear staining with BCL-2.