A neoplasm of follicle centre cells with an, at least partially, follicular pattern.
Constitutes 22-35% of all adult non-Hodgkin lymphomas and 70% of all "low-grade" lymphomas. Median age 59 years, unusual before 40 years and rare before 20 years of age. However, grade 3 disease may sometimes be seen in the head and neck, including tonsils, in boys.
Clinical feature
Sites of involvement are:
lymph nodes most commonly
spleen
bone marrow; present in 40% of cases at presentation.
Waldeyer's ring
skin
Disease is often of advanced stage at the time of presentation and involvement of non-haemopoietic sites is particularly associated with advanced stage disease. Apart from lymphadenopathy, however, patients are often asymptomatic.
Histopathology
There is also interfollicular infiltration by neoplastic centrocytes.
A follicular growth pattern may be seen in several types of lymphoma which colonise follicles, such as mantle cell lymphoma, marginal zone (MALT) lymphoma and LP Hodgkin disease, as well as in true follicular lymphomas. Focal follicular features have also been reported in tonsillar diffuse large B-cell lymphoma3. This pattern presumably arises from colonisation of non-neoplastic follicles.
The neoplastic cells consist of two types, centrocytes and centroblasts the former usually predominating. 10$ of cases show discrete foci of marginal zone or monocytoid cells. Rarely plasmacytoid or signet ring cell differentiation occurs.
Grading is based on the absolute count of centroblasts across ten representative neoplastic follicles, expressed per x40 high power field of 0.159 mm2. Care must be taken to distinguish large cleaved centrocytes and follicular dndrtitic cells from centroblasts.
grade 1; 0-5 centroblasts / HPF
grade 2; 6-15 centroblasts / HPF
grade3a; >15 centroblasts / HPF but centrocytes present
grade 3b; solid sheets of centroblasts
Variations in grade between different areas should be noted. Any area of diffuse large B-cell lymphoma indicates transformation.
Immunohistochemistry
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negative |
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positive |
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positive |
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positive |
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negative, except some grade 3 FL |
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CD79a |
positive |
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cutaneous FL is commonly bcl-2 negative |
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SIg |
+ (IgM, IgD, IgG or rarely IgA) |
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†: fresh frozen tissue only
CD21 and CD23 highlight the meshwork of FDCs.
Variants
diffuse follicle centre lymphoma is composed of a mix of centrocytes and centroblasts but does not form follicles. Both populations must be pan-B antigen positive, CD10+, bcl-2+ and bcl-6+
Follicular lymphoma with sclerosis
signet ring cell lymphoma
follicular lymphoma with extracellular eosinophilic deposits
Progression
Some cases progress to diffuse large B-cell lymphoma; mutations of p53 have been implicated in this process4.
Differential diagnosis
reactive follicular hyperplasia: non-neoplastic germinal centre B cells are bcl-2 negative. Intrafollicular T cells are bcl-2 positive; the examination of the centroblastic component avoids this pitfall. Reactive follicles show a higher rate of proliferation using Ki-67 or MIB-1 than do neoplastic follicles. Those cases of follicular lymphoma which are bcl-2 negative tend to have a higher proliferation index.
Floral variant of follicular lymphoma needs to be distinguished from progressive transformation of germinal centres2.
signet ring cell lymphoma - needs to be differentiated from signet ring cell carcinoma
References
World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.
Wotherspoon AC, Hasserjian RP. Immunophenotyping in the differential diagnosis of histologically low grade B cell lymphomas Current Diagnostic Pathology 2000;6:55-63.
2Jones D. Dismantling the germinal center: comparing the processes of transformation, regression and fragmentation of the lymphoid follicle. Advances in Anatomic Pathology 2002;9:129-138.
This page last revised 17.12.2002.
©SMUHT/PW Bishop