Diagnosis of follicular lymphoma from the peripheral blood

In patients with stage IV disease, it is often possible to diagnose follicular lymphoma from the peripheral blood, with the blood film being crucial for indicating this diagnosis. The top two images are from a middle-aged man with generalized lymphadenopathy and a previous history of splenectomy following a road traffic accident. His hemoglobin concentration (Hb) and platelet count were normal but the lymphocyte count was 10.5 × 10⁹/L. Examination of the blood film showed the expected post-splenectomy changes including an increase of cytologically normal lymphocytes, among which large granular lymphocytes were prominent (top left and top right Images). However there was also a population of small lymphocytes with dense chromatin and deep narrow nuclear clefts (top Images) suggesting the presence of follicular lymphoma in addition to post-splenectomy lymphocytosis. Immunophenotyping supported these diagnoses, showing 55% CD8-positive T cells, 40% CD4-positive T cells, and 17% clonal B cells expressing CD19, CD79b, CD10, and strong lambda light chain and not expressing CD5. The diagnosis of follicular lymphoma was confirmed by lymph node biopsy.

The bottom left image is from another middle aged man with lymphadenopathy, mild anemia (Hb 128 g/L), a normal platelet count, and a lymphocyte count of 89 × 10⁹/L.

The blood film showed small and medium sized lymphocytes with dense chromatin; some were nucleolated and some had deep narrow nuclear clefts. Immunophenotyping showed clonal B cells expressing FMC7 and strong kappa light chain and not expressing CD5 or CD10; follicular lymphoma was confirmed on a lymph node biopsy.

The bottom right image is from a young woman with mild splenomegaly, a normal Hb and platelet count, and a lymphocyte count of 11 × 10⁹/L. In addition to some nucleated red blood cells, there were small lymphocytes with similar features to those described in the first two patients. Clonal B cells expressed CD19, CD10, CD79b, FMC7, and strong kappa light chain with CD5 and CD23 being negative. The diagnosis of follicular lymphoma was confirmed on biopsy.

The blood film features most suggestive of follicular lymphoma are the presence of small lymphocytes with chromatin that is more uniformly condensed than that of chronic lymphocytic leukemia cells, with some cells showing deep, narrow nuclear clefts and with smear cells not being prominent. Immunophenotyping typically shows expression of pan-B markers with strong surface membrane immunoglobulin and no expression of CD23 or CD200; when there is some degree of pleomorphism, CD5 negativity helps to exclude mantle cell lymphoma and, when it is positive, CD10 expression supports the diagnosis of follicular lymphoma. This diagnosis can be confirmed by fluorescence in situ hybridization on peripheral blood cells, as well as by lymph node biopsy.

CONFLICT OF INTEREST

None.