Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (367 page)

   
Other
: Elevated serum LDH indicates aggressive disease.

Suggested Readings

Horn H, Ziepert M, Becher C, et al. MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma.
Blood.
2013;121:2253–2263.

Perry AM, Cardesa-Salzmann TM, Meyer PM, et al. A new biologic prognostic model on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma.
Blood.
2012;120:2290–2296.

FOLLICULAR LYMPHOMA (FL)

   Definition

FL is defined primarily by its morphologic pattern, and by the translocation t(14;18), that leads to deregulated expression of the antiapoptotic BCL-2 protooncogene. FL is the second most common lymphoma in Western countries comprising approximately 20% of all lymphomas. It is considered an indolent lymphoma because in general, the disease shows a slow rate of progression, in spite of its clinical presentation with advanced disease in the majority of patients. It is an incurable disease since most cases eventually transform into aggressive lymphomas. The prognosis can be determined by criteria known as The Follicular Lymphoma International Prognostic Index (FLIPI).

   Who Should Be Suspected?

Patients in their 50s or 60s, complaining of generalized, progressive lymphadenopathy and splenomegaly, but otherwise asymptomatic, despite the high incidence of bone marrow involvement and generalized disease.

   Laboratory Findings

The diagnosis is established by biopsy of an involved lymph node. According to the number of centroblasts present in the neoplastic infiltrate, FL is subdivided into grades 1 to 3A that constitute a biologic continuum. Grade 3B is composed exclusively of centroblasts and is usually negative for t(14;18), as is pediatric FL.

   
Bone marrow biopsy and peripheral blood
: Whenever the bone marrow is involved, paratrabecular lymphoid aggregates are seen. With leukemic involvement of the peripheral blood, notched or clefted lymphocytes are identified.

   
Immunohistochemistry
for BCL2 is valuable for the diagnosis of FL (see below).

   
Immunophenotype
: FL cells (obtained from lymph node, bone marrow biopsy, or peripheral blood) are positive for CD19, CD20, CD22, and CD79a. In most cases, the cells are also CD10 positive. Some cases especially in grade 3 (advanced) disease may lack CD10 expression. The cells also express BCL-2 and BCL-6 and lack expression of CD5 and CD43. Immunoglobulins heavy and light chains are rearranged. About half of the affected cells express IgM and 40% IgG.

   
Cytogenetics and molecular genetics
: One of the earliest events in the developing of FL is thought to occur in the B-cell precursors in the bone marrow, giving rise to the t(14;18) (q32;q21) translocation that juxtaposes the BCL2 gene on chromosome 18, to the immunoglobulin heavy chain gene locus, resulting in overproduction of the BCL2 protein. This translocation is observed in 85% of cases of FL, but it is not specific for FL, since 30% of DLBCL are also positive. Moreover, it was found that many healthy persons have this translocation in their circulating lymphocytes, without any evidence of FL.

   
CBC
: Hemoglobin below 12 g/dL is associated with advanced disease.

   
Other
: Serum LDH is usually normal, but a high LDH connotes a poor prognosis.

Suggested Readings

Solai-Celigny P, Roy P, Colombat P, et al. Follicular lymphoma international prognostic index.
Blood.
2004;104:1258–1265.

Stevenson FK, Stevenson GT. Follicular lymphoma and the immune system: from pathogenesis to antibody therapy.
Blood.
2012;119:3659–3667.