What is the WHO classification of follicular lymphoma?

Updated: Mar 03, 2020
  • Author: Lauren C Pinter-Brown, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

More recently, the WHO classification of lymphoid neoplasms adopted the REAL classification and proposed several changes, such as the following [21, 22, 23] :

  • The WHO classification changed the nomenclature from follicle center cell lymphoma to follicular lymphoma.

  • The WHO classification calls for grading of the follicular lymphoma from grades 1-3 based on the number of centroblasts per high-power field (hpf) and recognizes the importance of reporting on the presence of diffuse areas.

  • The WHO classification recognizes two variants of follicular lymphomas: cutaneous follicle center cell lymphoma and diffuse follicle center lymphoma. Nodal follicular lymphoma, according to the WHO classification, is staged as grade 1 (0-5 centroblasts per hpf), grade 2 (6-15 centroblasts per hpf), and grade 3 (>15 centroblasts). Variants include cutaneous follicle center cell lymphoma and diffuse follicle center cell lymphoma.

  • WHO classification further classifies grade 3 into grades 3A and 3B. [6] Grade 3A has centrocytes present whereas grade 3B has follicles composed of centroblasts. Clinically, grade 3B follicular lymphoma is treated like diffuse large B cell lymphoma.

Importantly, progression to diffuse large-cell lymphoma occurs in 10-50% of patients depending on the duration of disease presence. Transformation to diffuse large-cell lymphoma frequently is associated with rapid progression of the disease, including increasing adenopathy, development of systemic symptoms, and infiltration of extranodal sites.

Progression to large-cell lymphoma can be a poor prognostic factor. Many patients who experience transformation succumb to the disease, especially those who have received many lines of previous therapy. See the following image.

A patient with follicular lymphoma who was diagnos A patient with follicular lymphoma who was diagnosed 6 years earlier presents to his hematologist's office because of rapidly growing lymphadenopathy and onset of fever, severe night sweats, and weight loss. In the past, he had been treated with chlorambucil and prednisone when his submandibular lymph nodes became large enough to make him uncomfortable. This treatment had worked well, and he has not required any treatment recently. A biopsy of an involved lymph node is obtained. The diagnosis is transformation to diffuse non-Hodgkin lymphoma.

Xerri et al have demonstrated that high levels of MUM1 positivity are associated with shorter progression-free survival, based on analysis of the patient samples from the PRIMA study and correlating the patient outcomes. [24] Another study of 46 cases of follicular lymphoma was also able to correlate high levels of MUM1 expression with high-grade subtype and poorer outcome because of the propensity for transformation. [25]

The 2016 WHO classification includes three variants of follicular lymphoma: in situ follicular neoplasia (ISFN), duodenal-type follicular lymphoma, and pediatric-type follicular lymphoma. ISFN replaces the term in situ follicular lymphoma, reflecting the low risk of progression to lymphoma. In a long- term follow-up of ISFN, only one out of 21 patients progressed to overt follicular lymphpoma. [26] In ISFN, lymph nodes (or other lymphoid proliferations) have an intact architecture but scattered germinal centers with variably dense populations of BCL2-positive and CD10-positive lymphoid cells that are usually predominantly centrocytes, are monoclonal, and have a t(14;18) IGH/BCL2translocation.

Pediatric follicular lymphoma was confirmed as a definite entity, but named pediatric-type follicular lymphoma, as cases may rarely occur in older individuals. Pediatric-type follicular lymphoma is a localized clonal proliferation characterized by large, expansile, highly proliferative follicles that often have prominent blastoid follicular center cells rather than classic centroblasts (or centrocytes); BCL2 rearrangements must not be present, but there may be some BCL2 protein expression. Common sites of involvement are the cervical lymph nodes and tonsils. [27] Less likely sites of disease include the testis, gastrointestinal tract, salivary duct, kidney, and skin. Pediatric-type follicular lymphoma carries an excellent prognosis; a conservative therapeutic approach may be sufficient. [28]

Finally, the intestines, especially the duodenum, are a frequent site of extranodal follicular lymphoma. These cases are frequently found in the second part of the duodenum as polyps. Survival appears to be excellent even without treatment. The majority of gastrointestinal follicular lymphoma are low grade (grade 1 or 2). However, 85% of duodenal lymphomas can spread to the jejunum and ileum. [27]


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