Initial Diagnostic Workup of Follicular Lymphoma (FL)

The diagnosis of FL follows a similar workup for diagnosing other types of Non-Hodgkin’s Lymphoma (NHL).1

Diagnosis of NHL begins with a thorough history:

  • Evaluation of symptoms — onset, behavior, presence of B-cell symptoms (fever, night sweats, weight loss)2
  • Review of systems, noting any recent changes, infections1
  • Quantifying performance status1
  • Determining risk factors for NHL2

NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) for B-Cell Lymphomas provides diagnostic recommendations for FL.

Physical Examination The essential workup for FL includes a physical exam with particular attention to node-bearing areas.1
Laboratory Workup Certain laboratory studies are essential in patients suspected of having follicular lymphoma. Additional studies may be informative in specific clinical situations, depending on history and physical exam findings.1
Immunophenotyping
Cytogenetics
Molecular Profiling
Immunophenotyping is required to establish a diagnosis of follicular lymphoma. Cytogenetic analyses and molecular genotyping may be useful for identifying translocations and mutations characteristic of follicular lymphoma.1

Histology:

Tumor Biopsy
Bone Marrow Biopsy

NHL is complex, requiring physicians to differentiate among many different subtypes.3 Biopsies can be used to help identify follicular lymphoma and are required to document clinical stage.1
Imaging Studies Imaging is essential for diagnosis and staging of follicular lymphoma.1

Below are characteristics of FL, as defined by the WHO 2016 classification system of FL:

WHO subtype classification of FL4-6

 

Morphology Immunophenotype Cytogenetics Molecular biology Clinical features*
Centrocytes and centroblasts of germinal center origin
  • Pan-B+
  • CD5-
  • CD10+
  • slg+
t(14;18)
  • Comprehensive sequencing of somatic mutations in iNHL, like FL, remains limited
  • Distinctive mutations with functional relevance in FL have yet to be fully elucidated
  • Indolent behavior
  • Often no obvious symptoms at diagnosis
  • Common symptoms include lymphadenopathy, fatigue, dyspnea, night sweats, weight loss
  • Some transform over time into more aggressive disease

Morphology Centrocytes and centroblasts of germinal center origin
Immunophenotype
  • Pan-B+
  • CD5-
  • CD10+
  • slg+
Cytogenetics t(14;18)
Molecular biology
  • Comprehensive sequencing of somatic mutations in iNHL, like FL, remains limited
  • Distinctive mutations with functional relevance in FL have yet to be fully elucidated
Clinical features*
  • Indolent behavior
  • Often no obvious symptoms at diagnosis
  • Common symptoms include lymphadenopathy, fatigue, dyspnea, night sweats, weight loss
  • Some transform over time into more aggressive disease

*Consistent with low-grade, indolent FL and may not necessarily be accurate for aggressive forms.

 

iNHL, indolent non-Hodgkin’s lymphoma; NCCN, National Comprehensive Cancer Network; WHO, World Health Organization.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 10, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Merck Manual. 20th ed. Lane KAG, ed. Rahway, New Jersey: Merck & Co., Inc. 2018. 3. Cancer.net. Lymphoma—Non-Hodgkin: Subtypes. https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes. Accessed August 2, 2018. 4. Cuneo A. Classification of B-cell non-Hodgkin lymphomas (NHL). Atlas Genetics Cytogenet Oncol Haematol. 2006;4(1). 5. Krysiak K, Gomez F, White BS, et al. Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma. Blood. 2017;129(4):473-483. 6. Lymphoma Research Foundation. Follicular Lymphoma. http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300155. Updated June 2017. Accessed December 11, 2017.