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follicular B-cell lymphoma; follicular center lymphoma; chronic lymphatic leukemia type 2

Epidemiology: 1) 40% of adult non-Hodgkin's lymphomas 2) predominantly older individuals (rare < 20 years of age) 3) no sex predilection Pathology: 1) heavy chain enhancer adjacent to bcl-2 gene results in overexpression of bcl-2 & suppression of normal B-cell apoptosis 2) involvement of visceral sites is uncommon 3) bone marrow is frequently involved (75% at diagnosis) 4) B-cell lymphoma (CD19+) Microscopic pathology: 1) mixture of centrocytes (small cleaved follicle center cells) & centroblasts (large noncleaved follicle center cells) 2) grade I: small cell 3) grade II: mixed small and large cells 4) grade III: large cell Immunophenotype: - surface immunoglobulin + (usually IgM +/- IgD, IgG, IgA - CD19, CD20, CD22, CD79a: + (B-cell surface antigens) - CD5: - - CD10: +/-, stronger in follicles than interfollicular cells - CD11c: - - CD23: -/+ - CD25: - - CD43: -, occ. grade III positive - bcl-2: + majority of cases (overexpression) - cutaneous follicular lymphoma frequently bcl-2 negative - bcl-6: + Genetics: 1) associated with chromosomal translocations: a) t(14;18)(q32;q21) (Ig heavy chain enhancer & bcl-2) b) t(2;6)(p12;q25) involving ZC3H12D with IGK may be the cause of transformation of follicular lymphoma to diffuse large B-cell lymphoma c) t(1;22)(q22;q11) involving FCGR2B with overexpression of FCGR2B d) t(2;18)(p11;q21) involving KDSR with a Ig J kappa chain region 2) other implicated genes: BCL10 Clinical manifestations: - painless lymphadenopathy, frequently generalized [6] Laboratory: 1) complete blood count (CBC) with peripheral smear - leukemic cells in peripheral blood is uncommon 2) BCL2 gene rearrangement Special laboratory: - lymph node biopsy of lymph node with standardized uptake value (SUV) of > 17 Radiology: - PET scan if suspected malignant transformation Complications: - risk of transformed lymphoma at 5 years (usually to diffuse large B-cell lymphoma) is 11% [10] Management: 1) initial management - observation without treatment for asymptomatic patients [6] - early treatment does not improve survival in patients with grade 1 or grade 2 follicular lymphoma [6] - PET scan with lymph node biopsy prior to chemotherapy 2) rituximab-based chemotherapy a) induction with R-CHOP for follicular lymphoma grade 3 [6] - maintenance for 2 years with rituximab [5,6] b) rituximab (Rituxan)/lenalidomide (Revlimid), or R2 maybe useful as first-line treatment of advanced follicular lymphoma [13] - follow with rituximab maintenance c) single agent (+ rituxumab ?) for symptomatic lymphadenopathy or autoimmune disease such as immune thrombocytopenic purpura [6] 1] cyclophosphamide 2] chlorambucil 3] prednisone d) 5 year transformation rate is 10.7% [10] - lymph node biopsy for relapse/progression [6] e) median overall survival following transformation is 50 months [10] f) idelalisib FDA-approved for treatment failure 3) hematopoietic stem cell transplantation - only curative therapy [6] - may be appropriate for relapse [6] 4) radioimmunoconjugates are useful for maintenance but not appropropriate in the acute setting [6] 5) lymph node irradiation is inappropriate because follicular lymphocytes circulate & would re-establish upon completion of irradiation [6] 6) prognosis a) median survival 7-9 years, unaffected by treatment b) radiation therapy for early stage follicular lymphoma results in 50% 10 year disease-free survival [6] c) poorer prognosis with large cell follicular lymphoma

Interactions

disease interactions

Related

lymphoid follicle

Specific

follicle center lymphoma, grade I (follicular small cleaved cell lymphoma) follicle center lymphoma, grade II (follicular mixed small & large cell lymphoma) follicle center lymphoma, grade III (follicular large cell lymphoma)

General

peripheral B-cell lymphoid neoplasm

Database Correlations

OMIM 151430

References

  1. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 402, 700-704
  2. Cotran et al Robbins Pathologic Basis of Disease, W.B. Saunders Co, Philadelphia, PA 1989 pg 711-713
  3. Chan JK, Banks PM, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC, Grogan TM, Harris NL, Isaacson PG, et al. A revised European-American classification of lymphoid neoplasms proposed by the International Lymphoma Study Group. A summary version. Am J Clin Pathol. 1995 May;103(5):543-60. PMID: 7741099
  4. WHO Classification Tumours of Haematopoietic and Lymphoid Tissues. Jaffe et al. eds. IARC Press 2001
  5. Van Oers MHJ et al, Rituximab maintenance improves clinical outcome of relapsed/ resistance follicular non-Hodgkin lymphoma in patients with and without rituximab during induction: Results of a prospective randomized phase 3 intergroup trial. Blood 2006, 108:3295 PMID: 16873669
  6. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2021.
  7. Hainsworth JD, Litchy S, Burris HA et al Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. PMID: 12377971
  8. Czuczman M, Straus D, Gribben J, Bredenfeld H et al Management options, survivorship, and emerging treatment strategies for follicular and Hodgkin lymphomas. Leuk Lymphoma. 2010 Aug;51 Suppl 1:41-9 PMID: 20658953
  9. Buske C, Hoster E, Dreyling M et al The Follicular Lymphoma International Prognostic Index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to treatment outcome. Blood. 2006 Sep 1;108(5):1504-8. Epub 2006 May 11. PMID: 16690968
  10. Link BK et al. Rates and outcomes of follicular lymphoma transformation in the immunochemotherapy era: A report from the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource. J Clin Oncol 2013 Sep 10; 31:3272 PMID: 23897955 http://jco.ascopubs.org/content/31/26/3272
  11. Li ZM, Ghielmini M, Moccia AA. Managing newly diagnosed follicular lymphoma: state of the art and future perspectives. Expert Rev Anticancer Ther. 2013 Mar;13(3):313-25 PMID: 23477518
  12. Hochberg EP, Bierer MF, Winkfield KM et al Case 11-2017 - A 61-Year-Old Woman with Leg Swelling, Back Pain, and Hydronephrosis. N Engl J Med 2017; 376:1461-1471. April 13, 2017 PMID: 28402765 http://www.nejm.org/doi/full/10.1056/NEJMcpc1616023
  13. Ingram I Ditching Chemo Appears Viable in Frontline Follicular Lymphoma. PFS 'nearly identical' at 3 years with novel immunomodulatory combination. MedPage Today. June 06, 2018 https://www.medpagetoday.com/meetingcoverage/asco/73327 - Fowler NH, et al RELEVANCE: Phase III randomized study of lenalidomide plus rituximab (R2) versus chemotherapy plus rituximab, followed by rituximab maintenance, in patients with previously untreated follicular lymphoma. American Society of Clinical Oncology (ASCO) 2018; Abstract 7500.
  14. Casulo C, Burack WR, Friedberg JW. Transformed follicular non-Hodgkin lymphoma. Blood. 2015 Jan 1;125(1):40-7. Review. PMID: 25499449 Free Article
  15. Kahl BS, Yang DT. Follicular lymphoma: evolving therapeutic strategies. Blood. 2016 Apr 28;127(17):2055-63. Review. PMID: 26989204 Free Article