Follicular lymphoma is a type of blood cancer . This is the most common of the painless (slowly growing) non-Hodgkin lymphomas and the second most common form of non-Hodgkin lymphomas in general. It is defined as lymphoma of B-cells of the follicular center ( centrocytes and centroblasts ), which have some of the signs of follicular cells. It is positive for B-cell markers of CD10 , CD19 , CD22 and usually CD20 [1] , however, it is almost always negative for CD5 markers [2] .
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 A photomicrograph of follicular lymphoma showing characteristic abnormal lymphoid follicles that gave the disease its name. Spot H&E . | |
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There are several synonyms and outdated terms for this disease, such as CB / CC lymphoma (centroblastic and centrocytic lymphoma), nodular lymphoma [3] , as well as Brill-Symmers disease ( English Brill-Symmers Disease ) [4] . There is also a subtype: large cell follicular lymphoma [5] .
Content
Causes of occurrence
Translocation between chromosome 14 and 18 leads to overexpression of the bcl-2 gene [6] . Since bcl-2 protein is usually involved in the prevention of apoptosis , cells overexpressing this protein are mostly immortal. The bcl-2 gene is usually located on chromosome 18, and translocation moves the gene close to the enhancer element of the immunoglobulin heavy chain on chromosome 14.
In addition, this may be due to translocation of BCL6 to 3q27 [7] .
MicroRNA Expression
In 2014, it was described that short non-coding RNAs , called microRNAs , perform important functions in the biology of lymphoma, including follicular lymphoma. In malignant B cells, microRNAs are involved in the bonds that are fundamental for cell development, such as receptor signaling , rearrangement reaction, adhesion , intercellular interactions in immune niches, and the production and change of immunoglobin classes in .
Morphology
A tumor consists of follicles consisting of a mixture of centrocytes ( Kiel terminology accepted by WHO experts) or split cells of the follicular center (old American terminology), “ small cells ”, as well as centroblasts (Kiel terminology), or large undigested cells of the follicular center and “ large cells” ". These follicles are surrounded by non-cancerous cells, mainly T cells. In follicles, centrocytes usually prevail. Centroblasts are usually in the minority.
Diagnostics
Classification
According to WHO criteria, the disease is morphologically divided into [1] :
- level 1 (<5 centroblasts in the field of view under high magnification , high-power field (hpf))
- level 2 (6-15 centroblasts / hpf)
- level 3 (> 15 centroblasts / hpf)
- level 3A (centrocytes are still present)
- level 3B (follicles are almost entirely composed of centroblasts)
A 2008 WHO update classifies levels 1 and 2 as low-grade follicular lymphoma, while level 3A is classified as high-grade follicular lymphoma and level 3B as large-sized large-cell lymphoma B.
Treatment
There is no consensus on the best treatment protocol . It is necessary to pay attention to such factors as age, stage, as well as prognostic indicators (according to the International Prognostic Index ). Patients with advanced disease who do not have symptoms can benefit from the “ look and wait ” approach ”, Since early treatment does not ensure survival [8] [9] . When patients with symptoms, special treatment is requested, which may include various combinations of alkylation , a nucleoside analogue chemotherapy regimens containing anthracycline (e.g., CHOP ), monoclonal antibodies (e.g., rituximab ), radioimmunotherapy , autotransplantation and allograft transplantation of hematopoietic stem cells . Follicular lymphoma is considered incurable until the location of the lymphoma is detected. In this case, it can be cured by radiation . Although allogeneic stem cell transplantation can be healing, the mortality rate from this procedure is too high to be a primary measure.
In 2010, rituximab was approved by the European Commission for maintenance treatment follicular lymphoma as the primary product [10] . Preclinical evidence suggests that rituximab can also be used in combination with integrin inhibitors to overcome rituximab resistance mediated by stromal cells . However, rituximab will not achieve the goal with CD20 , which is negative for follicular lymphoma.
Test results published in June 2012 show that bendamustine , a drug first developed in East Germany in the 1960s, has a disease-free survival rate of more than two times that of rituximab. This polytherapy is in leaves patients with fewer side effects than the obsolete analogue (a combination of five drugs - rituximab, cyclophosphamide , doxorubicin , vincristine and prednisone , collectively called R-CHOP ) [11] .
There are many recent and ongoing clinical trials of follicular lymphoma [12] . For example, personalized idiotypic vaccines showed promising promise, especially prior therapy [13] , but remains to be proven in randomized controlled trials [14] .
Forecast
The average survival is about 10 years, but the range is wide, can range from 1 year to 20 years. Some patients may never need treatment. The overall survival over five years is 72–77% [15] . Recent advances and the addition of rituximab have improved average survival. In recent reports for the period from 1986 to 2012, average survival exceeds 20 years [16] .
Epidemiology
Of all types of cancer in which the same class of blood cells is involved ( Lymphoproliferative diseases ), 22% of the causes are follicular lymphomas [17] .
Notes
- ↑ 1 2 Follicular Lymphomas . pleiad.umdnj.edu. Date of treatment December 30, 2018.
- ↑ Barekman CL, Aguilera NS, Abbondanzo SL. Low-grade B-cell lymphoma with coexpression of both CD5 and CD10. A report of 3 cases. - Arch. Pathol. Lab. Med., 2001. - S. 951–953.
- ↑ Dorlands Medical Dictionary: follicular lymphoma . web.archive.org (May 18, 2009). Date of treatment December 30, 2018.
- ↑ Brill-Symmers disease . TheFreeDictionary.com. Date of treatment December 30, 2018.
- ↑ MeSH Browser . meshb.nlm.nih.gov. Date of treatment December 30, 2018.
- ↑ Bosga-Bouwer AG, van Imhoff GW, Boonstra R, et al. Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t (14; 18), 3q27, or other translocations: t (14; 18) and 3q27 are mutually exclusive. - 3. - 2003. - S. 1149-1154. - DOI : 10.1182 / blood.V101.3.1149 .
- ↑ Anneke G. Bosga ‐ Bouwer, Eugenia Haralambieva, Marije Booman, Ronald Boonstra, Anke van den Berg. BCL6 alternative translocation breakpoint cluster region associated with follicular lymphoma grade 3B (Eng.) // Genes, Chromosomes and Cancer. - 2005. - Vol. 44 , iss. 3 . - P. 301-304 . - ISSN 1098-2264 . - DOI : 10.1002 / gcc.20246 .
- ↑ T. Andrew Lister. Follicular Lymphoma: Perspective, Treatment Options, and Strategy . MD, FRCP . medscape.com. Date of treatment December 31, 2018.
- ↑ Watchful Waiting in Low – Tumor Burden Follicular Lymphoma in the Rituximab Era: Results of an F2-Study Database . ascopubs.org. Date of treatment December 31, 2018.
- ↑ Roche Gets EC Nod for Follicular Lymphoma Maintenance Therapy . GEN - Genetic Engineering and Biotechnology News (October 29, 2010). Date of treatment December 31, 2018.
- ↑ 'Rediscovered' Lymphoma Drug Helps Double Survival: Study (06/03/2012).
- ↑ Search of: follicular lymphoma - List Results - ClinicalTrials.gov . clinicaltrials.gov. Date of treatment December 31, 2018.
- ↑ Hendrik Veelken, Gottfried Dölken, Andrea Keppler-Hafkemeyer, Gabriele Ihorst, Cristina Bertinetti-Lapatki. Upfront immunization with autologous recombinant idiotype Fab fragment without prior cytoreduction in indolent B-cell lymphoma (English) // Blood. - 2011-02-03. - Vol. 117 , iss. 5 . - P. 1483-1491 . - ISSN 0006-4971 1528-0020, 0006-4971 . - DOI : 10.1182 / blood-2010-06-292342 .
- ↑ S. Inoges, A. de Cerio, E. Soria, H. Villanueva, F. Pastor. Idiotype Vaccines for Human B-Cell Malignancies (English) // Current Pharmaceutical Design. - 2010-01-01. - Vol. 16 , iss. 3 . - P. 300-307 . - ISSN 1381-6128 . - DOI : 10.2174 / 138161210790170111 .
- ↑ Follicular Lymphoma: Practice Essentials, Etiology and Pathophysiology, Epidemiology . - 2018-09-06.
- ↑ European Journal of Cancer . www.ejcancer.com. Date of treatment December 31, 2018.
- ↑ Turgeon, Mary Louise. Clinical hematology: theory and procedures . - 4th ed. - Philadelphia: Lippincott Williams & Wilkins, 2004 .-- ix, 570 pages p. - ISBN 0781750075 . - ISBN 9780781750073 .