Follicular Lymphoma (Non-Hodgkin Lymphoma) Staging
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The World Health Organization (WHO)/Revised European-American Lymphoma (REAL) classification and the Cotswolds modified Ann Arbor staging system for follicular lymphoma (non-Hodgkin lymphoma [NHL]) are provided below, [1, 2] as well as the Follicular Lymphoma International Prognostic Index (FLIPI) score. [3]
Follicular lymphoma (FL) is classified into the following 3 histologic grades [1, 2] :
Grade 1: 0-5 centroblasts/high-power field (HPF)
Grade 2: 6-15 centroblasts/HPF
Grade 3: > 15 centroblasts/HPF
The 2008 WHO classification consolidates cases with few centroblasts as FL grade 1-2 (low-grade). FL grade 3 is divided into 3A and 3B (absence of centrocytes). Diffuse areas in any grade 3 classification should be treated according to diffuse large B-cell lymphoma (DLBCL). [1]
The Cotswolds modification maintains the original 4-stage clinical and pathologic staging framework of the Ann Arbor staging system but also adds information regarding the prognostic significance of bulky disease (denoted by an X designation) and regions of lymph node involvement (denoted by an E designation). [4]
The A and B designations denote the absence or presence of symptoms, respectively; the presence of symptoms correlates with treatment response. The importance of imaging modalities, such as computed tomography (CT) scanning, is also underscored. [4]
Table. Cotswolds modification of Ann Arbor staging system (Open Table in a new window)
Stage
Area of involvement
I
Single lymph node group
II
Multiple lymph node groups on same side of diaphragm
III
Multiple lymph node groups on both sides of diaphragm
IV
Multiple extranodal sites or lymph nodes and extranodal disease
X
Bulk > 10 cm
E
Extranodal extension or single isolated site of extranodal disease
A/B
B symptoms: weight loss > 10%, fever, drenching night sweats
The development and validation of an accurate and easily available prognostic index for FL has facilitated the development of treatment algorithm plans, enabled the cross-talk between investigators, and improved understanding of the results of clinical studies.
Briefly, the FL International Prognostic Index (FLIPI) score was designed by studying clinical characteristics of 1795 newly diagnosed cases of FL between 1985 and 1992 across 27 different cancer centers. Several clinical parameters known to affect the outcome of FL patients were tested in the patient population using a univariate and multivariate analysis. The statistical analysis identified 5 variables that strongly and independently were associated with a poor clinical outcome, as provided below. [3]
Factors (1 point for each variable present) [3] :
Age > 60y
Ann Arbor Stage III-IV
Hemoglobin level < 12 g/dL
Lactate dehydrogenase (LDH) level > upper limit of normal (ULN)
≥ 4 nodal sites of disease
Risk category (factors) [3] :
Low risk (0 or 1)
Intermediate risk (2)
High risk (> 3)
Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program. 2009. 523-31. [Medline].
[Guideline] NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin’s Lymphomas. V1.2016. Available at http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf.
Solal-Céligny P, Roy P, Colombat P, et al. Follicular lymphoma international prognostic index. Blood. 2004 Sep 1. 104(5):1258-65. [Medline].
Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol. 1989 Nov. 7(11):1630-6. [Medline].
Stage
Area of involvement
I
Single lymph node group
II
Multiple lymph node groups on same side of diaphragm
III
Multiple lymph node groups on both sides of diaphragm
IV
Multiple extranodal sites or lymph nodes and extranodal disease
X
Bulk > 10 cm
E
Extranodal extension or single isolated site of extranodal disease
A/B
B symptoms: weight loss > 10%, fever, drenching night sweats
Francisco J Hernandez-Ilizaliturri, MD Professor of Medicine, Department of Medical Oncology, Associate Professor of Immunology, Department of Immunology, Chief, Lymphoma and Myeloma Section, Director, The Lymphoma Translational Research Program, Roswell Park Cancer Institute, University of Buffalo State University of New York School of Medicine and Biomedical Sciences
Francisco J Hernandez-Ilizaliturri, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Hematology
Disclosure: Nothing to disclose.
Jasmeet Anand, PharmD, RPh Adjunct Instructor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital; Medical Director, Deaconess Hospital Outpatient Infusion Centers; Chairman, Deaconess Hospital Cancer Committee
Christopher D Braden, DO is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology
Disclosure: Nothing to disclose.
Koyamangalath Krishnan, MD, FRCP, FACP Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine, James H Quillen College of Medicine at East Tennessee State University
Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, Royal College of Physicians
Disclosure: Nothing to disclose.
Follicular Lymphoma (Non-Hodgkin Lymphoma) Staging
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