Hodgkin Lymphoma Staging
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The World Health Organization (WHO)/Revised European-American Lymphoma (REAL) classification [1] and the Cotswolds modified Ann Arbor staging system for Hodgkin lymphoma (HL) are provided below [2] , as well as the risk stratification for HL.
Nodular lymphocyte-predominant HL:
Classic HL is grouped into the following 4 types:
Nodular sclerosis classic HL
Lymphocyte-rich classic HL
Mixed cellularity classic HL
Lymphocyte-depleted classic HL
For therapeutic purposes, nodular lymphocyte-predominant HL is managed in the same way as indolent non-Hodgkin lymphoma (see Follicular Lymphoma [non-Hodgkin Lymphoma]). [1]
Table 1. Cotswold 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 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). [2]
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. [2]
Based on the clinical scenario, staging and degree of end-organ damage in patients with HL can be categorized into the following 3 groups:
Early-stage favorable
Early-stage unfavorable (bulky and nonbulky)
Advanced-stage (this classification has impact in treatment selection and must be performed carefully in every patient with HL)
The following table shows examples of unfavorable risk factors for stages I and II. Data are included from 3 organizations, including the German Study Hodgkin Lymphoma Study Group (GSHG), European Organization for Research and Treatment of Cancer (EORTC), and the National Cancer Institute of Canada (NCIC).
Table 2. Unfavorable Risk Factors for Stages I and II Hodgkin Lymphoma (Open Table in a new window)
Risk Factor
GSHG
EORTC
NCIC
Age
≥ 50y
≥ 40y
Histology
MC or LD
ESR or B symptoms
> 50 if A or > 30 if B
> 50 if A or > 30 if B
> 50 or any B symptoms
Mediastinal mass*
MMR > 0.33
MMR > 0.35
MMR > 0.33 or > 10 cm
Number of nodal sites
> 2
> 3
> 3
Extranodal lesions
any
* Mediastinal mass is measured on chest x-ray by the mediastinal mass ratio (MMR), which is defined by the following: maximum width of mass/maximum intrathoracic diameter.
ESR = erythrocyte sedimentation rate; LD = lymphocyte depletion; MC = mixed cellularity.
Based on the criteria described above, patients are then classified as follows:
Early-stage favorable HL (includes patients with stage I or II HL and no risk factors by GSHG/EORTC or NCIC)
Early-stage unfavorable HL (includes patients with stage I and II HL and one or more risk factors)
Advanced-stage HL (includes patients with stages IIB, III, and IV)
Patients with advanced disease are further risk stratified using the International Prognostic Score (IPS), which includes the following risk factors (for each present factor, the patient receives 1 point) [3] :
Albumin < 4 g/dL
Hemoglobin < 10.5 g/dL
Male
Age ≥ 45y
Stage IV disease
Leukocytosis: white cell count (WBC) > 15,000/μL
Lymphopenia: lymphocyte count < 8% of WBC count and/or absolute lymphocyte count < 600 cells/μL
Based on the IPS score, patients with advanced disease can be categorized as follows [3] :
Good risk (IPS 0-1)
Fair risk (IPS 2-3)
Poor risk (IPS 4-7)
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].
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].
Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med. 1998 Nov 19. 339(21):1506-14. [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
Risk Factor
GSHG
EORTC
NCIC
Age
≥ 50y
≥ 40y
Histology
MC or LD
ESR or B symptoms
> 50 if A or > 30 if B
> 50 if A or > 30 if B
> 50 or any B symptoms
Mediastinal mass*
MMR > 0.33
MMR > 0.35
MMR > 0.33 or > 10 cm
Number of nodal sites
> 2
> 3
> 3
Extranodal lesions
any
* Mediastinal mass is measured on chest x-ray by the mediastinal mass ratio (MMR), which is defined by the following: maximum width of mass/maximum intrathoracic diameter.
ESR = erythrocyte sedimentation rate; LD = lymphocyte depletion; MC = mixed cellularity.
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.
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