Hodgkin’s lymphoma (HL) is a cancer that begins in the lymphatic system, a network of vessels, tissues, and organs that manages fluid balance and fights infection. This disease involves the uncontrolled growth of a specific type of immune cell, often originating in the lymph nodes of the neck, chest, or groin. Understanding the extent of the disease’s spread is the most important factor for determining the appropriate course of therapy. This process, known as staging, provides a standardized language for medical teams to classify the disease’s location and helps predict a patient’s outcome.
The Purpose of Staging
The Ann Arbor Staging Classification, updated by modifications such as the Cotswolds and Lugano classifications, is the standard system. The system’s primary framework is built upon the body’s anatomy, using the diaphragm—the sheet of muscle separating the chest cavity from the abdomen—as the defining anatomical boundary.
Determining the stage involves procedures to locate all affected areas. The evaluation begins with a physical examination and a review of the patient’s medical history and current symptoms. This is followed by a biopsy of an affected lymph node, which confirms the diagnosis and type of lymphoma.
Imaging tests play a large role in mapping the disease’s spread, particularly the use of Positron Emission Tomography-Computed Tomography (PET-CT) scans. These scans can highlight areas of increased metabolic activity, which often correspond to areas where the lymphoma cells are active. The information gathered from these diagnostic tools is synthesized to assign a final, comprehensive stage to the disease.
Defining the Four Stages
The core of the classification system is defined by four numerical stages, which describe the anatomical location of the lymphoma relative to the diaphragm and other organs. Stage I is designated when the lymphoma is found in only a single lymph node area or lymphoid organ, such as the thymus or spleen. This may also include involvement of a single site outside the lymphatic system (Stage IE).
Stage II indicates that the lymphoma is present in two or more lymph node regions, but these areas are all confined to the same side of the diaphragm, either all above it or all below it. This classification can include limited spread to a single, nearby extralymphatic organ or tissue, which would be designated Stage IIE.
The transition to Stage III signifies that the lymphoma has crossed the diaphragm boundary. This stage is defined by the involvement of lymph node regions on both sides of the diaphragm—both above and below. This classification may also include limited spread to an extralymphatic organ or tissue, or involvement of the spleen.
Stage IV is the most advanced classification, indicating that the lymphoma has spread beyond the lymphatic system to multiple or widespread sites in one or more non-lymphatic organs. This includes organs such as the liver, bone marrow, or lungs, with or without associated lymph node involvement.
Essential Staging Modifiers
Letter modifiers are used alongside the numerical stage to provide finer details about the disease’s characteristics, influencing prognosis and treatment planning. The most significant modifiers are the letters A and B, which relate to the presence of specific systemic symptoms. The designation ‘B’ is added to the stage number if a patient has experienced any of the so-called B symptoms.
B symptoms are defined as unexplained fever greater than 100.4°F, drenching night sweats, or unexplained weight loss of more than 10% of body weight over the previous six months. The presence of B symptoms, such as Stage IIB, often indicates a more aggressive disease presentation. If a patient does not have any of these systemic symptoms, the letter ‘A’ is assigned to the stage, such as Stage IIA.
Other letters further refine the anatomical description of the disease spread. The letter ‘E’ is used when the lymphoma has extended from a lymph node into a single, nearby organ or tissue outside of the lymph system (extranodal site). The letter ‘S’ denotes involvement of the spleen. Finally, the letter ‘X’ signifies bulky disease, which typically means a tumor mass is larger than 10 centimeters across or a mass in the chest is at least one-third the width of the chest.
How Staging Guides Treatment
The final stage classification directly dictates the treatment strategy. The initial stages, I and II, are grouped together as limited-stage disease. Patients with limited-stage disease are frequently treated with a combined approach, involving a shorter course of combination chemotherapy followed by radiation therapy to the affected areas.
Stages III and IV are categorized as advanced-stage disease, which requires a more intensive and systemic approach to treatment. The standard treatment for advanced stages is a longer course of multi-drug combination chemotherapy. Radiation is sometimes used in advanced disease, but it is reserved for specific areas with large tumor masses or sites where the disease is not responding well to chemotherapy.
The presence of B symptoms or bulky disease, indicated by the ‘B’ or ‘X’ modifiers, may shift a patient with an early numerical stage (I or II) toward a more intensive treatment regimen, similar to that used for advanced disease. The stage, along with the modifiers, is a component in the International Prognostic Score (IPS), a system that helps predict the likelihood of successful treatment and long-term remission.