Stage Information for Adult NHL
Stage is important in selecting a treatment for patients with non-Hodgkin lymphoma (NHL). Chest and abdominal computed tomographic (CT) scans are usually part of the staging evaluation for all lymphoma patients. The staging system is similar to the staging system used for Hodgkin lymphoma.
Common among patients with NHL is involvement of the following:
- Noncontiguous lymph nodes.
- Waldeyer ring.
- Epitrochlear nodes.
- Gastrointestinal tract.
- Extranodal presentations. (A single extranodal site is occasionally the only site of involvement in patients with diffuse lymphoma.)
- Bone marrow.
- Liver (especially common in patients with low-grade lymphomas).
Cytologic examination of cerebrospinal fluid may be positive in patients with aggressive NHL. Involvement of hilar and mediastinal lymph nodes is less common than in Hodgkin lymphoma. Mediastinal adenopathy, however, is a prominent feature of lymphoblastic lymphoma and primary mediastinal B-cell lymphoma, entities primarily found in young adults.
The majority of patients with NHL present with advanced (stage III or stage IV) disease that can often be identified with limited staging procedures such as CT scanning and biopsies of the bone marrow and other accessible sites of involvement. Laparoscopic biopsy or laparotomy is not required for staging but may be necessary to establish a diagnosis or histologic type. Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose can be used for initial staging and for follow-up after therapy as a supplement to CT scanning.[2-6] Interim PET scans after two to four cycles of therapy did not provide reliable prognostic information because of problems of interobserver reproducibility in a large cooperative group trial (ECOG-E344 [NCT00274924]) and lack of difference in outcome between PET-negative and PET-positive/biopsy-negative patients in two prospective trials.[7-9]Staging Subclassification System
Table 2. Anatomic Stage/Prognostic Groupsa
|I||Involvement of a single lymphatic site (i.e., nodal region, Waldeyer ring, thymus or spleen) (I).|
|Localized involvement of a single extralymphatic organ or site in the absence of any lymph node involvement (IE) (rare in Hodgkin lymphoma).|
|II||Involvement of two or more lymph node regions on the same side of the diaphragm (II).|
|Localized involvement of a single extralymphatic organ or site in association with regional lymph node involvement with or without involvement of other lymph node regions on the same side of the diaphragm (IIE). The number of regions involved may be indicated by a subscript Arabic numeral, for example, II3.|
|III||Involvement of lymph node regions on both sides of the diaphragm (III), which also may be accompanied by extralymphatic extension in association with adjacent lymph node involvement (IIIE) or by involvement of the spleen (IIIS) or both (IIIE, IIIS). Splenic involvement is designated by the letter S.|
|IV||Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement.|
|Isolated extralymphatic organ involvement in the absence of adjacent regional lymph node involvement, but in conjunction with disease in distant site(s). Stage IV includes any involvement of the liver or bone marrow, lungs (other than by direct extension from another site), or cerebrospinal fluid.|
|aReprinted with permission from American Joint Committee on Cancer: Hodgkin and non-Hodgkin lymphomas. In Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 607–11.|
The Ann Arbor staging system is commonly used for patients with NHL.[10,11] In this system, stage I, stage II, stage III, and stage IV adult NHL can be subclassified into A and B categories: B for those with well-defined generalized symptoms and A for those without such symptoms. The B designation is given to patients with any of the following symptoms:
- Unexplained loss of more than 10% of body weight in the 6 months before diagnosis.
- Unexplained fever with temperatures above 38°C.
- Drenching night sweats.
Occasionally, specialized staging systems are used. The physician should be aware of the system used in a specific report.
The E designation is used when extranodal lymphoid malignancies arise in tissues separate from, but near, the major lymphatic aggregates. Stage IV refers to disease that is diffusely spread throughout an extranodal site, such as the liver. If pathologic proof of involvement of one or more extralymphatic sites has been documented, the symbol for the site of involvement, followed by a plus sign (+), is listed.Table 3. Notation to Identify Specific Sites
|N = nodes||H = liver||L = lung||M = bone marrow|
|S = spleen||P = pleura||O = bone||D = skin|
Current practice assigns a clinical stage (CS) based on the findings of the clinical evaluation and a pathologic stage (PS) based on the findings made as a result of invasive procedures beyond the initial biopsy.
For example, on percutaneous biopsy, a patient with inguinal adenopathy and a positive lymphangiogram without systemic symptoms might be found to have involvement of the liver and bone marrow. The precise stage of such a patient would be CS IIA, PS IVA(H+)(M+).
A number of other factors that are not included in the above staging system are important for the staging and prognosis of patients with NHL. These factors include the following:
- Performance status.
- Tumor size.
- Lactate dehydrogenase (LDH) values.
- The number of extranodal sites.
To identify subgroups of patients most likely to relapse, an international prognostic index was compiled for 2,031 patients with aggressive NHL. After validation by several cancer centers,[13,14] the major cooperative groups have used this index in the design of new clinical trials. The model is simple to apply, reproducible, and predicts outcome even after patients have achieved a complete remission. The model identifies five significant risk factors prognostic of overall survival (OS):
- Age (<60 years vs. >60 years).
- Serum LDH (normal vs. elevated).
- Performance status (0 or 1 vs. 2–4).
- Stage (stage I or stage II vs. stage III or stage IV).
- Extranodal site involvement (0 or 1 vs. 2–4).
Patients with two or more risk factors have a less than 50% chance of relapse-free survival and OS at 5 years. This study also identifies patients at high risk of relapse based on specific sites of involvement, including bone marrow, central nervous system, liver, lung, and spleen. Patients at high risk of relapse may benefit from consolidation therapy or other approaches under clinical evaluation. Molecular profiles of gene expression using DNA microarrays may help to stratify patients in the future for therapies directed at specific targets and to better predict survival after standard chemotherapy.[15,16]References
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