Diagnostic Workup for Follicular Lymphoma

Loretta J. Nastoupil, MD:On a physical exam, the patient is a well-appearing female with lymph nodes in multiple regions, but otherwise, her chest exam is clear; no organomegaly on palpation. In regard to lymph nodes, she had bilateral axillary nodes that are approximately 2 cm in size. The remaining lymph nodes, other than a groin lymph node, are quite small. On imaging, including CT of the chest, abdomen, and pelvis, she has lymph nodes, again, in multiple regions above and below the diaphragm, with the largest being a right groin lymph node, approximately 4.5 cm, with the remaining lymph nodes less than 3 cm in size.

This patient undergoes an incisional right groin lymph node biopsy revealing abnormal lymphocytes characterized as small cleave cells intermixed with some larger cells. The phenotype reveals a CD10-positive, CD20-positive B cell lymphoma with a classic translocation 14:18, all consistent with the diagnosis of follicular lymphoma. This is an elderly patient. The typical age at presentation is around 60 to 62 years of age. This patient is immune suppressed from being on methotrexate for an underlying history of rheumatoid arthritis. In terms of presentation, we see a typical presentation with palpable lymph nodes, with the absence of other worrisome symptoms, such as weight loss, night sweats, or substantial fatigue.

In regard to the approach, this patient still needs to be staged. We generally are recommending a bone marrow biopsy in addition to imaging studies. The most recent Lugano criteria, which describes for clinicians how to do a workup for a newly diagnosed lymphoma patient, describes whether or not there’s still utility in pursuing bone marrow biopsies given that PET will oftentimes pick up extra nodal involvement. But we’re reserving those criteria recommendations for the aggressive lymphomas, so generally speaking, for our low-grade lymphomas, we’re still incorporating a bone marrow biopsy for the initial staging workup.

In regard to whether or not we should include a PET as part of the initial workup, we are advising that for patients with a newly diagnosed follicular lymphoma because we have learned that these lymphomas are generally PET-avid and, again, the current Lugano criteria advises a PET at diagnosis. It’s also carrying prognostic information at the end of therapy.

In regard to choosing a management strategy for a newly diagnosed follicular lymphoma patient, we often rely on our clinical criteria if there is great heterogeneity in terms of how we approach these patients. The first discussion I have with a newly diagnosed follicular lymphoma patient is quite broad, encompassing not only their diagnosis, but also the natural history of the disease, which we currently consider to be upwards of 20 years or longer and incorporating our more modern therapies and the outcomes that are improving. But the general approach can be as vast as observation to intensive chemoimmunotherapy. It’s often challenging for clinicians and for patients to grasp that concept, but both are acceptable in specific circumstances.

The general criteria we use when we decide a patient is a candidate for observation is based on the GELF criteria, which have been retrospectively identified using criteria that were mostly generated in the era of chemotherapy, but still in the modern era where we’re using more immune-based therapies. We believe these criteria to still be applicable. So, generally, when we’re looking for criteria that will identify the patient as a candidate for observation, and this patient has many of them.

We’re looking at the extent of the disease, which is usually determined by imaging studies: lymph nodes over 3 cm, including 3 or more, or 1 lymph node over 7 cm in size; whether or not they have splenomegaly, which, again, we’re usually radiographically defining whether or not they have infusions, including pleural infusions or ascites; and whether or not they have a possible obstruction that may occur as a result of the lymph node in a given location. Oftentimes, this can be derived from an imaging modality, such as CT or PET. There are other criteria that we also will evaluate, including the blood count—hemoglobin, platelets, neutrophil count—and the LDH, whether or not that is elevated. And generally, what I describe to patients is, we’re not looking for all of those criteria, but one would be an indication that it’s no longer appropriate to observe that patient. If they have none of those symptoms or have objective findings, an observation is still absolutely appropriate in the modern era because we know their life expectancy will not be hindered by observing until they meet one of those criteria.

We also know that about 2% to 3% of patients will have spontaneous regression of their disease in the absence of therapy, and we could have spared them the side effects or potential side effects of therapy. So, those are usually the criteria we apply when we’re discussing with a newly diagnosed patient whether or not they’re appropriate candidates for observation or treatment. And if a patient appears to have no or none of the GELF criteria, I do believe this would an appropriate candidate for observation.

Transcript edited for clarity.

January 2014

• A 71-year-old female reports having symptoms of bilateral axillary swelling of 1.5 years’ duration and presents with diffuse inguinal and cervical adenopathy.
• Past medical History: 15-year history of treatment for rheumatoid arthritis with methotrexate
• Physical examination:
  • The patient is generally well-appearing; temperature, pulse, blood pressure, and HEENT are all WNL; extremities show no edema.
  • Cardiac exam is normal; chest is clear
  • Abdomen shows no abnormal hepatosplenomegaly
  • Lymph nodes: left axillary 1.5 cm, right axillary 2 cm; cervical and inguinal nodes <1 cm bilaterally; non-tender
• Notable laboratory findings:
  • CBC with diff, WNL
  • LDH, 148
• Right groin excisional node biopsy shows small lymphocytes with nuclear indentations (centrocytes) and large lymphocytes without indentations (centroblasts).
  • Pathology: t(14;18); co-expression of Bcl2, CD10, CD20.
• CT shows scattered adenopathy in the cervical, axillary, mesenteric, and pelvic regions. The largest lymph node measures 4.5 cm. The remaining lymph nodes are smaller than 3 cm.