Staging Relapsed Follicular Lymphoma

Nathan H. Fowler, MD:A 65-year-old female with a history of neurogenic bladder and osteoporosis was referred to your clinic because she complained of bilateral cervical adenopathy along with night sweats. On physical exam, she was found to have cervical adenopathy bilaterally along with a spleen that measured approximately 2 cm below the left costal margin. Her ECOG performance status was 0. On her labs, she was found to have a slightly elevated white blood cell count of around 13,000. Her hemoglobin was 11.4, platelet count was 219, her LDH was normal at 242. She had a biopsy of the cervical node, which showed a population of small cells along with some admixed centroblasts, and it was felt that her diagnosis was most consistent with a grade 3a follicular lymphoma. The cells, as we would expect, were CD10-positive, BCL2-positive, and CD19-positive.

She had imaging studies, which included a PET scan. And on her PET scan, she was found to have enlarged nodes in the cervical region, bilaterally, in the axilla, along with a small area that showed increased uptake in the liver. The maximum SUV was 9. She had a bone marrow biopsy as well, which also showed approximately 40% of cells that were small and had the same immunophenotype as her lymph node biopsy, and it was felt to be that this was consistent with follicular lymphoma in the bone marrow.

So, her FLIPI score was 4, and she was considered high risk. Her oncologist started her on a course of bendamustine and rituximab. She received 6 cycles followed by 12 months of maintenance therapy with rituximab. After therapy, her best response was approximately 75% reduction in her total nodal volume, which would be a partial remission.

This is not an uncommon presentation of follicular lymphoma. Many times, patients present with low-volume adenopathy, sometimes with night sweats. And many times, patients, after we have staging, will find out there are many nodes that are outside of the areas that were initially felt on physical exam. For example, with this patient, we noted that there was enlarged spleen on physical exam, as well as some axillary adenopathy in a spot in the liver.

Because of the nature of this disease, follicular lymphoma grows very, very slow. And, again, many times for patients there is an involvement in their large nodes that really is only found on staging, which brings up staging. When patients are first seen in the clinic, we generally recommend full staging, and that would mean obtaining imaging studies really from the neck all the way down to at least the thighs. That can be done with a CT scan or a PET scan. We also recommend obtaining basic laboratory panels, which include looking at the patient’s CBC, their differential, along with LDH. And, finally, in most patients, to complete staging, we recommend obtaining a bone marrow biopsy with immunohistochemistry and flow cytometry.

Transcript edited for clarity.

June 2015

• A 65-year old female presented to her PCP complaining of night sweats and swelling in the neck
• PMH: osteoporosis, neurogenic bladder
• Physical examination:
  • Enlarged spleen 2 cm. below costal margin, bilateral cervical and axillary lymphadenopathy
• ECOG 0
• Laboratory findings:
  • WBC: 12 x 10⁹/L; 45% lymphocytes
  • Hb: 11.5 g/dL
  • Platelets: 213 x 10⁹/L
  • LDH 212 U/L
• Excisional biopsy of the lymph nodes:
  • IHC: CD10+, BCL2+
  • Follicular lymphoma, grade IIIa
• Bone marrow biopsy, 40% involved
• ¹⁸FDG-PET showed SUVmax of 9 with discrete masses bilaterally in the cervical and axillary region and increased uptake in the liver
• FLIPI 4 points, high risk
• The patient was started on bendamustine + rituximab (6 cycles) and was continued on rituximab maintenance therapy for 12 months
• She achieved a partial response with a 75% reduction in tumor volume

February 2018

• After 32 months, the patient complained of her symptoms returning
• CT showed disease progression in the axillary and hilar lymph nodes
• PET with SUV of 11
• Re-biopsy of lymph node, consistent with follicular lymphoma grade IIIa
• The patient was referred to an academic center for treatment
• She was enrolled in an open-label clinical trial of lenalidomide/rituximab (12 cycles)
• She achieved partial remission after 3 months

February 2019

• Twelve months later, the patient presents with low-grade fever and chills, she is otherwise well-appearing and continues to exercise regularly
• ECOG 0
• PET-CT showed further progression in the axillary lymph nodes
• The patient was treated with IV copanlisib and achieved a partial response after 4 cycles; she continues to do well on therapy