September 17, 2012
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PET/CT detected recurrent follicular lymphoma in stable, asymptomatic patient

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A 67-year-old man presented to his primary care physician with progressive fatigue and a 20-lb weight loss in 2 months.

He did not have any other complaints at the time.

His physical examination was unremarkable. His blood work showed marked anemia with very low hemoglobin of about 8 g/dL (normal hemoglobin for males is about 13 g/dL to 16 g/dL). Further work-up revealed anemia of chronic disease.

Due to an episode of exertional chest pain, he was admitted to the hospital and underwent cardiac work-up that was unrevealing. Given his anemia, he underwent upper gastrointestinal endoscopy and colonoscopy, both of which were normal.

A bone marrow biopsy was performed to further evaluate his anemia of chronic disease. It showed a lambda light chain restricted mature B-cell neoplasm that was positive for CD10, CD19, CD20 and CD45, and negative for CD5.

He underwent a PET/CT scan, which showed few enlarged lymph nodes adjacent to the left pectoralis minor muscle with standard uptake value (SUV) of 7.6, and a mixed lytic/blastic malignant-appearing lesion in the left third rib suspicious for lymphoma or malignancy. Spleen was noted to be enlarged, with few focal areas of abnormal activity with an increased SUV of 6.2.

Metabolically active lymph nodes were noted at multiple locations in the abdomen. He underwent a CT-guided left retroperitoneal lymph node biopsy. Histology confirmed the diagnosis of B-cell follicular center cell lymphoma that was positive for CD20, CD10 and B-cell lymphoma-2, and negative for CD3, CD5 and B-cell lymphoma-1. He was diagnosed with stage IV, grade-1 follicular lymphoma.

Given his constitutional symptoms, weight loss and anemia, the decision was made to begin chemotherapy. He was started on systemic chemotherapy with R-CVP (rituximab with cyclophosphamide, vincristine and prednisone). He received five cycles of the planned six cycles of chemotherapy. The sixth cycle of chemotherapy was held secondary to prolonged neutropenia for about 4 to 5 months.

Clockwise from top left: Axial CT, axial PET, maximal intensity projection and fused axial PET-CT performed on Jan. 30 over the mediastinum demonstrate no abnormal hypermetabolism in the skeletal structures.

Figure 1. Clockwise from top left: Axial CT, axial PET, maximal intensity projection and fused axial PET-CT performed on Jan. 30 over the mediastinum demonstrate no abnormal hypermetabolism in the skeletal structures.

Clockwise from top left: Axial CT, axial PET, maximal intensity projection and fused axial PET-CT performed on June 27 over the mediastinum demonstrate a hypermetabolic lytic lesion in the sternal manubrium measuring approximately 2 cm x 1.1 cm, with a maximum standardized uptake value of 8.7.

Figure 2. Clockwise from top left: Axial CT, axial PET, maximal intensity projection and fused axial PET-CT performed on June 27 over the mediastinum demonstrate a hypermetabolic lytic lesion in the sternal manubrium measuring approximately 2 cm x 1.1 cm, with a maximum standardized uptake value of 8.7.

Source: Reprinted with permission from Munir Ghesani, MD

A PET/CT scan performed after the fourth cycle of chemotherapy showed no evidence of lymphoma. He underwent a repeat surveillance PET/CT scan 9 months after chemotherapy, and it showed a solitary area of uptake in the sternum with no other evidence of disease (see Figures 1 and 2).

Biopsy of the sternum revealed grade-2/grade-3 follicular lymphoma. He was planned for radiation therapy to the chest and will follow with rituximab maintenance. He is asymptomatic at this time and does not have any complaints.

Discussion

Follicular lymphoma is an indolent lymphoma with a relapsing and remitting pattern. It accounts for approximately 20% of non-Hodgkin’s lymphoma.

Follicular lymphoma arises from germinal center B cells of lymphoid follicles. Most common chromosome abnormality is a translocation involving chromosomes 14 and 18 with overexpression of an oncogene BCL-2, located on chromosome 18, which induces resistance to apoptosis.

WHO classification divides follicular lymphoma based on the number of centroblasts/high-power field (HPF).

Grade 1 is 0 to 5 centroblasts/HPF, grade 2 is 6 to 15 centroblasts/HPF, and grade 3 is >15 centroblasts/HPF.

Diagnosis usually is made by lymph node biopsy. Staging work-up includes physical exam, serum LDH, B-2 microglobulin, PET/CT scan or CT scan of the chest, abdomen and pelvis, and bone marrow biopsy.

The Follicular Lymphoma International Prognostic Index is used as a prognostic marker. Poor prognostic markers include age older than 60 years, elevated serum LDH, hemoglobin <12 gm/dL, Ann Arbor stage III or IV, and more than four nodal sites. 

Management of asymptomatic WHO grade-1 and grade-2 follicular lymphoma is controversial.

For early stage disease — Ann Arbor stages I and II — locoregional radiation therapy usually is employed with curative intent. Advanced stage disease — Ann Arbor stages III and IV — usually is considered incurable with conventional treatments. For that reason, observation is frequently employed in asymptomatic patients.

The data are based on retrospective studies and three large randomized trials that compared observation with early treatment of asymptomatic patients. The data showed similar OS and similar transformation to aggressive lymphomas.

In this setting, treatment is usually employed for bulky or symptomatic disease. Generally, WHO grade-3 follicular lymphoma is considered aggressive and is treated in a similar fashion as diffuse large B-cell lymphoma.

Some of the common chemotherapy regimens employed for treatment of follicular lymphomas include R-CVP, R-CHOP, bendamustine (Treanda, Cephalon) and rituximab (Rituxan, Genentech), and fludarabine-based treatments.

Radioimmunotherapy with agents such as ibritumomab (Zevalin, Spectrum Pharmaceuticals) and tositumomab (Bexxar, SmithKline Beecham) have demonstrated efficacy in relapsed or refractory follicular lymphoma and are usually employed in the relapsed setting. Maintenance therapy with rituximab, given after completion of chemotherapy once every 2 months for a period of 2 years, is shown to improve PFS but not OS.

Conclusion

Overall, follicular lymphoma is an indolent lymphoma. More than half of patients achieve good initial response to chemotherapy, with eventual progression of the disease occurring in most patients.

References:
For more information:
  • Munir Ghesani, MD, is an attending radiologist at St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center, an associate clinical professor of radiology at Columbia University College of Physicians and Surgeons, and a HemOnc Today section editor. Rangaswamy Chintapatla, MD, is a fellow in hematology and oncology at St. Luke’s-Roosevelt Hospital Center. Janice Dutcher, MD, is director of immunotherapy, as well as an attending physician, in the department of hematology and oncology at St. Luke’s-Roosevelt Hospital Center. Digvijay Singh, MD, is a resident in the department of hematology and oncology, as well as the department of radiology, at St. Luke’s-Roosevelt Hospital Center.
  • Disclosure: Drs. Ghesani, Chintapatla, Dutcher and Singh report no relevant financial disclosures.