Imaging Analysis

Relative splenic and liver metabolic activity on FDG-PET in a patient with Hodgkin’s lymphoma

A 71-year-old woman presented to her physician after several months with enlarged cervical lymph nodes. A biopsy was done, confirming classical Hodgkin’s lymphoma. A staging FDG-PET/CT revealed extensive hypermetabolic cervical, axillary, mediastinal, left hilar, and abdominal lymphadenopathy and prominent activity throughout the bone marrow. However, a biopsy of the bone marrow was negative, and she was diagnosed with stage III Hodgkin’s lymphoma. Metabolic activity in the spleen was higher than that in the liver, raising the possibility of diffuse splenic infiltration with lymphoma. The patient underwent four cycles of standard chemotherapy with ABVD, and restaging FDG-PET/CT revealed decreased metabolic activity in the spleen relative to the liver, suggestive of positive response to therapy. It also revealed positive functional and anatomic response to therapy of all involved lymph node regions. Follow-up FDG-PET/CT two months after completion of chemotherapy confirmed this finding and FDG activity in the liver remained higher than in the spleen, consistent with ongoing response to treatment.

Figure 1: 4/17/08 - Clockwise from upper left - CT, PET, maximum intensity projections (MIP) PET, and PET/CT fusion images
Figure 1: 4/17/08 – Clockwise from upper left – CT, PET, maximum intensity projection (MIP) PET, and PET/CT fusion images. MIP PET image demonstrates intense FDG activity in numerous lymph nodes throughout the cervical, axillary, mediastinal, hilar, and abdominal lymph node chains. The selected axial image demonstrates an enlarged lymph node at the splenic hilum with intense FDG activity. In addition, the spleen demonstrates a relatively higher degree of metabolic activity (SUV 2.8) compared to the liver (SUV 2.1). This raises the possibility of diffuse splenic infiltration with lymphoma. Finally, there is diffuse increased metabolic activity throughout the bone marrow, which may be due to lymphoma infiltration vs. a reactive phenomenon in the setting of anemia or medications.

Source: M. Ghesani

Figure 2: 8/20/08 - Clockwise from upper left - CT, PET, maximum intensity projection (MIP) PET, and PET/CT fusion images
Figure 2: 8/20/08 – Clockwise from upper left – CT, PET, maximum intensity projection (MIP) PET, and PET/CT fusion images. MIP PET image demonstrates dramatic reduction of metabolic activity in the previously seen lymph node chains after chemotherapy treatment. The selected axial image demonstrates anatomic and functional normalization of the lymph node at the splenic hilum. There is also normalization of the distribution of metabolic activity in the spleen relative to the liver, suggesting positive response to chemotherapy on lymphomatous infiltration of the spleen. There is an increase in metabolic activity throughout the marrow containing structures of the skeleton consistent with a chemotherapy effect. This limits the characterization of potential lymphomatous involvement of the bone marrow.

Figure 3: 12/18/08 - Clockwise from upper left - CT, PET, maximum intensity projection (MIP) PET, and PET/CT fusion images
Figure 3: 12/18/08 – Clockwise from upper left – CT, PET, maximum intensity projection (MIP) PET, and PET/CT fusion images. MIP PET image demonstrates interval resolution of the metabolic activity in the lymph node chains. The metabolic activity in the spleen remains lower than that of the liver, which is physiologic. There is also a decrease in the metabolic activity in the marrow containing skeletal structures, consistent with resolving chemotherapy effect.

DISCUSSION

Use of FDG-PET or FDG-PET/CT in both non-Hodgkin’s and Hodgkin’s lymphoma continues to expand. FDG-PET is widely used to assess response to treatment after completion of chemotherapy in these patients and also in pretreatment staging and assessment of response during treatment. In pretreatment staging, PET cannot replace CT and bone marrow biopsy, but can certainly add complementary information, upstaging lymphoma in about 15% to 20% of cases. FDG-PET is significantly more accurate than CT alone for assessing response to therapy. It can distinguish a change in metabolic activity in an area that may not have changed by size criteria. This distinguishes between areas of active tumor and residual fibrosis. The role of PET for therapy monitoring is still under investigation, but several studies have shown that early PET improvement correlates with response at completion. This may, in the future, lead to significant changes in management.

Although the exact role for FDG-PET/CT in terms of diagnosis and management of lymphoma is not yet fully clear, we do know that in a patient with suspected lymphoma, the intensity of splenic FDG uptake appears to correlate with histopathology. In a retrospective series of 165 patients undergoing splenectomy at a single institution from 2004 to 2006, 10 were identified as being performed to evaluate known or suspected lymphoma and included a presplenectomy FDG-PET scan. Each patient was assigned a low-, intermediate- or high-splenic-metabolic activity based on SUV. Low activity was associated with benign findings or mantle cell lymphoma, intermediate with marginal zone lymphoma, and high activity with diffuse large B-cell lymphoma.

We also know that higher intensity FDG uptake in the spleen relative to the liver on initial staging FDG-PET scan may suggest diffuse splenic involvement by lymphoma, as presumed in our case. Hepatic FDG uptake is normally at least as intense as splenic uptake, reflecting the physiology of glucose metabolism in the liver. One retrospective series evaluating 341 FDG-PET scans for lymphoma performed between 2001 and 2004 revealed 67 patients in which baseline and follow-up studies were available for evaluation. The ratio of mean SUV values in the spleen over liver were calculated for each study, with 10 patient controls who had been referred for a lung malignancy but without prior history of malignancy, reticuloendothelial disorders, chemotherapy or anemia. In the control group, the mean spleen liver ratio was 0.69, or less than 1, as we would expect. In contrast, 12 of the 67 patients (18%) demonstrated more intense uptake in the spleen, with the mean SLR of 1.54 (range 1.11-10). In this subgroup of 12 patients, mean SLR value after chemotherapy decreased to 0.79 (range 0.56-1.6), an average decline of 93%. This indicates that higher intensity of FDG uptake in spleen relative to liver on FDG-PET imaging studies for lymphoma should raise the possibility of diffuse infiltration of spleen with lymphoma, and interval decline, as in our patient, of SUV value in the spleen would imply response to chemotherapy.

The 2007 Consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma states that diffusely increased splenic uptake that is greater than that of the normal liver — after chemotherapy — should be considered compatible with lymphoma unless the patient has a history of recent (within 10 days) cytokine administration. It has been shown that increased FDG uptake is observed in the spleen during and after G-CSF treatment, which is important to recognize when interpreting FDG-PET scans in patients with cancer undergoing cytokine therapy.

Although the specific role of FDG-PET scan in diagnosis and management of lymphoma is not yet fully clear, we can say with assurance that in patients with known or suspected lymphoma, the intensity of splenic FDG uptake appears to correlate with histopathology and that splenic hypermetabolism greater than liver prior to chemotherapy is highly suggestive of lymphomatous involvement. A relative decrease in the activity of the spleen relative to the liver during systemic chemotherapy can therefore be interpreted as a positive response.

Munir Ghesani, MD, is an Associate Clinical Professor of Radiology at Columbia University College of Physicians and Surgeons and Attending Radiologist at St. Luke’s-Roosevelt Medical Center.

Carrie Wasserman, MD, is a second year Hematology/Oncology Fellow at St. Luke’s-Roosevelt Hospital Center.

Neilish Gupta, MD, is a Radiology Resident at St. Luke’s-Roosevelt Medical Center.

For more information:

  • Leukemia Lymphoma. 2008;49:719-726.
  • Clinical Nuclear Medicine. 2006;31:366.
  • J Clin Oncol. 2007;25:571-578.
  • J Nucl Med. 1999;40:1456-1462.

A 71-year-old woman presented to her physician after several months with enlarged cervical lymph nodes. A biopsy was done, confirming classical Hodgkin’s lymphoma. A staging FDG-PET/CT revealed extensive hypermetabolic cervical, axillary, mediastinal, left hilar, and abdominal lymphadenopathy and prominent activity throughout the bone marrow. However, a biopsy of the bone marrow was negative, and she was diagnosed with stage III Hodgkin’s lymphoma. Metabolic activity in the spleen was higher than that in the liver, raising the possibility of diffuse splenic infiltration with lymphoma. The patient underwent four cycles of standard chemotherapy with ABVD, and restaging FDG-PET/CT revealed decreased metabolic activity in the spleen relative to the liver, suggestive of positive response to therapy. It also revealed positive functional and anatomic response to therapy of all involved lymph node regions. Follow-up FDG-PET/CT two months after completion of chemotherapy confirmed this finding and FDG activity in the liver remained higher than in the spleen, consistent with ongoing response to treatment.

Figure 1: 4/17/08 - Clockwise from upper left - CT, PET, maximum intensity projections (MIP) PET, and PET/CT fusion images
Figure 1: 4/17/08 – Clockwise from upper left – CT, PET, maximum intensity projection (MIP) PET, and PET/CT fusion images. MIP PET image demonstrates intense FDG activity in numerous lymph nodes throughout the cervical, axillary, mediastinal, hilar, and abdominal lymph node chains. The selected axial image demonstrates an enlarged lymph node at the splenic hilum with intense FDG activity. In addition, the spleen demonstrates a relatively higher degree of metabolic activity (SUV 2.8) compared to the liver (SUV 2.1). This raises the possibility of diffuse splenic infiltration with lymphoma. Finally, there is diffuse increased metabolic activity throughout the bone marrow, which may be due to lymphoma infiltration vs. a reactive phenomenon in the setting of anemia or medications.

Source: M. Ghesani

Figure 2: 8/20/08 - Clockwise from upper left - CT, PET, maximum intensity projection (MIP) PET, and PET/CT fusion images
Figure 2: 8/20/08 – Clockwise from upper left – CT, PET, maximum intensity projection (MIP) PET, and PET/CT fusion images. MIP PET image demonstrates dramatic reduction of metabolic activity in the previously seen lymph node chains after chemotherapy treatment. The selected axial image demonstrates anatomic and functional normalization of the lymph node at the splenic hilum. There is also normalization of the distribution of metabolic activity in the spleen relative to the liver, suggesting positive response to chemotherapy on lymphomatous infiltration of the spleen. There is an increase in metabolic activity throughout the marrow containing structures of the skeleton consistent with a chemotherapy effect. This limits the characterization of potential lymphomatous involvement of the bone marrow.

Figure 3: 12/18/08 - Clockwise from upper left - CT, PET, maximum intensity projection (MIP) PET, and PET/CT fusion images
Figure 3: 12/18/08 – Clockwise from upper left – CT, PET, maximum intensity projection (MIP) PET, and PET/CT fusion images. MIP PET image demonstrates interval resolution of the metabolic activity in the lymph node chains. The metabolic activity in the spleen remains lower than that of the liver, which is physiologic. There is also a decrease in the metabolic activity in the marrow containing skeletal structures, consistent with resolving chemotherapy effect.

DISCUSSION

Use of FDG-PET or FDG-PET/CT in both non-Hodgkin’s and Hodgkin’s lymphoma continues to expand. FDG-PET is widely used to assess response to treatment after completion of chemotherapy in these patients and also in pretreatment staging and assessment of response during treatment. In pretreatment staging, PET cannot replace CT and bone marrow biopsy, but can certainly add complementary information, upstaging lymphoma in about 15% to 20% of cases. FDG-PET is significantly more accurate than CT alone for assessing response to therapy. It can distinguish a change in metabolic activity in an area that may not have changed by size criteria. This distinguishes between areas of active tumor and residual fibrosis. The role of PET for therapy monitoring is still under investigation, but several studies have shown that early PET improvement correlates with response at completion. This may, in the future, lead to significant changes in management.

Although the exact role for FDG-PET/CT in terms of diagnosis and management of lymphoma is not yet fully clear, we do know that in a patient with suspected lymphoma, the intensity of splenic FDG uptake appears to correlate with histopathology. In a retrospective series of 165 patients undergoing splenectomy at a single institution from 2004 to 2006, 10 were identified as being performed to evaluate known or suspected lymphoma and included a presplenectomy FDG-PET scan. Each patient was assigned a low-, intermediate- or high-splenic-metabolic activity based on SUV. Low activity was associated with benign findings or mantle cell lymphoma, intermediate with marginal zone lymphoma, and high activity with diffuse large B-cell lymphoma.

We also know that higher intensity FDG uptake in the spleen relative to the liver on initial staging FDG-PET scan may suggest diffuse splenic involvement by lymphoma, as presumed in our case. Hepatic FDG uptake is normally at least as intense as splenic uptake, reflecting the physiology of glucose metabolism in the liver. One retrospective series evaluating 341 FDG-PET scans for lymphoma performed between 2001 and 2004 revealed 67 patients in which baseline and follow-up studies were available for evaluation. The ratio of mean SUV values in the spleen over liver were calculated for each study, with 10 patient controls who had been referred for a lung malignancy but without prior history of malignancy, reticuloendothelial disorders, chemotherapy or anemia. In the control group, the mean spleen liver ratio was 0.69, or less than 1, as we would expect. In contrast, 12 of the 67 patients (18%) demonstrated more intense uptake in the spleen, with the mean SLR of 1.54 (range 1.11-10). In this subgroup of 12 patients, mean SLR value after chemotherapy decreased to 0.79 (range 0.56-1.6), an average decline of 93%. This indicates that higher intensity of FDG uptake in spleen relative to liver on FDG-PET imaging studies for lymphoma should raise the possibility of diffuse infiltration of spleen with lymphoma, and interval decline, as in our patient, of SUV value in the spleen would imply response to chemotherapy.

The 2007 Consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma states that diffusely increased splenic uptake that is greater than that of the normal liver — after chemotherapy — should be considered compatible with lymphoma unless the patient has a history of recent (within 10 days) cytokine administration. It has been shown that increased FDG uptake is observed in the spleen during and after G-CSF treatment, which is important to recognize when interpreting FDG-PET scans in patients with cancer undergoing cytokine therapy.

Although the specific role of FDG-PET scan in diagnosis and management of lymphoma is not yet fully clear, we can say with assurance that in patients with known or suspected lymphoma, the intensity of splenic FDG uptake appears to correlate with histopathology and that splenic hypermetabolism greater than liver prior to chemotherapy is highly suggestive of lymphomatous involvement. A relative decrease in the activity of the spleen relative to the liver during systemic chemotherapy can therefore be interpreted as a positive response.

Munir Ghesani, MD, is an Associate Clinical Professor of Radiology at Columbia University College of Physicians and Surgeons and Attending Radiologist at St. Luke’s-Roosevelt Medical Center.

Carrie Wasserman, MD, is a second year Hematology/Oncology Fellow at St. Luke’s-Roosevelt Hospital Center.

Neilish Gupta, MD, is a Radiology Resident at St. Luke’s-Roosevelt Medical Center.

For more information:

  • Leukemia Lymphoma. 2008;49:719-726.
  • Clinical Nuclear Medicine. 2006;31:366.
  • J Clin Oncol. 2007;25:571-578.
  • J Nucl Med. 1999;40:1456-1462.