Obscured Bone Metastases After Administration of Hematopoietic Factor on FDG-PET

1. Obscured Bone Metastases After Administration of Hematopoietic Factor on FDG-PET from Clinical Nuclear Medicine Volume 31(6),�June 2006,�pp 328-330

2. Abstract FDG-PET scan in a patient with bony metastases from a rare tumor. The lesions were obscured by intense bone marrow activity after the administration of hematopoietic factor at the time of diagnosis. Correlative MRI, CT scan, and pathology findings have also been illustrated. Follow-up FDG-PET scan demonstrated the hypermetabolic lesions.

3. Cytokine-mediated diffusely hypermetabolic bone marrow is a known appearance on FDG-PET scans. However, it is less well reported that hypermetabolic metastatic foci may also appear as regional areas of decreased FDG uptake as a result of the marked stimulatory effect of G-CSF on the normal bone marrow.

4. CASE REPORT 63-year-old woman treated with a liver transplant after surgery for intrahepatic cholangiocarcinoma (CC). Pathology: poorly differentiated adenocarcinoma with a few positive lymph nodes at the hepatic hilum.

5. She received Cellcept (mycophenolate mofetil) and FK506 to prevent transplant rejection. Three months later, she developed leukopenia as a side effect to these drugs and was started on intravenous granulocyte colony stimulating factor (G-CSF).

6. During the course of treatment, she complained of acute onset of low backache. ?On physical examination, no neurologic deficit ?A whole spine MRI with contrast was performed,  which demonstrated peripherally enhancing cystic  expansile lesions in T9 and S1 vertebrae ?A CT scan of the chest, abdomen, and pelvis was performed and no locoregional recurrence or other distant metastases were identified.

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8. The lesions demonstrated active uptake on the subsequent single-phase bone scan (Fig. 2A, B), and a strong suspicion of bone metastases was raised in view of the known clinical history of CC. FDG-PET scan obtained on a Siemens ECAT mobile PET scanner demonstrated diffusely hypermetabolic bone marrow resulting from G-CSF treatment and the lesions, when compared with the stimulated normal marrow, appeared relatively cold (Fig. 2C, D). Subsequent CT-guided FNAB of the thoracic spine lesion was performed and poorly differentiated positive adenocarcinoma cells were identified confirming the presence of metastatic cholangiocarcinoma (Fig. 3A, B).

12. She received local radiation therapy to the spine lesions and G-CSF was discontinued after 2 weeks of therapy after normalization of the WBC count. A subsequent FDG-PET scan was performed after a month of discontinuation of G-CSF, which revealed abnormal metabolism in T9 and S1 vertebrae (Fig. 4A) and additional mediastinal and right supraclavicular lymphadenopathy. She was started on combination chemotherapy and follow-up FDG-PET scan performed after 6 months revealed near complete resolution of the spine lesions (Fig. 4B).

14. DISCUSSION Hematopoietic cytokines such as G-CSF, granulocyte-macrophage colony stimulating factors (GM-CSF), and erythropoietin are being used increasingly in conjunction with chemotherapy in patients with cancer and immunosuppressed patients. FDG-PET scans obtained during and after G-CSF treatment demonstrate increased FDG uptake in the spleen resulting from extramedullary hematopoiesis in 53% cases and in the bone marrow in 87% cases as compared with normal biodistribution of FDG in other tissues.

15. The dose of G-CSF and duration of treatment correlates well with extent of increase in FDG uptake in the bone marrow. It has been reported in scattered case reports that cytokine-mediated FDG uptake in bone marrow is often indistinguishable from that caused by disseminated metastatic disease.

16. One previous publication indicated that nonuniformly increased bone marrow uptake can appear as if bone metastases were present.?However, the demonstration of bone metastases presenting as relatively cold areas as a result of increased activity in underlying normal bone marrow was not found in the literature. ?This can be logically explained by the relative absence of normal cells in malignant foci, thus resulting in lack of response to G-CSF.

17. A similar appearance of regional decreased activity in patients on G-CSF may also be seen after radiation treatment as a result of lack of response to G-CSF in irradiated regions of the spine. Thus, focal cold areas in patients receiving G-CSF is not specific for active metastatic disease.

18. The diagnosis of bony metastases from peripheral cholangiocarcinoma was also interesting because of its rarity. In addition, the lesions also demonstrated an atypical cystic hemorrhagic appearance on MRI. However, active uptake on the single-phase bone scan helped decrease the likelihood that the lesions may represent benign cystic lesions like multiple hemangiomas.

19. This was confirmed on follow-up FDG-PET scans performed after 2 months, which not only revealed true appearance of lesions resulting from discontinuation of G-CSF, but also demonstrated additional lesions in the mediastinal lymph nodes and right supraclavicular lymph nodes (not shown) consistent with disease progression. The patient was started on local radiotherapy and combination chemotherapy, and follow-up PET scan revealed near complete resolution of the bony and visceral lesions.

20. CONCLUSION Regional areas of relative decreased activity may be seen in metastatic foci in the spine despite being metabolically active as a result of the marked effect of hematopoietic cytokines like G-CSF on normal bone marrow. These appearances should be differentiated from postradiation changes. Bone scans may confirm the findings or imaging may be delayed for a few weeks after discontinuation of G-CSF.

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