F-18 Fluorodeoxyglucose PET/CT and Post Hoc PET/MRI in a Case of Primary Meningeal Melanomatosis
A 17-year-old male, without any relevant medical history, was admitted to our hospital with an acute headache, nausea, and vomiting. The neurologic examination showed mental alertness without any significant focal neurologic signs. The brain CT revealed hyperdense lesions in the right temporal lobe suggesting subarachnoid hemorrhage or non-infectious meningitis. He received non-surgical conservative treatment because CT angiography did not demonstrate any vascular abnormalities. With progressive worsening of the symptoms, brain MRI was performed 3 months later. We used 3.0T MRI system (Signa Excite, General Electric Healthcare, Milwaukee, WI, USA) to obtain T1-wighted contrast-enhanced MR images (TR/TE = 550/12) after administration of gadolinium chelates. The imaging showed diffuse thickening of the leptomeninges on the right temporal and frontal lobes, which were hyperintense on T1-weighted MR images and hypointense on T2-weighted MR images, with contrast-enhancement. F-18 FDG PET/CT was also obtained with integrated PET/CT scanners (Discovery STE, GE Healthcare, Milwaukee, WI, USA). CT and PET scans were obtained with the patient in supine position with quiet respiration. CT scan was performed without contrast enhancement in order to generate an attenuation correction map for the PET scan. PET scan was performed with a 3 minutes emission acquisition per bed position. PET images were reconstructed with a 128 × 128 matrix, an ordered subset expectation maximum iterative reconstruction algorithm (4 iterations, 8 subsets), a Gaussian filter of 5.0 mm, and a slice thickness of 3.27 mm. All images were transferred to a dedicated workstation for analysis (Advantage Workstation 4.5, General Electric Healthcare, Milwaukee, WI, USA). The initial whole body F-18 FDG PET/CT scan revealed hypermetabolic lesions, along the leptomeninges on the frontal and temporal lobes bilaterally, but no other hypermetabolic lesions were detected throughout the body (). Maximum standardized uptake values (SUVmax) were measured in several foci of hypermetabolic leptomeningeal lesions. SUVmax measured in the right temporal, right frontal, left temporal and left frontal lobes was 25.3, 14.7, 7.8 and 6.8, respectively. The PET images were co-registered with contrast-enhanced T1-weighted MRI images using an Integrated Registration application of GE Advantage Workstation 4.5. The post hoc PET/MRI fusion images revealed a perfect co-localization of the hyperintense lesions on T1-weighted contrast-enhanced MRI images and hypermetabolic lesions on the F-18 FDG PET/CT images. The post hoc PET/MRI images showed F-18 FDG uptake on PET images corresponding to enhancing lesions on T1-weighted contrast-enhanced MRI images (). In addition, we found more lesions in the left frontal and temporal lobes in the post hoc PET/MRI images than the unenhanced F-18 FDG PET/CT images.\nAnalysis of the CSF showed the following: 2 white blood cells/µL, with a lymphocyte predominance; a low glucose level, 27 mg/dL; protein, 23 mg/dL; lactate dehydrogenase, 249.2 U/L; and absence of atypical or abnormal cells. CSF analysis was repeated 5 days later, and the results were as follows: 1 white blood cell/µL, with a lymphocyte predominance; low glucose level, 25 mg/dL; protein, 35 mg/dL; and lactate dehydrogenase, 354 U/L. The serum tumor markers, which were measured, including alpha-fetoprotein, carcinoembryonic antigen, prostate specific antigen, cancer antigen (CA) 125, CA 19-9, and CA 15-3, were all negative. Because the presumptive clinical diagnosis was tuberculosis meningitis, the patient was treated with an anti-tuberculosis regimen and steroids; however, his neurologic symptoms were not relieved.\nBecause of the diagnostic uncertainty, the patient eventually underwent an open biopsy. Under general endotracheal anesthesia, a small temporal craniotomy was performed on the right side. The exposed dura mater revealed no abnormalities. After incising the dura, however, a dark black solid mass was noted through the translucent arachnoid membrane. The exposed subarachonoid space was completely filled with the dark tumor mass; the flow of CSF was not identified. A small tumor specimen was obtained for tissue diagnosis.\nMicroscopic examination of the meningeal biopsy stained with hematoxylin and eosin revealed proliferation of polygonal epithelioid tumor cells (). The tumor cells had large pleomorphic vesicular nuclei with prominent eosinophilic nucleoli and dusty intracytoplasmic melanin pigment. Nuclear pleomorphism and mitoses were also noted. The tumor cells were immunohistochemically positive for human melanoma black-45 (HMB-45) and S-100, and the Ki-67 labeling index was approximately 10%. The histopathologic and immunohistochemical findings were consistent with malignant melanoma.\nA thorough physical examination, by a dermatologist, did not show abnormal pigmented lesions in the skin and mucous membranes, except for the presence of a small dermal nevus on the chest wall, which was biopsied and confirmed to be a benign nevus. An ocular examination, by an ophthalmologist, excluded any intraocular tumors.\nPrior to radio- and chemotherapy, a second pre-treatment F-18 FDG PET/CT performed, at one week after the initial diagnosis, revealed aggravation of the hypermetabolic leptomeningeal lesions, compared with that of the initial F-18 FDG PET/CT images (). SUVmax of the hypermetabolic leptomeningeal lesions in the right temporal, right frontal, left temporal and left frontal lobes was changed from 25.3, 14.7, 7.8 and 6.8 to 36.5 (+44.3%), 19.4 (+32.0%), 15.0 (+92.3%) and 12.8 (+88.2%), respectively, and the extent of the each lesion was increased. However, no extracranial abnormal hypermetabolic lesions were found on the whole body scan. Brain MRI also demonstrated a progression of the disease. The patient was treated with whole brain radiotherapy and a chemotherapeutic regimen with dacarbazine, carmustine, cisplatin, and tamoxifen. Pre-treatment post hoc PET/MR fusion images also demonstrated that F-18 FDG uptake on PET images was positionally-matched with enhancing lesions on T1-weighted contrast-enhanced MRI images (). After 8 cycles of chemotherapy, a third F-18 FDG PET/CT scan showed a considerable decrease in F-18 FDG uptake, and the extent of the hypermetabolic leptomeningeal lesions compared with those on pre-treatment F-18 FDG PET/CT (). SUVmax of the hypermetabolic leptomeningeal lesions in the right temporal, right frontal, left temporal and left frontal lobes was changed from 36.5, 19.4, 15.0 and 12.8 to 18.3 (-49.9%), 10.5 (-45.9%), 7.8 (-48.0%) and 8.1 (-36.7%), respectively. Post-treatment MRI showed a slight decrease in the size of the enhancing leptomeningeal lesions on contrast-enhanced T1-weighted MR images, which suggested partial therapeutic response like PET. Post-treatment post hoc PET/MR images also showed a considerable decrease in the F-18 FDG uptake and the extent of hypermetabolic leptomeningeal lesions on PET images, positionally-matched with enhancing lesions on T1-weighted contrast-enhanced MR images ().