A. Aggarwal 1 , J. Brainard 1 , D. Brotman 1 ; 1 Cleveland Clinic Foundation, Cleveland, OH LEARNING OBJECTIVES: 1. Recognize that glucagonomas can present with spinal metastases. 2. Appreciate that the absence of cutaneous, endocrinologic and gastrointestinal manifestations does not rule out the presence of a glucagonoma. 3. Know that tissue staining for neuroendocrine peptides can confirm that a tumor is of pancreatic origin, even when there is no radiographically identifiable pancreatic mass. CASE INFORMATION: A 38 year-old African-American woman presented to the emergency department with low back pain of three months duration. The pain involved both flanks and radiated to the buttocks and posterior thighs bilaterally, as well as to the right groin and medial right thigh. By exam, she was thin and appeared uncomfortable. Shotty nodes were palpable in multiple regions, but none were fixed or enlarged. There was percussion tenderness of the lumbar spine, but motor function and reflexes were normal in the lower extremities. Serum chemistries were notable for an elevated alkaline phosphatase but otherwise normal liver enzymes. Serum calcium and glucose were normal. CT of the abdomen and pelvis showed peripancreatic lymphadenopathy and numerous hepatic lesions suggesting metastases. MRI of the spine demonstrated a destructive lesion in the second lumbar vertebra with soft-tissue extension compressing the spinal cord (figure). Whole body bone scan showed diffuse osseous metastases to the upper and lower extremities as well as the axial skeleton. Ultrasound-guided biopsy of the peri-pancreatic adenopathy revealed a low-grade neuroendocrine tumor that stained positive for glucagon, but stained negative for serotonin, pancreatic polypeptide and gastrin. The serum glucagon level was normal. Due to widespread metastases, the patient was deemed a poor surgical candidate, however she did undergo radiation therapy to the spine and to painful lesions in the right humerus and left femur. Subsequently she was treated with systemic chemotherapy consisting of adriamycin and streptozocin with no initial reduction in tumor mass. DISCUSSION: Glucagonomas have previously been reported to metastasize to bone, but to our knowledge there is only one other reported case of bony metastases as the initial manifestation of the tumor. This may be because most glucagonomas come to early clinical attention via the effects of high serum levels of glucagon. It has previously been reported that systemic and endocrine manifestations of glucagonomas are more common in advanced disease and are directly related to tumor size. This is clearly not the case in our patient. Notably absent were the typical skin rash (necrolytic migratory erythema), diarrhea, hyperglycemia, stomatitis and chelosis associated with the classic glucagonoma syndrome. Another important clinical feature in our patient was the absence of a radiographically identifiable pancreatic mass despite widespread metastases. While the absence of a clear primary source is not an uncommon situation in cancer patients, the identification of the primary tumor carries particular importance for neuroendocrine malignancies. Metastatic small-cell carcinoma of the lung has a more rapid progression than both carcinoid and islet cell tumors, and the treatment is different for these three types of malignancies. In our patient, tissue staining for neuroendocrine markers allowed a specific diagnosis to be made and appropriate treatment to be instituted. We conclude that the absence of clinical evidence of hormonal activity should not dissuade the physician from considering the possibility of a pancreatic islet cell primary when a patient presents with metastatic neuroendocrine malignancy, even when there is no radiographic evidence of pancreatic mass. Stains for neuroendocrine peptides are of crucial importance to making the diagnosis in such patients.