Vascular thrombosis as a cause of abdominal pain in a patient with neuroendocrine carcinoma of pancreas: Findings on (68)Ga-DOTANOC PET/CT.

Neuroendocrine tumors of pancreas are relatively rare neoplasms and are classified as either functioning or non-functioning tumors. A 55-year-old female diagnosed with a large, well-differentiated, non-functional neuroendocrine carcinoma of pancreas, presented with abdominal pain of increasing severity. A contrast-enhanced examination of the abdomen was performed to reveal a large, diffuse, enhancing pancreatic mass with multiple filling defects within the mesenteric vasculature. We present findings on (68)Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI(3)-Octreotide, positron emission tomography-computed tomography ((68)Ga-DOTANOC PET/CT) and the importance of somatostatin receptor-based PET imaging in such patients.

INTRODUCTION

Endocrine tumors of the pancreas (EPTs) are rare tumors with an incidence of approximately 4-12 per million in a given population.[1] They are classified mainly into two distinct entities. The functional pancreatic tumors are usually small and present with clinical symptoms of hormonal excess coupled with biochemical evidence of the same.[2] In contrast, the non-functioning tumors are usually silent and present later in the course with large masses producing symptoms arising mainly from the tumor bulk.[3] Different imaging modalities have been used in the diagnosis and detection of such neoplasms. Role of somatostatin receptor imaging using the single photon emission computed tomography (SPECT) agent 111In-octreotide is well-established in these tumors.[4] However, they are increasingly being replaced with PET imaging using the novel isotope 68Ga labeled with different octreotide analogs, providing superior anatomical information and image resolution.[5] We present here the findings of a case of non-functioning neuroendocrine tumor of pancreas imaged with 68Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-Octreotide (-Octreotide (68Ga-DOTANOC) PET/CT.

CASE REPORT

A 53-year-old female was diagnosed with a pancreatic tumor when she initially presented with anorexia and weight loss. Contrast-enhanced CT (CECT) examination at that time revealed a large, homogenous enhancing mass involving almost the entire pancreas with no evidence of local invasion or nodal involvement. A biopsy examination of pancreatic tissue revealed features of a well-differentiated tumor of neuroendocrine origin (neuroendocrine carcinoma proliferating index, 4%). In view of extensive disease involving pancreas, surgery was deferred and the patient was put on octreotide therapy. The patient was apparently well for a period of 4 months when she started having abdominal pains, which progressed in severity over the next month. A repeat contrast-enhanced examination of the abdomen revealed no significant alterations of the primary pancreatic mass, but showed numerous filling defects within the mesenteric vasculature. In view of the disease progression, a staging PET/CT using 68Ga-DOTANOC was performed [Figure 1]. Intense radiotracer uptake was noted in the primary tumor (SUVmax-53). Also seen was an arborizing area of abnormal tracer uptake within the abdomen, which was subsequently traced to mesenteric vessels [Figure 2]. Thus, 68Ga-DOTANOC PET/CT helped confirm the presence of mesenteric vascular thrombosis and localize the cause of abdominal pain to be the same. In addition, the whole body examination revealed no other areas of abnormal uptake that could suggest presence of other metastatic sites.

Figure 1

Whole body 68Ga-DOTANOC PET MIP (maximum intensity projection) image of a 53-year-old female diagnosed with a primary neuroendocrine tumor of the pancreas, showing area of intense radiotracer uptake within the abdomen (bold arrow). Also noted are areas of abnormal tracer uptake in an arborizing fashion distal to the area of primary abnormality (arrows)

Figure 2

Sequential unenhanced CT, 68Ga-DOTANOC PET, and fused PET/CT images are shown. Upper row images display the primary pancreatic mass, which is homogenously enlarged and bulky, (a) and shows intense tracer avidity (b, SUVmax-53). Fused PET/CT image shows the tumor with uptake compatible with a pancreatic neuroendocrine tumor (c). Middle row images are axial sections to define the abnormal arborizing uptake seen on the MIP image. CT image shows enlarged mesenteric vessels (d, arrow) although a contrast-enhanced examination was not performed. Increased tracer uptake is noted in the area corresponding to enlarged blood vessels (e). Axial PET/CT section reveals enlarged primary inferior mesenteric vessels and its branches showing intense tracer uptake suggestive of tumor thrombus (f). Lower row images represent distal sections of the vasculature with similar findings (g-i). No areas of nodal of visceral tracer uptake were identified that may suggest metastatic disease. Hence, a diagnosis of primary pancreatic neuroendocrine tumor with mesenteric vessel thrombosis could be confirmed with 68Ga-DOTANOC PET/CT imaging

DISCUSSION

Tumor thrombosis of blood vessels have been most commonly described in association with hepatocellular and renal cell carcinomas.[6] Tumor thrombosis in pancreatic adenocarinomas has also been frequently described in the literature.[7] Presence of tumor-induced vascular thrombosis usually implies a less favorable prognosis and has a direct bearing on management and treatment outcomes. However, a similar association in context of pancreatic neuroendocrine tumor (NET) is exceedingly rare and only few case reports have demonstrated this association in the past.[8] Tumor thrombosis by a pancreatic NET has also been described previously on fluorodeoxyglucose (FDG) PET imaging.[9] Two previous reports also demonstrate tumor thrombosis on somatostatin receptor PET/CT imaging using the radiotracers DOTATATE, where 68Ga-DOTATATE was used to confirm the presence of tumor thrombosis within inferior mesenteric vessels.[1011] However, role of 68Ga-labeled tracer DOTANOC to detect tumor thrombosis in pancreatic NETs have not been described in the past, which has a broader spectrum of receptor affinity as compared to other octreotide analogs.[12] 68Ga-DOTANOC PET/CT can play additional roles besides confirming the presence of tumor thrombosis and localizing it as the source of abdominal pain. Intense tracer uptake by tumor tissue (SUVmaxas in this case) is an in vivo demonstration of presence of somatostatin receptors on tumor cell surface in a high density. This can be exploited for therapy purpose using peptide-based radionuclide therapy using 90Y- or 177Lu-labeled octreotide analogs.[13] Also, the candidate can be followed up further using sequential imaging to either monitor the response to therapy or evidence of progression.