Pancreatic neuroendocrine tumor with metastasis to the spleen: a case report

Neuroendocrine tumors are rare, but their reported incidence has increased over the last decades, which is attributed to improved diagnostic modalities and surveillance [4, 7]. In one study, the incidence from 1974 to 2004 more than doubled, from 1.4 new cases per million to 3.0 [10]. Gastrointestinal neuroendocrine tumors have a higher likelihood of presenting with metastases, which are present in about 50–65% of patients at the time of diagnosis. With the availability of new treatment modalities, long-term survival is reported, even in patients who present with metastatic disease. A recent review showed that the combination of long-acting somatostatin analogue therapy with aggressive cytoreductive surgery can result in long-term survival in some patients with metastatic NETs originating in the gastrointestinal tract [4].

In a series of 46 patients with pNETs, 48% presented with loco-regional disease and 52% presented with metastases [11]. All patients without metastases underwent resection, and the authors report a three-year survival of 86% with a median 42 months follow-up. Patients with metastatic disease were treated with a variety of modalities including resection, ablation, chemoembolization and others, and had a three-year survival of 70%. The authors credit their use of a multidisciplinary multimodal approach. An aggressive approach to these lesions was also reported by Touzios et al [1], who categorized the treatment of 60 patients with pNET into three groups: no treatment, resection, and transarterial chemoembolization. Five-year survival was 25% in the no treatment group, 72% for the resection group and 50% for the transarterial treated group. They also found poor outcomes in patients with >50% involvement of the liver.

The impact of lymph node involvement on survival in patients with pNET was studied by Krampitz and colleagues [12]. They found that disease-related survival decreased as a function of the number of lymph nodes involved. However, in patients with liver metastases and lymph node metastases, the major determinant of survival is the presence of liver metastases. The probability of survival at 10 years is 30% in this series. In a large series of patients with non-functional pNETs, tumor size and nodal status were not associated with survival, while tumor grade and systemic metastases were associated [10].

Somatostatin receptor scintigraphy is an important modality in the evaluation of these patients, and peptide receptor radionuclide therapy has shown promising results in the therapy of these lesions [13]. Transplantation has been used in select patients with results similar to transplantation performed for hepatocellular carcinoma [14]. These authors advise waiting for stabilization of liver disease prior to proceeding to transplantation. However, transplantation is generally not considered as a first-line therapy for metastatic neuroendocrine tumors [4].

The presence of splenic metastases is usually reported in the context of a pre-terminal event with multiple visceral metastases. In this patient, it is of interest that the single spleen metastasis was found at the initial presentation. The origin of the splenic metastasis is the subject of some speculation. In the spleen, it is believed that reticulo-endothelial create an unfavorable environment for the growth and survival of tumor cells [6, 7, 15]. Splenic metastases are believed to originate from the splenic artery, splenic vein, or lymphatics [8]. However, there are few lymphatic ducts to the spleen, and most metastases are considered of hematogenous origin [16]. Marymont et al demonstrated that splenic metastases are seen in the venous sinusoids and /or red pulp, supporting a hematogenous origin [17]. The splenic artery would appear to be the most common origin of splenic metastases although this suggests systemic circulation of tumor cells, and metastases in other organs may be expected, making solitary splenic metastases less likely. In patients with pNET, liver metastases from the portal vein are extremely common. In the present patient, although histologic evaluation of the portal vein showed no evidence of portal vein thrombus, the huge tumor mass and minimal invasion of the splenic vein seen on histologic evaluation, may have affected portal vein outflow, leading to congestion of the splenic vein and possibly resulting in development of a splenic metastasis [18].

In patients with late appearance of splenic lesions, treatment may be futile but splenectomy may benefit patients who experience significant pain due to splenomegaly. Isolated splenic metastases were extremely rare in a series of 92 splenic metastases, representing just 4% of the lesions [6]. In that series, 26% of the spleens weighed more than 200 g. It is estimated that only about 100 cases of isolated splenic metastases have been reported [19], from diverse primary tumors. Splenectomy for isolated metastases can result in long term survival [7]. It has been suggested that splenic metastases may result from the growth of early blood-borne tumor cells, after a latent period [7]. Laparoscopic splenectomy is a reasonable surgical option in a patient with an isolated splenic metastasis.

Despite an extensive review of the literature including multiple databases (keywords “spleen”, “metastases”, “neuroendocrine”), there are no reports of patients with metastases to the spleen from pNETs. In one review of unusual locations for metastases from neuroendocrine tumors, there were no lesions metastatic to the spleen [20]. Metastases to the spleen have been reported for bronchial carcinoid tumors [21, 22]. The spleen has been reported to be involved with neuroendocrine tumors of the pancreas, including a tumor thrombus in the splenic vein without a mass in the spleen [23] and as a splenic mass from direct extension and gastric varices [24]. The rarity of splenic metastases is not entirely surprising, since pNETs and splenic metastases are both rare entities.