Isolated Synchronous Multiple Splenic Metastases From Rectal Cancer: a Case Report and Review of the Literature

Background: Isolated splenic metastasis emanating from colorectal cancer is an extremely rare nding, which usually indicates widely disseminated and multiple metastatic cancer. There have only been 39 cases of isolated splenic metastasis reported in the English literature to date. Case presentation: We report a case of synchronous and isolated multiple splenic metastases derived from rectal cancer. An 84-year-old woman, who presented with and an increased serum carcinoembryonic antigen (CEA) level, was diagnosed with rectal cancer with splenic metastases by abdomen computed tomography (CT). The patient underwent a radical resection of rectal cancer and splenectomy, and the postoperative histopathology con ﬁ rmed that the splenic lesions were derived from the adenocarcinoma of the rectum. After surgery, the patient recovered well and was recommended for further chemotherapy. Conclusion: Our ndings enrich the database of this rare clinical entity and provide experience in the management of splenic metastasis. In addition to revealing a rare case, we also performed a literature review, including a brief discussion about the atypical isolated splenic metastasis from colorectal cancer (CRC).

artery, and then enter into the portal vein system. Thus, the blood ow is from the spleen to the liver, and the retrograde venous blood from the portal vein system to the spleen is very rare, making it di cult for tumor cells to reach the spleen. On the other hand, the venous blood ow below the dentate line is capable of owing into the inferior vena cava through the internal iliac vein and internal pudendal vein, making it is almost impossible to directly enter the vasculature of the spleen. In addition, the acute angulations of the spleen artery and the rhythmic contraction of the splenic capsule signi cantly limit the ability of the tumor embolus to implant in the spleen (12). Besides, the reticuloendothelial system of the spleen is capable of inhibiting tumor cell proliferation. Furthermore, the lack of afferent lymphatics also limits lymphogenic metastases. More interestingly, some researchers proposed that splenic cells possess a phagocytic capability and are capable of producing anti-tumor substances, which can effectively inhibit the progression of tumors (13). Signi cantly, one study also proposed that although disseminated cancer cells can easily reside in splenic parenchyma, the special microenvironment of the spleen may suppress the growth and progression of these cells (4). Consequently, the splenic micrometastatic foci cannot be detected through traditional clinical methods, resulting in the clinically detectable isolated metastases of the spleen being reported as 4.4% for colon cancer and 1.6% for rectum cancer (14). In comparison, the incidence of splenic micrometastases at autopsy is approximately 7.1% (15).
Splenic metastasis has to be distinguished from the primary splenic lesion, such as malignant lymphoma, vascular tumors, infections disease, septic emboli, and granulomatous diseases (4). Recently, with the development of medical imaging techniques, such as positron emission tomography (PET)-CT and PETmagnetic resonance imaging (MRI), it has become easier to detect splenic metastases, thereby increasing their apparent incidence. Consequently, it is important to trace the patient's disease history, in which a history of malignancy increases the possibility of splenic metastasis (16). Interestingly, one study reported a patient with rectosigmoid adenocarcinoma with splenic lesions; however, the postoperative pathological diagnosis revealed a primary splenic malignant lymphoma (17). Therefore, histopathology remains the gold standard for diagnosis.
Interestingly, in terms of splenic lesions, there were only 4 cases of multiple metachronous splenic metastases, and most cases (35) were solitary. In this study, we described the rst case of a synchronic splenic metastasis from a malignant tumor of the rectum. Our case was also (47)previous reports. Among these cases, based on their primary tumor sites, we observed that the most common lesion was in the sigmoid colon (12 cases), accounting for 30.8%.
In comparison, the two most uncommon sites were the transverse colon in one case and the hepatic exure in two cases. Others included six cases in the cecum, four cases in the ascending colon, three cases in the splenic curvature, six cases in the descending colon, and three cases in the rectum. In particular, two patients presented with multiple primary cancers. For the one patient, the primary tumors were found in the descending colon and sigmoid colon together, and the tumors of the other patient were located in the sigmoid colon and rectum. Based on these ndings, we deduced that the primary tumors of splenic metastasis are most commonly found in the left hemi-colon in 24 cases, accounting for 61.5%, which might re ect the fact that these tumor cells can enter counter-currently into the splenic vein via the inferior mesenteric vein. In terms of primary tumor stage (1 case with stage I, 7 cases with stage II, 23 cases with stage III, 3 cases with stage IV, and 5 cases in which the stage was not mentioned), indicating that most isolated splenic metastasis is derived from the median or advanced colorectal cancer.
Among reported cases, 29 of the 39 patients presented with an elevated CEA level. In accordance with the above results, the CEA level reached a maximum of 57.57 ng/mL in our case. In terms of cases of metachronous splenic metastasis cases, the disease-free interval ranged from 3 to 144 months (average, 31.7 months). In addition, for most of the patients, the isolated splenic metastases were found during postoperative follow-up by radiological examinations, such as abdomen computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), ne-needle aspiration, and even uorodeoxyglucose-positron emission tomography (FDG-PET). According to the literature, only one patient did not undergo curative splenectomy. For most patients, splenectomy and chemotherapy were the two main optimal treatment strategies.
In our case, both the primary rectal cancer and metastasis splenic lesions showed caudal type homeobox 2 (CDX2) expression (Fig. 2). CDX2, a homeobox protein, is believed to be an important factor in maintaining the intestinal phenotype and regulating colorectal tumor metastasis (48). Importantly, we observed that splenic lesions express special AT-rich sequence-binding protein 2 (SATB2) (Fig. 2), which is used as a diagnostic marker of colorectal origin cancer (49).
One study found that more than 93% of colorectal origin tumors showed SATB2 positive staining, which was consistent with our results (50).

Conclusion
We reported a case of the rare occurrence of isolated synchronous multiple splenic metastases from rectal cancer. Our ndings enrich the database of this rare clinical entity and provide experience in the management of splenic metastasis. To the best of our knowledge, splenic metastasis of colorectal carcinoma is very uncommon. With improvements in examining techniques, increased numbers of patients with isolated splenic metastasis might be found. Over the long term, it is essential to follow up patients with colorectal cancer postoperatively, which could effectively improve the management and prolong the survival of these patients with isolated splenic metastases. The common therapeutics options include splenectomy, chemotherapy, targeted therapy, and radiotherapy. However, to date, only a small number of cases have been reported and long-term follow-up is absent; therefore, standardized clinical treatment strategies for splenic metastasis have not been established. In future studies, more attention should be paid to this rare entity.