Invasive and metastatic solid pseudopapillary tumor in a young male patient

Solid pseudopapillary tumor is a rare neoplasm with incidence less than 2% of exocrine pancreatic neoplasms. This tumor was first coined by Dr. Frantz in 1959 and had various terms until 1996 when World Health Organization unified the term as solid pseudopapillary tumor (SPT). This tumor tends to occur in young female and has low malignant potential. We encountered a patient with atypical features of SPT, including male gender, metastasis at time of diagnosis, extrapancreatic invasion, and tumor size more than 5 cm. A 28-year-old male without any significant medical history presented with left upper quadrant abdominal pain for 2 days. He had no previous history of hospitalization. Physical examination revealed left upper quadrant abdominal tenderness and no definite palpable mass. Abdominal ultrasound demonstrated an irregular hypoechoic mass at tail of pancreas and a 3-cm mixed echoic tumor with mural nodules in the liver Segment 7 (Fig. 1). Laboratory test results including tumor markers (carcinoembryogenic antigen, alpha-fetoprotein, CA 19-9) were within normal limits. Abdominal ultrasound to the left showed an irregular hypoechoic mass at tail of pancreas; abdominal ultrasound to the right showed a 3-cm mixed echoic tumor with mural nodules in the liver Segment 7. Both Abdominal CT and MRI showed a heterogeneous mass about 7cm in diameter involving the pancreatic tail and a low density 3-cm-mass with mural nodular enhancement in the liver (Fig. 2), suspecting pancreatic tumor with liver metastasis. PET-CT further revealed tumor metastasis to perihepatic parietal peritoneum and multiple lymph nodes, including left subphrenic, gastrohepatic, and gastrosplenic area, and hemoperitoneum (Fig. 3). EUS-guided fine needle aspiration (EUS-FNA) of the pancreatic tumor and the liver tumor biopsy both revealed the diagnosis of solid pseudopapillary tumor with characteristic pseudopapilla formation and central cystic components. Both Abdominal CT (A) and MRI (B) showed a heterogeneous mass about 7cm in diameter involving the pancreatic tail and a low density 3-cm-mass with mural nodular enhancement in the liver. PET-CT further revealed tumor metastasis to perihepatic parietal peritoneum and multiple lymph nodes, including left subphrenic, gastrohepatic, and gastrosplenic area, and hemoperitoneum. Patient underwent aggressive tumor debulking surgery, including distal pancreatectomy, splenectomy, partial gasrectomy, left hemicolectomy, S7-8 partial hepatectomy, peritoneal metastatic lesion excision, and regional lymph node dissection (Fig. 4). Cell morphology showing alternating solid and pseudopapillary formation and immunohistochemical stains confirmed the diagnosis of solid pseudopapillary tumor (Fig. 5). Stage pT3N1M1, stage IV. Immunohistochemical stains were strongly positive for vimectin, CK19, and beta-catenin. Only small clusters of cells were positive for CK7, CD10, and synaptophysin. These findings were consistent with diagnosis of SPT. Patient underwent aggressive tumor debulking surgery, including distal pancreatectomy, splenectomy, partial gastrectomy, left hemicolectomy. The gross specimen to the left showed tumor directly invaded to peri-gastric soft tissue. Gross specimen to the right showed the mural nodular appearance of the SPT metastasized to the liver. Cell morphology showing alternating solid and pseudopapillary formation. He received radiation therapy postoperatively. Unfortunately, recurrence of SPT in liver was found soon after debulking surgery and radiotherapy. Further debulking surgery was suggested but refused by patient. Patient survived for 19 months after diagnosis of SPT was made. Last abdominal CT done for patient showed progression of metastases on the left kidney, progression of peritoneal metastasis along the right perihepatic parietal peritoneum, and progression of hepatic metastatic mass (3.7 cm) in S6. SPTs are rare tumors of pancreas with a low malignant potential and a female predilection [1]. Analysis of 1014 patients reported in the literature revealed only 137males (13.5%). Males had a twofold higher incidence of metastases and a threefold higher death rate [2]. In collective reviews, SPTs of the pancreas arising in older patients and in males are more likely to behave aggressively [3]. The reasons for more aggressive behavior in male patients are not clear. The only difference is that male patients are older than females, but the clinical presentation (tumor location, incidental findings, and symptoms) were the same [4]. It was postulated that SPT is a sex-hormone dependent neoplasm. However, the expression of sex hormone receptors in SPN remains controversial. Progesterone receptors have been reported as positive in more than 80% of these patients, whereas estrogen receptors were usually negative [5]. Evaluations of patients with SPT are usually made by CT or MRI. Patients with SPT present most commonly with nonspecific abdominal pain (50%), as our patient did, and followed by palpable abdominal mass (35%). 15% of patients were diagnosed incidentally. PET-CT helped to detect the subtle metastasis as pointed out by Kim et al [6]. In our case, PET-CT helped to further delineate the extent of metastasis to liver, peritoneum, and lymph nodes. Most SPTs have an indolent clinical course. Following successful surgical resection appears to have a greater than 97% 5-year survival. Nevertheless, it is apparent that approximately 15% of SPTs develop hepatic or peritoneal metastases either at the time of presentation or, less commonly, some years after resection of the primary tumor; interestingly, lymph node metastases are rarely described [7]. In Yu et al's review of 553 cases in the Chinese literature, only 2 out of 553 cases were found to have hepatic metastasis (0.3%) at the time of diagnosis [8]. Our patient not only has liver metastasis, but also has peritoneum and lymph node metastasis at the time of diagnosis. Cases with multiple sites of metastasis as in our case are almost not found in the literatures. Even with liver metastases, patients are clinically stable for years. For the most part, it appears that the 5-year survival is not significantly altered even in the presence of metastatic disease [7]. However, cases with multiple metastatic sites at the time of diagnosis were not yet reported in the literatures thus far. Prognosis of metastatic SPT treated with aggressive surgical resection is good [1,2]. Our patient has several features demonstrating the more aggressive behaviors of SPT; such as male gender, multiple metastases at the time of diagnosis, and the large size of the tumor. The experience with the management of disseminated disease is very limited in the literature. Surgery still remains to be the main treatment of SPTs. There were anecdotal cases of SPT underwent chemotherapy. The regimens used include cisplatin and 5-flurouracil, and gemcitabine [1,9]. Radiothepray is seldom used for unresectable tumor [9]. Nonetheless, our patient received radiotherapy after debulking surgery and seemed to have only limited effect preventing further progression of disease. Trans-arterial emobolization (TAE), trans-arterial chemoembolization (TACE) [1], and radiofrequency ablation (RFA) [1,10] have been applied to treat the liver metastasis of SPT. However, the results are still controversial. All authors declare no conflicts of interest. The authors received grant support from Changhua Christian Hospital research fund 104-CCH-IRP-008.