05 June 2023: Articles
Liver Transplantation for Liver Metastasis of a Pseudopapillary Pancreatic Neoplasm in a Male Patient
Unusual clinical course, Unusual setting of medical care, Rare diseaseRobert Sznajder Granat1EF*, Antonio Romano1E, Christina Villard12E, Mattias Lissing23E, Jeanna Joneberg4E, Olof Danielsson5BE, Carlos Fernández Moro5BE, Carl Jorns1E
Am J Case Rep 2023; 24:e938678
BACKGROUND: Solid pseudopapillary neoplasm (SPN) of the pancreas, which predominantly affects young women, is an uncommon condition with low malignant potential. It is often asymptomatic. This tumor has a low metastatic rate and a good prognosis in contrast to other pancreatic tumors. Approximately 14% of SPNs develop liver metastasis, but for SPNs with malignant features liver metastasis has been reported to occur in over 55% of cases. Complete surgical resection is the treatment of choice for increasing the survival rate in metastatic recurrent disease. When surgical resection is impossible, liver transplantation has shown promising results in a few cases. The purpose of this article is to present the first case of a male patient who underwent liver transplantation for this indication.
CASE REPORT: We present the case of a 60-year-old male patient who previously had pancreas surgery, numerous liver resections, and chemotherapy for SPN, but nevertheless developed recurrence of multiple liver metastases. His metastatic liver disease was regarded as unresectable. The lymphatic structure was also affected. The patient underwent orthotopic liver transplantation with a deceased donor graft after multidisciplinary evaluation. Resection of involved lymphatic structures was also performed. At 2-year follow-up, the patient was alive and recurrence free.
CONCLUSIONS: This is the first published report of a male patient who underwent liver transplantation due to SPN metastasis. Our case demonstrates that liver transplantation should be further investigated for selected cases of SPN of the pancreas with liver metastatic disease when surgical resection is deemed unattainable.
Keywords: Liver Transplantation, Pancreatic Neoplasms, Neoplasm Metastasis
Solid pseudopapillary tumor of the pancreas, also known as the Franz tumor, first described by V. K. Franz in 1959, is a potentially malignant tumor that is observed primarily in women in their 20s to 40s. It is an uncommon neoplasm, accounting for approximately 2% of all pancreatic tumors. Nevertheless, due to extensive usage and improving precision of radiological imaging, SPN is being detected more frequently .
Clinically, it is often asymptomatic, but patients can present with abdominal pain, nausea, dyspepsia, vomiting, and jaundice. Blood biochemistry, including pancreatic amylase, liver function tests, and tumor markers, is usually unaffected . Malignancy potential is suggested to be correlated with tumor size and Ki-67 index .
Metastasis from SPNs is rare, with a median prevalence of 14% (range, 2–28%) . The liver is the most common site for metastasis. The optimal treatment for improving survival of metastatic disease is surgical resection [4,5]. Liver transplantation has been reported in a few cases of irresectable liver metastasis. Disease-free survival varied from 9 months to 2 years [6–10].
Here, we present the first case of a male patient with recurrent unresectable and non-ablatable liver metastasis from solid pseudopapillary pancreatic neoplasm who underwent liver transplantation (LT).
A 60-year-old male patient presented with jaundice. Computed tomography showed an 11-cm tumor with central necrosis in the pancreatic head and a 2.5-cm solitary metastasis in segment 6 of the liver. The tumor compressed the vascular structures of the portal vein, the superior mesenteric vein, and the common hepatic artery (Figure 1A).
A Whipple procedure was performed, including resection of the superior mesenteric vein and local liver resections of segment 6 and the gallbladder bed for the suspected liver metastasis. Radical resection was obtained. Histopathological analysis of the pancreas and liver samples showed monomorphic epithelial cells with round-to-oval nuclei and vacuo-lated cytoplasm, which exhibited a predominantly solid pattern (Figure 2A, 2F). Degenerative changes, including necrosis, hemorrhage, and areas of pseudopapillary formations, were observed. Extrapancreatic and vascular invasion were noted as aggressive features. The larger liver metastasis showed a predominantly encapsulated pattern, but smaller ones showed direct contact between the tumor cells and the hepatocytes, the so-called replacement growth pattern. The tumor cells in both the pancreas and liver showed identical immunohistochemical profiles (Figure 2B–2E, 2G–2J) with diffuse, distinct, nuclear, and cytoplasmic immunoreactivity for beta-catenin. They were also positive for vimentin and negative for cytokeratins and synaptophysin. Ki-67 index was 15%. Overall, histomorphology and immunohistochemical analyses were highly consistent with a solid pseudopapillary neoplasm of the pancreas and synchronous liver metastasis.
Due to local intrahepatic recurrence with 4 metastases, a local liver resection was performed 18 months later. This was followed by adjuvant chemotherapy with 3 cycles of Paclitaxel+Gemcitabin and then 4 cycles of the Folfirinox regimen. A new recurrence occurred 12 months later with 1 metastasis and the patient underwent another local liver resection.
Radiological imaging 48 months after the first operation showed 21 liver metastases engaging all liver segments (Figure 1B), and an enlarged lymph node located next to the SMV was observed. After multidisciplinary discussion by the hospital Liver Transplant Board and Ethics Committee, the patient was accepted to the liver transplant waiting list.
The patient underwent liver transplantation 3 months later (Figure 3). The enlarged lymph node was extirpated intraoperatively and showed no signs of malignancy. The postoperative course was complicated by a ruptured mycotic pseudoaneurysm of the hepatic artery, which required surgical resection and endovascular stenting. No adjuvant radio- or chemotherapy was given. Follow-up included alternating MRI and ultrasound every 3–6 months. Histopathological analysis of the explanted tissue confirmed SPN (Figure 2A–2E). The enlarged lymph node showed no signs of malignancy.
Two years following the liver transplantation, the patient is doing well with no sign of disease recurrence and with good graft function (Figure 1C). Immunosuppression consists of low-dose tacrolimus (1.5 mg twice daily) and 5 mg of prednisolone.
Here, we present the first case of liver transplantation for metastasis of SPN in a male patient. SPN affects women in an almost 10: 1 female-to-male ratio and it has a low malignant potential and a good survival rate . However, 10–15% of cases of SPN have metastatic disease at the time of diagnosis and the most common site is the liver. Tanue et al reported that in patients with malignant feature SPN, liver metastasis occurs in 57.1% of cases . Sperti et al reported occurrence of hepatic metastasis 2–168 months after diagnosis of the primary tumor .
Survival rates are significantly decreased in untreated metastatic disease. In metastatic disease, radical surgical resection improves patient survival compared to chemotherapy ; patients with distant metastasis undergoing surgical resection have similar median survival rates as patients without metastatic disease. In contrast, patients with distant metastases who do not undergo surgical resection have a median survival of 2.1 years with a higher mortality risk compared to patients with metastatic disease who underwent resection (HR 18,
Liver metastasis has generally been considered a contraindication for LT due to poor results. However, recent studies suggest that careful patient selection and advances in multimodality approaches have substantially improved these results . Only a few cases for SPN liver metastasis treated with LT are described in the literature [6–10]. One of these case reports reported disease recurrence after transplantation. However, the follow-up was short except for 1 case with 5 years of follow-up . These studies suggest that LT is a possible treatment when other surgical and/or oncological treatments are not recommended or suitable.
It is important to consider the suspected effect of immunosuppressive medication accelerating tumor growth in possible residual disease and how the perioperative treatment can be optimized to avoid this occurrence. We applied the center-standard immunosuppression protocol with a combination of tacrolimus and prednisolone, although an mTOR inhibitors regimen may be considered.
In LT for metastatic disease, post-transplant adjuvant treatments may also be considered. In the presented case reports no treatments were offered to the patients. Wojciak et al described a case of lymph node recurrence 1 year after transplantation that was treated with excision, radiotherapy, and switching to mTOR inhibition immunosuppression . Lymph node status was carefully evaluated in our case. The preoperatively enlarged lymph node did not contraindicate LT. It was a singular local lymph node that was assessed as resectable during LT surgery.
This is the first published case report of a male patient who underwent liver transplantation for treating liver metastasis of solid pseudopapillary neoplasm with disease-free follow-up of 2 years. This case report suggests that liver transplantation should be considered as a treatment for selected cases of SPN liver metastatic disease.
FiguresFigure 1.. (A) Preoperative computed tomography of upper abdomen in coronal plane, showing the primary SPN in the pancreatic head, marked with yellow arrow, and liver metastasis in segment 6, marked with a red arrow. (B) Magnetic resonance imaging of the liver in a transverse plane before liver transplantation. There were multiple metastases in all segments of the liver. One large tumor is marked with a diameter of 64 mm. (C) Magnetic resonance imaging of the liver in transverse plane 2 years after liver transplantation. There are no signs of metastasis. Figure 2.. (A, F) Histology of primary and liver metastasis of solid pseudopapillary neoplasm of the pancreas on hematoxylin and eosin (H&E) staining. The photomicrographs show monomorphic epithelial cells with vacuolated cytoplasm in solid sheets. (B–E, G–J) Immunohistochemical staining demonstrates the characteristic profile of solid pseudopapillary neoplasm of the pancreas: beta-catenin (B-cat: nuclear and cytoplasmic positivity), vimentin (Vim: positive), cytokeratins (CK18, CK5: negative), synaptophysin (Syp: negative). Text colors correspond to the staining chromogens. Yellow dotted area (F, G, I, J) indicates atrophic peritumoral hepatocytes. Green arrows (B, G) indicate beta-catenin+tumor cell nuclei. Figure 3.. Sagittal cross-section of the explanted liver with multiple metastases. A centimeter ruler is shown in figures for scale.
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