Hepatic metastasis in Frantz’s tumor: A case report

Highlights • This is a borderline tumor with indolent biological behavior.• There are still multiple poorly understood factors that can dictate its malignant transformation and prognosis.• Here, a rare tumor whose age and survival are tangent the literature reports describe.• There is a need for a long and rigorous segment to identify possible long-term metastases.

dopapillary Neoplasm (SPN) according to its histogenesis [1]. It is a rare tumor with an incidence of 1-2% among exocrine tumors of the pancreas most common in young women [2,3]. The SPN is solitary tumor, well circumscribed and encapsulated, that presents a solid-cystic pattern, necrosis, hemorrhage and cystic degeneration [4,5]. According to the World Health Organization (WHO), it is a solid pseudopapillary neoplasm, with morphological classification M-8452/1, with boderline features [6].
Although the malignancy criteria are still not clearly, it occurs in about 15% of the cases, with deep invasion of the pancreatic parenchyma, perineural, angioinvasion or distant metastasis (liver, peritoneal and lymph-nodal) [7].
The present study, based on guidelines for case reports (SCARE), aimed to report a case of SPN in a 13-year-old child, attended at a teaching public hospital in the Amazon region of Brazil that evolved with liver metastases, but it has a high overall survival thanks to the surgical treatment performed.

Presentation of case
A female adolescent, student, aged 13 years, no family history of cancer, realized the first consultation in January of 2012, presented a principal complaint of epigastric and left-hypochondrium pain, weight loss, fever and vomiting. She denies comorbidities, history of alcohol use, tobacco use or cancer in the family. The findings from imaging evidenced a heterogeneous expansive process in the tail of the pancreas (6.5 × 5.6 cm) (Fig. 1). The laboratory exams and tumor markers did not present alterations in relation to the reference values.
In March of 2012, she was submitted to caudal body pancreatectomy, splenectomy, segmental colectomy at 15 cm of the transverse, colo-coloanastomosis and resection of 18 regional lymph nodes (Fig. 2). It should be emphasized that intraoperatively, the surgeon observed macroscopically tumoration of approximately 8 cm occupying the body and tail of the pancreas, adhering to the transverse mesocolon, posterior wall of the stomach, third duodenal portion, and closely related to the spleen; absence of ascites, of peritoneal carcinomatosis and of liver metastasis.
The histopathology and immunohistochemistry concluded the presence of solid pseudopapillary neoplasm, encapsulated, measuring 4.5 × 4.3 × 3.5 cm, with bulging external surface, accentuated cystic alteration, hemorrhage and extensive area of necrosis, with free surgical margins, without evidence of vascular or neural invasion, absence of lymph-nodal metastasis and positive for Vimentin, Cytokeratins (AE1/AE3) and CD10 (CALLA, 56C6).
During 30 postoperative months, the patient reported retrosternal "burning" during outpatient accompaniment, with improvement after the use of pantoprazole. The result of Total Abdominal USG showed the liver with irregular form, wrinkled surface and enlarged dimensions, parenchyma with altered echogenicity and heterogeneous echotexture. The liver vessels did not present alterations and serology was negative for viral hepatites. Then in the 38th month, the patient complained of a frequent, diffuse, slight pain in the abdominal region.
In the 46th postoperative month, she referenced a sensation of postprandial gastric plenitude and sporadic fever. Abdominal ultrasound showed 4 hypoechoic rounded cystic images with interior trabeculated in segments VI, VII and VIII, measuring between 2 and 2.6 cm. Computed tomography of the abdomen identified the liver of normal size, with heterogeneous attenuations of the parenchyma, the largest of which being 4.8 cm in segment VIII, of lobulated contours and well-defined limits, without significant enhancement after injection of contrast (Fig. 3).
Given the suspicion of liver metastasis, magnetic resonance of the upper abdomen was solicited (performed 50 months after surgery), which evidenced multiple oval encapsulated formations, diffuse in the liver parenchyma, with an aspect that was solid, cystic and non-characteristic, suggesting relation to secondary neoplastic implants. The tumor markers and thoracic CT did not present alterations.
Magnetic resonance was repeated in the 56th postoperative month, and revealed the liver with normal dimensions and contours, but with multiple nodular images, without significant uptake of liver-specific contrast medium, suggestive of cysts (5 cm in segment VIII and 4.6 cm in segment VI, on the major axial axes). Yet another lesion was noted (5 cm in segment VIII), without signifi-cant uptake of contrast medium, possibly corresponding to a cyst with high protein/hematic content. Serology was also solicited for hydactidosis as a differential diagnosis and its result was negative.
After 3 months of the same, the patient complained of pain in the right hypochondrium with irradiation toward the right costal gradient and right shoulder, with worsening upon inhalation; she also referenced dyspnea associated with clinical pain, being hospitalized for controlling pain and diagnostic elucidation.
Given this presentation, at 63 months after the first surgery, the patient was referred to a surgical center to undergo exploratory laparotomy for enucleation of cystic lesions. However, in the intraoperative period it was possible to observe macroscopically lesioning in liver segments V, VI and VII, with biopsy being carried out by freezing of the lesion in segment V, which confirmed liver metastasis, with the surgeon opting to convert the surgery to right-sided hepatectomy, with removal of segments V, VI, VII and VIII. Immunohistochemistry of liver metastasis revealed expression positive for ␤ catenin clone 14 and CD10 (CALLA, 56C6), findings consistent with solid pseudopapillary neoplasm (SPN) [10].
The patient was hospitalized for 27 days and then discharged from the hospital, after which she received monthly outpatient follow-up with clinical oncology and the general surgical team, without complaints and with negative tumor markers (Alpha-fetoprotein, CEA and CA 19.9), total abdominal CT without alterations.
Starting in May of 2017, the outpatient return consultations became quarterly with the surgical team and semiannual with oncology. Adjuvant chemotherapy was not performed while laboratory and imaging exams were maintained within normality patterns, totaling global survival of 100 months after the first treatment, the first surgery.

Discussion
This study showed a patient who at 13 years of age presented epigastric pain, weight loss and imaging findings suggestive of pancreatic tumor, with surgery being indicated. The literature highlights that SPN is most common in young women, with an average age of 30 years, and is rarer at 13 years [4,7,8].
She developed left hypochondrium pain and epigastric pain, palpable mass accompanied by nonspecific symptoms secondary to pancreatic compression (nausea and fever), similar to previous studies [7,9,10]. The tumor occupied the body and tail of the pancreas, but some studies cite the tail of the pancreas as the topography most commonly affected, followed by the head and body, or even manifesting synchronically in the head and tail of the pancreas [11].
The initial treatment of SPN is surgical, and it depends on the clinical-pathological characteristics of each patient, for which there is no standardization [4,8]. Some authors emphasize that intraoperative analysis being decisive related to differential diagnosis and histopathological and immunohistochemical exams [12]. Aggressive surgeries were associated with improved prognoses, revealing a divergence in the choice of surgical technique to be applied, in which macroscopic evaluations may favor incomplete resection, recurrence and distant metastasis [7].
In this study, the histopathological result evidenced disease limited to the pancreas, with capsule intact and hemorrhagic signals on the external surface of organs adhering to the pancreatic tumor mass. Furthermore, after 30 months, the patient evolved with multiple liver metastases, even in total tumor resection.
Local recurrence or distant metastasis is described in about 15% of SPN cases, with the liver being the most affected organ [8], associated with tumor rupture or invasion of an adjacent organ [7,13]. According to the American Joint Committee on Cancer (AJCC) and the WHO, angioinvasion, unequivocal perineural invasion and deep invasion of the present pancreatic parenchyma are histological criteria that indicate greater probability of recurrence or metastasis, classifying this as a tumor with uncertain malignant potential [6].
Here, the patient manifested liver images suggestive of metastasis at 30 months after surgery, diverging from the liver metastasis incidence (15%) more commonly described from the early form (between 3 and 17 months after initial surgery) [7,14].
Total tumor resection has ensured prolonged survival above 95% when SPN is limited to the pancreas or even curative in the resection of metastatic liver disease [4,8]. In addition, the survival times of 5 years even in metastatic disease and 10 years in total tumor resection exceed 90% [14]. Currently, the patient is in the outpatient segment without complaints correlated with the basic disease, and without laboratory or imaging alterations, totaling global survival of 100 months.
It is concluded that this case report is important for ratifying the prognostic and clinical polymorphism spectrum of SPN. Furthermore, it is understood to be a borderline tumor with indolent biological behavior, there are still multiple poorly understood factors that can dictate its malignant transformation and prognosis. Therefore, there is a need for a long and rigorous segment to identify possible long-term metastases. It is necessary to conduct additional epidemiological studies, and molecular and clinical trials that can augment the knowledge on TSP.

Conclusion
The present study followed the guidelines for case reports (SCARE) [15] and concluded some importants thinks. First, this case report is important for ratifying that the prognostic and clinical polymorphism spectrum of SPN. Furthermore, it is understood to be a borderline tumor with indolent biological behavior, there are still multiple poorly understood factors that can dictate its malignant transformation and prognosis. Therefore, there is a need for a long and rigorous segment to identify possible long-term metastases.
Secondly, the surgical procedure associated with regular and prolonged postoperative follow-up favored the diagnosis and resection of liver metastases in a timely manner, with positive impact on patient survival and quality of life. Currently, she is in the semi-annual and disease-free outpatient segment, with a total of 96 months overall survival. Lastly, it is necessary to conduct additional epidemiological studies, and molecular and clinical trials that can augment the knowledge on TSP.

Declaration of Competing Interest
None.

Sources of funding
Funded by the authors.

Consent
Written informed consent was obtained at 18 years old patient to publish this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this