Laparoscopic spleen-preserving distal pancreatectomy for epidermoid cyst in an intrapancreatic accessory spleen

Abstract Rationale: Pancreatic tail cystic lesions are increasingly encountered in clinical practice, however, it is difficult to make a correct diagnosis preoperatively because there are many types of pancreatic neoplastic and non-neoplastic cysts. Epidermoid cyst in an intrapancreatic accessory spleen (ECIPAS) is a rare non-neoplastic cyst locating in the pancreatic tail, and it is commonly misdiagnosed as another cystic neoplasm. Patient concerns: A 51-year-old man was admitted for investigation of abdominal pain. The physical examination and laboratory tests found no abnormalities, except for an elevation of carbohydrate antigen (CA)19-9. Imaging revealed a cystic lesion within the pancreatic tail, and the solid component surrounding the cyst was enhanced similarly to those of the splenic tissue. Diagnosis: ECIPAS was diagnosed based on the pathology after surgery. The mass was composed of a cyst and brown solid spleen-like tissue. The microscopic analysis demonstrated that the solid component was accessory splenic tissue, and the cyst wall was lined with a thin stratified squamous epithelium. Interventions: Laparoscopic spleen-preserving distal pancreatectomy was performed. Outcomes: The patient was discharged on day 5 postoperatively after an uneventful recovery. CA19-9 returned to normal after surgery. During a 2-years follow-up, there was no evidence of tumor recurrence. Lessons: Although rare ECIPAS should be considered in the differential diagnosis of pancreatic tail cystic lesions, and the typical imaging features might facilitate the preoperative diagnosis. Laparoscopic distal pancreatectomy is a safe and effective approach for treating ECIPAS.

evidence of tumor recurrence. CONCLUSION We describe typical imaging features of ECIPAS and showed that laparoscopic distal pancreatectomy was safe and effective for treating ECIPAS.

Background
Although pancreatic tail cystic lesions are being increasingly encountered in clinical practice, it is di cult to make an exact diagnosis preoperatively [1][2][3]. Epidermoid cyst in an intrapancreatic accessory spleen (ECIPAS) is an exceedingly rare entity, and all the ECIPAS cases reported so far have been found in the pancreatic tail [4,5]. ECIPAS should therefore be considered in the differential diagnosis of pancreatic tail cystic lesions. It is di cult to diagnose ECIPAS preoperatively using conventional imaging, thus it is commonly misdiagnosed as another cystic neoplasm, such as a mucinous cystic neoplasm (MCN), solid pseudopapillary tumor (SPT), intraductal papillary mucinous neoplasm (IPMN) or cystadenocarcinoma [6][7][8][9]. ECIPAS was thought to be benign until recently when it was found to develop into a malignant tumor during 6-years follow-up [10], which highlights its malignant potential. Thus, it would be necessary to make a de nitive diagnosis of this disease as well as to differentiate it from other potentially malignant pancreatic tail cystic neoplasms. We describe a case that was speculated to be ECIPAS, treated by laparoscopic spleen-preserving distal pancreatectomy.

Case Presentation
A 51-year-old man was admitted to our hospital with a history of abdominal pain for 6 months. The patient had no symptoms of fever, nausea, vomiting or weight loss. The patient's symptoms started 6 months ago, with recurrent episodes of abdominal pain that could relieve spontaneously. No history of trauma or pancreatitis was recorded. The physical and laboratory examinations were normal, except for elevation of carbohydrate antigen (CA)19 − 9 to 55 U/mL (normal range 0-37 U/mL). Contrast-enhanced computed tomography (CT) found a cystic lesion measuring 2.6 cm within the tail of the pancreas, and the thick solid wall surrounding the cyst was enhanced similarly to those in splenic tissue (Fig. 1A-1D). Upon magnetic resonance imaging (MRI), the cyst was hyperintense in T1-weighted imaging and heterogeneous in T2-weighted imaging ( Fig. 1E and 1F); therefore, the cystic component was considered to be mucinous or bloody liquid. The solid component showed high signal intensity in diffusion-weighted imaging and high intensity in T1-weighted imaging, and the capsule wall showed visible enhancement ( Fig. 1E-1I). Endoscopic ultrasonography (EUS) indicated a unilocular cystic solid lesion in the pancreatic tail and the cyst was not found to communicate with the main pancreatic duct ( Fig. 2A and   2B). Contrast-enhanced EUS using sulfur hexa uoride microbubbles showed that the solid component was enhanced in the arterial phase ( Fig. 2C and 2D). Additionally, an EUS based ne-needle aspiration (FNA) using a 22-G needle from the solid component was performed. The FNA sample consisted predominantly of leukocytes and proteinaceous debris, and no squamous epithelial cells or malignant cells were found.
Based on the radiographic and pathological ndings, ECIPAS was speculated. Considering the symptoms and the di culty to completely exclude the malignant tumor due to elevation of CA19-9, laparoscopic spleen-preserving distal pancreatectomy was performed. The surgical specimen revealed a well-de ned cystic mass, measuring 2.5 cm at its greatest diameter, located in the tail of pancreas (Fig. 3A). The cut surface showed that the mass was composed of a cyst and brown solid spleen-like tissue (Fig. 3A).
Microscopic analysis demonstrated that the solid component was accessory splenic tissue, and the cyst wall was lined with a thin strati ed squamous epithelium (Fig. 3B). The nal pathological diagnosis was ECIPAS. The patient was discharged at day 5 postoperatively after an uneventful recovery. CA19-9 returned to normal after surgery. During 2-years follow-up, there was no evidence of tumor recurrence.

Discussion And Conclusions
ECIPAS is an extremely rare entity. ECIPAS was thought to be benign until recently malignant transformation was found during 6-years follow-up [10]. Li et al [11] reviewed 56 cases of ECIPAS since the rst case was diagnosed by Davidson et al in 1980 [12]. Most of the cases were incidentally detected, while the others had symptoms of abdominal pain, discomfort, nausea, vomiting, back pain, fever, or weight loss. In all cases, the cystic lesions were found in the pancreatic tail. The cysts could be either unilocular or multilocular, lined by a keratinized or nonkeratinized strati ed squamous epithelium or a cuboidal epithelium. The average cyst size was 4.3 cm (range 1.3-15 cm). Although most cases of ECIPAS were benign, it was necessary to differentiate it from other potentially malignant pancreatic tail cystic neoplasms, including MCN, SPT, pseudocyst, IPMN and cystic pancreatic neuroendocrine tumor (p-NET).
Elevation of serum CA19-9 level was common in ECIPAS patients. Hu et al reported that nearly 40% of ECIPAS showed high levels of CA19-9 [5,13], hence increasing the di culty to distinguish ECIPAS from malignant tumors preoperatively. It has been reported that the squamous epithelial lining of ECIPAS expressed CA19-9 in an immunohistochemical analysis, and serum CA19-9 levels markedly decreased to normal levels postoperatively in patients [14]. These ndings suggest that serum CA19-9 is secreted by the epithelial lining cells of ECIPAS. In the current case, although ECIPAS was speculated, the symptoms and high CA19-9 level encouraged us to perform surgery.
Preoperative diagnosis of ECIPAS is di cult. MCN, cystadenocarcinoma, pseudocyst, cystic p-NET or potential malignant tumor is suspected in most cases [15][16][17][18]. Including the present case, only six (10.7%) among the 56 reported cases were correctly diagnosed preoperatively [15,[19][20][21][22]. Most cases of ECIPAS were diagnosed after surgery based on the pathological ndings [23]. Advances in imaging techniques facilitated the diagnosis of ECIPAS as compared with previously; however, few studies have reported the imaging characteristics of ECIPAS. ECIPAS is a well-de ned, unilocular or multilocular cystic mass located in the tail of the pancreas on multimodality imaging. The well-de ned boundary is a differentiating morphological feature suggestive of a benign tumor. The cystic wall of ECIPAS showed contrast enhancement similar to that of the spleen during multiphasic CT or MRI. Therefore, the accessory spleen surrounding the cyst was a key component for correct diagnosis. However, only a few cases of ECIPAS had a su cient solid component that allowed splenic tissues be detected through radiological imaging. Fortunately, there was a large amount of solid tissue present in our case; therefore, correct preoperative diagnosis of ECIPAS was achieved. Including the present case, four of 56 cases were diagnosed as ECIPAS preoperatively based on the similar density on enhanced CT and intensity on MRI between the solid component and the spleen [15,20,21]. The cystic component of ECIPAS usually appears to be hypodense on nonenhanced CT, hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging. However, it sometimes appears hyperdense on nonenhanced CT and hyperintense on T1-weighted imaging, in the presence of hemorrhage or keratinized materials within the cyst [5,24,25]. In the present case, the cystic component was hyperdense on nonenhanced CT and hyperintense on T1weighted imaging, and remained unenhanced during multiphasic scans. Thus, the cystic content was considered to be mucinous or bloody liquid that was con rmed by the resected specimen following surgery.
EUS-FNA is a commonly used technique to evaluate pancreatic masses, and it has been investigated for diagnosis of ECIPAS. In Tatsas et al's report, three of six cases of intrapancreatic accessory spleen were diagnosed successfully; however, one case of ECIPAS failed to be diagnosed by EUS-FNA [26]. In the only case of ECIPAS diagnosed postoperatively, the FNA sample revealed only predominant macrophages and proteinaceous debris; therefore, no pathological evidence of ECIPAS was acquired prior to surgery [26]. Among the remaining ve cases of ECIPAS reported in the English-language literature, one was correctly diagnosed by EUS-FNA[17, 21, 27-29]. Matsumoto et al reported a case of ECIPAS that was accurately diagnosed by EUS-FNA [21]. Their histological ndings showed that sinusoids and abundant polymorphous lymphocytes were consistent with an intrapancreatic accessory spleen [21]. Therefore, to acquire pathological evidence of ECIPAS using EUS-FNA seems to be di cult. This is mainly because the amount of splenic tissue surrounding the epidermoid cyst was too small in most cases to be successfully aspirated by FNA. In the present case, although leukocytes were found, we failed to reveal splenic sinusoids and endothelial cells within the acquired specimen.
Treatment of ECIPAS consists of surgical resection and follow-up. As most cases of ECIPAS are reported not to have malignant potential, unnecessary surgery can be avoided with a correct preoperative diagnosis. However, in cases of ECIPAS with symptoms, or in those in which it is di cult to completely exclude malignancy, laparoscopic spleen-preserving distal pancreatectomy is suggested since this procedure has been commonly used to treat benign or low-grade malignant tumors of the pancreatic tail.
Fujii et al [30] reported that laparoscopic distal pancreatectomy could be a useful, minimally invasive surgical approach for treating ECIPAS with additionally decreased postoperative pain, length of stay and associated mortality and morbidity. In the present case, the symptoms and serum CA19-9 level encouraged us to perform surgery in this patient. The patient recovered uneventfully and had no evidence of tumor recurrence during 2-years follow-up, suggesting laparoscopic spleen-preserving distal pancreatectomy is effective and safe for ECIPAS.
In conclusion, it is di cult to make an exact diagnosis of pancreatic tail cystic lesions preoperatively.
ECIPAS is an exceedingly rare entity, and all cases reported so far have been found in the pancreatic tail. Therefore, although rare, ECIPAS should be considered in the differential diagnosis of pancreatic tail cystic lesions. Imaging and endoscopic evaluation may be helpful in the diagnosis, but preoperative diagnosis is still challenging. A similar enhancement between the solid component of the cystic lesions and the splenic parenchyma is critical for correct diagnosis. Treatment of ECIPAS by laparoscopic distal pancreatectomy is an effective procedure with the advantages of minimal invasiveness. The datasets used and analyzed in this report are available from the corresponding author on reasonable request.

ACKNOWLEDGMENTS
The patient signed a written informed consent form for the purpose of publication of the results of this case study.
Author contributions: Zheng X reviewed the literature, acquired the data and contributed to manuscript drafting; Zhou B analyzed and interpreted the pathological and immunohistochemical ndings, and contributed to manuscript drafting; Sun JQ and Jin M analyzed and interpreted the imaging ndings and contributed to manuscript drafting; Yan S acquired the data and was responsible for revision of the manuscript for important intellectual content; all authors issued nal approval for the version to be submitted. This work was supported by grants from the Natural Science Foundation of Zhejiang Province (No. LQ19H100004). The funder of LQ19H100004 was Xiang Zheng who was the rst author, responsible for the overall study concept and design as well as the revision and nal drafting of the manuscript.
Our study was approved by the Ethics Committee of Second A liated Hospital of Zhejiang University School of Medicine. Written informed consent was obtained from all subjects in our study.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Con ict-of-interest statement: The authors declare that they have no con ict of interest.