Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review

Abstract Mucinous cystic neoplasms (MCN) are rare premalignant neoplasms of the pancreas typically found as single lesions in the pancreatic body and tail of women in the fifth and sixth decade of life, constituting 2–5% of pancreatic neoplasms. We present a 50-year-old female patient with a large tail mass of the pancreatic body (size of 15 cm × 12 cm) with elevated tumor indicators. Computed tomography and magnetic resonance imaging revealed a large cystic lesion with septa and wall nodules. During the operation, the tumor capsule wall adhered to the left half colon and mesentery and could not be detached. Splenectomy and left hemicolectomy were performed. The postoperative pathological examination of the specimens confirmed a premalignant pancreatic mucous cystic tumor with moderate heterocytosis. The preoperative diagnosis of pancreatic MCN and MCN with invasive carcinoma is discussed, considering the characteristics of this case. Age, tumor size, texture, tumor marker elevation, and cystic wall condition are important characteristics of malignant MCN. Nevertheless, it is still very difficult to determine accurately whether an MCN is malignant or not before an actual pathological examination of the resected specimen.

Here, we report a middle-aged female with a large 15 cm × 12 cm MCN with the capsule adhering to the left half colon and mesentery. Before and after the operation, it looked more like an invasive MCN, and distal pancreatectomy, splenectomy, and left hemicolectomy were performed.

Case report
A 50-year-old female patient was hospitalized on December 12, 2019, due to back pain for 2 years. She had no history of trauma or other diseases. On abdominal examination, a 10 cm × 10 cm mass in the left abdomen was found, with a clear boundary and poor mobility. The abdomen was soft, and there was no tenderness. The other physical examinations were unremarkable. Table 1 presents the tumor marker levels at admission. Abdominal enhanced computed tomography (CT) revealed a large mass with an unclear boundary at the lower margin of the pancreas (Figure 1a). Abdominal enhanced magnetic resonance imaging (MRI) revealed a large mass with slightly high T1 and T2 signals in the left abdominal cavity, with a size of 15 cm × 12 cm. There were septa and wall nodules (Figure 1b). There was a patch of short T1 signal at the wall nodules, and the scanning interval and wall nodules were significantly enhanced. The adjacent pancreas was compressed and pushed upward, with unclear lesions' boundaries. The tumor was in the left abdomen, in the body and tail of the pancreas, posterior to the stomach and adjacent to the spleen. No enlarged lymph nodes and mass shadows were observed in the retroperitoneum. The abdominal wall had no special structure (Figure 1). No obvious abnormality was found in blood, stool, hepatic and renal functions, and coagulation function tests.
The preoperative diagnosis was MCN, but malignant changes could not be excluded. An exploratory laparotomy was performed on December 19, 2019, and a large thick-walled cystic lesion filled with a turbid purulent thick liquid was found ( Figure 2a). The upper boundary of the tumor was intimately adhering to the pancreatic tail, with obvious infiltration, and the tumor capsule wall also had dense adhesions to the left half colon and mesentery and could not be detached. The intraoperative pathological examination suggested an MCN with moderate hyperplasia, and malignancy could still not be excluded. Therefore, the operation was expanded, and distal pancreatectomy, splenectomy, and left hemicolectomy were performed.
The postoperative pathology suggested that the tumor was multilocular and cystic. The tumor was composed of two distinct components: epithelial cells and dense spindle cells (Figure 2b). At high magnification, a small number of tumor cells were well-differentiated and columnar (Figure 2c). The nuclei were in the cell basement, and there was no atypia. There were mucous vacuoles in the cytoplasm. The glands were disorganized, and part of the epithelium formed a papillary structure. The cells were pseudostratified. The nuclei were enlarged, crowded, vacuous, and visible ( Figure 2c). A mitotic figure could be seen.
A pancreatic fistula occurred 1 week after surgery, with about 30 mL of drainage fluid daily. The drainage fluid was turbid with elevated amylase (19,610 U/L). No drainage tube blockage or abdominal pain was observed. The amount of drainage fluid decreased after 3 weeks without treatment. The follow-up showed no abnormality  There were septa and wall nodules, and the enhanced scanning septum and wall nodules were significantly enhanced. The adjacent peritoneum was slightly thickened, and the adjacent pancreas was pressurized and pushed upward, with an unclear boundary with the lesion. (c) Postoperative CT at 3 months after surgery.
by June 2020. A follow-up CT scan revealed no obvious lesion ( Figure 1c).
Ethics approval and patient consent: The study was approved by the Ethics Committee of Shaoxing People's Hospital. Written informed consent has been obtained from the patient in this study.

Discussion
In 2010, the World Health Organization divided MCNs into three subtypes: MCN with low-or moderate-grade atypia, MCN with high-grade dysplasia, and MCN with invasive carcinoma [7]. MCN is a rare occurrence, but with the development of imaging techniques, the incidence of MCN has increased significantly [1,8]. MCN is a cyst-forming tumor produced by columnar epithelial cells, with ovarian stroma and potential malignancy, especially in patients with a long disease course and large tumors [7]. MCN and MCN with invasive carcinoma are difficult to distinguish clinically. The clinicopathological features and imaging findings of pancreatic MCN malignancy have been reported in different studies [2]. Yamao et al. [3] showed that age and tumor size were predictors of the benign/malignant nature of the lesion. They showed that 56 years of age and a tumor size of 51 mm were the thresholds suggesting malignancy, while sex, symptoms, and tumor location were not associated with malignant MCNs.
Most laboratory examinations of patients with MCN are within the normal ranges, but most patients with MCN and invasive carcinoma show CA199 elevation, and the literature suggests that elevation of carcinoma embryonic antigen (CEA) or CA199 indicates an increased possibility of malignancy [9]. Endoscopic ultrasound (EUS) is an ideal diagnostic method for a pancreatic tumor. In addition to obtaining high-resolution images of the lesion, it can also be used for biopsy. When EUS is combined with CEA and CA199 to diagnose cystadenocarcinoma, the sensitivity reaches 94.4% [10,11]. B-mode ultrasound or

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Huge mucinous cystic colon neoplasm with adhesion  2133 CT-guided percutaneous aspiration of vesicle fluid with positive detection of k-ras gene mutation is also suggestive of cystadenocarcinoma [10,12]. B-mode ultrasound examination can accurately locate the tumor, but the disadvantage is that the gastrointestinal tract is prone to gas interference. CT is a commonly used imaging examination method and has important value in the differential diagnosis of pancreatic mucinous cystic tumors. It can detect cystic pancreatic lesions and show the imaging characteristics of the cystic wall and lumen. Visser et al. [13] reported that in all kinds of imaging examinations, the diagnostic accuracy of MRI and CT ranged from 44 to 83%, and the imaging performance of MRI cross-section was roughly the same as that of CT. Another study showed that MRI was superior to CT for the diagnosis of MCN (45 vs 9%) [6]. Yan et al. [14] reported that the thickness of the capsule wall and the presence of solid components could be important differentiating factors between benign and malignant pancreatic MCNs, as supported by the case reported here. The differences in the thickness of the capsule wall, the heterogeneous enhancement of the capsule wall, and the heterogeneous enhancement of the solid component between the benign and the malignant groups were statistically significant.
The preoperative examinations can provide some reference for the preoperative prediction of pancreatic mucous cystadenocarcinoma and pancreatic mucous cystadenoma. Nevertheless, the diagnosis still requires pathological confirmation. Benign and malignant epithelial cells can coexist in MCNs and must be removed. A simple biopsy is unreliable since it can easily miss small malignant foci. Only a careful examination of the specimen can confirm a benign diagnosis; otherwise, there is the possibility of a misdiagnosis of cystadenocarcinoma [15]. In the case reported here, several preoperative aspects (tumor size, tumor index elevation, imaging features, and the intraoperative relationship between the tumor and surrounding tissues) suggested mucinous cystadenocarcinoma, but pathologically, it was confirmed as mucinous cystadenoma with moderate heterocytosis, which is a precancerous lesion.
Since MCN has a malignant tendency and is not sensitive to chemotherapy or radiotherapy, surgery is the preferred treatment [4]. MCN has a good prognosis, and the specific surgical method should be determined according to the tumor location, size, relationship with surrounding tissues, and intraoperative freezing pathology. Most patients with invasive MCN cancer can also be cured by surgery [5].
A literature review was performed in PubMed using the keywords ("mucinous cystic neoplasm") AND (case report) AND (pancreatic) AND (big or huge or large). Only the articles published from 2000 to now were kept. Cases with tumors <10 cm, not MCN, and published in another language than English were excluded. Finally, 15 articles were included [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Table 2 presents the 15 cases. These 15 cases are relatively heterogeneous, and it is difficult to draw a relationship between imaging and malignancy from them. Still, the cases with malignant lesions at final pathological examination usually showed complex cystic masses with intracystic masses, necrosis, and hemorrhage. Still, complex cystic masses were also observed in some benign cases. Of course, considering the size of the lesions, invasive foci might have been missed at microscopic examination.
With the improvements in imaging technologies and the use of screening CT and MRI, the incidence of MCN is expected to increase, and clinicians must be aware of its possibility and management. In addition to the traditional and already known risk factors for MCN (i.e., women in their fifth and sixth decade of life), this case report and literature review suggest that tumor size, elevated tumor markers, tumor texture, and cystic wall at imaging might be indicative of a higher likelihood of malignant MCN. Nevertheless, since the lesion's final benign or malignant nature can only be determined pathologically, the best course of action remains surgery, and the patients should be referred accordingly. A multidisciplinary team discussion (including radiologists, surgeons, pathologists, oncologists, and radiation oncologists) is also probably warranted to explore all treatment options.
In conclusion, age, tumor size, texture, tumor marker elevation, and cystic wall condition are important characteristics of malignant MCN. Nevertheless, it is still very difficult to accurately determine whether the exact nature of MCN is malignant or not before an actual pathological examination of the resected specimen.
Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.