Cancer, Pancreas, Mucinous Cystic

Article Author:
Hani Babiker
Article Editor:
Alejandro Recio-Boiles
Updated:
10/27/2018 12:31:46 PM
PubMed Link:
Cancer, Pancreas, Mucinous Cystic

Introduction

Mucinous cystic pancreatic neoplasms (MCPN) are rare tumors of the pancreas which mostly occur in middle-aged females. The survival rate for this disease is far better than pancreatic ductal adenocarcinomas. The tumors frequently are confused with intraductal papillary mucinous neoplasms (IPMN). According to the World Health Organization (WHO) intraductal papillary mucinous neoplasms differ from mucinous cystic pancreatic neoplasms because ovarian stroma is observed in the latter.

Etiology

The etiology of mucinous cystic pancreatic neoplasms is unclear. Professionals hypothesize that these tumors are related to female hormones due to the preponderance of these tumors in women. This is believed to be the case because ovarian mucinous cystic neoplasms share the same histology and characteristics as mucinous cystic pancreatic neoplasms. These shared characteristics include the mucinous secreting columnar epithelium and the surrounding ovarian stroma that are seen in both ovarian and pancreatic mucinous cystic lesions. Also, the presence of estrogen receptors in mucinous cystic pancreatic neoplasms is another feature alluding to a hormonal cause. Finally, another common feature is the benign nature of the ovarian mucinous cystic tumors, which rarely metastasize to other organs or involve lymph nodes akin to mucinous cystic pancreatic neoplasms. However, due to the rarity of these tumors, other etiologies are unknown. A benign mucinous cystic pancreatic neoplasm can potentially evolve into an aggressive cancer, and hence, surgical resection is recommended in younger patients.

Epidemiology

Few studies have investigated the true prevalence and incidence of mucinous cystic pancreatic neoplasms. Mucinous cystic pancreatic neoplasms mostly affect females, particularly middle-aged women [48 +/- 15 years (84% < 60 y)] as shown in a retrospective study that identified the disease in 95% of women. A recently published study indicated an incidence rate of 2.4% and a prevalence rate of 2.6%, although other retrospective trials reported a prevalence rate as high as 17.5%. Mucinous cystic pancreatic neoplasms are mostly (93%) located in the body or tail of the pancreas. Median size was 5 cm (61% > or = 5 cm). These tumors are identified in 10% to 20% of resected pancreatic tumors. Those tumors are usually benign (72%), borderline (10.5%), in situ carcinoma (5.5%), and invasive carcinoma (12%). Invasive mucinous cystic pancreatic neoplasm usually presents in elderly patients, and the difference in average age between benign and malignant disease of 11 years alludes to the fact that benign lesions can be precancerous. The five-year disease-specific survival for benign and malignant mucinous cystic pancreatic neoplasms is 100% and 57%, respectively. Patients who develop recurrence of their disease have a guarded prognosis.

Pathophysiology

Mucinous cystic pancreatic neoplasms have two distinct histologic components which are the inner epithelial layer composed of tall mucin-secreting cells, and dense cellular ovarian stroma. The latter was described in 1978 by Compagno and Oertel, and the disease was distinguished from other serous cystic tumors and intraductal papillary mucinous neoplasms. Mucinous cystic pancreatic neoplasms are usually benign tumors and rarely metastasize. The high prevalence of these tumors in females indicates hormonal factors as a potential instigator as mentioned above. A study found high expression of estrogen receptors in these tumors (ovarian stroma). Mucinous cystic pancreatic neoplasms with invasive carcinoma typically have malignant neoplastic cells beyond the epithelial lining of the cyst. These tumors are divided into two distinct types which are intracapsular, if neoplastic invasion did not penetrate through the wall of the capsule, and extracapsular if extension through the capsular wall is evident and tumor extends into the surrounding pancreatic or extrapancreatic parenchyma. These cystic lesions, as opposed to intraductal papillary mucinous neoplasms, do not connect with pancreatic ducts, and this is often a distinguishing characteristic. Conversely, most mucinous cystic pancreatic neoplasms lesions are benign and rarely metastasizes to lymph nodes or other organs.  It is believed that benign lesions can transform into malignant mucinous cystic pancreatic neoplasms due to the older age of presentation in patients with invasive cancer. Tumors that are larger than 4 cm and have nodules are most likely malignant. WHO nomenclature use the term mucinous cystic pancreatic neoplasms in conjunction with a histologic grade (low-grade dysplasia, intermediate-grade [moderate] dysplasia, or high-grade dysplasia).

History and Physical

Patients with mucinous cystic pancreatic neoplasms often present with abdominal pain (62.2%), weight loss (11%), abdominal mass (11%), acute pancreatitis (9.6%), fatigue (8.9%), and 16% were asymptomatic. Large mucinous cystic pancreatic neoplasms can compress surrounding organs and structures leading to abdominal pain and a sensation of fullness. Conversely, many patients are asymptomatic, and lesions are found incidentally on imaging. Patients occasionally (16.5%) have elevated levels of CA 19-9 (> 37 U/L). On physical examination, patients can have abdominal tenderness and distention, and occasionally an epigastric mass can be palpated if it is significantly large. These lesions are often located in the body and tail of the pancreas and thus, rarely cause obstructive jaundice. If patients present with a pancreatic head mucinous cystic pancreatic neoplasm, then jaundice may be evident.

Evaluation

Physicians should follow an essential physical examination and laboratory studies, including a complete blood count (CBC), comprehensive metabolic panel (CMP), and a CA 19-9. They should also order a computed tomography (CT) or magnetic resonance (MR) scans. An MRI can be quintessential to assess major vessel involvement and resectability and help distinguish intraductal papillary mucinous neoplasms from mucinous cystic pancreatic neoplasms. Rarely, if a cytology or a biopsy is needed, an endoscopic ultrasound (EUS) with fine needle aspiration (FNA) should be performed.

Treatment / Management

Treatment of mucinous cystic pancreatic neoplasms mainly involves surgical resection. The surgery involves distal pancreatic resection with or without splenectomy. Other surgical procedures include pancreaticoduodenectomy, enucleation, middle pancreatectomy, or total pancreatectomy. In published trials, there is no significant mortality associated with surgery. However, postoperative morbidity can be as high as 49%. It is still recommended practitioners pursue non-operative management for tumors that are smaller than 3 cm and without mural nodules, specifically in elderly patients with co-morbidities. This is because mucinous cystic pancreatic neoplasms that are smaller than 4 cm and with no nodules are usually adenomas or borderline neoplasms. Hence, the patients mentioned above can be followed with serial imaging. Conversely, middle-aged women with a long life expectancy presenting with mucinous cystic pancreatic neoplasms, surgical resection is recommended as many of the benign lesions can progress to invasive carcinoma. Since we still cannot distinguish lesions that progress from those that can remain benign, it is recommended to resect all mucinous cystic pancreatic neoplasms regardless of size in patients who are a fit candidate for surgery. No patient with noninvasive disease had a recurrence after resection. Moreover, since small mucinous cystic pancreatic neoplasms without nodules are most likely benign, lymphadenectomy can be avoided, and parenchyma-sparing surgery such middle-pancreatectomy and enucleation can be performed as these less invasive surgeries decrease the rate of postoperative pancreatic insufficiency and have been proven to be safe and well tolerated. This decreases the development of postoperative pancreatic endocrine and exocrine insufficiency. In lesions that are less than 5 cm, minimally invasive procedures should be considered. In large surgical centers, laparoscopic resection of neoplasms was safe and well tolerated and decreased the length of postoperative hospitalization, surgical wound healing, and led to spleen preservation in distal pancreatectomy surgeries. Considering the rarity of this tumor, the need to distinguish it from intraductal papillary mucinous neoplasm, and the improved outcome in high-volume surgical centers, it is recommended to manage patients with mucinous cystic pancreatic neoplasms in specialized centers. Extrapolating from data in pancreatic adenocarcinoma, after surgical resection of the pathologic assessment shows invasive carcinoma then adjuvant chemotherapy with gemcitabine or gemcitabine in conjunction with capecitabine is recommended.

Pearls and Other Issues

It is imperative to distinguish intraductal papillary mucinous neoplasm from mucinous cystic pancreatic neoplasms. Surgical resection of mucinous cystic pancreatic neoplasms is recommended in fit patients given the potential for malignant transformation.