Primary pancreatic cystic neoplasms revisited. Part I: serous cystic neoplasms

Primary pancreatic cystic neoplasms have been recognized increasingly during the two recent decades and include mainly serous cystic neoplasms, mucinous cystic neoplasms, and intraductal papillary mucinous neoplasms. Serous cystic neoplasms represent about 30% of all cystic neoplasms of the pancreas and are characterized by their microcystic appearance (on imaging, macroscopically, and microscopically) and their benign biologic behavior. Modern diagnostic methodology allows the preoperative diagnosis with an acceptable accuracy. Currently, indications for resection of serous cystic neoplasms of the pancreas include the presence of symptoms, size > 4 cm (because these ‘large’ neoplasms have a more rapid growth rate and probably will soon become symptomatic), and any uncertainty about the diagnosis of a serous versus a mucinous cystic neoplasm. Resection should also be considered for lesions in the body/tail of the pancreas. Conservative treatment is a reasonable option in selected patients (for example in the presence of small, asymptomatic lesions in the pancreatic head, especially in the frail or elderly patient).     

胰腺黏液性囊性肿瘤的诊治进展

胰腺囊性肿瘤是一种比较少见的胰腺肿瘤,主要包括黏液性囊性肿瘤、浆液性囊性肿瘤、导管内乳头状黏液瘤。其中,胰腺黏液性囊性肿瘤是常见的原发性胰腺囊性肿瘤之一,由于它是一种具有潜在恶性的肿瘤,故术前诊断具有重要意义。近年来,随着现代影像技术如 CT、MRI 及 EUS 等的提高和完善,术前胰腺黏液性囊性肿瘤的诊断率比以往已有大大提高,但在治疗方面仍然没有统一的指南或规范。本文着重对胰腺黏液性囊性肿瘤的诊断、治疗进展做一综述。     

Cystic neoplasms of the pancreas; what a clinician should know

Primary cystic neoplasms of the pancreas (serous cystic neoplasms, mucinous serous neoplasms, and intraductal papillary mucinous neoplasms) are lesions of emerging importance. With the wide availability of modern imaging methods, these neoplasms are being recognized with increasing frequency. Due to the improvement of these sophisticated imaging techniques, it is often possible to differentiate preoperatively these primary pancreatic cystic neoplasms not only from other cystic pancreatic disorders (such as pancreatic pseudocysts) but also from one another. This differentiation is very important for the clinician, since these neoplasms have radically different biologic behavior. Serous cystic neoplasms are uniformly benign and usually do not mandate resection unless the lesion is symptomatic. In contrast, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms have a premalignant or overtly malignant tendency, and therefore should be managed aggressively by pancreatic resection. In these mucinous cystic neoplasms, recognition of an underlying malignancy is often not possible without a detailed histopathologic examination of the entire resected specimen. In the absence of invasive disease, prognosis is excellent after appropriate surgery. The presence of invasive malignancy signifies a poor prognosis.     

Cystic pancreatic neoplasms: 12-year surgical experience

Cystic pancreatic neoplasms have been increasingly diagnosed in the last years. Resection is recommended in most cases, but their management has not been standardized since an accurate nonoperative differentiation is often difficult. A retrospective review of 30 patients undergoing surgical resection for cystic pancreatic neoplasms between 1993 and 2005 was performed. Median age of the patients was 63 years and 63.5% were female. Twelve patients (40%) were asymptomatic. Twenty-nine had curative resections. Pathologic analysis revealed 13 serous cystadenomas, 9 mucinous cystadenomas, 3 mucinous cystadenocarcinomas, 4 intraductal papillary mucinous neoplasms and 1 solid pseudopapillary neoplasm. Overall mortality was 6.5% (2 patients). Postoperative complications occurred in 12 patients (41%). Pancreatic fistula occurred in 7 cases (24%). Reoperation was required in 2 patients (6.5%). Two patients operated for mucinous cystadenocarcinoma and invasive intraductal papillary mucinous neoplasms died of recurrence at 24 and 7 months postoperatively. Excluding another patient died from other cause, all others are currently alive with no evidence of disease. Diagnostic accuracy for cystic pancreatic neoplasms is still limited. Considering the good prognosis and acceptable morbidity and minimal mortality after surgical treatment in specialized centers, resection seems still justified in most cases.     

Management of Mucin‐Producing Cystic Neoplasms of the Pancreas

During the last decade small lesions of the pancreas have been increasingly recognized in clinical practice. Among these lesions, mucin‐producing cystic neoplasms represent a recently described and unique entity among pancreatic tumors. In 1996, the World Health Organization distinguished two different types of mucinous cystic tumors: intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, which are characterized by mucin production, cystic dilation of the pancreatic ducts, and intrapapillary growth, and mucinous cystic neoplasms (MCNs), which are defined by ovarian‐like stroma and in most cases do not communicate with pancreatic ducts. Further, IPMNs can be subdivided into main‐duct type, mixed‐type, and branch‐duct type tumors. Older data did not distinguish among different subsets of cystic neoplasms of the pancreas, and consequently many databases were inconsistent. Histopathologically, both IPMNs and MCNs demonstrate a wide spectrum of cellular atypia ranging from mild mucinous hyperplasia to invasive adenocarcinoma. Because mucinous cystic neoplasms of the pancreas show significant differences in clinical behavior from patient to patient, knowledge of the clinicopathologic characteristics and natural history of specific subtypes of IPMNs and MCNs has become crucial for physicians working in the field of gastroenterology. The present work offers an overview of current and generally accepted clinical guidelines for the diagnosis and treatment of IPMNs and MCNs.     

Primary pancreatic cystic neoplasms revisited: part II. Mucinous cystic neoplasms

Mucinous cystic neoplasms (MCNs) of the pancreas represent one of the most common primary pancreatic cystic neoplasms, accounting for approximately half of these cases. MCNs are observed almost exclusively in women, and most commonly are located in the body/tail of the pancreas. In contrast to SCNs, MCNs have malignant potential. Proliferative changes (hyperplasia with or without atypia, borderline changes, non-invasive or carcinomas in-situ, and invasive carcinomas) can often be observed within the same neoplasm. Several risk factors for the presence of underlying malignancy within an MCN have recently been recognized. Cross-sectional imaging is of key importance for the diagnostic evaluation of patients with a cystic pancreatic lesion. Cyst fluid examination (cytology, biochemical/genetic analysis) is possible by using fine needle aspiration of the MCN, usually under endoscopic guidance, and may provide useful information for the differential diagnosis. Since MCNs have malignant potential, surgical resection is the treatment of choice.     

Giant mucinous cystic neoplasms of pancreas and liver with unusual adipose tissue component: a case report

Simultaneous occurrence of pancreatic and hepatic mucinous cystic neoplasms is very rarely reported in the literature. We present a case with extensive fatty component of the pancreatic tumour arising from the head of the pancreas and attaining a huge size before being treated by Whipple’s pancreatoduodenectomy and subsequently by a right hepatectomy for the hepatic tumour.Key Words: Pancreas, mucinous cystic neoplasm, giant, cystadenoma, whipple’s pancreatoduodenectomy, liver, hepatectomy, adipose     

Primary pancreatic cystic neoplasms revisited. Part III. Intraductal papillary mucinous neoplasms

Intraductal papillary mucinous neoplasms (IPMNs) represent about 25% of all primary pancreatic cystic neoplasms and are increasingly recognized during the last two decades. They are characterized by intraductal proliferation of neoplastic mucinous cells forming papillary projections into the pancreatic ductal system, which is typically dilated and contains globules of mucus. IPMNs may be multifocal and have malignant potential. Modern imaging is essential in establishing preoperative diagnosis and in differentiating different subtypes of IPMNs (i.e., main-duct vs. branch-type disease). Endoscopic retrograde or magnetic resonance cholangiopancreatography accurately delineate the morphologic changes of the pancreatic ductal system. Endoscopic ultrasonography (usually used in conjunction with image-guided FNA and analysis of the aspirated material) is commonly used for differential diagnosis of IPMNs from other pancreatic cystic lesions. Surgical resection (usually anatomic pancreatectomy, depending on the location of the disease) is the treatment of choice. Total pancreatectomy may occasionally be required in selected patients, but is associated with formidable long-term morbidity. A conservative approach has recently been proposed for carefully selected patients with branch-duct IPMNs. Recurrences following surgical resection can be observed, especially in patients with multifocal disease or in the presence of underlying malignancy.     

Cystic neoplasms of the pancreas: a heterogeneous disorder.

Cystic neoplasms of the pancreas are rare tumors with a relatively better prognosis as compared to other pancreatic cancers. They may be mistaken for pseudocysts. Seventeen patients who underwent surgical resection were analyzed. Seventy percent of the patients were females and 76.7% of the tumors were located in the tail of the pancreas. Preoperative diagnosis was made on the basis of ultrasonography and/or computed tomography findings in 60% of patients. Retrospective review of the imaging modalities revealed one or more findings suggestive of cystic neoplasms in 90% of the patients. These included multiloculated cysts, thickened cyst wall, intracystic mass or calcifications, and presence of liver metastasis. All the tumors were completely or partly excised. The final histopathological diagnosis was microcystic adenoma in 2, mucinous cyst adenoma in 1, papillary cystic neoplasm in 3, cystic neuroendocrine tumor in 5, and cystadenocarcinoma in 6. Of the 17 patients, 10 had malignant tumors. Seven patients with benign tumors and 3 patients with malignant tumors are disease free 12-30 months after resection. Cystic neoplasm must always be considered as a possibility when dealing with cystic lesions of the pancreas and a careful evaluation of ultrasonography and computed tomographic scan may give a clue to the diagnosis.     

c-Ki-ras point mutations in ductectatic-type mucinous cystic neoplasms of the pancreas

Ductectatic-type mucinous cystic neoplasms of the pancreas constitute a recently recognized new human pancreatic tumor entity. Examination for the presence of point mutations at codon 12 of K-ras by oligonucleotide hybridization in 5 adenomas and 3 carcinomas revealed alteration in 3 and 2, respectively. In 4 of these positive cases, the transition was GGT----GAT (Gly----Asp) with the remaining one, found in a cancer, being GGT----GTT (Gly----Val). In two carcinoma cases, the same point mutation was detected both in the carcinoma area and in a coexisting adenoma component. Thus K-ras point mutation appears to be associated with this particular type of neoplasm in the same manner as observed for typical exocrine pancreas carcinomas. Our study also indicates the possible existence of an adenoma-carcinoma sequence in the evolution of this type of neoplasm and we suggest that K-ras activation may be an important event in the phase of adenoma development.     

Detection of gastric mucins (M1 antigens) in cyst fluid for the diagnosis of cystic lesions of the pancreas

Mucinous cystic tumors of the pancreas must be distinguished from other cystic lesions because of their potential malignancy. Our purpose was to assess the reliability of gastric M1 mucin analysis in the fluid of cystic lesions of the pancreas in comparison or association with carcinoembryonic antigen. M1 mucin and carcinoembryonic antigen were measured in cyst fluid obtained preoperatively by fine-needle aspiration. The lesions consisted of 12 serous cystadenomas, 9 mucinous cystadenomas, 8 cystadenocarcinomas and 6 intraductal mucinous hypersecreting neoplasms. Thirty pancreatic pseudocysts complicating well-documented chronic pancreatitis were also examined. In addition, M1 mucins were localized by immunoperoxidase staining in fetal and normal adult pancreas and in mucinous and serous tumors. Carcinoembryonic values of >20 ng/ml and M1 mucin values of >50 U M1/ml represented 82 and 78% sensitivity, respectively, as well as 100% specificity for distinguishing mucinous lesions from serous cystadenomas; the sensitivity for this purpose was 100% using these criteria in combination. Carcinoembryonic antigen values of >300 ng/ml and M1 mucin values of >1,200 U M1/ml represented 56 and 30% sensitivity, respectively, as well as 100% specificity for distinguishing mucinous lesions from pseudocysts; the sensitivity for this purpose was 60% using these criteria in combination. By immunohistology, M1 mucins were detected in the wall of mucinous lesions but not in fetal and normal adult pancreas and in serous cystadenomas. Measurement of M1 mucin antigen in cyst fluid could thus improve the diagnosis of mucinous cystic lesions of the pancreas. Int. J. Cancer 74:286-290, 1997. © 1997 Wiley-Liss, Inc.     

胰腺囊性肿瘤222例临床诊治分析

目的 总结本中心收治的胰腺囊性肿瘤（PCN）的诊治情况及预后,为PCN的临床处理提供一定依据。方法 回顾性分析2005年1月至2016年10月南京鼓楼医院收治的PCN病例,分析各类PCN的临床特征、超声内镜下表现、治疗方式及预后情况。结果 本研究共纳入222例PCN病例,包括94例导管内乳头状黏液瘤（IPMN）,58例黏液性囊性肿瘤（MCN）,43例浆液性囊性肿瘤（SCN）及27例实性假乳头状肿瘤（SPN）。各型PCN患者的男女比例1∶1.55,平均年龄为（56.0±15.7）岁,大部分PCN患者（64.0％,142／222）在就诊时有临床表现,其中以腹痛最常见（47.3％,105／222）。各型PCN术后病理提示分别有7例IPMN（16.3％,7／43）和5例MCN（9.1％,5／55）为恶性（伴浸润性癌或重度异型增生）,而SCN和SPN术后病理均为良性（P=0.027）。未手术的PCN患者中,分别有4例IPMN（8.3％,4／48）和2例SPN（66.7％,2／3）在随访过程中发生癌变。获随访的188例PCN患者的5年生存率为86.0％。124例PCN患者术后的5年生存率为90.0%,SCN、MCN和SPN的术后5年生存率分别为100.0％、92.1％和938％,而IPMN仅为74.0％,差异有统计学意义（P=0.003）。结论 PCN好发于中年女性,大部分患者就诊时有临床症状,最常表现为腹痛。MCN、IPMN和SPN具有恶变倾向,应在符合手术条件的情况下行手术切除;而SCN则可采取保守治疗。各类PCN预后差异显著,IPMN预后最差,MCN、SCN及SPN术后预后均较好。     

Histo-molecular oncogenesis of pancreatic cancer: From precancerous lesions to invasive ductal adenocarcinoma

Pancreatic cancer is a lethal malignancy, whose precursor lesions are pancreatic intraepithelial neoplasm, intraductal papillary mucinous neoplasm, intraductal tubulopapillary neoplasm, and mucinous cystic neoplasm. To better understand the biology of pancreatic cancer, it is fundamental to know its precursors and to study the mechanisms of carcinogenesis. Each of these precursors displays peculiar histological features, as well as specific molecular alterations. Starting from such pre-invasive lesions, this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer, with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.     

Ductectatic-type Mucinous Cystadenoma and Cystadenocarcinoma of the Human Pancreas: A Novel Clinicopathological Entity

A new type of mucinous cystic pancreatic neoplasm is described. The lesions, which have been recognized only recently with the progress of diagnostic techniques and have not previously been described in the literature, are characterized by multilocular cysts with papillary proliferation of the lining epithelium. They occur exclusively in the head and body, predominantly in males, and coexistence of well-differentiated adenocarcinoma as well as adenoma components is frequently encountered. These lesions are quite different from hitherto described mucinous cystic neoplasms of pancreas, not only in terms of gross features but also with regard to intrapancreatic location, and sex and age distributions. We propose to classify these lesions as a new pancreatic tumor entity: the ductectatic-type mucinous cystadenoma/cystadenocarcinoma.     

Solid, infiltrating variety of papillary cystic neoplasm of the pancreas

Four tumors with histologic, histochemical, and ultrastructural characteristics of papillary cystic neoplasm of the pancreas but lacking the capsule commonly observed in papillary cystic neoplasm and infiltrating interiorly into the pancreatic parenchyma were seen in two men and two women who were 39 to 51 years old. These tumors contrasted with typical encapsulated papillary cystic neoplasms that show extrapancreatic growth and that are detected as a palpable abdominal mass in young women. These four tumors, although unpalpable, were all detected by nodular images of calcification in abdominal plain radiography. The tumors had a mean diameter of 3.1 cm (range, 1.7 to 4.5 cm), were confined within the pancreatic parenchyma, and showed central fibrosis accompanied by dystrophic changes such as calcification and ossification. A small necrotic cyst contiguous to the fibrous focus also was observed in the tumor in three patients. Tumor cells similar to those of a papillary cystic neoplasm had infiltrated among the pancreatic parenchyma in solid and pseudopapillary patterns, and pleomorphic atypism was observed in some parts of the tumor in three patients. These tumors were tentatively designated solid, infiltrating variety of papillary cystic neoplasms to differentiate them from ordinary encapsulated papillary cystic neoplasms. Although no signs of recurrence have been noticed after surgical treatment in these patients, the infiltrating growth pattern and the presence of pleomorphic atypism suggest higher malignancy than the ordinary papillary cystic neoplasm. The contrasting growth pattern and possible malignancy may warrant establishment of these tumors as a papillary cystic neoplasm subclass.     

恶性与交界性胰腺囊性疾病的临床因素分析

目的探讨良恶性胰腺囊性疾病（cystic lesions of the pancreas,CLP）的临床因素。方法回顾性分析手术后经病理证实的49例CLP的临床特征。结果胰腺管状腺癌囊性变5例;肉瘤样癌囊性变1例;黏液性囊性肿瘤8例（恶性2例,交界性5例,良性1例）;胰腺实性假乳头状肿瘤14例（恶性1例,交界性13例）;囊性胰腺内分泌肿瘤2例（良恶性各1例）;浆液性囊腺瘤10例（均为良性）;无恶性潜能的CLP9例（海绵状血管瘤2例,慢性胰腺炎伴潴留性囊肿3例,胰腺黏液性非肿瘤性囊肿1例,胰腺假性囊肿1例,潴留性囊肿1例,良性上皮性囊肿1例）。恶性肿瘤组患者的年龄为（64．70±11．23）岁,明显高于交界性肿瘤组[（34．33±15．83）岁]和良性病变组[（47．29±14．068）岁]。恶性肿瘤组肿瘤最大直径（8．09±3．98）cm,明显大于良性病变组[（5．25±3．22）cm]。恶性肿瘤组CA19-9的阳性率为60．0％,明显高于交界性肿瘤组（0）和良性病变组（11.8％）。恶性肿瘤组CEA的阳性率为40．O％,其余两组均正常。CT诊断CLP的符合率为87．9％,肿瘤的边界是否清楚、有无实性成分有助于区别良恶性。结论对于男性、年龄大,血清肿瘤学标志物升高明显、影像学表现为边界不清或有实性成分的CLP患者应采取积极治疗。     

Main-duct intraductal papillary mucinous adenoma of the pancreas with a large mural nodule

Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized entity representing a spectrum of benign and malignant neoplasms of the pancreas. Preoperative distinction between benign and malignant IPMNs remains difficult. Reported predictive factors for malignancy are size of the main pancreatic duct, cystic neoplasm, and mural nodule. We report herein the case of a 50-year-old woman in whom a large mural nodule (30 mm) in the dilated main pancreatic duct (16 mm in diameter) was detected by ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography. Because the large mural nodule and dilatation of the main pancreatic duct were also detected by endoscopic ultrasonography (EUS) and intraductal ultrasonography (IDUS), the main-duct IPMN was considered to have malignant potential. Thus, pylorus-preserving pancreaticoduodenectomy with lymph node dissection was performed. The resected intraductal tumor appeared polypoid with a broad stalk and comprised a proliferation of mucin-containing columnar epithelial cells with papillary structures without malignant features. The final diagnosis was intraductal papillary mucinous adenoma of the pancreas. The size of the mural nodule and the final diagnosis in this case suggest that the introduction of a novel molecular-biological approach might be necessary for the precise preoperative diagnosis of main-duct IPMN and adequate surgical treatment.     

Simultaneous intraductal papillary neoplasms of the bile duct and pancreas treated with chemoradiotherapy

Some authors have suggested that intraductal papillary mucinous neoplasms of the bile duct(IPMN-B) could be the the biliary counterpart of IPMN of the pancreas(IPMN-P) since they share several clinical-pathological features.These include prominent intraductal papil-lary proliferation pattern,a gastrointestinal phenotype,frequent mucin hyper-secretion and progression to mu-cinous carcinoma.To date there are just four reported cases of patients with synchronous IPMN-B and IPMN-P all of which were treated surgically.We hereby report the case of a 76-year-old woman who was incidentally diagnosed with both an asymptomatic 3 cm bulky uid lesion obstructing the bile duct lumen,diagnosed as a malignant IPMN-B,and synchronous multiple pancreatic cystic lesions(10-13 mm) communicating with an irreg-ular Wirsung,diagnosed as branch duct IPMN-P.Since surgery was ruled-out because of the patient’s age and preferences,she underwent a conservative manage-ment regimen comprising both chemotherapy and radio-therapy.This was effective in decreasing the mass size and in resolving subsequent jaundice.This is also the f irst reported case of IPMN-B successfully treated with chemoradiotherapy.Clinicians should consider medical treatment as an option in this clinical scenario,in pa-tients who may be unf it for surgery.     

胰腺导管内乳头状黏液肿瘤的CT诊断

目的 探讨胰腺导管内乳头状黏液肿瘤的CT和MRI表现,分析其诊断要点。方法 回顾性分析12例经手术切除和病理学证实的胰腺导管内乳头状黏液肿瘤的临床、CT和MRI资料。结果 （1）分支胰管型7例,均位于胰头和钩突,CT和MRI主要表现为分叶状或葡萄串样囊性病变,其间可见分隔,增强后囊性区域无强化,囊壁和分隔可强化。（2）混合型5例,4例为胰头或钩突分支胰管扩张合并主胰管扩张;1例同时伴有胰体分支胰管扩张,扩张的主胰管直径为4～7mm。（3）该病多发于老年人,临床主要表现为腹痛和胰腺炎。结论 胰腺导管内乳头状黏液肿瘤有相对特征性的影像学表现,CT和MRI对其诊断有重要价值。     

Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN

Growth factors have been implicated in pancreatic carcinogenesis. In this study we analyzed the effect of Tgfa overexpression in addition to mutant Kras(G12D) by crossing Elastase-Tgfa mice with p48(+/Cre);Kras(+/LSL-G12D) mice. We show that concomitant expression of TGFalpha and Kras(G12D) accelerates the progression of mPanIN lesions to metastatic pancreatic cancer and leads to the development of cystic papillary lesions resembling human intraductal papillary mucinous neoplasms (IPMN). Microarray data in mice revealed an IPMN signature and IPMNs expressed MUC1 and MUC5AC but not MUC2, similar to human pancreatobiliary IPMNs. Invasive ductal adenocarcinoma developed from PanINs and IPMNs, suggesting precursor lines for both lesion types in this model. In conclusion, Egfr signaling in synergy with oncogenic Kras may be a prerequisite for IPMN development and progression to pancreatic cancer.