Pancreatic incidentalomas: Investigation and management

The incidence of pancreatic incidentalomas (PIs) detected in otherwise asymptomatic patients is growing with the increasing quality and use of advanced imaging techniques. PI can present as isolated main pancreatic duct dilation or as a solid or cystic lesion. Although historically thought to be relatively rare, PIs are rather common, particularly cystic lesions of the pancreas, which can be detected in up to 49% of the general population. With the poor prognosis of pancreatic cancer, PIs are an opportunity for prevention and early diagnosis, but when managed poorly, they can also lead to overtreatment and unnecessary morbidity. The management of PI should begin with a dedicated pancreas protocol computed tomography (CT) scan or magnetic resonance imaging (MRI) to accurately characterize duct size, lesion characteristics and establish an accurate baseline for subsequent follow up. Diagnosis and subsequent management depends on the extent of main duct dilation and solid versus cystic appearance. Solid lesions are highly concerning for malignancy. Cystic lesions can be further categorized as intraductal papillary mucinous neoplasms of the pancreas (IPMNs) or mucinous cystic neoplasms (MCNs), both of which harbour malignant potential, or as serous cystic neoplasms (SCNs) that are benign. In this paper, we summarize the major challenges related to PI and present pragmatic suggestions for management.     

Risk of malignancy in serous cystic neoplasms of the pancreas

BACKGROUND: In contrast to mucinous cystic neoplasms of the pancreas, which are known to have considerable malignant potential, the serous variant is generally thought to be benign. There are, however, several reports of malignancy in serous cystic neoplasms of the pancreas. AIMS: To assess the risk of malignancy of serous cystic tumors of the pancreas and to investigate specific clinical and histological features. METHODS: Clinical and pathological characteristics of benign and malignant serous cystic neoplasms of the pancreas were investigated by a review of the literature and documented by a case of a serous cystadenocarcinoma and immunohistochemical analysis of a series of serous cystadenomas. Reviewing the literature prevalence, age and sex distribution of serous cystic neoplasms were analyzed. RESULTS: The prevalence of cancer among serous cystic neoplasms reported since 1989 was 3%. Serous cystadenoma of the pancreas present at an earlier age (61 years) than serous cystadenocarcinoma (66 years; p = 0.056) and are symptomatic in the majority of patients.Pathological examination of the primary tumor was not able to distinguish cystadenoma from cystadenocarcinoma in 38% of cases. In 25% the diagnosis of cancer was established only after growth of metachronous metastases. In the present case, nuclear atypia, papillary structures, proliferation marker Ki-67 and p53 protein were increased in the primary tumor and/or metachronous metastasis. CONCLUSION: Serous cystic neoplasms of the pancreas do have malignant potential with a risk of malignancy of 3% and should be surgically treated if the operative risk is acceptable. Routine analysis of genetic and proliferation markers may improve diagnosis of malignancy in these tumors.     

Resektion zystischer Pankreastumoren

Cystic tumors of the pancreas are diagnosed increasingly more due to increasing life expectancy and the moderate use of modern radiological diagnostics. Intraductal papillary mucinous neoplasms of the pancreas (IPMN), mucinous cystic neoplasms (MCN), solid pseudopapillary neoplasms (SPN) and serous cystic neoplasms (SCN) represent over 90?% of all cystic neoplasms of the pancreas. Although serous cystic lesions have a low or even no potential for malignant transformation, they are mostly resected when symptomatic. In contrast, mucinous lesions have an increased malignant potential and should therefore be resected in almost all cases. While this is true for all cases of MCNs and SPNs this is controversial for all IPMNs as they show a wide spectrum of morphological variants. The IPMNs may arise in the main pancreatic duct, major side branches or in both (mixed type). Although all IPMNs are considered to be precursor lesions to pancreatic adenocarcinomas it is not clear what the time course of such potential neoplastic transformation might be and whether all lesions progress to malignant tumors. As no currently used diagnostic test can reliably differentiate between benign and malignant tumors, the majority of newly diagnosed IPMNs should undergo surgical resection. According to current treatment guidelines (Sendai criteria), asymptomatic side branch IPMNs of less than 3 cm in diameter without suspicious radiological features, such as nodules, thickness of the cystic wall or size progression can be treated conservatively without the need for surgical resection. Recently, this approach has become controversial due to a relevant number of IPMNs reported as Sendai negative that showed malignant transformation on final histological examination.     

Serous cystic neoplasm of the pancreas-indications for surgery

BACKGROUND/AIMS: Serous cystic neoplasm is a rare pancreatic tumor. Almost all of these tumors are benign and only 9 cases of serous cystadenocarcinoma have been reported. Although serous cystic neoplasm is typically a microcystic lesion, there is a wide range of cyst sizes from micro to macro and even unilocular cysts have been reported. Thus, the diagnosis is difficult and indications for surgery are controversial. We aimed to elucidate the clinicopathological and imaging features of serous cystic neoplasm of the pancreas. METHODOLOGY: We investigated 15 cases of resected and 6 cases of nonresected cases of serous cystic neoplasm, evaluating the symptoms, imaging findings, preoperative diagnosis, macroscopic morphology, microscopic findings, and results of follow-up. RESULTS: Imaging diagnosis of serous cystic neoplasm was not easy, because not so many tumors had the typical microcystic pattern. Most of the resected serous cystic neoplasms were non-microcystic or were small tumors, which could not be precisely evaluated. CONCLUSIONS: Small serous cystic neoplasms, which can be diagnosed by imaging, do not need to be resected because serous cystadenocarcinoma is rare. Tumors of the pancreas that cannot be confirmed to be serous cystic neoplasm should be resected because of the possibility of pancreatic cancer, mucinous cystadenocarcinoma, or mucinous cystadenoma with malignant potential.     

Evaluation and management of cystic pancreatic tumors: emphasis on the role of EUS FNA.

Cystic lesions of the pancreas are increasingly recognized and usually represent pseudocysts or cystic pancreatic tumors (CPTs), but also include congenital cysts, acquired cysts, extrapancreatic cysts, or cystic degeneration of solid tumors. It is important to distinguish CPT lesions given their varied prognosis and therapy. Mucinous varieties of CPTs (mucinous cystic neoplasms and intraductal papillary mucinous tumors) are premalignant or malignant, and surgical resection is generally recommended in good operative candidates. In contrast, nonmucinous CPTs include serous cystadenomas with a very low malignant potential, or pseudocysts, which are always benign. As a result, nonmucinous CPTs are generally resected only when inducing symptoms or complications. Review of the clinical, imaging, laboratory, and pathology information may clarify the specific tumor type. The relatively limited accuracy of any one modality requires that we consider the combined results when making management decisions.     

Molecular biomarkers have the potential to improve the diagnostic work-up of pancreatic cystic lesions

Pancreatic cysts are increasingly diagnosed due to the widespread use of cross-sectional imaging, and some of these lesions harbor malignant potential. Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are the major premalignant cystic neoplasms of the pancreas. A variety of diagnostic tools are used to predict the malignant potential of these cysts, but specificity and sensitivity are limited. Thus, many patients undergo unnecessary operations for benign cysts. Balancing the risks of watchful waiting with those of operative management is key in managing these lesions. During the last decade, genetic changes of pancreatic cysts have been examined extensively to estimate their malignant potential. In this review, we provide an overview of the latest molecular and genetic aspects of pancreatic cysts and how they may contribute to the differential diagnosis in patients with pancreatic cystic neoplasms.     

Malignant serous cystic neoplasm of the pancreas: report of a case and review of the literature

BACKGROUND: In general, serous cystic neoplasms of the pancreas are thought to be benign. Malignant serous cystic neoplasm of the pancreas is a rare clinical entity. CASE REPORT: We report the case of an 87-year-old woman with a serous microcystic neoplasm in the tail of the pancreas that behaved in a malignant fashion. The neoplasm had also invaded the colonic mesentery and splenic hilum. The pancreatic lesion was diagnosed as a large malignant serous cystic neoplasm, and the patient underwent distal pancreatectomy with splenectomy and segmental colectomy. The resected specimen contained a large tumor, 12 x 9 x 8 cm, which occupied the body and tail of the pancreas. Histologically, the tumor was indistinguishable from serous cystadenoma. However, the tumor had invaded surrounding tissues including the splenic vein, and there were splenic invasion and a regional lymph node metastasis. The postoperative course was uneventful. DISCUSSION: There are few reported cases of malignant serous cystic neoplasm, in which malignancy was histologically confirmed in the resected specimen. There are no reports of a negative outcome with complete resection of the tumor. Surgical treatment should be considered for serous cystic neoplasms, especially large ones, because of the malignant potential.     

Cystic lesions in the pancreas: When to watch, when to resect

The diagnosis of cystic lesions in the pancreas is becoming more common, largely due to the increases in diagnostic imaging done for other reasons. This review considers pseudocysts, mucinous cystic neoplasms, intraductal papillary mucinous tumors, and serous cystadenomas in some detail. The emphasis is on the fact that, through a careful history, physical examination, radiologic studies, and, often, cyst fluid analysis, a diagnosis can be reached expeditiously. This pursuit is important because two thirds of pancreatic cystic neoplasms are malignant or premalignant and should be resected, whereas pseudocysts and serous cystadenomas are benign, and, depending on the case, may be treated through observation, resection, or, for pseudocysts, by internal drainage.     

Cystic neoplasms of the pancreas

Cystic neoplasms of the pancreas, including 4 patients with serous cystadenoma and 11 with mucinous cystic neoplasm, were studied. Serous cystadenomas composed of epithelial cells with glycogen in the cytoplasm were benign in all, whereas mucinous cystic neoplasms consisted of four benign, two borderline, and five malignant lesions. The average size was 1.8 cm in the greatest diameter in benign mucinous cystadenomas, about 5 cm in borderline tumors, and more than 8 cm in mucinous cystadenocarcinomas. Histologically, in all borderline and malignant lesions, the cysts contained areas lined with epithelium and had a benign appearance, comparable with that of mucinous cystadenoma. These observations suggest a borderline or malignant disease in the case of a benign mucinous cystadenoma. An immunohistochemical study for carcinoembryonic antigen and carbohydrate antigen 19-9 showed denser and diffuse localizations of such materials in the cytoplasm and the stroma in the case of malignant lesions, as compared to findings in borderline and benign cases.     

Endoscopic ultrasound in the diagnosis of pancreatic intraductal papillary mucinous neoplasms

Pancreatic cystic lesions are increasingly recognised due to the widespread use of different imaging modalities.Intraductal papillary mucinous neoplasms(IPMNs)of the pancreas represent a common,but also heterogeneous group of cystic tumors with a significant malignant potential.These neoplasms must be differentiated from other cystic tumors and properly classified into their different types,main-duct IPMNs vs branchduct IPMNs.These types have a different malignant potential and therefore,different treatment strategies need to be implemented.Endoscopic ultrasound(EUS)offers the highest resolution of the pancreas and can aid in the differential diagnosis,classification and differentiation between benign and malignant tumors.The addition of EUS fine-needle aspiration can supply further information by obtaining fluid for cytology,measurement of tumor markers and perhaps DNA analysis.Novel techniques,such as the use of contrast and sophisticated equipment,like intraductal probes can provide information regarding malignant features and extent of these neoplasms.Thus,EUS is a valuable tool in the diagnosis and appropriate management of these tumors.     

Cystic and solid lesions of the pancreas

More than 95% of malignant tumours of the pancreas are exocrine carcinomas. The exocrine carcinomas have to be distinguished from benign serous cystadenomas and tumours, the latter including mucinous cystic neoplasms, serous cysts, and solid pseudopapillary neoplasms. Cystic lesions have to be separated from pseudocysts, which are the most common cysts. Pseudocysts are due to extensive confluent autodigestive tissue necrosis caused by alcoholic, biliary, or traumatic acute pancreatitis. This review focuses on the classification of the different types of solid and cystic lesions based on histological criteria. The various imaging procedures are also discussed, along with their strengths and limitations.     

Cystic ductal adenocarcinoma of pancreas: an unusual variant.

Cystic lesions of the pancreas are usually pseudocysts (90%); only 10% of them are cystic tumors. These cystic tumors constitute less than 10% of all pancreatic neoplasms, making them an extremely uncommon type of pancreatic malignancy. What is more important is that these tumors are very easily misdiagnosed as pseudocysts because their characteristics are very similar to those of the benign pseudocysts. This gains importance as the cystic tumors have a high cure rate and good prognosis if diagnosed and treated on time. Of all the cystic tumors, the most common are the benign serous cystadenomas, mucinous cystic tumors, intraductal papillary mucinous neoplasms etc. Ductal adenocarcinoma of pancreas presenting in cystic form is an uncommon type of cystic tumor, making it extremely rare among all pancreatic malignancies (solid or cystic). We present the following case report. The review of literature concerning the diagnosis and management has also been discussed.     

MRI对胰腺囊性肿瘤的诊断价值

目的探讨MRI对胰腺囊性肿瘤的诊断价值。方法回顾分析23例经手术病理证实的胰腺囊性肿瘤资料,总结其影像表现。结果黏液性囊性肿瘤10例,囊性肿块较大,肿块平均直径超过10 cm,由较厚的纤维壁分隔成多房囊肿,外壁光滑,边界清楚。浆液性囊腺瘤6例,病灶较小,囊内有分隔而呈放射状排列,中心瘢痕为其特征性表现。胰腺囊性转移瘤3例,均有肿瘤病史,表现不典型,需结合肿瘤病史定性。胰胚细胞瘤2例,幼儿发病,肿块巨大,肿瘤坏死囊变,形成假-假性囊肿。胰腺乳头状囊实性肿瘤1例,表现为边界清楚的囊实性肿块,囊壁上有壁结节。胰腺毛细血管瘤1例,表现与浆液性囊腺瘤相似,难以术前诊断。结论MRI对胰腺囊性肿瘤具有高度敏感性,不同病变有一定的特征性表现, 对术前定性极有价值。     

Pancreatic Cysts and Guidelines

Pancreatic cysts, especially incidental asymptomatic ones seen on noninvasive imaging such as CT or MR imaging, remain a clinical challenge. The etiology of such cysts may range from benign cysts without any malignant potential such as pancreatic pseudocysts and serous cystadenomas to premalignant or frankly malignant cysts such as mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, cystic degeneration associated with solid tumors such as pancreatic ductal adenocarcinoma or pancreatic endocrine neoplasms, and solid pseudopapillary neoplasms. The clinical challenge in 2017 is to accurately preoperatively diagnose them and their malignant potential before deciding about surgery, surveillance or doing nothing. This review will focus on the currently available clinical guidelines for doing so.     

Accuracy of CT in predicting malignant potential of cystic pancreatic neoplasms

Background. Cystic lesions of the pancreas are being identified more frequently. Deciding which asymptomatic lesions can be safely followed with serial imaging and which require resection due to malignant potential is an increasingly common question. Current clinical practice is to rely on characteristics of the lesions on CT scan, and additional information from endoscopic ultrasound with fine-needle aspiration (EUS-FNA) and cyst fluid analysis or endoscopic retrograde pancreatography (ERCP) to assess malignant potential. Hypothesis. The malignant potential of pancreatic cystic lesions cannot be accurately predicted by CT scan. Methods. CT scans from 48 patients with cystic lesions of the pancreas were stripped of patient identifiers and retrospectively presented to two expert radiologists. The radiologists recorded specific characteristics of the lesions thought to be important in the differential diagnosis and their opinion of the likely diagnosis. Diagnostic accuracy was assessed by comparing the radiologists’ diagnoses to the final pathologic diagnosis after resection. To determine if clinical history, EUS-FNA or ERCP findings improved diagnostic accuracy, medical records were retrospectively reviewed and scored as either supporting or not supporting malignant potential of the lesion. Results. Specific diagnoses based on CT findings alone were correct in an average of 39% of the cases. Even when diagnoses were dichotomized as benign (43%) or potentially malignant (57%, papillary mucinous neoplasms, mucinous cystic neoplasms, cancer), determinations based on CT alone were accurate in an average of 61% of cases. Accuracy rates were 60.4 and 62.5% for the two radiologists, although there was only fair agreement between them (Kappa=0.28, 95% CI=(0.01–0.55), p=0.05). When all clinical information available was considered together as a single dichotomous indicator of malignant potential, the indicator was accurate in 90% of the cases (Kappa=0.73, 95% CI=(0.51–0.95, p<0.0001)). Conclusion. Specific preoperative diagnosis of pancreatic cystic neoplasms by CT alone is substantially inaccurate. Complementary tests such as EUS-FNA with fluid analysis and ERCP should be recommended to improve diagnosis especially if nonoperative treatment is planned.     

Cystic pancreatic lesions: Current evidence for diagnosis and treatment

Abstract

Pancreatic cystic neoplasms are detected at an increasing frequency due to an increased use and quality of abdominal imaging. There are well known differential diagnostic difficulties concerning these lesions. The aim is to review current literature on the diagnostic options and the following treatment for cystic lesions in the pancreas focusing on serous cystadenomas, primary mucinous neoplasm of the pancreas and mucinous cystadenocarcinomas, as well as intraductal papillary mucinous neoplasms, starting with excluding pseudocysts. A conservative approach is feasible in patients with a clinical presentation suggestive of an asymptomatic serous cystadenoma. Surgical management, as well as follow-up, is discussed for each of the types of neoplastic lesions, including an uncharacterized cyst, based on patient data, symptoms, serum analysis, cyst fluid analysis and morphological features. Aspects for future diagnostics and management of these neoplasia are commented upon.     

Macrocystic serous cystadenoma of the pancreas

Summary Background. Serous cystic neoplasms of the pancreas are uncommon tumors classified as microcystic adenomas. In this article, the authors report clinico-pathologic features of seven cases of macrocystic variant of the serous cystadenoma. Methods. Seven patients (5 females and 2 males) with a diagnosis of cystic lesion of the pancreas were observed after 1995. Clinical, radiological, and pathologic features, including immunohistochemistry, were reported. Enzymes and tumor markers CEA, CA 19-9, CA 125, CA 15-3, CA 72-4, and mucin-like carcinoma-associated antigen (MCA) were investigated in the serum and cyst fluid of the patients. Cytology was also performed. Results. Six patients were symptomatic complaining abdominal pain. All cases had radiologic evidence of unilocular cyst of the pancreas. The suspected diagnosis was consistent with mucinous cystic neoplasm. Serum tumor markers were all in the normal range. After surgery, pathology showed in all cases a cyst lined with cuboidal, periodic acid-Schiff (PAS)-positive epithelium, without mucin content or atypia. Minute microcysts were found surrounding the main cavity. Immunohistochemical stains were positive for cytokeratin, CA19-9, CA15-3, CA 72-4, and MCA. CEA was unexpressed. CA 125 in the cyst fluid were found elevated in three cases and CA 19-9 in three cases. Cytology was negative in all cases. Conclusion. When a unilocular pancreatic cyst is found, without history of pancreatitis and gallstones, having low serum tumor markers levels and negativity of CA 72-4 and MCA in the cyst fluid, the diagnosis of the macrocystic variant of the serous cystadenoma may be suggested. At present, the diagnosis is still based on pathological examination after cyst removal.     

Endosonography in the diagnosis and management of pancreatic cysts

Rapid advances in radiologic technology and increased cross-sectional imaging have led to a sharp rise in incidental discoveries of pancreatic cystic lesions. These cystic lesions include non-neoplastic cysts with no risk of malignancy, neoplastic non-mucinous serous cystadenomas with little or no risk of malignancy, as well as neoplastic mucinous cysts and solid pseudopapillary neoplasms both with varying riskof malignancy. Accurate diagnosis is imperative as management is guided by symptoms and risk of malignancy. Endoscopic ultrasound(EUS) allows high resolution evaluation of cyst morphology and precise guidance for fine needle aspiration(FNA) of cyst fluid for cytological, chemical and molecular analysis. Initially, clinical evaluation and radiologic imaging, preferably with magnetic resonance imaging of the pancreas and magnetic resonance cholangiopancreatography, are performed. In asymptomatic patients where diagnosis is unclear and malignant risk is indeterminate, EUSFNA should be used to confirm the presence or absence of high-risk features, differentiate mucinous from non-mucinous lesions, and diagnose malignancy. After analyzing the cyst fluid for viscosity, cyst fluid carcinoembryonic antigen, amylase, and cyst wall cytology should be obtained. DNA analysis may add useful information in diagnosing mucinous cysts when the previous studies are indeterminate. New molecular biomarkers are being investigated to improve diagnostic capabilities and management decisions in these challenging cystic lesions. Current guidelines recommend surgical pancreatic resection as the standard of care for symptomatic cysts and those with high-risk features associated with malignancy. EUSguided cyst ablation is a promising minimally invasive, relatively low-risk alternative to both surgery and surveillance.     

Pancreatic tuberculosis masquerading as pancreatic serous cystadenoma

Solitary pancreatic involvement of tuberculosis is rare, especially in an immunocompetent individual, and it may be misdiagnosed as pancreatic cystic neoplasms. Pancreatic cystic neoplasms are being identified in increasing numbers, probably because of the frequent use of radiology and advances in endoscopic techniques. However, they are composed of a variety of neoplasms with a wide range of malignant potential, and it is often difficult to differentiate pancreatic tuberculosis mimicking cystic neoplasms from benign or malignant pancreatic cystic neoplasms. Non-surgical diagnosis of pancreatic tuberculosis is inconclusive and continues to be a challenge in many cases. If so, then laparotomy should be employed to establish the diagnosis. Therefore, pancreatic tuberculosis should be kept in mind during the differential diagnosis of solitary cystic masses in the pancreas. We report a patient who had solitary pancreatic tuberculosis masquerading as pancreatic serous cystadenoma.