Cystic Neoplasms of the PancreasO.BenjaminovRabin Medical CenterBeilinson Campusbenjaminovo@clalit.org.ilParis 2008

Becourt in 1830,

"the size of a childs head and composed of very strong fibrous walls Becourt PJ BG, Recherches sur le pancreas: ses functions et ses alterations organique. Strasbourg: Levrault 1830

Cystic Neoplasms of the Pancreas Serous cyst

Mucinous Cyst

IDPMT

Other rare cystic tumors

Incidentalomas

-- Pancreatic pseudocysts

Most common of pancreatic cystic neoplasms

95% women, 4th 6th decade

70%-90% pancreatic tail or distal body

Usually multilocular (six or more cysts > 2 cm). May be unilocular.

Malignant potential

May have scattered/peripheral Ca (18%).

Malignancy correlates with multilocularity, mural nodules, thick walls, thick septations and calcifications.

Sahani, D. V. et al. Radiographics 2005;25:1471-1484

Serous (micro) Cystadenomas of the PancreasSecond most common cystic neoplasm of pancreas

Benign tumor

Women > 50 y.o

Predilection for the pancreatic head

Multiple cysts (0.2-2.0 cm) avg. 10 cm.

central stellate scar that can calcify (Ca=38%)

Association between VHL and SCA 15%-30%

VHL Von Hippel Lindau1

potential malignancy risk - 3%

Since 1989: 673 SCA(71 series, 40 case reports 10 CA)

Digestion 2003;68:24-33

macrocystic serous adenoma

and

micro-macro (mixed) serous cystadenoma

1982 Ohaishi (triad)

Mucin producing tumors

Wirsung dilatation

Protruding papilla

M=F, 60-80 y.o

Incidental diagnosis 30%, most are symptomatic: Pancreatitis like pain, diabetes

Malignant potential, more curable than pancreatic adenocarcinoma

1/2

2/2

1/2

2/2

Solid and papillary epithelial neoplasms (Hamoudi Tumor)Young females (95%) 25 y.o

Low malignant potential

Large avg. 9-10 cm

Fibrous capsule, hemorrhage, necrosis

Cystic Neoplasms of the PancreasCystic degeneration

Cystic Neoplasms of the Pancreas

Cystic Neoplasms of the Pancreas

Cystic Neoplasms of the PancreasLymphoma

IncidentalomasIncidence 0.2-0.7% (autopsy 24%)Natural history data limited More than half of them are either malignant or pre-malignant. They are unlikely to be pseudocysts however cysts < 2cm are unlikely to cause morbidity or mortalityArch Surg. 2003; 138: 427-434 Annals Surg 2004;239:651AJR 2005;184:20-23Am J Gastroenterol 2007; 102: 2339-2349

Algorithm for the management of incidental pancreatic cystsMGH 2003

Algorithm for the management of incidental pancreatic cystsMayo Clinics 2005

The American Society for Gastrointestinal Endoscopy (ASGE)Cystic lesions of the pancreas, even when found incidentally,require diagnostic evaluation regardless of size because they may represent malignant or premalignant neoplasm.

March 2006 also supported by: American College of Gastroenterology Oct . 2007

ConclusionsCystic Neoplasms of the Pancreas In the absence of clear evidence of previous pancreatitis cystic lesions are considered neoplastic.

Imaging plays an important role in defining architectureand relation to surrounding organs as well as communication with the pancreatic ductal system. A multimodality approach should be taken.

Incidental cystic lesions management controversialfor lesions asymptomatic < 2 cm a conservative approach is reasonable

MerciThank You

Epidemiology of Cystic Pancreatic TumorsPseudocysts account for > 70% of all cystic lesions Cystic neoplasms thought to account for 20% of cystic lesions Cystic neoplasms represent only 1% of all pancreatic neoplasms. This figure may be incorrect as many asymptomatic cystic tumors do not have surgery or FNA The prevalence of the more common cystic tumors:Mucinous cystic neoplasm (MCN) 10 - 45% Intraductal Papillary Mucinous Tumor (IPMT) 21 - 33% Serous cystadenoma 32 - 40% Solid pseudopapillary tumor (SPT) < 10% Others are rare: acinar cell cancer < 1%

Cystic Neoplasms of the PancreasCystic Islet Cell Tumor

Pancreatic MetastasesCystic Neoplasms of the Pancreas

Cystic Neoplasms of the PancreasCystic lymphangioma

Simple CystMucinous CystMucinous CystPseudocystSerous Cyst

Slide 13

Minerva Chir 2004; 59:185-207

Focal PancreatitisFP/FP

*I would like to thank our hosts for this very interesting afternoon session and would like to end it as time permits with a short review on pancreatic cystic neoplasms.Cystic pancreatic neoplasms have always been on the agenda. The Medline search will yield hundreds of papers on the subject. This proves that there has always been a concern and dilemma concerning their management.*

I have actually found that the first cystic tumor of pancreas to be described was in a french journal in 1830. It was described as a mass in a size of a childs head composed of very strong fibrous walls.

*I would like to open this talk with this casewhich really encapsulates what were confronted with on a daily basis. We are all familiar of a acse where a patiet is sent for abdominal CT whether it is for abdominal pain or renal colic and we do the CT and find this.Now what do we do? We all know that these may be little neoplasms, but when we are confronted with a case like this how do we handle it?So I hope that in the next 20 minutes I can help you understand how to approach a case like this by reviewing the major subtypes of Cystic Pancreatic neoplasms.*There is a wide variety of pancreatic cysts as you can see from this table which was published by the WHO. There are congenital cysts. Acquired cysts such as parasitic cysts, pseudocysts and there are the cystic neoplasms. But I am going to confine my talk to cystic pancreatic neoplasms.*I will talk about the three major ones The serous, Mucinous and Intraductal papillary ones and the other rare types and end with the incidentalomas.We always have to keep in mind when we are considering cystic pancreatic lesions that with the absence of a clear history pancreatitis one should assume that a cystic lesion is a neoplasm. With such a history it is sometimes difficult to make the diagnosis.*The Mucinous cystic neoplasms are the most common of the cystic neoplasms. They arise within the pancreatic parenchyma and are formed of a thick wall and many of them have ovarian stroma within the wall which explains the prevalence in women usually in the 4th 6th decade. They are predominantly located within the tail of the pancreas and usually are multilocular with 6 ot more cysts of 2 cm or more. The tumors are considred premalignant to frankly malignant. The malignancy correlates with the multilocularity. With the presence of mural nodules thick septations and calcifications which are usually found in the periphery.

*This is an example of a multiloculated cyst located in the neck-body region of the pancreas with proximal dilatation of the pancreatic duct. The largest cystic compartment of this mass is above 2 cm. The walls are somehow thick and one may see some nodularity in the middle of the mass. It does not matter much if this is benign or malignant most people would recommend to resect it. This turned out to be a mucinous cyst adenocarcinoma.*At times such tumors can be unilocular such as this one in the tail of the pancreas. On US they may have echogenic debri due to the mucin content or hemorrhage and EUS may reveal septations. These are also the cases in which it is difficult to differentiate with a pseudocyst and therefore usually these will be aspirated under EUS. Mucin will be confirmed and those patients will undergo resection of these tumors. *Here is another complicated case. This 55 y.o woman presented with abdominal pain. She had an ultrasound which was normal. Following that US, a few weeks later she took a trip to Europe, and had another severe abdominal pain attack and was hospitalized. She had a CT which revealed this huge cystic mass. It actually looks like multiple fluid collections. This was thought as a pseudocyst although there really was no clear evidence that she had pancreatitis besides the abd pain event a few weeks earlier and a normal ultrasound. It was decided to do an EUS and FNA and this turned out to be a MCN.*Cases like these in which there are enhancing nodules and irregular septa and the level complexity rises makes one think more towards a Mucinous adeno carcinoma. This reminds us of the Bosniak classification of Renal Cysts which is well established and has proved to be a reasonably accurate method for assessing the risk of malignancy in renal cysts Using a similar approach, some have suggested a classification scheme for pancreatic cysts that is based on the imaging morphologic features of these cysts.*

The serous cystadenomas are the secons most common cystic neoplasms of the pancreas. They are considered benign and therefore important to diagnose. So making such a diagnosis is a powerful statement.They are predominantly seen in women and have a predilection for the head of the pancreas.They are usually composed of multiple cysts ranging from the size of 2 20 mm all together giving a huge mass of a 10 cm diameter.When they calcify the calcification is usually central.

*So how do they look like? Here are two examples one in the head of the pancreas and the other in the neck region. A cystic mass with numerous septations or a cluster of tiny cysts. You may see the dense fibrous septa which provides a honeycomb matrix but at time it may be very difficult to identify the multiloculrity and they may resemble solid masses.*This honeycomb structure may be better appreciated on ultrasound. The presence of posterior enhancement due to the cystic structure of the neoplasm may help rising with the correct diagnosis.

, . .

68-year-old female with palpable abdominal mass found to be a microcystic adenoma. (A) Contrast-enhanced CT demonstrates the complex cystic nature of this 9.5 cm 7.0 cm mass. Internal septations and external lobulations are present. (B) Sonogram demonstrates a heterogenous, solid-appearing mass that exhibits posterior acoustic enhancement. The multiple acoustic interfaces give this lesion its solid appearance sonographically *MRI can also be useful in learning the morphology of these neoplasms. It will clearly demonstrate the microcystic structure of these neoplasms which will resemble a bunch of grapes. MRCP will also help in establishing that these are not connected with the main pancreatic duct and we will discuss about this later.*As I have mentioned the calcification is usually central described as a sunburst calcification and may be large as in this case. And notice that it is very difficult to recognize the nicro cystic nature of this mass however location and central calicification have raised the diagnosis. It was resected and turned out to be a serous cyst.*

The calcification may also be small. And there is great correlation between the radiological image to the macroscopic appearenec. It resembles a honeycomb with the septations composed of fibrotic structures giving rise to this appearance.

*I would like to mention a few more points about these neoplasms The first one is that there is an association between VHL ro thes eneoplasms. This is a case which I carry from my fellowship of a young patient with multiple serous cyst adenomas in his pancreas. Unfortunately he also developed a cystic RCC with lung metastases.

**

The second point is the risk for malignancy. Although they are considered benign there is a 3% risk for malignancy. This is also the reason for the calsiification of the WHO which includes both serous cystadenoma and serous adenocarcinoma.. An article published in 2003 has concluded that the prevalence of cancer in serous cystic neoplasms reported since 1989 was 3% based on a literarture review of 673 cases. So although considered benign one must remember that serous cystadenomas of the pancreas may have the biologic ability to undergo malignant transformation. So this paper suggests that surgical treatment may be recommended if the operative risk is low.

*A third point to raise which further complicates things as if we do not have enough complications is that just as we saw previously the unilocular type of MCA there us also a unilocular macrocystic serous adenoma or the mixed type as you can see in this case (click mouse) which was thought to be a macrocyst adenoma but turned out to be a macro serous cyst adenoma.

*IPMT was fisrt described by a japanese endoscopist in 1982. He revealed and described a buldging papilla with mucin pouring out of it and a dilated wirsung. This triad is the classical endoscopy appearance of IPMT.*

It affects men and women equally and although historically it was diagnosed in the 7th decade it is now discovered at a younger age. Patients compalin of a pancreatitis like abdominal pain which is assocaited with meals and patinets complain of weight loss.It is histoligically classified as an adenoma, borderline or a carcinoma. The natural history is not clear however an interval of 5 years has been observed between adenoam to invasive carcinoma.

*There are 4 types of IPMTs which actually breakdown to two varieties those that arise in the main pancreatic duct and those that arise in the side branches.They can exclusively be in the main duct, part of the duct, side branches only or combined forms.But, with all forms there is a connection with the main duct.*Here is a case of 70 y.o Male who complained of abdominal pain and was sent for a CT. The CT demonstrates dilatation of the main pancreatic duct and side branches and thought to represent Chronic Pancreatitis . Since his pain did not resolve he decided to go to another physician who agin sent him for a CT which demonstrated on the 16/9/06 worsening and was highlysuspicious of IPMT

*On MRI the diffuse cystic nature is nicely observed and the pancreatic duct was obscured by the cysts. MRCP better demonstrated this appearance.The patient was referred to surgery and this indeed turned out to be an IPMT.* 2690045Mucinous cystadenoma and also adenocarcinoma*Here is a sample of a diffuse form of an IPMT. This resembles chronic pancreatitis but with the absence of a proper histroy this is unlikely.*On the other hand here is a case of a 60 y.o women with these irregular cysts along her MPD which also seems somewhat irregular.She is known to have chronic pancreatitis and these have been followed up for several years and have not changed.

*We often have patients coming for MRCP to further evaluate a cystic neoplasm incidentally discovered. The question for us to answer is whether there is a connection with the MPD thus making the diagnosis of an IPMT.This patient is extremely difficult. You can see a mass adjacent to the pancreatic duct, Although I could not clearly see the communication I could not separate the MPD from the mass and conclude whether this was a SCA or an IPMT. It was decided to follow up on this patient.

*And here is another case referred to MRCP because of a pancreatic cyst. The MRCP looking at different angles was able to separate this cyst from the pancreatic duct and a connection was not found. This still could be a mucinous cyst adenoma but with a history of pancreatis, which is the case here this is a pseudocyst.So MRCP is helpful in these cases to see if a connection with the MPD exists but to a limited degree.*Another tumor that I would like to mention briefly is the SPEN tumor the solid pseudopapillary tumor so called Hamoudi Tumors*These are rare tumors however are now being found in a higher frequency. In 95% it will be seen in young women at the age of 25.The cystic regions reflect hemorrhage . They contain a thick fibrous capsule and may reach a large size.They have a malignant potential and can be cured when completely resected.Histologically they are composed of branching papillae and a myxoid stroma.*One must always keep in mind that every lesion can fo cystic degeneration, Here is an example of a pancreatic carcinoma with cystic degenreation. And look at the starnding and solid component around that usually the cystic tumors will not demonstarte when you discover them and when they do it will usually mean that they are aggressive.*. Here is a pancreatic mass that looks malignant was called a carcinoma. Patient was referred to surgery and this turned out to be focal pancreatitis*This is an example of a pancreatic neuroendocrine tumor in the tail of the pancreas which has gone cystic degeneration. It is bright on T2W and enhances only on the peripehery. The surrounding walls are thick. This you will mainly see in non functioning NET as the Functioning will clinically be descovered earliers**Now, going back to our incidentaloma of a 2 cm or so. The incidence is about 0/2-0/7%. With this number you will probably run into one at least once a week if you read many body CTs. The data on their natural history is limited but from several papers published in the recent years one learns that more tham half of them are either malignant or pre-malignant, no matter size. They are unlikely to be pseudocysts and cysts that are smaller than 2 cm are unlikely to cause mortality or morbidity.

*The management of these cysts is controversial and many algoriths have been published. Most of them consider size as the main criteria above 2 cm in a young patient will go for resection. Smaller lesions observation. In older patients do an EUS and FNA first. *A paper from Mayo Clinics suggest something similar but the size criteria is different taking 2.5 cm as the upper limit and 1-2.5 as a borderline size in which EUS and FNA should be performed.and the most accurate aspirate is CEA levels.*The ASGE and ACG require a diagnostic evaluation regardless of size. And these guidelines of the ACG has only been published Very recently in October 2007. **43-year-old female with islet cell tumor. Contrast-enhanced CT demonstrates 7 cm 10 cm mass arising from pancreatic tail. The mass has central low attenuation compatible with necrosis and a thick, irregular wall (closed arrow) with enhancement. The patient had portal and splenic vein obstruction with cavernous transformation of the portal vein (open arrow) and multiple vascular collaterals (arrowhead). Hypervascular liver metastases are also present (not shown). * - MRCP .*

This is an example of a necrotic mass due to FP that showed cystic areas on US and was falsey diagnosed as cancer by both reviewers.