9.19: Cystic pancreatic masses

Ritu K. Kashikar, Shrinivas B. Desai, Pooja Punjani Vyas, Nilesh Doctor, Vivek Shetty

Introduction

Advancement and extensive use of imaging in recent times has to lead to increased detection and recognition of cystic pancreatic masses. Imaging however, plays a vital role in noninvasive diagnosis of these lesions, avoiding unnecessary intervention and planning management and follow up guidelines.

The aetiology of pancreatic cysts ranges from primary cystic neoplasm to cystic degeneration of solid neoplasm to nonneoplastic cysts (Table 9.19.1). Cystic tumours of the pancreas comprise around 10%–15% of cystic lesions of the pancreas. The aim of this chapter is to educate the reader regarding imaging features of cystic lesions of pancreas, how to differentiate between cysts which can be left alone and those that require further management and also emphasize on latest international guidelines used in stratification of these lesions.

TABLE 9.19.1

Classification of Cystic Pancreatic Masses

Imaging techniques

Ultrasonography (USG)

Cystic pancreatic lesions are often incidentally detected on USG abdomen performed for other reasons. Although USG is an excellent modality for evaluation of cystic lesions elsewhere, it is unable to adequately characterize pancreatic cysts due to retroperitoneal location of the organ and other confounding factors such as obesity and gases. Most lesions detected on USG require characterization with either MDCT or MRI with MRCP.

CEUS improves accuracy in the differentiation between a solid and a cystic lesion and also in determining whether enhancing septa or nodules are present within the cystic lesion.

Currently USG also does not have a role in follow up algorithms of pancreatic cystic lesions.

MDCT

Multidetector CT evaluation of pancreatic lesions is best performed with a multiphasic technique (Table 9.19.2). The phases include a precontrast scan, an early arterial angiographic phase, a pancreatic parenchymal phase, and a portal venous phase. The precontrast scan is important for detection of calcification, which may be diagnostic of some lesions. Mucinous cystic neoplasms may be hyperdense on nonenhanced scan suggesting mucin content or haemorrhage.

TABLE 9.19.2

MDCT Protocol

Precontrast Scan
Arterial phase	18–20 seconds
Pancreatic parenchymal phase	35–45 seconds
Portal venous phase	60–70 seconds

The arterial phase aids in detection of hyperenhancement neovascularity and arterial involvement in pancreatic masses. Optimal parenchymal enhancement of the pancreas is achieved at 35–45 seconds after initiation of injection of contrast agent. This is the pancreatic parenchymal phase. It is in this phase that the tumour pancreas contrast is maximum (Fig. 9.19.1, Table 9.19.3). Most hypoenhancing pancreatic lesions are best detected in this phase. The portal venous phase allows in detection of venous involvement and hepatic metastasis. Delayed phase is typically not required in cystic masses.

Fig. 9.19.1 (A) Normal CT imaging protocol of pancreas – Nonenhanced image a showing normal pancreatic density. B. Postcontrast early arterial phase showing mild enhancement of pancreas. Pancreatic parenchymal phase (C) showing good enhancement of gland. It is this phase that’s provides the best pancreas/lesion contrast. Venous phase images (D) is acquired to diagnose venous involvement and detection of liver metastasis.

TABLE 9.19.3

MRI Protocol

• T2-weighted single-shot fast spin-echo with and without fat suppression
• T1-weighted in-phase and opposed-phase gradient echo
• T2W1 MRCP
• Diffusion-weighted imaging
• Post contrast protocol includes dynamic three-dimensional T1-weighted fat-suppressed spoiled gradient-echo (in arterial, pancreatic and portal venous phases)

MDCT has an accuracy of 56%–85% for characterization of cystic pancreatic lesions.

MRI

MR imaging affords the best noninvasive means for the evaluation of cystic lesions of the pancreas due to superior soft tissue resolution. The helpful distinguishing characteristics of cystic pancreatic lesions, morphology of septae, relation to pancreatic duct are easier to detect at MR imaging and MR cholangiopancreatography (MRCP) than at CT (Table 9.19.4). Studies however indicate that MDCT and MRI are comparable in identifying malignant behaviour of cystic pancreatic lesions.

TABLE 9.19.4

Advantages of MRI Over CT in Cystic Pancreatic Masses

• Better delineation of cyst fluid content
• Identification of internal septations and mural nodules is superior
• Relationship between the cystic neoplasm and pancreatic duct is better demonstrated

The MRI protocol for evaluation of cystic lesions of pancreas includes T2-weighted single-shot fast spin-echo, T1-weighted in-phase and opposed-phase gradient echo, diffusion-weighted imaging, T2-weighted fat-suppressed fast spin-echo. Three-dimensional T1-weighted fat-suppressed spoiled gradient-echo T2-weighted MRCP. Postcontrast protocol includes dynamic three-dimensional T1-weighted fat-suppressed spoiled gradient-echo (in arterial, pancreatic and portal venous phases) (Fig. 9.19.2, Table 9.19.3).

Fig. 9.19.2 Normal precontrast MRI protocol of pancreas. TW1 T2W1 image (A) showing normal pancreas appearing isointense to liver. T1W1 image (B) showing pancreas as the most hyperintense structure in the abdomen. Other sequences include T1 in- and opposed-phase (C and D), diffusion (E) and MRCP (F). Postcontrast protocols are similar to MDCT.

DWI has not found much utility in cystic neoplasms owing to overlap in ADC values. Some studies suggest role in distinguishing malignant from benign tumours in the case of mucinous cystadenoma and IPMN.

Secretin-enhanced MRI

Secretin is a peptide hormone produced in the intestinal mucosa, which stimulates the secretion of bicarbonate-rich fluid into the pancreatic ducts and transiently increases the tone of the sphincter of Oddi. The increased fluid distention of the pancreatic duct allows better study of ductal anatomy and identifying communication of pancreatic cystic lesions with the pancreatic duct.

EUS

EUS is excellent in characterization of cystic lesions of pancreas.

The proximity between the transducer and the lesions allows precise definition of the structural component of the cysts and components such as small mural nodules are better visualized with EUS than with other modalities. The other advantage of EUS is that cysts fluid aspiration and cytology can be performed. Tumour markers, genetic markers can be evaluated in the aspirated fluid. This allows comprehensive evaluation of cystic lesion. EUS also has therapeutic advantages allowing endoscopic draining of pseudocysts. Recently endoscopic ablation of cysts has been performed. These advantages have led to increasing use of EUS in recent years.

This modality is however not indicated in all lesions and imaging should be able to stratify lesions requiring further invasive investigations.

PET CT

Studies have found PET CT comparable to PET alone or CT to determine presence of malignancy in cystic lesions. False positive findings may however be problematic. There is however no consensus for routinely using PET CT in characterization of cystic pancreatic masses.

Serum tumour markers

Serum CA19-9 and CEA are routinely done in all pancreatic masses. Though role in cystic lesions is still controversial.

Serous cystadenoma

Serous cystadenoma is a benign neoplasm composed of glycogen-rich epithelial cells that form innumerable small thin-walled cysts containing serous fluid. It is the prototype microcystic pancreatic neoplasm. They occur frequently in older women (median age, 65 years) and is also called as grandmother lesion.

Location

Approximately 40% of pancreatic serous cystadenoma arise from the pancreatic head and uncinate process and 60% arise from the pancreatic body and tail.

Clinical features

Serous cystadenomas are usually discovered incidentally at imaging; however, those that are large may cause symptoms. Patients may present with abdominal pain, palpable mass, anorexia, fatigue/malaise, or weight loss. Rarely the patient may present with jaundice.

Genetics

Genetic alterations similar to those in VHL are seen in sporadic SCA and include tumour suppressor gene VHL mutations and overexpression of vascular endothelial growth factor (VEGF). Allelic loss in chromosome 3 have seen in up to 40% cases of sporadic SCA.

Histopathology

Gross appearance

Serous cystadenomas are variable in size. The size ranges from <0.1 to 25 cm. The tumours are grossly well demarcated from the surrounding parenchyma. The gross appearance of the lesions is variable. It could be microcystic, consisting of innumerable small cysts giving the macroscopic appearance of a sponge or honeycomb. The presence of multiple, microscopic SCN is characteristic of von Hippel–Lindau (VHL). This variety show a centrally located area of fibrotic scar.

In Macrocystic/oligocystic variant, borders with the surrounding parenchyma are less defined and the cystic lesion generally does not exhibit a central scar. The Solid variant, the lack of cystic spaces on gross inspection often gives the initial impression of a neuroendocrine or solid pseudopapillary neoplasm.

Serous cystadenomas show nonviscous, clear-to-yellow cyst fluid, which provides an important clue to the distinction of SN from mucinous neoplasms. In contrast to intraductal papillary mucinous neoplasm, there is no connection with main or branch pancreatic ducts.

Microscopic morphology

These are clinically benign pancreatic epithelial neoplasms exhibiting serous morphology, characterized by a monotonous, cuboidal epithelial cell proliferation with marked cytoplasmic clearing due to intracellular glycogen. The centrally located epithelial cell nuclei are uniformly round to ovoid and not particularly large or hyperchromatic. Abundant diastase-sensitive cytoplasmic glycogen is highlighted by a periodic acid–Schiff stain.

These lesions do not show evidence of necrosis, infiltrative architecture, or lymphovascular/perineural invasion, and mitotic figures are generally not observed. A variably prominent pseudocapsule of fibrosis divides parenchyma from the neoplasm

Patterns of pancreatic serous cystadenoma

• Microcystic pattern: This pattern is the commonest, present in 70% cases of serous cystadenomas and comprises of multiple cysts, usually more than 6 cm in size. The size of individual cysts ranges between few mm to 2 cm. The lesions usually show a lobulated contour. Specific feature is presence of a central stellate scar with or without calcification and is seen in up to 30% cases (Fig. 9.19.3).
• Honeycomb pattern: This pattern consists of multiple tiny cysts resembling a honeycomb or sponge and is seen in 20% cases. These closely packed cysts and intervening fibrous septae are responsible for these lesions appearing as soft tissue density masses.
• Oligocystic pattern: This a relatively uncommon variant, seen in less 10% cases. It is composed of fewer cysts which may be >2 cm in size, giving it a macrocystic appearance (Fig. 9.19.4). These lesions also lack the central stellate scar, classic of the microcystic variant Owing to macrocystic appearance these often need to be differentiated form mucinous cystic neoplasm or IPMN. Distinguishing features that aids in diagnosis includes presence of external lobulations and absence of ductal dilatation.
• Solid pattern: Rare cases of solid variant of serous cystadenoma have been described. These serous cystadenomas do not contain any cystic spaces on histopathology.
• Aggressive behaviour of atypical serous cystadenomas: Aggressive features like direct invasion into large blood vessels, nerves, lymph nodes can be seen in a small subset. These however resemble typical serous cystadenomas on histology lacking cytological atypia.

Fig. 9.19.3 Classic shapes of serous cystadenoma. A. Classic lobulated appearance with microcystic appearance. B. depicts the central stellate scar.

Fig. 9.19.4 Appearance of oligocystic variety. This variety lacks the tiny innumerable cysts seen in the microcystic variety and is comprised of fewer larger cysts.

Imaging appearance

Ultrasound

On USG the microcystic variant shows lobulated contour with multiple tiny anechoic cysts separated by septae. the central scar containing calcification can be seen if present. Extremely microcystic, honeycomb variant may resemble a solid lesion at conventional US.

The macrocystic type, can be mixed type with multiple large (>20 mm) and small cysts, and the unilocular type, which is more difficult to differentiate from mucinous cystadenoma (MCA).

Contrast-enhanced US

Enhancement of the intralesional sepatations is seen on contrast-enhanced USG allowing better characterization of the lesion. The central scar can show homogenous enhancement. Honeycomb variety appears as a hypervascular lesion owing to its extremely microcystic morphology and may resemble solid masses like neuroendocrine tumours.

CT

Pancreatic serous cystadenoma can have a varied appearance on CT depending on the morphologic patterns. Serous cystadenomas are typically solitary but may be multiple in von Hippel–Lindau disease, causing an appearance of disseminated involvement (Table 9.19.5).

TABLE 9.19.5

CT Features of Serous Cystadenoma

• Lobulated lesions with multiple small cysts >6 in number and <2 cm in size
• Stellate calcification is best seen on CT
• Contrast study shows enhancement of the septae
• Honeycomb pattern show poor demarcation of cysts and appear almost solid showing strong enhancement
• Lobulated contour, lack of a prominent thickened peripheral wall, and location in the head of the pancreas are features of oligocystic variant

Polycystic pattern

As mentioned previously, the polycystic pattern is the most common appearance of serous cystadenoma. A pattern of a bosselated collection of cysts that usually number more than six is seen. Each cyst may range from a few millimetres to 2 cm in size (Fig. 9.19.5).

Fig. 9.19.5 Classic serous cystadenoma. Contrast-enhanced CT showing a well-defined lobulated multicystic lesion with internal enhancing septae (arrows in A and B). Lesion shows central calcification (arrows in D). Note the intralesional vascularity (yellow arrows in B and C).

The other classic CT features include a lobulated contour and presence of a central stellate scar with calcification. This scar is seen in 30% cases and when present is strongly suggestive of the diagnosis. The intralesional fibrous septae show early enhancement after contrast administration. This is a distinguishing feature, as serous cystadenoma is the only hypervascular lesion among the cystic pancreatic neoplasms.

Honeycomb pattern

Tiny cysts mimicking a honeycomb are the hallmark of this variant and may be poorly depicted as individual cysts on CT. On unenhanced CT, the honeycomb pattern may appear as a well-marginated lesion with soft tissue or mixed attenuation, depending on the size of the cysts and the amount of fibrous tissue. Moderate to strong enhancement is seen in these lesions (Fig. 9.19.6).

Fig. 9.19.6 Honeycomb type of serous cystadenoma. Contrast-enhanced CT (A) and MRI (B) showing honeycomb variety of serous cystadenoma. Note the multiple tiny closed packed cysts with intervening fibrous septae mimicking a sponge.

Macrocystic or oligocystic pattern

This appears as a unilocular cyst or it may contain fewer large (>2 cm) cysts. Imaging Features include a lobulated contour, lack of a prominent thickened peripheral wall, and location in the head of the pancreas (Fig. 9.19.7).

Fig. 9.19.7 Oligocystic variety of serous cystadenoma. Contrast-enhanced CT showing well-defined lobulated lesion in head of pancreas with thin internal sepate. Not absence of microcysts within the lesion.

MRI features

Owing to its supreme soft tissue resolution, MRI is the modality of choice in diagnosis of serous cystadenomas.

The classic MRI features of microcystic variant includes a lobulated lesion with multiple small T2 hyperintense and T1 hypointense cysts with intervening hypointense fibrous sepate. These lesions do not communicate with the pancreatic duct; hence no dilatation is usually seen. Dilatation of pancreatic duct has however been reported in larger lesions. After the administration of gadolinium, the hypervascularization of the central scar and of internal septa may be seen. The morphology of the honeycomb pattern may also be better depicted on MRI. Multiple tiny T2 hyperintense cysts with intervening hypointense septae are seen (Fig. 9.19.8).

Fig. 9.19.8 MRI in classic serous cystadenoma. T2W1 axial images (A and B) showing a well-defined lobulated lesion in the pancreatic head composed of multiple tiny cysts T2W1 coronal image (C) showing central hypointense dot representing calcification (arrow). Note the duct (yellow arrow) causing posterior to the lesion without upstream dilatation.

The oligocystic variant shows fewer larger T2 hyperintense and T1 hypointense cysts and can mimic mucinous cystadenoma. However, the lobulated contour, together with the absence of wall enhancement and a wall thickness less than 2 mm, suggest the correct diagnosis (Fig. 9.19.9) (Table 9.19.6).

Fig. 9.19.9 MRI showing combined oligocystic and microcystic serous cystadenoma. T2W1 axial images (A and B) showing well-defined lobulated lesion in the pancreatic head with multiple large and microcysts (blue and yellow arrow). Post contrast images (C) and (D) showing enhancement of septae within the microcystic portion.

TABLE 9.19.6

MR Features of Serous Cystadenoma

• Cysts appear hyperintense, surrounded by hypointense septa and sometimes with a hypointense central scar
• Enhancement of septae and scar on contrast-enhanced images
• No ductal dilatation or communication
• Oligocystic variant shows lobulated contour, absence of enhancement and wall thickness less than 2 mm

Atypical imaging appearance

1. Giant serous cystadenoma with ductal dilatation: Giant cystadenoma are lesions larger than 10 cm in diameter. These tumours may present with complications such as rupture, compression and invasion of adjacent structures like bile ducts and postoperative recurrences. Lesions may present with pain, obstructive jaundice and often require treatment (Fig. 9.19.10).
2. Serous cystadenoma with haemorrhage: Rarely intratumoural haemorrhage has been reported in serous cystadenomas. This leads to heterogeneous appearance on imaging with haemorrhage, necrosis and cystic degeneration. These lesions may be difficult to differentiate from islet cell tumour and solid cystic papillary epithelial neoplasm (SPEN). (image)
3. Disseminated variant: Disseminated SCA have been described in setting of Von Hippel-Lindau disease. Fifty-six per cent cases with VHL syndrome have pancreatic lesions, which include cysts, serous cystadenomas and islet cell tumours. The lesions when present in combination lead to diffuse involvement with heterogeneous appearance of pancreas.
4. Solid Variant: There are few case reports in the literature of solid serous adenoma of the pancreas, a rare variant of serous cystadenoma. It is formed by the cells that line the cysts of other forms of serous cystadenoma but with an absence of any cystic spaces on histopathology. It has been reported on CT as having the appearance of an enhancing solid pancreatic mass.

Fig. 9.19.10 Giant cystadenoma with atypical features: contrast-enhanced CT showing a large combined micro and oligocystic serous cystadenoma in the pancreatic head with enhancing septae (blue arrow). Note the compression over the common bile duct with resultant biliary dilatation (yellow arrow in A and B). There is additionally compression over the pancreatic duct which is also dilated with distal glandular atrophy (blue arrow in A and B).

Differential diagnosis

The differential diagnosis of serous cystadenoma depends on the variety and are listed in Tables 9.19.7 and 9.19.8.

TABLE 9.19.7

Honeycomb Pattern

Serous Cystadenoma	Neuroendocrine Tumour	SPEN
Lobulated contour	Presence of hypervascular halo	Presence of haemorrhage
Multiple tiny cysts giving a sponge like appearance	Centre may be necrotic	Thick enhancing capsule

TABLE 9.19.8

Oligocystic Variant

Serous Cystadenoma	Pseudocyst	Mucinous Cystic Neoplasm	IPMN
Lobulated contour	Smooth external contour	Smooth external contour	Pleomorphic and tubular external contour
No enhancing septae or wall	Peripancreatic stranding	Relatively thick enhancing wall, septations and mural nodule in the case of malignancy	Communication with main pancreatic duct or side-branch
No calcification in this variant	Clinical history of pancreatitis	Peripheral calcifications	Thick internal septations and nodularity suggestive of malignancy

Role for cyst fluid analysis

Lesions with classic imaging features do not require further investigation or fluid analysis. The fluid in classic cystadenomas is yellow in colour and does not show elevated amylase, mucin or tumour markers. Approximately 20%–50% cases show cytological positivity for periodic acid-Schiff and cytokeratin AE1 and 3. Hemosiderin laden macrophages also do not have high diagnostic accuracy and are seen in only about 43% cases.

Management

Current management guidelines suggest (Table 9.19.9).

• If cystic lesion reveals classical imaging features of serous cystadenoma – no further investigations/fluid aspiration is needed
• Size is no longer a criteria to decide treatment or resection
• Resection is reserved only for truly symptomatic lesions

TABLE 9.19.9

Management Algorithm of Cystic Pancreatic Masses – Tanaka Guidelines

Surgery

Resection involves distal pancreatectomy or Whipples, depending on location of the tumours and is currently reserved for truly symptomatic cases.

Mucinous cystadenoma

Mucinous cystic tumours are a rare subset of cystic neoplasms, constituting approximately 2.5% of pancreatic exocrine tumours.

TABLE 9.19.10

Serous Cystadenoma – Pearls

• Lobulated microcytic lesions
• Less common variants include honeycomb, oligocystic, solid pattern
• Common in older women, 60% occur in tail.
• On imaging-lobulated lesions with multiple small cysts >6 in number and <2 cm in size
• Central scar present in classic variety, which may show calcification
• Enhancement of septae seen
• No ductal communication
• No further evaluation or cysts fluid analysis needed when imaging diagnosis is straightforward
• Resection only in truly symptomatic cases, size not a criterion for deciding management

The defining and characteristic histopathologic feature of mucinous cystic neoplasms (MCNs) is the presence of ovarian-type stroma similar to that observed in biliary cystadenomas.

International Association of Pancreatology recommend that all suspected MCNs be surgically resected.

Epidemiology

A significant female predilection is seen with approximately 99.7% cases seen in women. As opposed to serous cystadenomas these lesions occur in middle aged women and hence the term mother lesions is used to describe these. The approximate age of occurrence is 50 years with a range from 20–82 years. Mucinous cystic tumours are a dominant cyst that is round or oval and is encapsulated. MCNs may grow slowly over time, at an average rate of 4 mm per year.

Location

The most common locations are the pancreatic body and tail (up to 75%).

Histology

Stromal elements similar to ovarian stroma are the hallmark and key feature that aids in differentiation from IPMN, whose stromal elements are ductal in origin. Tall columnar cells with intracellular mucin arranged in a single row or vertically, forming papillary or polypoidal projections, constitute the epithelial elements. Portions of benign appearing epithelium can be seen adjacent to areas of invasive carcinoma in the same tumour. These lesions show smooth contour on gross appearance with few internal sepate. Peripheral calcification, mural nodule if present suggest malignant cyst (Fig. 9.19.11, Table 9.19.11).

Fig. 9.19.11 Morphologic appearance of mucinous cystic lesions. A. macrocystic with septae B. macrocystic with peripheral egg shell calcification. C. macrocystic with mural nodule.

TABLE 9.19.11

Mucinous Cystic Neoplasm – Spectrum

• Mucinous cystadenoma
• Borderline mucinous cystic tumour
• Mucinous cystic tumour with carcinoma in situ
• Mucinous cystadenocarcinoma

Presentation

Lesions may be asymptomatic in 25% cases. Patients my present with pain in abdomen. Mucinous cystadenoma can also present with pancreatitis. Considering most lesions are located in distal body and tail involvement of splenic vein may lead to left sided portal hypertension.

Imaging

Ultrasound

Mucinous cystic tumour is a well-circumscribed cystic mass in the pancreas. Lesions can have an irregular contour to the wall, septations, mural nodularity, and peripheral calcifications. The lesion may however be echogenic due to high by mucin content or haemorrhage which may impair the detection of other features.

CEUS may improve detection rate of septa and mural nodules.

CT

Lesions are typically well-circumscribed with smooth contour. On unenhanced CT, mucinous cystadenoma may appear hypodense or slightly hyperdense content, due to the presence of variable amount of mucin and haemorrhage. Curvilinear calcifications occur along the periphery of the lesion and are seen in 15% of cases, in contrast study enhancement of the fibrous cyst wall along with enhancement of any septations or mural nodules is seen (Figs. 9.19.12 and 9.19.13).