Pancreatic lesions

Pancreatic cystic lesion differential

Unilocular
- Pseudocyst
- IPMN
- Serous cystadenoma
- Simple pancreatic cyst
- Cystic neuroendocrine tumour of the pancreas
Diffuse pancreatic cysts
- In association with VHL, ADPKD, isolated poycystic disease of the pancreas, or pancreatic cystosis (in CF)
Macrocystic: multilocular
- Mucinous cystic neoplasm of the pancreas
- IPMN
- Serous cystadenoma
- Acinar cell cystadenocarcinoma
- Hydatid cyst
Microcystic
- Serous cystadenoma
Cystic with a solid component
- Walled off necrosis
- Macrocystic tumours
- Solid pseudopapillary tumour of the pancreas
- Primary ductal pancreatic tumour with cystic degeneration
- Cystic degeneration of islet cell tumours (insulinoma or glucagonoma)
- Cystic teratoma
- Metastases to pancreas

Pancreatic solid lesions differential

Neoplastic
- Pancreatic ductal adenocarcinoma
- Acinar cell carcinoma
- Endocrine tumours - PNETs - functional and non-functional
Non-neoplastic
- Focal pancreatitis, including autoimmune
- Fatty infiltration-replacement
- Intra-pancreatic accessory spleen
- Peri-pancreatic lymph node
- Congenital abnormalities - prominent lobulations, bifid pancreatic tail
- Sarcoidosis
- Castleman disease

Key demographic and clinical features of patients with pancreatic cystic neoplasms[1-4]

	Serous cystadenoma	Mucinous cystic neoplasm	Main-duct intraductal papillary mucinous neoplasm	Branch-duct intraductal papillary mucinous neoplasm	Solid pseudopapillary neoplasm
Age of presentation	Variable, usually 5th to 7th decade	Variable, usually 5th to 7th decade	Variable, usually 5th to 7th decade	Variable, usually 5th to 7th decade	Usually 2nd to 3rd decade
Gender distribution	Females >males	Exclusively females	Females = males	Females = males	Females >males
Typical clinical presentation	Incidental, less commonly abdominal pain or mass effect	Incidental, less commonly abdominal pain or malignancy related	Incidental or pancreatitis or pancreatic insufficiency or malignancy related	Incidental, less commonly pancreatitis or malignancy related	Incidental or abdominal pain or mass effect
Typical imaging characteristics	Microcystic/honeycomb appearance Oligocystic appearance less common May have central scar or calcification	Unilocular or septated cyst ± wall calcifications Solid component, if present, may suggest malignancy	Dilated main pancreatic duct ± parenchymal atrophy Solid component, if present, may suggest malignancy	Dilated pancreatic duct branch or branches Solid component, if present, may suggest malignancy	Solid and cystic mass ± calcifications
Typical aspirate characteristic	Thin, often bloody	Viscous	Viscous	Viscous or thin	Bloody
Typical cytology findings	Cuboidal cells that stain positive for glycogen; yield <50%	Columnar cells with variable atypia Stains positive for mucin; yield <50% High yield from solid component for malignancy	Columnar cells with variable atypia Stains positive for mucin; yield <50% High yield from solid component for malignancy	Columnar cells with variable atypia Stains positive for mucin; yield <50% High yield from solid component for malignancy	Characteristic branching papillae with myxoid stroma High yield from solid component
Typical carcinoembryonic antigen (CEA) level	<5 to 20 ng/mL in majority of lesions	>200 ng/mL in approximately 75% of lesions	Typically elevated (limited data)	>200 ng/mL in approximately 75% of lesions	Insufficient data
Typical glucose level	>50 mg/dL in majority	<50 mg/dL in majority	<50 mg/dL (limited data)	<50 mg/dL in majority	Insufficient data
Typical DNA analysis	VHL mutation specific	K-ras mutation specific (>90%), not sensitive (<50%) TP53, PTEN, PIK3CA mutations seen in malignancy	K-ras and GNAS mutation specific (>90%), not sensitive (<50%) TP53, PTEN, PIK3CA mutationsseen in malignancy	K-ras and GNAS mutation specific (>90%), not sensitive (<50%) TP53, PTEN, PIK3CA mutationsseen in malignancy	CTNNB1 mutation specific
Relative malignant potential	Negligible	Moderate	High	Low to moderate	Moderate to high
Treatment	Resect if symptomatic	Resection	Resection and post-resection surveillance	Monitor or resect Post-resection surveillance required	Resection

Cystic neoplasms (classified according to WHO histologic criteria)

Mucinous

Intraductal papillary mucinous neoplasms (IPMN)

- - Mucinous epithelial neoplasms which arise from pancreatic ducts
  - Pathophysiology
    - Composed of mucin-producing columnar cells
    - Classified as low-grade, moderate, and high-grade dysplasia; and presence or absence of invasive malignancy
    - Four subtypes:
      - Gastric
        Primarily BD-IPMN
        
        Typically low-grade
      - Intestinal
        Most common type of MD-IPMN
        
        Found in pancreatic head
      - Pancreaticobiliary
        Typically involves main duct, in pancreatic head
        
        Greatest likelihood of malignancy
        
        Poor prognosis
      - Oncocytic
  - Classification
    - Main duct
      - Diffuse or segmental involvement of the main PD, with radiographic findings of main duct >5mm without any other cause of obstruction
      - Risk of high-grade dysplasia or invasive carcinoma (30-50% risk of invasive cancer at time of presentation)
    - Branch duct
      - Involve smaller side branches but not main duct
      - Typically occur in younger patients
      - More common than main duct (10:1)
      - Can occur anywhere in pancreas
      - Often multifocal (multiplicity of cysts favours BD-IPMN)
      - Lower risk of malignant transformation
      - Overall risk of invasive malignant disease is 10-15% (2-3% per year)
    - Mixed
      - Side branch IPMNs that extend into the main duct, and often lead to upstream dilation
      - Behave clinically like main duct lesions - 30-50% risk of invasive malignancy at presentation
  - Clinical presentation
    - Most commonly 50-70yo
    - Mostly found incidentally
    - If symptoms are present, they are non-specific
    - Can develop pancreatitis-like symptoms, especially with MD-IPMN
  - Diagnosis
    - Imaging
      - CT and MRI are equivalent for tumour type, location, development of additional lesions, lymph node and organ mets, invasion
      - MRI better for ?septae and ?mural nodules and ?solid components and more accurately defines involvement of main PD
    - Endoscopy
      - Fish-mouth sign - pathognomic
      - Other features below on EUS
  - Management
    - MD-IPMN or mixed-type IPMN: Resect if medically fit
    - BD-IPMN: Risk stratification with Fukuoka guidelines
      - High-risk stigmata (surgery recommended if any one of these)
        Enhancing mural nodule >5mm
        
        Main duct size >=10mm
        
        Obstructive jaundice
      - Worrisome features (needs EUS if any of these)
        Size >3cm
        
        Main PD size 5-9mm
        
        Abrupt change in calibre of PD with distal pancreatic atrophy
        
        Symptoms other than jaundice
        
        Thickened, enhancing cyst walls
        
        Enhancing mural nodule <5mm
        
        Extra worrisome features according to Sabiston: clinical pancreatitis, elevated CA 19-9, cyst growth of >5mm over two years
      - EUS/histo features: (operate if any of these)
        Definite mural nodule/s >=5mm
        
        Main duct features suspicious for involvement
        
        Cytology suspicious or positive for malignancy
      - Other factors
        FHx pancreatic cancer (two or more first-degree relatives)
        
        Inability to tolerate surgery
        
        Patient preference
    - Operations
      - Extent of resection depends on location and pathologic features
      - BD-IPMN - target the lesion of concern with partial pancreatectomy
      - MD-IPMN - harder to determine the extent of microscopic abnormality within the duct. Generally right-sided pancreatectomy with frozen section, with total pancreatectomy for those with HGD/cancer at margin.
  - Prognosis
    - Survival 77% 5 years for non-invasive IPMNs
    - 43% for invasive IPMNs
  - Surveillance
    - See below
  - Extra-pancreatic malignancy
    - High-risk for cancer in other places
    - Frequent locations include breast, colon and prostate

Mucinous cystic neoplasms (MCN)

- Mucin-producing cystic tumours which do not communicate with the pancreatic duct (therefore different from IPMN)
- Pathophysiology
  - Dysplastic neoplasms with clear-cut malignant potential
    - Felt to follow adenoma-to-carcinoma sequence - malignancy risk 5-15%
    - When invasive type, not as aggressive as ductal adenocarcinoma
    - 5 year survival 50-60% expected after resection
    - Mostly offer adjuvant chemotherapy, especially with positive nodes
  - Singular, large, thick-walled cysts, lined with mucin-secreting columnar epithelium, almost never communicating with ductal system
  - Pathology shows 'ovarian-type' stroma within the cyst capsule, typically seen histologically after resection
  - Stain positive for oestrogen and progesterone in most cases
- Presentation
  - Strong female predilection, most commonly seen in body and tail of pancreas
  - Mean age at presentation 45yo
  - 20% have had pancreatitis
  - Often initially misdiagnosed as pseudocyst - to differentiate, may need FNA with aspirate showing a fluid high in mucin and CEA (pseudocyst is higher in amylase)
  - Typically asymptomatic - 50% can have vague abdominal pain
- Imaging
  - Solitary cyst with fine septations and a rim of calcification
  - Eggshell calcification, larger tumour size, or a mural nodule on cross-sectional imaging are suggestive of malignancy
- Aspirate
  - Mucin-rich
  - CEA > 192mg/ml
  - Low amylase
- Management
  - Recommend resection in ALL suitable operative candidates - usually distal pancreatectomy. Curative if no invasive malignant disease.
  - Observation may be considered in medically unfit patients
Nondysplastic mucinous cysts (NDMC)
- Unclear whether these cysts are entirely benign or represent the earliest stage of MCNs
- Solid pseudopapillary neoplasm
- Lymphoepithelial cysts

Serous cystic neoplasm

- Serous cystadenoma
  - Epidemiology
    - Tend to occur in older patients
  - Pathology
    - Benign
    - True epithelium lined with glycogen-rich, clear, cuboidal cells that stain positive for periodic acid-Schiff
    - Don't communicate with ductal system
    - Mostly found HOP, but can be anywhere in gland, variable size and morphology
    - FNA of cyst fluid yields clear serous fluid low in CEA and mucin
    - Sometimes see cellular atypia leading to diagnostic uncertainty
  - Presentation
    - Often completely asymptomatic
    - Commonly present with vague pain
    - Can cause mass symptoms (uncommon)
      - Bile duct obstruction
      - Pancreatic duct obstruction
      - Gastric outlet obstruction
  - Imaging
    - Thin-walled capsule with microcystic pattern with thin-walled septae
    - 'Sun-burst' pattern due to central calcification and radiating septa (seen in 10-20%)
  - Management
    - Given they are overwhelmingly benign, observation is the rule
    - Some will increase in size, up to about 0.5cm/year
    - Larger cysts can increase more quickly
    - Intervention indications
      - Symptomatic lesions (generally need to be >4cm)
      - Consider intervention for larger cysts or rapidly-enlarging ones
- Serous cystadenocarcinoma (very rare)
  - Thought to represent malignant degeneration of SCA
  - There are only about 50 cases in the literature

Solid pseudopapillary neoplasms (SPN)

- Usually occur 10-30yo
- F>M (90%)
- Usually incidental, or abdominal mass effect causing pain
- Typically seen as a solid and cystic mass +/- calcifications
- Bloody aspirate
- Cytology - characteristic branching papillae with myxoid stroma
- Resect when found
- Generally considered a low-grade malignancy, although prognosis is good if resected

Autoimmune pancreatitis

See section under pancreatitis

Acinar cell carcinoma

Rare, with unique features
Arise from acinar cells - site of synthesis of exocrine enzymes
Risk factors
- Mid-50s
- Males
Presentation
- Non--specific symptoms
- Often >5cm at diagnosis
- Sometimes generate lipase - can cause paraneoplastic syndromes in some patients
  - Polyarthralgia
  - Eosinophilia
  - Subcutaneous fat necrosis and rashes ('pancreatic panniculitis')
- Mostly malignant - should be resected
- Better prognosis than PDAC

Primary pancreatic lymphoma

Exceedingly rare - once in a career type diagnosis
Vague symptoms including B symptoms
Diagnosed on FNA
Treatment
- Chemotherapy is first-line (CHOP)
- Resection is very difficult and fraught with complications

Metastatic lesions

Rare
RCC can do it
Also melanoma, breast, lung, colon, gynae
Mostly seen as hypervascular tumours, which is unusual in the pancreas