Editing 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]'''
{| class="wikitable"
| 
|'''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


[[Category:Pancreas]]