Pancreaticobiliary Cytology Flashcards
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Pancreatic cysts: IPMN, MCN, SCA, SPN, and pseudocyst
Where are they found? CEA/Amylase? Genetics?
“High risk” genetic features of an IPMN or MCN?
p53, SMAD4, or p16/CDKN2A mutations
Reporting Terminology System for Pancreaticobiliary Cytology
- Nondiagnostic
- Negative for malignancy
- Atypical
- Neoplastic (Benign - serous cystadenoma, Other - mucinous cyst, well-differentiated neuroendocrine tumor, solid-pseudopapillary neoplasm)
- Suspicious for malignancy
- Positive for malignancy (PDAC, ACC, Neuroendocrine carcinoma, lymphoma, metastatic disease)
When aspirating from the pancreaticobiliary system, basically any _ is abnormal.
When aspirating from the pancreaticobiliary system, basically any mucin is abnormal.
You can have rare goblet cells in the large pancreatic and biliary ducts, but that is the only exception.
Most branch duct IPMNs are lined by. . .
. . . foveolar-type cells
You should always be conscious that individual cells with even high-grade atypia in a pancreaticobiliary cytology specimen may be. . .
. . . PanIN
Clues to an invasive pancreatic carcinoma
- Cells adjacent to attached adipose tissue
- Cells adjacent to arteries or nerves
- Reactive myxoid or desmoplastic stroma
How to tell apart cholangiocarcinoma from PDAC
Morphologically, they are IDENTICAL
You need IHC.
Biliary and pancreatic ductal stents
Can cause significant reactive changes and atypia.
You should hesitate to make a definitive diagnosis of malignancy in this setting.
The same is true of primary biliary processes, such as primary biliary cirrhosis and sclerosing cholangiitis.
PDAC (or cholangiocarcinoma, by morphology)
Adenosquamous variant PDAC
3-4% of PDAC.
Squamous component will be p40+.
Undifferentiated (anaplastic) pancreatic carcinoma
0.3 to 10% of PDAC.
Add “with osteoclast-type giant cells,” if present.
KRAS mutations will be found in ~90%, p53 mutations in ~50%. Giant cells, if present, will be negative for these mutations.
Well-differentiated pancreatic neuroendocriune tumor
Also called islet cell tumor
Associated with one of two mutually exclusive mutations in DAXX and ATRX. May occur at any age, but are most common in adults with a mean age of 40. Tend to be a circumscribed mass.
Rarely, may be secretory and may secrete: insulin, glucagon, somatostatin, VIP, pancreatic polypeptide, serotonin, ACTH, or calcitonin.
In the pancreas 65-80% of NETs demonstrate uneqivocal featuers of malignancy.
DDx for a circumscribed vs uncircumscribed pancreatic mass
Circumscribed: NET, SPN, acinic cell carcinoma
Uncircumscribed: PDAC
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Genetic alterations associated with pancreatic cysts
Serous cystadenoma: 3p25 deletion
IPMN: KRAS or GNAS alteration (high risk if p53, sMAD4, or p16 alteration)
Mucinous cystic neoplasm: KRAS alteration (high risk if p53, sMAD4, or p16 alteration)
Solid pseudopapillary neoplasm
Generally presents as a well circumscribed, encapsulated, heterogeneous pancreatic lesion with cystic degeneration on imaging. Usually in the pancreatic tail of a young woman (~30’s). Cyst fluid with low CEA and low amylase.
Characterized by plasmacytoid cells with reversed polarity surrounding “pseudopapillary” fronds, but slightly discohesive. Intracytoplasmic eosinophilic hyaline globules may or may not be present (shown).
Diffusely beta-catenin positive, alpha-1-antichymotrypsin positive. ~60% synapto positive, ~10% chromo positive.
E-cadherin membranous staining should be lost, and the tumor is slightly discohesive, although not like signet ring or lobular carcinoma.
Acinar cell carcinoma
Presents as a relatively large mass with a well defined margin, exophytic growth and heterogeneous enhancement. Serum AFP may be elevated. If metastatic, serum lipase may be elevated – in rare cases this may cause disseminated fat necrosis as a paraneoplastic syndrome.
May be associated with Lynch syndrome, FAP, or Carney complex, however most cases are sporadic.
Cytologically, cells come in acinar-like clusters, have prominent nucleoli, and oncocytic granular cytoplasm with a relatively preserved N:C ratio. As far as oncocytic neoplasms go, this is one of the relatively smaller ones. Cytoplasmic zymogen granules may be hard to see, but will be PAS positive and diastase resistant. Sometimes, you may just have stripped nuclei on a granular background.
Poor prognosis with an average life expectancy of ~20 months.
IHC: Diffusely BCL-10 positive and trypsin positive.
Mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN)
To make this diagnosis, the minor component should comprise at least 30% of the neoplasm. Components should have differentiation confirmed by IHC.
The neuroendocrine component tends to be a poorly differentiated neuroendocrine carcinoma, but rarely may be a well-differentiated neuroendocrine tumor. The non-neuroendocrine component can be PDAC or acinic cell carcinoma (sometimes both).
These tumors comprise only ~2% of PDACs, but 15-20% of acinar carcinomas.
These neoplasms are very rare and have a poor prognosis. Average ~70 years.
Serous cystadenoma
Grossly has multiple cysts, a central scar, and thin fibrous septae.
Histologically, cystic spaces are lined by bland appearing cuboidal to low columnar epithelial cells with abundant clear, glycogen rich (PAS+, diastase sensitive) cytoplasm. Nuclei are round and remarkably uniform with dense, homogenous chromatin and inconspicuous nucleoli. Often clear cell or regular low cuboidal, rarely may have an oncocytic cytology.
On cytology specimens, tumor is composed of uniform cuboidal cells in small clusters and flat sheets with round central-to-slightly eccentric nuclei and scant but visible cytoplasm that is homogeneous to clear.
IHC: Inhibin, CA9, HIF1a, VEGF, GLUT1 positive. Often good to throw on synapto/chromo, since every now and then a neuroendocrine will suprise you.
Molecular: VHL deletions (3p25 deletions). KRAS and GNAS mutations should NOT be identified – these suggest IPMN/PDAC.
Lymphangioma
Numerous small, mature lymphocytes
No epithelial cells (some duodenal/gastric contamination from biopsy is okay)
Nonmucinous background
Establishing mucin production in a cyst
- CEA over 192 (80% accurate)
- Visibly:
* Thick, colloid-like extracellular material
* Cellular or inflammatory debris within mucin
* Thin mucin covering the slide, confirmed with special stains for mucin (Alcian blue or mucicarmine) - KRAS/GNAS mutation
- Neoplastic cells with mucinous features, including
* Mucin within cytoplasm
* Mucinous caps
* Goblet cells
* Signet ring morphology
Calling suspicious for malignancy in a pancreas cyst
- Nuclei with irregular nuclear membranes
- Mucin-filled cytoplasmic vacuoles
- Marked nuclear crowding with overlapping nuclei
- Loss of polarity
- Nuclear moulding
- Size variation which approaches 4:1
- Significantly elevated N:C ratio (although not necessarily as high as other anatomic sites)
Pancreatoblastoma
Rare malignancy that most commonly occurs in childhood, but may happen in adults. Less aggressive when found in children.
Primarily acinar differentiation, but may have ductal or neuroendocrine differentiation as well. Often contain squamoid nests, the cells of which frequently have pseudoinclusions, which is a diagnostic feature. These pseudoinclusions contain intranuclear collections of biotin.
Labs: serum AFP often elevated (~70% of cases)
Molecular: Alterations in WNT apthway, chromosome 11p LOH, Beckwith-Wiedemann syndrome, FAP.
IHC: Squamous nests stain for beta catenin, CK5, and EMA.
Lipid rich pancreatic neuroendocrine tumor
A variant of pancreatic neuroendocrine tumor. Be sure to double check, as metastatic RCC and ectopic adrenocortical tissue can be mimics.
Pancreatic pseudocyst
By definition, these lesions lack an epithelial cyst lining. So, you shouldn’t see epithelial cells OTHER than in-transit biopsy contaminants (gastric or duodenal).
Should be otherwise entirely composed of inflammatory cells with prominent histiocytes. Yellow hepatoidin-like pigment is usually present.
On cyst fluid studies, CEA should be essentially dead negative while amylase will be sky high.
Lymphoepithelial cyst
Composed of anucleate squams, abundant keratin debris. Occasional mature squamous cells and lymphocytes of variable cellularity.
Cholesterol crystals may be present.
This is a solidly benign finding.
Ectopic spleen
Dense, cohesive tissue fragments with numerous dispersed small lymphocytes and plasma cells.
Large aggregates of platelets can be a good hint.
Best confirmed by demonstrating venous sinusoids with a CD8 stain, which is a hallmark of splenic tissue (shown).
Solid pseudopapillary neoplasm
Stromal metachromatic magenta material (arrows, corresponding to myxoid stroma) and foamy macrophages are classically seen.
Acinar cell carcinoma
Not always granular! These can be tricky and look a lot like a neuroendocrine tumor or solid pseudopapillary. Be sure to keep this on your differential!
Stains for digestive enzymes (trypsin) are best for confirmation.
