Hepatopancreatobilary Flashcards
35F head of pancreas lesion
Dx?
Key features?
IHC?
solid pseudopapillary neoplasm.
Well-demarcated, large mass
Solid, monomorphic sheets of polygonal cells
Delicate vessels surrounded by hyalinized or myxoid stroma
Characteristic degenerative change leading to pseudopapillae
Cytoplasmic eosinophilic hyaline globules, PAS-D positive
Uniform round to oval nuclei with finely dispersed chromatin
Neoplastic cells often have nuclear grooves
IHC: Immunohistochemistry: Nuclear β-catenin, loss of membrane E-cadherin, nuclear progesterone receptor, positive TFE3 and SOX11
acinar cell carcinoma of pancrease
(+) IHC
(+) chymotrypsin, trypsin, lipase, BCL10 (antibody directed against the -COOH terminal portion of BCl10 protein is highly specific). NB: Also can be (+) for AFP, Hep-PAR-1, glypican 3, albumin mRNA.
pancreas
solid pseudopapillary neoplasma IHC
nuclear b-catenin (+); CD10, CD56 (+)
E-cadherin shows lost membraneous staining
pancreatic ductal adenocarcinoma
Most common mutation?
KRAS activation point mutations.
> 90% show this (also in PanIN)
solid pseudopapillary neoplasm
immunophenotype:
Consistently (+) for:
- PR
- Abnormal beta-catenin
- vimentin
- alpha-1-antitrypsin
Consistently (-) chromogranin
Variable expression other neuroendocrine markers: SYN, CD56, NSE; epithelial markers EMA/keratin; other hormone receptors: OR/inhibin
Frequently mutated genes in pancreatic ductal adenocarcinoma vs IPMN
Types of IPMN and immunophenotype
ductal adenocarcinoma vs chronic pancreatititis
ductal adenocarcinoma vs chronic pancreatitis
38F pancrease
dx?
Neuroendocrine tumour
well circumscribed lesion head of pancreas
Dx?
Key features?
IHC?
Acinar cell carcinoma
Key features:
Unlike conventional ductal adenocarcinoma, this tumor is highly cellular and with scant fibrous stroma
Cells show moderate amounts of granular eosinophilic cytoplasm containing PAS positive diastase resistant zymogen granules
Nuclei are uniform with a typically present, single and prominent nucleolus
Can have different architectures and growth patterns, including cystic, acinar, glandular and intraductal
IHC:
(+): CK7, CK8/18, CK19, BCL10, trypsin
(-): chromo/synapto
Image: showing monomorphic nuclei with prominent nucleoli. NB: atypical and amorphous zymogen material
IPMN
subtypes (3) and which is most common?
Major mutations
Gastric (most common, 70%); gastric foveolar type epithelium + scattered goblet cells, most are low-grade
Intestinal type (2nd most common), intestinal type epi forming villous papillae, tall columnar cells with cigar shaped nuclei. Usu reveal HGD
Pancreatobiliary (least common):
Mutations: KRAS and GNAS (although KRAS is nearly a precursor to PDAC, GNAS is rarely found in these neoplasms)
IPMN vs IOPN vs ITPN
IHC comparison
cystic lesions in the pancreas
ddx
IMPN
IOPN
ITPN
Mucinous cystic neoplasm
Retention cysts
IMPN
IPMC may be associated with invasive carcinoma. Describe the types of carcinoma associated with which IPMN subtypes
The invasive ca can be of 2 main types:
1. Colloid carcinoma: infiltrating epithelial elements separated by abundant stromal mucin arising in a/w intestinal type IPMN.
2. Tubular (ductal) adenocarcinoma which is morphologically similar to conventional PDAC, arises either in a/w pancreaticobiliary type or gastric type IPMN.
60F pancreatic head lesion, cystic
Dx
IHC
IPMN, gastric type
IHC: CK7+, CK20-, EMA-, MUC2 -, MUC5AC+, MUC6 -/+, CDX2-
55M head of pancreas lesion
dx
IHC
IPMN, intestinal type
IHC
62M cystic lesion pancreas head
dx
IHC
IPMN, pancreaticobiliary
Note: the image shows cells to have little mucin production and enlarged round nuclei.
70M cystic lesion head of pancreas
dx
IHC
IPMN, intestinal type with HGD
IHC
NB: image shows complex architecture and the nuclei are stratified, hyperchromatic, and pleomorphic.
Neuroendocrine neoplasms of pancreas
types and grading
mixed neuroendocrine neoplasm
Diagnosis, % of each component etc
For a tumour to qualify as MiNEN, each component should account for ≥ 30% of the tumour cell population. Non-neuroendocrine carcinomas with scattered neuroendocrine cells by immunohistochemistry do not fulfil this criterion; the presence of focal (< 30%) neuroendocrine differentiation can be mentioned but does not affect the diagnostic categorization. MiNEN is a conceptual category rather than a discrete entity; individual diagnoses indicating the specific cellular components should be applied (i.e. mixed acinar-neuroendocrine carcinoma, mixed ductal-neuroendocrine carcinoma, etc.)
pancreatic neuroendocrine neoplasms
commonly mutated gene
The MEN1 gene is somatically inactivated in about 40% of PanNETs (TSG).
Approximately 40% of PanNETs showed mutation in either DAXX or ATRX. The function of DAXX and ATRX proteins is to maintain chromatin remodelling at telomeric and pericentromeric regions.
head of pancreas lesion, 67F
dx
IHC
Pancreatic neuroendocrine carcinoma, small cell type
Essential: a poorly differentiated neoplasm of small or large cells, with vague neuroendocrine features; usually weak expression of neuroendocrine markers; mitotic count of > 20 mitoses/2 mm2 and Ki-67 proliferation index > 20%.
Desirable: Ki-67 proliferation index > 50%.
acinar cell carcinoma
IHC
(+) trypsin, chymotrypsin, BCL10 (ab directed against the -COOH terminal portion of BCL10 protein) - highly specific and sensitive); CK7, CK19
NB: can be (+) for AFP, Hep-par 1, glypican 3, ablumin mRNA (FISH)
NB: can have focal + for chromo and synapta
serous cystadenoma (pancreas)
Associated with which condition
von Hippel Lindau disease
autoimmune pancreatitis
differences b/w type 1 and type 2
solid pseudopapillary neoplasm
key features and IHC
Nuclear grooves, foamy cells, eosinophilic DPAS globules, pseudopapillae, (+) ofor CD10 and nuclear beta catenin
PDAC vs chronic pancreatitis key features
cholecystectomy
Dx?
& key features.
Dx: adenomyoma.
Key features: Cystically dilated benign biliary glands accompanied by smooth muscle hypertrophy of gallbladder wall, thickened / fibrotic subserosa
IHC for HCC:
HSP70, glypican 3 and glutamine synthetase
Positivity for at least two of these markers strongly indicates HCC, with a near 100% specificity and 72% sensitivity. (WHO)
In terms of premalignant lesions for HCC, what is the difference between dysplastic nodules and dysplastic foci?
Dysplastic foci are < 1mm in diameter and are incidental lesions discovered on histo examination of livers w/ advanced fibrosis. Further subclassified into large-cell change, small-cell change and iron-free foci.
DN are usu 5-15 mm in diameter and detected either macroscopically or by imaging in cirrhotic livers. Classified into low-grade or high-grade based on the degree of cytological and architectural atypia. The vascular remodelling of DNs leads to a progressive shift from a venous to an arterial blood supply. Portal tracts are commonly retained in DNs, but they may be reduced in number as newly formed unpaired lobular arteries gradually increase from LG DN to HG DN to HCC.
Describe four morphological patterns of intracholecystic papillary neoplasm and associated IHC?
What % are a/w inv carcinoma.
Biliary: CK7/EMA (+)
Gastric morphology: (gastric foveolar). diffusely (+) MUC5AC.
Intestinal morphology: Resembles colonic adenoma. (+) CK20, CDX2, MUC2
Oncocytic: Diffusely (+) for EMA and NO labelling for MUC6
An associated invasive ca is identified in about half of all ICPNs.
Described the histological features (7) used to distinguish pancreatic ductal adenocarcinoma from chronic pancreatitis?
mutations in IPMNs and Mucinous cystic neoplasms
IPMN: KRAS, GNAS
MCN: KRAS
molecular pathology for solid pseudo papillary neoplasm
somatic activating mutation in exon 3 of CTNNB1 is the only genetic alteration known in SPNs.
Hepatocellular adenoma
RF
subtypes
Morphological features of subtypes
DDX + how to differentiated
RF: OCP, anabolic steroids, glycogenesis types 1 and 3, galactosaemia, tyrosinaemia.
Subtypes:
HNF1A-inactivated
Inflammatory HCA
beta-catenin activated HCA
beta-catenin activated inflammatory HCA
Morphology:
ALL: ill defined tumours, lacks fibrous capsule, b/g liver usu non-cirrhotic; cell plates 1-2 cells thick.
HNF1A-inactived: lobulated contours, diffuse macro/microsteatosis, ballooned and clear cells +/-pseudoglands
Inflammatory: sinusoidal dilatation, congestion, foci of inflammation, thick arteries+/- ductalr reaction. Fibrotic bands and nodular organization may be misleading for FNH.
b-acatenin-activated: cytoarchitectural atypia, pseudoglands, andpigments.
Ddx:
FNH (ddx for iHCA): map-like GS and (+) staining with inflammatory markers (serum amyloid A and C-reactive protein) in IHCA
HCC: thick cell, freq pseudoglands, small cell change, mitoses, and loss/fragmentation of the reticulin network are typical of HCC. IHC: glypican 3, HSP70, GS. Arterialised sinusoids (CD34+) are freq seen in HCCs (but can be seen in benign lesions include focal nodular hyperplasia and HCA)
Epithelioid angiomyolipoma: can show diffuse GS staining. demonstration of myomelanocytic differentiation by IHC confirms dx.
Pancreas IPMN
Commonest mutations?
KRAS and GNAS
Two subtypes of pancreatic inv ca arising in IPMN? associated with which type of IPMN?
Colloid and tubular.
Colloid -> intestinal (better px)
Tubular -> pancreaticobiliary
Pancreas, ITPN mutations
chromatin remodelling genes (KMT2A [MLL1], KMT2B [MLL2], KMT2C [MLL3], BAP1)
PI3K pathway genes (PIK3CA, PTEN)
A subset of cases harbour FGFR2 fusions { 28776573 }, which might be targetable.
genetic syndromes assocaited with PDAC
familial atypical multiple mole melanoma syndrome (FAMMM) (CDKN2A), Peutz-Jeghers syndrome (STK11), Lynch syndrome, hereditary pancreatitis (PRSS1), mutations in BRCA2/1 Hereditary breast and ovarian cacner syndrome), and mutations in Fanconi anemia complementation genes.
morphologic features used to distinguish PDAC vs chronic pancreatitis?
Histologic pattern
Rupture or incomplete glands
companian muscular vessel
Nuclear pleomorphism
PNI
angioinvasion
mitoses
common mutations in PDAC? (4)
KRAS
TP53
CDKN2A
SMAD4
most sensitive markers for acinar cell carcinoma
trypsin
chymotripsin
BCL10
genetic syndromes a/w PanNET
multiple endocrine neoplasia type 1 (MEN1 gene somatically inactivated in about 40%).
VHL
neurofibromatosis type 1
tuberous sclerosis
glucagon cell hyperplasia and neoplasia
familial insulinomatosis.
Mutations in MEN1, VHL, NF-1, and DAXX/ATRX
solid pseudopapillary neoplasm, IHC:
(+) PR, nuclear/cytoplasmic beta catenin, CD99 (dot-like), cyclin D1.
(-) trypsin and CGN, loss of E-cadherin.
pancreatoblastoma associated with which syndromes?
Beckwith-Wiedemann and Familial adenomatosis polyposis.
