Week 9 Part 1 - Liver FNA

Question 1

Advantages: FNA vs Biopsy

Answer 1

Less invasive thus less complications
Samples over a wider area
Multiple passes

Question 2

Disadvantages: FNA vs Biopsy

Answer 2

Not useful in diffuse disease
Limited material thus less architectural information
Requires skilled radiologist and cytologist

Question 3

Complications in FNA

Answer 3

Haemorrhage (bleeding disorders are a contra-indication)
Peritonitis
Seeding by tumours
Anaphylaxis in hydatid disease

Question 4

Pitfalls in FNA

Answer 4

The radiological appearance or clinical history may be misleading
Cells from other structures picked up en route eg mesothelium,
bowel
The material is not representative

Question 5

Benign Liver FNA - Presentation

Answer 5

Asymptomatic
Symptomatic: mass, pain, liver dysfunction, systemic effect of tumour

Question 6

Benign Liver FNA - Cytology

Answer 6

Sheets or aggregates in trabecular arrangement
Nuclei: single (binucleated), central, round, even chromatin, single nucleolus
Low N/C ratio
Cytoplasm: abundant, polygonal, dense, distinct border
Cytoplasm can have lipid
Sheets/tubules of bile duct epithelium

Question 7

Hepatocellular Carcinoma (HCC) - Architecture

Answer 7

Large fragments and dispersed cells
Widened trabeculae
Rounded islands/acini
Necrosis

Question 8

HCC Vasculature

Answer 8

Well defined capillaries traversing fragments
Endothelial rimming of islands

Question 9

HCC Cell Cytology

Answer 9

Polygonal cells with central nuclei
Increased nuclear size
Increased N/C ratio

Question 10

HCC Nuclear Cytology

Answer 10

Atypia: hyperchromasia and irregular nuclear membranes
Macronucleoli
Multinucleation
Intranuclear inclusions
Stripped atypical nuclei

Question 11

HCC Cytoplasm

Answer 11

Fat and glycogen
Bile as coarse plugs

Question 12

HCC Cell Block

Answer 12

Fragments with the reticulin stain showing reduced reticulin
Wide trabeculae
Rounded islands
Acini
Reticulin stain - widened trabeculae

Question 13

HCC Subtypes - Fibrolamellar Hepatocellular Carcinoma

Answer 13

Fibrous lamellae with adherent malignant hepatocytes
Round nuclei, prominent nucleoli and abundant granular cytoplasm

Question 14

HCC Subtype - Clear Cell Hepatocellular Carcinoma

Answer 14

The clear cytoplasm may represent fat, glycogen or degenerative change

Question 15

HCC Subtype - Pleomorphic (Giant Cell) HCC

Answer 15

The giant cells are mixed with malignant hepatocytes of more normal size

Question 16

Well Differentiated HCC (WDHCC) vs Benign

Answer 16

Reticulin stain - discontinuous
CD34 +ve
P53 +ve
HepPar1 +ve
PCNA (proliferating cell nuclear antigen +ve)
AgNORs (Argyrophilic tech for nucleolar organiser regions)
DNA Ploidy
Telomerase shortening and microsatellite instability
CDKN2A and CDKN1A no expression = HCC
ßcatenin or TP53 mutations are never seen in preneoplastic liver lesions

Question 17

Reticulin Staining in Benign vs WDHCC

Answer 17

Benign: a normal sinusoidal framework
Malignant: a loss of the framework

Question 18

Poorly Differentiated HCC vs Other Malignancies

Answer 18

Cytologic features of HCC differentiation
IHC:
- alpha-feto protein (other protiens)
- Hep Par 1 (OCH1E5)
- albumin (IPOX or ISH)
- cytokeratins (7, 19, 20)
- polyclonal CEA (also CD 10)
- MOC-31
EM - glycogen, lipid, mitochondrial FEATURES

Question 19

Common Differential Diagnoses - Liver FNA

Answer 19

FNH vs Adenoma vs HCC
HCC vs MRN in cirrhosis
HCC vs Metastases vs Cholangiocarcinoma

Question 20

Metastases in Liver FNA

Answer 20

Very common, the liver acts as a filter
Usually show the characteristics of the primary tumour
History is very important

Question 21

Cholangiocarcinoma - Overview

Answer 21

An adenocarcinoma arising from the biliary epithleium
Difficult to differentiate from metastatic adenocarcinoma

Question 22

Cholangiocarcinoma - Cytology

Answer 22

Cohesive groups with nuclear enlargement and pleomorphism
Cuboidal/columnar cells with eccentric, round to oval nuclei and abundant cytoplasm

Question 23

IHC in Cholangiocarcinoma

Answer 23

Usually P53, bcl-2 and Ki-67 are helpful to discriminate Cholangio ca from HCC
Difficult to determine less well differentiated carcinomas of cholangio type from metastatic adenocarcinoma, particularly those of pancreatic origin
- both positive for CK7 and CK19
- negative for CK20
Distinction from HCC relies on adenocarcinoma showing + for mucin and diffuse cytoplasmic staining for CK7, CK19 and pCEA and HCC shows staining for alph fetoprotein and HepPar-1

Question 24

GIST

Answer 24

Gastrointestinal Stromal Tumours
GIST are rare mesenchymal neoplasms of the GIT and are rare < 40yrs age
Derived from malignant transformation of Cajal, c-kit positive cells of neuroendocrine origin, that play a role in peristalsis
GIST are somatic mutations in the tyrosine kinase kit gene
Most common sites of origin include:
- stomach (60%)
- jejunum and ileum (30%)
- duodenum (5%)
- colorectum (<5%)

Question 25

GIST Patient Disease

Answer 25

Patients with GIST usually have localised (resectable) or advanced (met and locally advanced, unresectable) disease
Advanced gist; inhibition of mutated c-kit with imatinib, a tyrosine kinase inhibitor has improved long term outcome, OS >55 months
Pre-imatinib; patients with adv disease, overall survival were <12 months
Surgical resection is the standard care for localised primary gists

Question 26

GIST Clinical Presentation

Answer 26

10-30% of patients with GIST may be completely asymptomatic with the tumour being incidentally discovered
Symptoms at the time depend on the location and size of the tumour
Dysphagia and weight loss appear to be the most common symptoms of oesophageal GIST’s
Associated with GIT bleeding (20% - 50%), abdominal pain (40%-50%) or a palpable mass (25%-40%)
Partial or complete intestinal obstruction and intussusception can occur
Malignant behaviour such as invasion to adjacent organs

Question 27

GIST and EUS-FNA

Answer 27

EUS-FNA has emerged as an important diagnostic tool for patient’s with GIST
However, differentiating benign from malignant GIST can be challenging and requires further IHC methods
CB preparation must be performed for CD117 expression, highly specific for GIST lesions
Ki-67 expression is required to determine the mitotic activity and cell proliferation for a malignant diagnosis
EUS-FNA used in this setting demonstrates a sensitivity and specificity of 100% for malignant gist lesions

Question 28

GIST Cytology

Answer 28

Characterised by tightly or loosely cohesive clusters of spindle-shaped cells
Elongated blunt ended uniform nuclei and scant eosinophilic cytoplasm with occasional cytoplasmic vacuoles indenting nucleus
Cell may be embedded in a delicate fibrillary background
In epithelioid cell types, the cells are loosely cohesive, round or polygonal with a coarsely granular chromatin and slightly irregular nuclear membrane
Req IHC for dx, and >5 mitoses/50 hpf
Presence of necrosis is helpful