Week 9 Part 1 - Liver FNA Flashcards
Advantages: FNA vs Biopsy
Less invasive thus less complications
Samples over a wider area
Multiple passes
Disadvantages: FNA vs Biopsy
Not useful in diffuse disease
Limited material thus less architectural information
Requires skilled radiologist and cytologist
Complications in FNA
Haemorrhage (bleeding disorders are a contra-indication)
Peritonitis
Seeding by tumours
Anaphylaxis in hydatid disease
Pitfalls in FNA
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
Benign Liver FNA - Presentation
Asymptomatic
Symptomatic: mass, pain, liver dysfunction, systemic effect of tumour
Benign Liver FNA - Cytology
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
Hepatocellular Carcinoma (HCC) - Architecture
Large fragments and dispersed cells
Widened trabeculae
Rounded islands/acini
Necrosis
HCC Vasculature
Well defined capillaries traversing fragments
Endothelial rimming of islands
HCC Cell Cytology
Polygonal cells with central nuclei
Increased nuclear size
Increased N/C ratio
HCC Nuclear Cytology
Atypia: hyperchromasia and irregular nuclear membranes
Macronucleoli
Multinucleation
Intranuclear inclusions
Stripped atypical nuclei
HCC Cytoplasm
Fat and glycogen
Bile as coarse plugs
HCC Cell Block
Fragments with the reticulin stain showing reduced reticulin
Wide trabeculae
Rounded islands
Acini
Reticulin stain - widened trabeculae
HCC Subtypes - Fibrolamellar Hepatocellular Carcinoma
Fibrous lamellae with adherent malignant hepatocytes
Round nuclei, prominent nucleoli and abundant granular cytoplasm
HCC Subtype - Clear Cell Hepatocellular Carcinoma
The clear cytoplasm may represent fat, glycogen or degenerative change
HCC Subtype - Pleomorphic (Giant Cell) HCC
The giant cells are mixed with malignant hepatocytes of more normal size
Well Differentiated HCC (WDHCC) vs Benign
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
Reticulin Staining in Benign vs WDHCC
Benign: a normal sinusoidal framework
Malignant: a loss of the framework
Poorly Differentiated HCC vs Other Malignancies
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
Common Differential Diagnoses - Liver FNA
FNH vs Adenoma vs HCC
HCC vs MRN in cirrhosis
HCC vs Metastases vs Cholangiocarcinoma
Metastases in Liver FNA
Very common, the liver acts as a filter
Usually show the characteristics of the primary tumour
History is very important
Cholangiocarcinoma - Overview
An adenocarcinoma arising from the biliary epithleium
Difficult to differentiate from metastatic adenocarcinoma
Cholangiocarcinoma - Cytology
Cohesive groups with nuclear enlargement and pleomorphism
Cuboidal/columnar cells with eccentric, round to oval nuclei and abundant cytoplasm
IHC in Cholangiocarcinoma
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
GIST
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%)
GIST Patient Disease
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
GIST Clinical Presentation
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
GIST and EUS-FNA
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
GIST Cytology
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
