Liver Cytology

Basics

Hepatic abscess

Hyatid cyst

Solitary cyst

Cirrhosis

Focal nodular hyperplasia (FNH)

Hepatic adenoma

Bile duct Hamartoma

Hemangioma

Angiomyolipoma

Hepatocellular carcinoma (HCC)

Cholangiocarcinoma

Hepatoblastoma

Angiosarcoma

Epithelioid Hemangioendothelioma

Metastatic malignancies

Basics

 

Core bx done c diffuse dz, whereas FNA done on masses or to eval transplants

- hepatitis not usually evaled by FNA

 

Normal liver cells are polygonal c central round slightly pleomorphic nuclei, binucleation is common, prominent nucleoli c lots of granular cytoplasm; common to see nuclear inclusions and pigmentation

- normal liver has hepatocytes, bile ductocytes (honey-comb sheets of polygonal cells slightly smaller than hepatocytes), Kupffer cells (macros) and mesotheliocytes

 

Hepatic adenoma, focal nodular hyperplasia, regeneration, and steatosis (has lipid vacuoles) can be mistaken as malig

 

 

Hepatic abscess

 

May be 2/2 bacteria, fungi, amoebas; MCC is staph/strep or enteric bacteria

- bacterial / fungal abscess has lots of neutros and possibly can see orgs

- amoebic has "anchovy paste", debris, little to no inflam, and amoebic trophozoites that can look like histiocytes (round nuclei c peripheral margination of chromatin c lots of cytoplasm)

 

 

Hyatid cyst

 

usually 2/2 Echinococcus granulosus

- can see the worm c scolix, hooklets, and frags of laminated membrane

 

 

Solitary cyst

 

Lined by simple cuboidal / columnar epithelium (similar to bile duct)

- FNA usually hypocellular

- ciliated foregut cysts have ciliated columnar cells and mucus cells present

 

 

Cirrhosis

 

Normal architecture replaced by liver cells surrounded by fibrous tissue

- can see hepatocytes c steatosis, but usually look normal; possibly may have focal atypia (severe nuclear pleomorphism, binucleation and prominent nucleoli)

-- may be difficult to differentiate from HCC (which has inc NC, thick trabecular arrangement of liver cells surrounded by endothelial cells and atypical naked nuclei)

 

 

Focal nodular hyperplasia (FNH)

 

 

2/2 focal vasculopathy, this b9 dz can be a solitary or multiple masses; MC in women in 20s-30s

- nodules usually have central scar (on imaging)

- hepatocytes are significantly atypical c normal trabeculae and sometimes steatosis

- not possible to differentiate just on cyto from b9 adenoma, regeneration or normal liver on FNA (need imaging) - though differentiating from adenoma should be done 2/2 malig potential of adenoma

-- core bx can be more helpful

 

IHC: (+) HepPar2, TTF-1, ARG-1, CAM5.2 and CEA (in canaliculi)

 

 

Hepatic adenoma

 

Rare, b9 dz in women <30 yo; assoc c OCP use that present c abdominal pain

- may rupture and have inc risk HCC (thus important to ddx from FNH [bile duct epithelium excludes adenoma])

 

Micro: no portal triads, normal hepatocytes c normal trabeculae, but "naked artioles" in cell block and bx

 

IHC: (+) HepPar2, TTF-1, ARG-1, CAM5.2 and CEA (in canaliculi)

 

 

Bile duct Hamartoma

 

Multiple small nodules throughout liver c strange bile duct arrangement and fibrous stroma, though are usually small (<1 cm) and subcapsular

- FNA is hypocellualr c b9 ductal cells in sheets c b9 liver cells

 

 

Hemangioma

 

MCC b9 liver tumor; core bx shows dilated vascular spaces c surrounding endothelial cells

- usually able to see on imaging and FNA not necessary (though may get FNA'd if look unusual)

 

Cyto: may only see blood or b9 hepatocytes; 3D config of spindle cells, which can be compact or solitary

 

 

Angiomyolipoma

 

MC in kidney, but may be seen in other places (liver is MC extrarenal location)

- pt usually ~50 yo; usually symptomatic, uncommonly rupture

- well-circumscribed; may be able to dx on imaging (just like in the kidney); only bx'd if atypia present

 

Cyto: amt of each component varies per lesion (ie fat, muscle, vessels); but usually see clusters of epitelioid, spindly, or fat cells, BVs and EMH

 

IHC: (+) HMB45 and MelanA (in myoid cells)

 

 

Hepatocellular Carcinoma (HCC)

 

MCC primary liver ca; usually in pts >50 yo c cirrhosis c AFP > 4000

 

3 classic patterns: trabecular, pseudoglandular (acinar) and compact

- subtypes exist such as fibrolamellar ca, scirrhous HCC, undifferentiated, lymphoepithelioma-lika and sarcomatoid

-- fibrolamellar variant seen in younger pts (mid 3rd decade) not assoc c cirrhosis, excellent px

- also a lot of variants (spindle cell, pleomorphic, fatty change) that can mimic other carcinomas

 

Spectrum of well- (resemble normal liver) to poorly-differentiated (pleomorphic c giant tumor cells)

- may be hard to differentiate b9 liver from well- and moderately-differentiated HCC

 

Cyto: hypercellular c some single or naked cells c large nuclei and inc NC sometimes intranuclear inclusions (nonspecific) and prominent cytoplasmic bile (more specific)

- cellular monomorphism, macronuclei, crowding, mits, nuclear crowding, multinucleation and capillaries in tumor groups

- thick fibrous trabeculae wrapped c endothelial cells

- acini, still c inc NC (better seen on cell block)

 

IHC: (+) reticulin (highlights thick trabeculae; hepatocytes >2 cells thick); CD34 (endothelial cells); Glypican-3 (GPC-3; usually negative in b9 hepatocytes); HepPar1; canalicular CEA / TTF-1 / ARG-1, CK 8 / 18

- negative CK7 / 17 / 19; cytoplasmic CEA, mucicarmine

 

 

Cholangiocarcinoma

 

2nd MCC primary liver ca; risk factors: primary sclerosing cholangitis, hepatolithiasis; parasites (Clonorchis sinensis), nonbiliary cirrhosis; thorotrast deposition; pts present c obstructive jaundice

- transperitoneal bx assoc c inc risk of mets

 

Klatskin tumor (hilar cholangiocarcinoma) is a cholangiocarcinoma arising near junction of rt or lt hepatic ducts

 

Cyto: isolated, clustered, crowded cuboidal / columnar cells c glandular differentiation and big pleomorphic nuclei

 

IHC: (+) mucicarcmine, AE1 keratin, polyclonal CEA (diffuse cytoplasmic), CK 7 / 17 / 19, p53

- negative SMAD4

 

 

Hepatoblastoma

 

Rare, seen in inflancy; mimics HCC

 

 

Angiosarcoma

 

Rare (<1% of hepatic ca's); assoc c cirrhosis (in 1/3 of pts), polyvinyl chloride, Thorotrast

- FNA / bx can cause massive bleeding

 

Cyto: well-diff has spindle cells that can be isolated or in tight clusters

- poorly-diff has big spindlly or epithelioid cells c pleomorphic multinucleated GCs

- can also look rhabdoid

 

IHC: (+) CD31 / 34, ERG

 

 

Epithelioid Hemangioendothelioma

 

Rare, seen in liver and elsewhere; less aggressive than angiosarcoma

 

Cyto: usually hypocellular in clean background; solitary large polymorphic cells c folded nuclear outline; metachromatic stroma; binucleation / MNGCs; round irreg nuclei c prominent nucleoli, abundant lacy / dense cytoplasm sometimes c intracytoplasmic lumina

 

 

Metastatic Malignancies

 

Colorectal - tall, dark necrotic; (+) CK20, CDX2, SATB2

 

Gastric - intestinal / signet ring morphology

 

Breast ca - ductal / lobular / variable differentiation; sometimes signet ring; (+) mammaglobin, GCDFP-15; ER/PR, HER2neu

 

Prostate - microacini, prominent nucleoli; (+) PSA or prostatic acid phosphatase

 

Well-diff neuroendocrine tumors - eccentric nuclei c "salt n peppa" chromatin, lots of granular cytoplasm, single cells in loosely cohesive clusters and rosettes; (+) synaptophysin, chromogranin, CD56; islet-1 and PAX-8 (if pancreatic)

 

Small cell ca - isolated / loosely cohesive, nuclear molding, hyperchromatic nuclei c finely granular chromatin, paranuclear blue bodies

 

Squamous cell ca - small dark nucleus w/o discernible texture, abundant cytoplasm c glassy appearance; (+) keratins, p63

 

Melanoma - single cells c intranuclear pseudoinclusions and macronucleolus, abundant cytoplasm, (+) S-100, HMB-45, Mart-1

 

Sarcoma - spindle-shaped, round or pleomorphic

 

References

 

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