Hepatic Malignancy Diagnostic

Testing Update
Brian Wasita
Department of Pathological Anatomy Faculty of Medicine
Universitas Sebelas Maret/Moewardi General Hospital Surakarta
 Tumors Classification

Anatomical Pathology Diagnosis of Liver Malignancy

Tissue Biomarkers

Outline Diagnostic Problems in Liver Malignancy

Blood Biomarkers

Future Biomarkers

Cases (Moewardi General Hospital Experience)

 Pathological diagnosis is the gold standard of
primary liver cancer, whose main detection
methods include hematoxylin and eosin (H&E)
staining and immunohistochemistry (IHC).

Pathology Tissue biomarkers are the true reflection of tumor

Anatomic tissue structure and cell morphology and are
more objective and accurate than various

Diagnosis imaging
examinations.
examinations and chemical

Therefore, tissue biomarkers serve an important

role in the diagnosis, differential diagnosis,
treatment and prognosis of patients with benign
tumors, HCC, ICC and cHCC-CC

(Gao et al, 2020)

 Cytological diagnosis

Anatomical
Histopathological
Pathology diagnosis
Diagnosis
Molecular diagnosis
1. Cytological diagnosis
• Diagnosis based on cells morphology
• Sample sources: Fine Needle Aspiration Biopsy (FNAB),
Ascites
• Fine needle aspiration (FNA) and small needle core
biopsies of the liver under a guidance of computed
tomography (CT) or ultrasound (US) are very useful
approach in the diagnosis of malignant liver neoplasms,
with sensitivity ranging from 75% to 94% and specificity
ranging from 87% to 100% (Chen et al, 2014).
Fine Needle Aspiration Biopsy (FNAB)

(Dean and Gharib, 2000)

(Appelbaum et al, 2009)
(Orell and Sterrett, 2012)
 • Diagnosis based on tissue
morphologies
• Sample sources : core biopsy,
tumor resection
2. • Staining : Haematoxilin-Eosin
Histopathological staining
diagnosis • Gold Standard diagnosis:
Histopathological diagnosis
with molecular diagnosis
Core Biopsy
1. Thin needle biopsies.
• These typically yield cores with a diameter of less than 1 mm.
This width is adequate for evaluation of mass lesions but is
not recommended for evaluation of diffuse liver diseases
2. Large needle biopsies.
• These can be performed using suction needles (Menghini,
Klatskin, Jamshidi) or cutting needles (Vim-Silverman,
Trucut).

(Ferrell and Kakar, 2011)

Sample Adequacy
Core biopsy:
• Biopsies at least has 1.5 cm in length and at least has 1 mm
in width
• Biopsy spesimen should have more than 11 complete portal
tracts.

(Ferrell and Kakar, 2011)

(Ferrell and Kakar, 2011)
(Ferrell and Kakar, 2011)
 Diagnosis based on protein expression
of cells and tissue

Sample sources : cytology and

3. histopathology sample

Molecular Method : immunohistochemistry

diagnosis staining

Molecular diagnosis is companion

diagnosis of cytological and
histopathological diagnosis
Immunocytochemistry/Immunohistochemistry

• Immunochemistry is the identification of a certain

antigen in a histological tissue section or
cytological preparation via an antibody specific
to the antigen.

• IHC/ICC is one of the methods to detect protein

(Khoury et al, 2009)

(Key et al, 2006)
Application of IHC in Cancer

1. Diagnosis of tumors of uncertain origin

(carcinoma, sarcoma, lymphoma, melanoma,
cancer metastasis etc.)
2. Prediction of response to therapy (ER,PR,HER2,
CD117, PD-L1 etc)
3. Prognostic markers in cancer (Ki-67,HER2, etc)

(Duraiyan et al, 2012)

(Gao et al, 2020)
(Orell and Sterrett, 2012) (Ferrell and Kakar, 2011)
 Hepatocelular carcinoma vs
metastasis carcinoma

Diagnostic Hepatocelular carcinoma vs

intrahepatic cholangiocarcinoma
Problems in
Liver Hepatocelular carcinoma vs
Malignancy hepatoblastoma

Hepatocelular carcinoma with

intrahepatic cholangiocarcinoma
Hepatocelular carcinoma vs
metastasis carcinoma
IHC:
Positive: (CK) 8/18, Hep Par 1 Glypican-3, and
p-CEA
Negative : CK7, CK20, synaptophysin, CDX-2,
TTF-1), PSA.

(Ferrell and Kakar, 2011)

(Ferrell and Kakar, 2011)
(Ferrell and Kakar, 2011)
IHC:
Positive: MOC31, ER, and mammaglobin
Negative: Hep Par 1.
(Ferrell and Kakar, 2011)
(Ferrell and Kakar, 2011)
IHC
Positive: Vimentin and CD117
Negative: GPC-3, pCEA, CK19, Pancytokeratin, S-100, Melan-A, SMA

(Ferrell and Kakar, 2011)

Hepatocelular carcinoma vs
intrahepatic
cholangiocarcinoma
(Ferrell and Kakar, 2011)
IHC
Positive: MOC 31, CK7, CK19, pCEA
Negative: Hep Par 1, AFP, CK5/6, p63, chromogranin, synaptophysin

(Ferrell and Kakar, 2011)

Hepatocelular carcinoma vs
hepatoblastoma
(Ferrell and Kakar, 2011)
Hepatocelular carcinoma
with intrahepatic
cholangiocarcinoma
(Ferrell and Kakar, 2011)
The glandular component is positive for
cytokeratin AE1/AE3, CAM 5.2, CK7, and CK19 and
negative for Glypican 3 and Hep Par 1 and also
focally positive for cytoplasmic mucicarmine.
The hepatocellular component is positive for Hep
Par 1 and Glypican 3 and negative or weakly and
focally positive for CK7

(Ferrell and Kakar, 2011)

Blood
Biomarker

(Gao et al, 2020)

Promising
Biomarker

(Gao et al, 2020)

(Gao et al, 2020)
(Gao et al, 2020)
Cases (Moewardi General
Hospital Experience)
• A 47-year-old woman with jaundice
• USG: multiple liver nodules, intra and extra
hepatic cholestasis
• AFP : 5.8
• Biopsy: 0.1 cc of tissue fragments
HepPar 1 CK 7 CK 20

Diagnosis: Intrahepatic Cholangiocarcinoma

• A 56-year-old woman with abdominal
pain and history of hepatitis B
• USG: multiple liver nodules
• Biopsy: 0.4 cc of tissue fragments
 CD117

Diagnosis: Metastasis GIST

• A 4-year-old girl with tumors in the kidney
and liver
• Liver biopsy: 0.7cc of tissue fragments
Synaptophisin Chromoganin

HepPar 1 : negative
CK7 and CK20 : negative
Diagnosis: Metastasis Neuroblastoma
There can be miracles
When you believe
Though hope is frail, it's hard to kill
Who knows what miracles you can achieve?
When you believe, somehow you will
You will when you believe

Mariah Carey, Whitney Houston

References
• Duraiyan J, Govindarajan R,Kaliyappan K,Palanisamy M. Applications of
immunohistochemistry. J Pharm Bioallied Sci. 2012; 4(Suppl 2): S307–S309
• Ferrell LD and Kakar S. Liver Pathology. 1st ed. New York: Demos Medical Publishing;2011
• Gao YX, Yang TW, Yin JM, Yang PX, Kou BX, Chai MY, Liu XN, Chen
DX.(2020).Progress and prospects of biomarkers in primary liver cancer (Review). Int
J Oncol. 2020 Jul;57(1):54-66.
• Key M. Immunohistochemical Staining Methods. 4th ed. Dako : California; 2006.
• Khoury T, Sait S, Hwang H, Chandrasekhar R, Wilding G, Tan D, Kulkarni S. Delay to
formalin fixation effect on breast biomarkers. Mod Pathol. 2009; 22(11):1457-1467.
• Orell SR and Sterrett GF. Orell & Sterrett’s Fine Needle Aspiration Cytology. 5th ed. New
York: Elsevier; 2012.
THANK YOU