Vol 3 Issue 1 Bio Sci Article No

281 | P a g e International Standard Serial Number (ISSN): 2319-8141
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International J ournal of Universal Pharmacy and Bio Sciences 3(1): J anuary-February 2014
INTERNATIONAL JOURNAL OF UNIVERSAL
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Bio Sciences RESEARCH ARTICLE !!!

HISTOMORPHOLOGICAL STUDY OF TUMOURS OF LIVER
Balramsingh Thakur
1
, Sharanbasappa Karaddi
2
, Sujatha B. Thakur
3
, Yogendra Patwari
4

1
Professor, Department of Pathology, Navodaya Medical College, Raichur, Karnatak, India.
2
Associate professor, Dept. of Forensic Medicine, Navodaya Medical College, Raichur, Karnatak,
India.
3
Consultant Gynecologist, Raichur, Karnatak, India.
4
Assistant Professor, Department of Pathology, Navodaya Medical College, Raichur, Karnatak,
India.

KEYWORDS:

Liver; Tumours;
Diagnosis.
For Correspondence:
Sharanbasappa Karaddi *
Address: Assistant
professor, Department of
ophthalmology, R L
Jalappa medical college ,
Tamaka Kolar,
Karnataka, India.

ABSTRACT
Metastastic tumours are more in number than primary metastastic
tumours. In the present study period metastatic tumours in the liver
were less frequent comparatively. This may be due to the fact that,
most of the malignant tumours after histological examination are
referred to referal cancer hospitals for further management. Needle
biopsies showed poorly differentiated carcinoma in four cases where
primary was unknown. As primary remained unknown in majority of
these metastatic lesions, examination by ultrasound guided needle
biopsy became essential for establishing the lesion. Aetiological
diagnosis of hepatic metastases is based on histological features of
these lesions. Tumour cell types observed in liver, in the decreasing
order of frequency were hepatic type; pleomorphic type; clear cell
type; anaplastic type; and spindle cell type. Intracellular inclusions
observed in this study were intranuclear cytoplasmic inclusions
globular hyaline bodies and Mallorys hyaline inclusions in varying
number of cases.


INTRODUCTION:
Liver is organ being affected by both benign and malignant tumours. The tumours can be
classified according to the indigenous cells of the liver from which they arise. Among the
primary malignant tumours, hepatocellular carcinoma is the most frequent worldwide male
cancer
3
. There is marked disparity in the incidence of this is based on geographic region which
suggests the role of environmental and hereditary causative factors. The different histological
patterns and cytologic variants of the tumours of liver and their association with certain diseases
makes their study, more challenging and interesting
1,2,3,4
. The metastatic malignant tumours in the
liver may produce the histology of lesions. At times, they may be anaplastic and give no hint of
their origin.
5
Such problems in histological interpretation of liver biopsy, emphasise the need to
take up this study.
MATERIALS AND METHODS:
This study was undertaken to observe the histomorphological features in primary and metastatic
malignant tumours of the liver. The material for the present study was collected from the data
available in the Pathology Department, Navodya Medicla college, Raichur, during the period of
ten years from January 2008 to December 2013. The study material consisted a total of 300 liver
tissue samples with histologically proven malignancy.
Liver tissue sampling and method of obtaining liver tissue were at the discretion of the clinician.
Liver tissue samples were subjected to naked eye examination and were fixed in 10% formalin.
They were routinely processed to obtain 5-7 micron thick paraffin sections. They were routinely
stained with Haematoxylin and Eosin stain. Other stains employed when required were Von
Giesons stain; Gomoris reticulin stain; Periodic acid schiff stain (with or without diastase) and
Prussian blue stain.
OBSERVATIONS:

0
50
100
150
200
250
300
350
21 30 31 40 41 50 51 60 61 70 71 80 Total
Males
Females
Total

Age: Age of the patients having hepatocellular carcinoma ranged from 21 years to 74 years. Peak
incidence was seen in the age group of 41-50 years.
Sex:Hepatocellular carcinoma was seen in 249 male patients and 48 female patients. Sex
incidence in the different age group showed male preponderance in all the age groups. Higher
incidence of hepatocellular carcinoma in males was seen in the age group of 41-50 years, while in
females there was varying incidence.
Laboratory Investigations: Serum bilirubin was higher in unconjugated fraction was seen in 39
patients with the values ranging from 4mg% to 7mg%. AST was high in 150 patients with the
values ranging from 50 to 110 I.U/L ALT was higher in 138 patients with the values ranging from
65 to 150 I.U/L. Serum alkaline phosphatase was in the range of 52 to 84 K.A. units in 138
patients. Albumin to globulin ratio in serum was reversed in two cases. Serum was found to be
positive for HbsAg in six patients, among 48 patients who were tested for HbsAg. Test for HCV
antibodies was done in one patient which showed absence of HCV antibodies. In 60 cases, where
ascites was seen, malignant cells were non seen in ascitic fluid.
Macroscopy: Needle biopsy was done in these specimens, were examined in 300 patients of
HCC. They were 0.5 to 1.5cms in length. Linear biopsies were obtained in 150 cases. Operative
wedge biopsy of liver was examined in one case of HCC. Size of the tissue was 3 x 2 x 1cms. It
was grey brown in colour and friable.
Microscopy:
Histological pattern: The histological pattern of tumour cells seen in this study, in the order of
frequency were trabecular pattern; trabecular and pseudoglandular pattern; compact pattern; and
pseudoglandular pattern.

Sl. No.
1
2
3
4
0
100
200
300
Histological Pattern
No. of Cases

1 Trabecular
2 Trabecular and pseudoglandular
3 Compact or solid pattern
4 Pseudoglandular

Trabecular pattern: This was seen in 192 cases. Tumour cells were arranged in cords which
were separated by sinusoids lined by flat endothelial cells.
Pseudoglandular pattern: This was seen in 15 cases. Tumour cells were arranged around a
central cystic space containing degenerated cells.
Trabecular and Pseudoglandular pattern: This was seen in 48 cases. In these cases, tumour
cells were arranged in both trabecular and pseudoglandular pattern.
Compact or solid pattern: This was seen in 42 cases. Tumour cells were apparently in solid
masses and sinusoids were inconspicuous. Scirrhous pattern was not noted in this study.
Cytological Features: In this study tumour cells of HCC were hepatic type, pleomorphic type,
clear cell type, anaplastic type and spindle cell type in the decreasing order of frequency.
TABLE V: SHOWING THE INCIDENCE OF TUMOUR CELL TYPES IN HCC
Sl.
No.
Clinical Features No. of Cases
1 Hepatic type 246
2 Pleomorphic type 30
3 Clear cell type 12
4 Anaplastic cell type 6
5 Spindle cell type 6
Total 300

Hepatic type: This type of tumour cells were more frequent, being observed in 246 cases. In
these cases tumour cells were polygonal with vesicular nuclei containing conspicuous nucleoli
and granular, slightly basophilic cytoplasm. In 75 cases, intranuclear cytoplasmic inclusions were
seen. In one case there were intracytoplasmic mallorys hyaline inclusions of irregular shape.
Intracellular and extracellular globular hyaline bodies of varying sizes were seen in two cases.
Intracytoplasmic bile droplets were seen in three cases.
Pleomorphic type: This type of tumour cells were observed in 30 cases. In these cases tumour
cells were having marked variation in cellular and nuclear size and staining. Nuclear
hyperchromasia was prominent. In these tumour cells, intranuclear cytoplasmic inclusions were
seen in two cases.

Clear cell type: This type of tumour cells were observed in 12 cases. These tumour cells were
having clear cytoplasm and large hyperchromatic nuclei. Para nuclear intra cytoplasmic globular
hyaline was observed in one case.
Anaplastic type: This type of tumour cells was observed in 6 cases. Tumour cells were poorly
differentiated and they were arranged in multiple cell plates. Intra nuclear cytoplasmic inclusion
was observed in one case.
Spindle cell type: This type of tumour cell was observed in 3 cases and the tumour cells were
spindle shaped and had irregular hyperchromatic nuclei and granular acidophilic cytoplasm.
Stroma: Stroma was very scanty containing delicate fibrous tissue in 294 cases. In one case
where ultrasonography revealed evidence of cirrhosis, stroma was showing abundant
fibrocollagenous tissue, but there was no conclusive evidence of cirrhosis in the needle biopsy
study.
Grading: According to the grading system devised by Edmondson, based on the degree of
cellular and architectural differentiation, majority of the tumours belonged to grade II in the
present study.
FIGURE SHOWING INCIDENCE OF HISTOLOGICAL GRADE.

Grade I: In this study 54 cases were categorized as grade I. Here the tumour cells were of
similar size of normal hepatocytes and were arranged in thin trabeculae.
Grade II: In this study 201 cases were categorized as grade II. In these cases tumour cells
were larger than hepatocytes and had large hyperchromatic nuclei.
No. of Cases
I
II
III
IV
Total

Grade III: In this study 33 cases were categorized as grade III. In these cases tumour cells
had large hyperchromatic nuclei occupying more than 50% of the cell.
Grade IV: In this study three cases were categorized as grade IV. In these cases, tumour cells
had large nuclei occupying most of the cell and intra sinusoidal growth was observed.
Macroscopy:
In these six patients ultrasound guided biopsy was performed, needle biopsies were linear, grey
white in colour, and measured 0.5 to 1cm in length.
Microscopy:
In these cases tumour cells were arranged as narrow tubular structures forming tubular pattern in
two cases. In one case tumour cells were forming compact masses.
In the remaining three cases, there was mixed pattern, where tumour cells were arranged in both
tubular pattern and compact masses. Tumour cells were large and were predominantly cuboidal in
all the six cases. A few columnar cells associated with mucous secretion was seen in one case. All
these tumours showed abundant fibrous stroma. Bile was not seen in these tumours.
HEPATOBLASTOMA
Micrscopy:
Tissue sections in this patient showed small fusiform tumour cells with hyperchromatic nuclei and
little cytoplasm. These cells were arranged in sheets. Stroma was showing primitive
mesenchyme. A diagnosis of mixed epithelial and mesenchymal type was considered in this case,
in view of ultrasonography findings.
METASTATIC TUMOURS IN LIVER
In the present study metastatic tumours in liver were less frequent. They were seen in 57 patients
among 125 cases of malignant liver tumours. Commonest histological type of metastatic tumour
was well differentiated adenocarcinoma, which was seen in 48 cases. Among these, primary was
in stomach in one patient, and another one was in the lower end of oesophagus. In the remaining
twelve cases, primary could not be identified. In four patients metastatic lesion was poorly
differentiated carcinoma and primary was unknown. Metastatic embryonal tumour was detected
in one patient by liver biopsy, where primary could not be located.


TABLE 4: SHOWING HISTOLOGICAL TYPES IN PRIMARY LESION IN
METASTATIC TUMOURS OF LIVER
Sl.
No.
Histological type
Primary
site
No. of
Cases
1 Well differentiated adenocarcinoma Stomach 3
2 Well differentiated adenocarcinoma Oesophagus 3
3 Well differentiated adenocarcinoma Unknown 48
4 Poorly differentiated carcinoma Unknown 12
5 Embyronal tumour Unknown 3
Total 69

Age:
Age of these patients having metastatic liver tumours ranged from 11 years to 71 years. 18
patients (31.58%) belonged to the age group of 41-50 years.
Sex:
In this study of 57 patients, 45 patients were males and 12 patients were females. Male to female
ratio was 3.75:1. Higher incidence of metastatic liver tumour 31.58% was observed in the age
group of 41-50 years.
Microscopy:
Metastatic adenocarcinoma was seen in 42 cases, where liver biopsy showed well differentiated
adenocarcinoma. Tumour cells were forming glandular pattern. These tumour cells were large
and had large vesicular nuclei with conspicuous nucleoli and pale vacuolated cytoplasm.
Subsequently these patients were subjected for detail examination to locate the primary. In one
patient repeat ultrasonography revealed an irregular growth in the body of stomach. In one case,
patient had growth in the lower end of oesophagus, detected by endoscopy. In the remaining 36
patients primary remained unknown.
In 12 patients liver biopsy showed metastatic poorly differentiated carcinoma, where tumour cells
were forming compact masses and sheets. These tumour cells were large and had large vesicular
nuclei pale staining cytoplasm, nuclear chromatin was irregularly condensed. In these patients
primary could not be ascertained.
DISCUSSION
Age incidence of tumors in the present study showed, more number of cases belonging to the age
group of 41-50 years. Many other authors have quoted increased incidence of tumors in the age
group of 41-50 years and 51-60 years.
5

Laboratory investigations revealed increased uncongugated fraction of serum bilirubin in 39
patients, increased AST values in 150 patients, increased ALT values in 138 patients and

increased serum alkaline phosphatase in 138 patients. In liver tumours, elevations in serum
alkaline phosphatase and lactic dehydrogenase levels are commonly found, LDH levels were not
estimated in this study. Mild to moderate transminase elevations are known to occur. None of
these parameters correlates well with the extent of the liver involvement. These parameters are
indicative of the need for further investigations and should never be used as sole criteria for the
diagnosis of liver tumours. Albumin to globulin ratio was reversed in two cases, where
ultrasonography revealed the evidence of cirrhosis with multifocal tumors.
In this study needle biopsy specimens were obtained in 300 patients of HCC and operative wedge
biopsy was examined in one case. Lobectomy specimens were not encountered. As needle
biopsies were done under ultrasonographic guidance, associated liver diseases were not identified
by histopatholgoy. Histological patterns of tumour cells observed in this study were trabecular
followed by trabecular and pseudoglandular, compact and only pseudoglandular patients. In other
studies also, the commonest histological pattern observed was trabecular pattern, followed less
frequently by other patterns.
7
Tumour cells were commonly of hepatic type and less frequently encountered tumour cell types
were pleomorphic type; clear cell type, anaplastic cell type and spindle cell type. Similar
observations were made in other studies.
8
In the present study intranuclear cytoplasmic
inclusions, intracytoplasmic Mallorys hyaline inclusions and globular hyaline bodies were seen
in a few cases. The commonest type of inclusion was eosinophilic intranuclear inclusion which
was showing characteristics of liver cell cytoplasm.
The value of this grading system is limited, since several grades may co-exist in a given tumour
and it was devised when fibrolamellar tumors was not clearly separated from classic tumors.
Although this grading method is disputed, there is no widely accepted method for grading
analplasia other than this.
In this study variants of tumors having improved prognosis with prolonged survival, which
includes, minute, small or encapsulated tumors, pedunculated tumors and fibrolamellar tumors
were not encountered.
9
The hepatoblastoma is one, in a unique category of malignant tumours that occur in children, and
whose histopatholgoic features recapitulate the developmental stages of the organs in which they
arise.
10
In the present study microscopy of hepatoblastoma showed mixed epithelial and
mesenchymal components.
With increasing use of guided needle biopsies in the diagnosis of malignant liver tumours,
histopathological study has become an important diagnostic tool. The clinician may now choose

from a variety of imaging techniques. It is recommended that these patients have base line and
serial liver scans, liver function tests and tumour marker estimations. There is no doubt that rapid
technologic improvements will continue to alter our diagnostic approach to this disease.
2
CONCLUSION
Primary malignant epithelial tumours were hepatocellular carcinom; cholangiocarcinoma and
hepatoblastoma. Hepatocellular carcinoma formed majority of malignant liver tumours.
In liver tumors, increase in uncongugated bilirubin, increase in transaminases and alkaline
phosphatase levels were observed in varying number of cases. A:G ratio was reversed in two
cases. Six patients of tumors were positive for HBs Ag.
Tumour cell types observed in liver, in the decreasing order of frequency were hepatic type;
pleomorphic type; clear cell type; anaplastic type; and spindle cell type. Intracellular inclusions
observed in this study were intranuclear cytoplasmic inclusions globular hyaline bodies and
Mallorys hyaline inclusions in varying number of cases. Majority of these belonged to grade II
according to grading system of Edmondson and Steiner. Metastatic tumours in liver formed some
of malignant liver tumours. Commonest histological type of metastatic lesions, was well
differentiated adeno-carcinoma. Primary was detected only in two cases of metastatic well
differentiated adeno-carcinoma. In the remaining cases, primary could not be located.
In the recent years there are rapid advances in the diagnostic imaging technology. This has led to
differences in experiences and results among investigators. Liver biopsy has become an essential
tool and diagnostic efficiency can be further improved when combined with immune
histochemistry, electron microscopic study and molecular biology techniques, coupled with
serological marker study.
References:
1. Crawford, J.M. The liver and the biliary tract. Chapter 19 in Robbins Pathologic basis of
disease, Ed. 6, Edt. by Kumar Cotran Robins, Singapore, Har Court Asia, 1999, 845-901.
2. Gibson, J.B. Histological typing of tumours of the liver, biliary tract and pancreas. In
International Histological Classification of Tumours, No. 20, Geneva, WHO, 1978, 15-29.
3. Ishak, K.G. and Rodney S. Marking. Liver. Chapter 57 in Andersons Pathology, Ed.
10, Edt. by Damjanov Ivan and James Linder, Philadelphia, Mosby, Vol. 2, 1996, 1779-
1858.
4. Kenneth W. Barwick and Rosai J. Liver. Chapter 13, in Ackermans surgical Pathology,
Ed. 8, Edt. by Juan Rosai, Singapore, Harcourt Brace and Co., Asia PTE Ltd., Vol. 1,
1996, 857-943.

5. Sherlock, S and James Dooley. Hepatic tumours. Chapter 28 in Diseases of the liver and
biliary system, Ed.10, Edt. by Sherlock S and James Dooley, London, Blackwell Science,
1996:531-560.
6. Nakashima, T. et al. 1983 Pathology of hepatocellular carcinoma in Japan 232
consecutive cases autopsied in ten years. Cancer, 51: 863-877.
7. Smalley, S.R. et al. 1988 Hepatoma in the non cirrhotic liver. Cancer, 62: 1414-1424.
8. Anthony, P.P. Tumours and Tumour like lesions of the liver and Biliary tract: Etiolgoy
epidemiology and Pathology. Ed. 4, Edt. by Macsween R.N.M et al, Edinburgh Churchill
Livingstone, 730-955.
9. Anthony, P.P. Tumours of the liver in Recent advances in histopathology, No. 10,
Chapter 10, Edt. by P.P. Anthony and N. Wool, Edinburgh, 2002: Churchill Livingstone,
214-222.
10. Manivel, C. et al. 1986 Teratoid hepatoblastoma The nosologic dilemma of solid
embryonic neoplasms of childhood. Cancer, 57: 2168-2174.

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