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www.currentmedicine.org Current Medicine Volume 2 Issue 1 pages 1-4 Pathology Current Medicine Current Medicine Volume 2 Issue 1 Pages 1-4 Pathology An Unnecessary Hepatectomy as Consequence of a False Positive of Liver Biopsy Massimo Bolognesi * , MD General Practice Medicine, Internal Medicine Specialist, AUSL della Romagna, District of Cesena, Via Ungaretti, 494 47521, Cesena (FC), Italy Correspondence: Tel: +390547645074, E-mail: [email protected] Accepted date: 10 May 2019 Citation: Bolognesi M. An Unnecessary Hepatectomy as Consequence of a False Positive of Liver Biopsy. Curr Med. 2019; 2(1):1-4. Copyright: ©2019, Current Medicine. Reprints: [email protected] ABSTRACT Pathological anatomy is a branch of medicine that can easily be involved in diagnostic errors, primarily because the examination procedure is complex and demanding. One of the most frequent errors is the so-called false-positive diagnosis (e.g. diagnosed incorrectly a liver adenoma as carcinoma). In fact, here the author describes an unexpected error that was consequent from a misinterpretation of a liver biopsy of a liver mass of uncertain interpretation as described from radiological images that has subsequently led to incorrect patient management plans. Keywords: Pathologic mistake; Hepatocellular Carcinoma (HCC); Hepatic biopsy INTRODUCTION Nowadays, the role of the aspirated needle biopsy (FNA) of the liver has changed dramatically. Technological developments in imaging methods have reduced the need for tissue confirmation in hepatocellular carcinoma (HCC). Otherwise, there are many difficulties in the cytodiagnosis of HCC, which mainly include how to correctly distinguish malignant neoplastic lesions from benign hepatocellular lesions, such as regenerative nodules, dysplastic nodules, focal nodular hyperplasia and hepatocellular adenoma from reactive hepatocytes. It follows that the best possible result depends on a number of clinical and instrumental factors that require supervision and collaboration between clinical physicians and pathologists, in order to avoid interpretative errors to reduce indeterminate diagnosis of highly differentiated hepatocellular lesions. CASE REPORT A 69-year-old male obese patient was recently operated on suspected well-differentiated hepatocellular Carcinoma. The patient’s history is as follows: inguinal cryptorchidism; diabetes mellitus type 2; hypercholesterolemia; hypertension; obesity. In March 2008 he underwent radical robotic prostatectomy (onset PSA=14; Gleason score 8; pT2bN0Mx) with good outcomes. In the follow up the PSA had risen and he

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Page 1: An Unnecessary Hepatectomy as Consequence of a False ... · Current Medicine Volume 2 Issue 1 pages 1-4 Pathology REFERENCES 1. Llovet JM, Fuster J, Bruix J, Barcelona-Clínic Liver

www.currentmedicine.org

Current Medicine Volume 2 Issue 1 pages 1-4 Pathology

Current Medicine

Current Medicine Volume 2 Issue 1 Pages 1-4 Pathology

An Unnecessary Hepatectomy as Consequence of a False Positive of

Liver Biopsy

Massimo Bolognesi*, MD

General Practice Medicine, Internal Medicine Specialist, AUSL della Romagna, District of Cesena,

Via Ungaretti, 494 47521, Cesena (FC), Italy

Correspondence: Tel: +390547645074, E-mail: [email protected]

Accepted date: 10 May 2019

Citation: Bolognesi M. An Unnecessary Hepatectomy as Consequence of a False Positive of Liver

Biopsy. Curr Med. 2019; 2(1):1-4.

Copyright: ©2019, Current Medicine. Reprints: [email protected]

ABSTRACT

Pathological anatomy is a branch of medicine that can easily be involved in diagnostic errors, primarily because the

examination procedure is complex and demanding. One of the most frequent errors is the so-called false-positive diagnosis

(e.g. diagnosed incorrectly a liver adenoma as carcinoma). In fact, here the author describes an unexpected error that was

consequent from a misinterpretation of a liver biopsy of a liver mass of uncertain interpretation as described from

radiological images that has subsequently led to incorrect patient management plans.

Keywords: Pathologic mistake; Hepatocellular Carcinoma (HCC); Hepatic biopsy

INTRODUCTION

Nowadays, the role of the aspirated needle biopsy (FNA) of the liver has changed dramatically. Technological

developments in imaging methods have reduced the need for tissue confirmation in hepatocellular carcinoma

(HCC). Otherwise, there are many difficulties in the cytodiagnosis of HCC, which mainly include how to

correctly distinguish malignant neoplastic lesions from benign hepatocellular lesions, such as regenerative

nodules, dysplastic nodules, focal nodular hyperplasia and hepatocellular adenoma from reactive hepatocytes. It

follows that the best possible result depends on a number of clinical and instrumental factors that require

supervision and collaboration between clinical physicians and pathologists, in order to avoid interpretative

errors to reduce indeterminate diagnosis of highly differentiated hepatocellular lesions.

CASE REPORT

A 69-year-old male obese patient was recently operated on suspected well-differentiated hepatocellular

Carcinoma. The patient’s history is as follows: inguinal cryptorchidism; diabetes mellitus type 2;

hypercholesterolemia; hypertension; obesity. In March 2008 he underwent radical robotic prostatectomy (onset

PSA=14; Gleason score 8; pT2bN0Mx) with good outcomes. In the follow up the PSA had risen and he

Page 2: An Unnecessary Hepatectomy as Consequence of a False ... · Current Medicine Volume 2 Issue 1 pages 1-4 Pathology REFERENCES 1. Llovet JM, Fuster J, Bruix J, Barcelona-Clínic Liver

Bolognesi, 2019

Current Medicine Volume 2 Issue 1 pages 1

underwent Radio-Therapy treatment was completed in April 2010 (64 Gy on the prostate l

initial reduction, increased to 2.33 (December 2010), so a scintigraphy and PET

were performed and resulted negative for disease localization.

hyperaccumulation of the prostate lodge indicative of recurrence of disease and doubt of lympha

inguinal right (<1 cm). A subsequent specialist examination of radiotherapy did not give an indication for

radiotherapy reprocessing. Because of PSA <0.003, bhcg <0.1, alphetop

was suspended in January 2016). However, in October 2016, a follow

formation of about 40 mm in the left liver lobe. The m

adenoma in relation to hormonal therapy. However,

CT-guided liver biopsy which showed specimen features of Hepatic Steatosis. In November 2018 an

oncological follow up with CT scan found in

currently 70 × 68 mm (Vs 40 × 40 mm) suggestive for adenoma or maybe for primary hepatic lesion. A few

slightly enlarged lymph nodes near the hepatic hilum, the largest in the porto

stable. Oncologists decided to carry out another biopsy of the liver mass that showed needle

liver parenchyma with small cell dysplasia, reticulum alteration, and absence of portal spaces (

staining showed capillarization. In conclusion, the findings of specimens were difficult to interpret but the

totality of the data favored the hypothesis of well

discussed at a multidisciplinary meeting, where resect

consent. Hepatic lobectomy was performed on 12 February, 2019. The report of the pathologist described a

typical Hepatocellular adenoma (Figure 2)

glutamine-synthetase, glypican-3 and showed a very low proliferative index (Ki

immunohistochemical investigation. Beta

The hepatocytes appeared rather regular and only at times, they showed images of discreet nuclear

polymorphism. The morphological characteristics of the lesion were similar to those of the previous histological

biopsy. In view of the histological picture obviously no indication of

In spite of this clear histological picture no indication whatsoever of medical treatment was given. In the end,

only the oncologist requested a complete abdomen ultrasound in 6 months and complete blood count wi

formula, liver function, kidney, blood sugar, vit. D and PSA reflex.

Figure 1: Hystologic findings of hepatic biopsy that showed needle

small cell dysplasia, reticulum alteration, and absence of portal spaces.

Issue 1 pages 1-4

Therapy treatment was completed in April 2010 (64 Gy on the prostate lodge). PSA, after

initial reduction, increased to 2.33 (December 2010), so a scintigraphy and PET-TC choline (January 201

ative for disease localization. A subsequent PET with carbon acetate showed

prostate lodge indicative of recurrence of disease and doubt of lympha

). A subsequent specialist examination of radiotherapy did not give an indication for

PSA <0.003, bhcg <0.1, alphetoprotein 1.9 values, Enantone drug therap

). However, in October 2016, a follow-up abdomen CT scan revealed a hepatic

formation of about 40 mm in the left liver lobe. The most likely hypothesis expressed after an MRI was for

to hormonal therapy. However, biopsy confirmation was recommended. So, he underwent a

guided liver biopsy which showed specimen features of Hepatic Steatosis. In November 2018 an

oncological follow up with CT scan found in the context of liver steatosis a growing mass of the II segment

40 mm) suggestive for adenoma or maybe for primary hepatic lesion. A few

slightly enlarged lymph nodes near the hepatic hilum, the largest in the porto-caval site of 23 ×

stable. Oncologists decided to carry out another biopsy of the liver mass that showed needle-

liver parenchyma with small cell dysplasia, reticulum alteration, and absence of portal spaces (Figure 1

larization. In conclusion, the findings of specimens were difficult to interpret but the

totality of the data favored the hypothesis of well-differentiated hepatocarcinoma, stage G1. Then this case was

multidisciplinary meeting, where resection surgery was deemed necessary. The patient gave his

consent. Hepatic lobectomy was performed on 12 February, 2019. The report of the pathologist described a

(Figure 2) with focal dysplastic aspects. In fact, the lesion wa

3 and showed a very low proliferative index (Ki-67), equal to about 1% in the

immunohistochemical investigation. Beta-catenin had a normal membrane expression. No mitosis was observed.

rather regular and only at times, they showed images of discreet nuclear

polymorphism. The morphological characteristics of the lesion were similar to those of the previous histological

biopsy. In view of the histological picture obviously no indication of any kind of medical treatment to complete.

In spite of this clear histological picture no indication whatsoever of medical treatment was given. In the end,

only the oncologist requested a complete abdomen ultrasound in 6 months and complete blood count wi

formula, liver function, kidney, blood sugar, vit. D and PSA reflex.

Hystologic findings of hepatic biopsy that showed needle-like frustules of liver parenchyma with

small cell dysplasia, reticulum alteration, and absence of portal spaces.

Curr Med 2(1): 1-4

Pathology

odge). PSA, after

TC choline (January 2011)

A subsequent PET with carbon acetate showed

prostate lodge indicative of recurrence of disease and doubt of lymphadenopathy

). A subsequent specialist examination of radiotherapy did not give an indication for

rotein 1.9 values, Enantone drug therapy

up abdomen CT scan revealed a hepatic

likely hypothesis expressed after an MRI was for

biopsy confirmation was recommended. So, he underwent a

guided liver biopsy which showed specimen features of Hepatic Steatosis. In November 2018 an

a growing mass of the II segment

40 mm) suggestive for adenoma or maybe for primary hepatic lesion. A few

× 11 mm, resulted

-like frustules of

Figure 1). CD34

larization. In conclusion, the findings of specimens were difficult to interpret but the

differentiated hepatocarcinoma, stage G1. Then this case was

The patient gave his

consent. Hepatic lobectomy was performed on 12 February, 2019. The report of the pathologist described a

with focal dysplastic aspects. In fact, the lesion was negative for

67), equal to about 1% in the

catenin had a normal membrane expression. No mitosis was observed.

rather regular and only at times, they showed images of discreet nuclear

polymorphism. The morphological characteristics of the lesion were similar to those of the previous histological

any kind of medical treatment to complete.

In spite of this clear histological picture no indication whatsoever of medical treatment was given. In the end,

only the oncologist requested a complete abdomen ultrasound in 6 months and complete blood count with

like frustules of liver parenchyma with

Page 3: An Unnecessary Hepatectomy as Consequence of a False ... · Current Medicine Volume 2 Issue 1 pages 1-4 Pathology REFERENCES 1. Llovet JM, Fuster J, Bruix J, Barcelona-Clínic Liver

Bolognesi, 2019

Current Medicine Volume 2 Issue 1 pages 1

Figure 2: The definitive hystologic findings of the liver mass showed the typical features of Hepatocellular

adenoma. No mitosis was observed. The hepatocytes appeared rather regular and only at times, they showed

images of discreet nuclear pol

Hepatocellular carcinoma (HCC) is a primary malignant cancer of the liver which mainly affects patients

suffering from a pre-existing condition, i.e. chronic liver disease and/or cirrhosis

of the liver is generally diagnosed at an advanced stage, the reoccurrence rate is high and the chances of

successful treatment are narrow. Thus the prognosis is very poor

diagnosis and prognosis of HCC [3]. However, as a result of the considerable progress which has been made in

imaging technology, some recommendations and guidelines have been set which limit the use of biopsy to

specific cases only. This is the reason why carrying ou

hepatocellular carcinoma is more than often subject to controversy. Moreover, biopsy may also cause side

effects such as needle tract seeding of tumour, a minor risk of complications. But above all technica

interpretative errors are likely [4]. Besides, tissue analysis of the lesion is frequently necessary owing to the fact

that the imaging is sometimes unclear. This is due to limited experience and lack of advanced technology in

several centers, especially when it comes to imaging limits for the diagnosis of initial or mixed forms of HCC.

Furthermore, biopsies are quite often needed for trials on new drugs and targeted therapies

characteristics and morphology based correlates of mol

the management and prognosis of the disease. This brief report has provided a description of how

histopathology mistakes and the role of biopsy in the diagnosis, management and prognosis of HCC may be

cause of errors in plans and inappropriate surgery. Taking into account that the evidence in literature concerning

diagnostic error is poor, clinicians should play a key role in reducing pathology mistakes by adopting several

approaches, such as the appropriate order of the tests, gaining precise clinical information regarding the patients,

obtaining high quality samples and acquiring second opinions

clinical impression and pathology diagnosis).

CONFLICT

The author declared there is no conflict of interest

Issue 1 pages 1-4

The definitive hystologic findings of the liver mass showed the typical features of Hepatocellular

adenoma. No mitosis was observed. The hepatocytes appeared rather regular and only at times, they showed

images of discreet nuclear polymorphism.

DISCUSSION

Hepatocellular carcinoma (HCC) is a primary malignant cancer of the liver which mainly affects patients

existing condition, i.e. chronic liver disease and/or cirrhosis [1]. Unfortunately, carcinoma

of the liver is generally diagnosed at an advanced stage, the reoccurrence rate is high and the chances of

successful treatment are narrow. Thus the prognosis is very poor [2]. Liver biopsy plays a crucial role in the

. However, as a result of the considerable progress which has been made in

imaging technology, some recommendations and guidelines have been set which limit the use of biopsy to

specific cases only. This is the reason why carrying out a biopsy on a mass or lesion suspected of being

hepatocellular carcinoma is more than often subject to controversy. Moreover, biopsy may also cause side

effects such as needle tract seeding of tumour, a minor risk of complications. But above all technica

. Besides, tissue analysis of the lesion is frequently necessary owing to the fact

that the imaging is sometimes unclear. This is due to limited experience and lack of advanced technology in

ally when it comes to imaging limits for the diagnosis of initial or mixed forms of HCC.

Furthermore, biopsies are quite often needed for trials on new drugs and targeted therapies [5]

characteristics and morphology based correlates of molecular subtypes give extremely helpful information for

the management and prognosis of the disease. This brief report has provided a description of how

histopathology mistakes and the role of biopsy in the diagnosis, management and prognosis of HCC may be

cause of errors in plans and inappropriate surgery. Taking into account that the evidence in literature concerning

diagnostic error is poor, clinicians should play a key role in reducing pathology mistakes by adopting several

propriate order of the tests, gaining precise clinical information regarding the patients,

s and acquiring second opinions in specific situations (e.g. incongruity between

clinical impression and pathology diagnosis).

CONFLICT OF INTEREST

The author declared there is no conflict of interest.

Curr Med 2(1): 1-4

Pathology

The definitive hystologic findings of the liver mass showed the typical features of Hepatocellular

adenoma. No mitosis was observed. The hepatocytes appeared rather regular and only at times, they showed

Hepatocellular carcinoma (HCC) is a primary malignant cancer of the liver which mainly affects patients

. Unfortunately, carcinoma

of the liver is generally diagnosed at an advanced stage, the reoccurrence rate is high and the chances of

. Liver biopsy plays a crucial role in the

. However, as a result of the considerable progress which has been made in

imaging technology, some recommendations and guidelines have been set which limit the use of biopsy to

t a biopsy on a mass or lesion suspected of being

hepatocellular carcinoma is more than often subject to controversy. Moreover, biopsy may also cause side

effects such as needle tract seeding of tumour, a minor risk of complications. But above all technical and

. Besides, tissue analysis of the lesion is frequently necessary owing to the fact

that the imaging is sometimes unclear. This is due to limited experience and lack of advanced technology in

ally when it comes to imaging limits for the diagnosis of initial or mixed forms of HCC.

]. Finally, tissue

ecular subtypes give extremely helpful information for

the management and prognosis of the disease. This brief report has provided a description of how

histopathology mistakes and the role of biopsy in the diagnosis, management and prognosis of HCC may be the

cause of errors in plans and inappropriate surgery. Taking into account that the evidence in literature concerning

diagnostic error is poor, clinicians should play a key role in reducing pathology mistakes by adopting several

propriate order of the tests, gaining precise clinical information regarding the patients,

in specific situations (e.g. incongruity between

Page 4: An Unnecessary Hepatectomy as Consequence of a False ... · Current Medicine Volume 2 Issue 1 pages 1-4 Pathology REFERENCES 1. Llovet JM, Fuster J, Bruix J, Barcelona-Clínic Liver

Bolognesi, 2019 Curr Med 2(1): 1-4

Current Medicine Volume 2 Issue 1 pages 1-4 Pathology

REFERENCES

1. Llovet JM, Fuster J, Bruix J, Barcelona-Clínic Liver Cancer Group. The Barcelona approach:

diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl. 2004; 10: S115-20.

2. Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A

prospective study of 22 707 men in Taiwan. Lancet. 1981; 2 (8256): 1129-33.

3. Sparchez Z, Mocan T. Contemporary role of liver biopsy in hepatocellular carcinoma. World J

Hepatol. 2018; 10(7): 452–461.

4. Doyle A, Morris S. Liver Biopsy for Hepatocellular Carcinoma (HCC): Should this be a Routine?

Current Hepatology Reports. 2017; 16: 46–50.

5. Richard SF. The Role of Liver Biopsy in Hepatocellular Carcinoma. Gastroenterol Hepatol (NY).

2016; 12(10): 628–630.

This article is accepted and published in under the section of Pathology in “Current Medicine” open magazine. The copy

rights reserved; however, can be cited as per the international publication guidelines.