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      Cytologic Comparison Between Malignant and Regenerative Nodules in the Background of Cirrhosis

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          Abstract

          Background

          Incidence of hepatocellular carcinoma has been increased as the sixth most common cancer in the world. Improvement in imaging techniques has decreased the need for tissue confirmation in diagnosis of hepatocellular carcinoma (HCC). Meanwhile, false negative and positive cases are present. Fine needle aspiration (FNA) biopsy can be helpful to identify well-differentiated HCCs with low risk of vascular invasion and better prognosis following transplantation.

          Objectives

          We conducted this study to find useful criteria for cytological differential diagnosis between nodules of well differentiated hepatocellular in the background of cirrhosis and pure cirrhotic regenerative nodules in cytology smears.

          Materials and Methods

          140 fine needle aspirations (FNA) of fresh cirrhotic hepatectomy specimens were studied (100 pure regenerative nodules and 40 HCC nodules). All slides were reviewed by two expert pathologists. The most useful criteria were selected and evaluated in 560 cytology smears stained by Pap and Wright methods.

          Results

          None of the smears from cirrhotic patients showed mitosis, transgressing endothelium, eccentric nuclei, and scant cytoplasm, but thick nuclear membrane, spindle cells and abundant, thick and monotonous cytoplasm were found in many cases with cirrhosis. Large nucleoli (2 %), multiple nucleoli (6 %), increased N/C ratio (4 %), and broad cores (2 %) were found very rarely in the smears of regenerative nodules, but they were present in 50 %, 72.5 %, 87 %, and 77.5 % of HCC nodules, respectively.

          Conclusions

          Combination of cytologic criteria can be helpful for differential diagnosis between HCC and regenerative nodules.

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          Most cited references12

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          Fine needle aspiration biopsy of the liver: Algorithmic approach and current issues in the diagnosis of hepatocellular carcinoma

          Aileen Wee (2005)
          The role of fine needle aspiration biopsy (FNAB) in the evaluation of focal liver lesions has evolved. Guided FNAB is still useful to procure a tissue diagnosis if clinical, biochemical and radiologic findings are inconclusive. Major diagnostic issues include: (i) Distinction of benign hepatocellular nodular lesions from reactive hepatocytes, (ii) Distinction of well-differentiated hepatocellular carcinoma (WD-HCC) from benign hepatocellular nodular lesions, (iii) Distinction of poorly differentiated HCC from cholangiocarcinoma and metastatic carcinomas, (iv) Determination of histogenesis of malignant tumor, and (v) Determination of primary site of origin of malignant tumor. This review gives a general overview of hepatic FNAB; outlines an algorithmic approach to cytodiagnosis with emphasis on HCC, its variants and their mimics; and addresses current diagnostic issues. Close radiologic surveillance of high-risk cirrhotic patients has resulted in the increasing detection of smaller lesions with many subjected to biopsy for tissue characterization. The need for tissue confirmation in clinically obvious HCC is questioned due to risk of malignant seeding. When a biopsy is indicated, core needle biopsy is favored over FNAB. The inherent difficulty of distinguishing small/early HCC from benign hepatocellular nodular lesions has resulted in indeterminate reports. Changing concepts in the understanding of the biological behavior and morphologic evolution of HCC and its precursors; and the current lack of agreement on the morphologic criteria for distinguishing high-grade dysplastic lesions (with small cell change) from WD-HCC, have profound impact on nomenclature, cytohistologic interpretation and management. Optimization of hepatic FNAB to enhance the yield and accuracy of diagnoses requires close clinicopathologic correlation; combined cytohistologic approach; judicious use of ancillary tests; and skilled healthcare teams.
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            Fine needle aspiration biopsy of hepatocellular carcinoma and hepatocellular nodular lesions: role, controversies and approach to diagnosis.

            Bryan Wee (2011)
            The role of fine needle aspiration (FNA) biopsy of the liver has evolved. Advances in imaging modalities have obviated the need for tissue confirmation in clinically classic hepatocellular carcinoma (HCC). The risks of needle tract seeding and haematogenous dissemination have been actively debated. Nowadays, cytopathologists are confronted by smaller and smaller nodules, detected due to increased surveillance of high-risk cirrhotic patients. Tissue characterization of small well-differentiated hepatocellular nodular lesions (size less than and equal to 2 cm) is extremely challenging and has therapeutic implications. Major issues in the cytodiagnosis of HCC include: (i) distinguishing benign hepatocellular nodular lesions, namely, large regenerative nodules, dysplastic nodules, focal nodular hyperplasia and hepatocellular adenoma from reactive hepatocytes; (ii) distinguishing well-differentiated HCC from benign hepatocellular nodular lesions; (iii) distinguishing poorly differentiated HCC from intrahepatic cholangiocarcinoma and metastatic carcinomas; (iv) determining the histogenesis of a malignant tumour; and (v) determining the site of origin of a malignant tumour. An overview of the biological evolution and histopathological aspects of dysplastic nodules, small HCCs and 'nodule-in-nodule' lesions is presented in tandem with clinically relevant nomenclature. An algorithmic approach to FNA diagnosis of HCC and hepatocellular nodular lesions is outlined. Optimal results depend on (i) a dedicated radiologist-cytopathologist team; (ii) an on-site cytology service, (iii) a combined cytohistological approach, (iv) immunohistochemistry, and (v) clinicopathological correlation. As we move towards personalized medicine, it is envisaged that hepatic FNA is likely to become a point of care in the management protocol as it takes on the additional role of procurement of tumour and peritumoural tissues for genomic and proteomic profiling to enable targeted molecular therapy. © 2011 Blackwell Publishing Ltd.
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              Highly well differentiated hepatocellular carcinoma and benign hepatocellular lesions. Can they be distinguished on fine needle aspiration biopsy?

              To determine whether highly well differentiated hepatocellular carcinoma can be distinguished from benign hepatocellular lesions on fine needle aspiration biopsy (FNAB). Ninety-five FNABs from 88 patients with hepatic masses/diffuse conditions were reviewed according to new cytologic criteria established by Takenaka et al. They were classified into well-, moderately and poorly differentiated hepatocellular carcinomas (W-, M- and P-HCC) and benign aspirates and histologically verified. There were 21 W-HCC, 39 M-HCC, 10 P-HCC, 3 problematic and 22 benign aspirates. The most useful criteria for diagnosing highly W-HCC were architectural features on the smears/cell block sections, including hypercellularity; arborescent, cohesive clusters; broad trabeculae; transgressing and peripheral endothelium; and cytologic details of small, monotonous hepatocytes with nuclear crowding, decreased cytoplasm, increased nuclear/cytoplasmic ratio, atypical naked nuclei and tumor giant cells. Well-defined cytoplasmic borders, abundant thick and monotonous cytoplasm, eccentric nuclei, thick nuclear membranes, irregular nuclear contours, increased chromatin density, irregular chromatin distribution and macronucleoli were not always detectable in highly W-HCC. In fact, some of them were seen in dysplastic hepatocytes. Deficient reticulin patterns and diffuse sinusoidal CD34 reactivity were helpful. Experience, attention to architectural and cytologic details in smears/cell blocks and clinicopathologic correlation should reduce the number of indeterminate reports. However, there will always remain some cytohistologically challenging cases.
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                Author and article information

                Journal
                Hepat Mon
                Hepat Mon
                Kowsar
                Hepatitis Monthly
                Kowsar
                1735-143X
                1735-3408
                July 2012
                30 July 2012
                : 12
                : 7
                : 448-452
                Affiliations
                [1 ]Department of Pathology, Shiraz University of Medical Sciences, Shiraz, IR Iran
                [2 ]Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
                Author notes
                [* ]Corresponding author: Bita Geramizadeh, Department of Pathology, Transplant Research Center, Shiraz University of Medical Sciences, P.O. Box: 71345-1864, Shiraz, IR Iran. Tel.: +98-7116474331, Fax: +98-7116474331, E-mail: geramib@ 123456sums.ac.ir
                Article
                10.5812/hepatmon.5954
                3437456
                23008725
                cfc1279b-b76c-44b3-953b-086ef6b0f37e
                Copyright © 2012, Kowsar Corp.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 May 2012
                : 08 June 2012
                : 31 May 2012
                Categories
                Original Article

                Infectious disease & Microbiology
                carcinoma, hepatocellular,biopsy, fine-needle,liver cirrhosis

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