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  Table of Contents    
CASE REPORT  
Year : 2012  |  Volume : 55  |  Issue : 4  |  Page : 528-530
Pigmented hepatocellular adenoma with complete CD34 immunostaining pattern: A diagnostic dilemma


1 Department of Pathology, Global Hospital and Health City, Chennai, Tamil Nadu, India
2 Department of Hepatobiliary Surgery and Liver Transplantation, Global Hospital and Health City, Chennai, Tamil Nadu, India

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Date of Web Publication4-Mar-2013
 

   Abstract 

WHO defines hepatocellular adenoma (HCA) as a benign tumor composed of cells closely resembling normal hepatocytes, which are arranged in plates separated by sinusoids. It is more common in women. The present concerns a 41 years female who was found to have a mass lesion in liver on ultrasound while undergoing routine evaluation for dyspepsia. Computed tomography scan of abdomen showed 10 × 8 cm lesion in liver. Extended left hepatectomy was performed. Grossly hepatic cut surface showed circumscribed tumor with dark gray or black color. Microscopy revealed hepatocellular adenoma with abundant Dubin Johnson like pigment deposition. CD34 immunostaining showed complete sinusoidal pattern. We labeled the tumor as pigmented hepatic adenoma with complete CD34 staining pattern. To the best of author's knowledge only eight cases of pigmented hepatocellular adenoma are described in world literature.

Keywords: Adenoma, CD34, hepatocellular, immunohistochemistry, pigment

How to cite this article:
Vij M, Patra S, Rela M. Pigmented hepatocellular adenoma with complete CD34 immunostaining pattern: A diagnostic dilemma. Indian J Pathol Microbiol 2012;55:528-30

How to cite this URL:
Vij M, Patra S, Rela M. Pigmented hepatocellular adenoma with complete CD34 immunostaining pattern: A diagnostic dilemma. Indian J Pathol Microbiol [serial online] 2012 [cited 2019 Mar 24];55:528-30. Available from: http://www.ijpmonline.org/text.asp?2012/55/4/528/107801



   Introduction Top


WHO defines hepatocellular adenoma (HCA) as a benign tumor composed of cells closely resembling normal hepatocytes, which are arranged in plates separated by sinusoids. [1] It is more common in women. Most patients have a known risk factor, especially the use of contraceptive or anabolic steroids. Glycogen storage disease has also been associated. Pigment deposition is rare in hepatocellular adenoma. CD34, a marker of vascular endothelial cell is expressed only in periportal or periseptal sinusoids in non-neoplastic liver. CD34 antibody strongly stains the endothelial lining cells of hepatocellular carcinoma (HCC). HCA usually have incomplete CD34 staining pattern. Sometimes, HCA can have an identical staining pattern like HCC. [2] To the best of author's knowledge only eight cases of pigmented hepatocellular adenoma are described in world literature. [3],[4],[5],[6],[7],[8],[9] We describe an extremely rare case of hepatocellular adenoma with Dubin Johnson like pigment deposition and strong complete CD34 expression. We also discuss the relevant literature.


   Case Report Top


The present case concerns a 41-year-old female who was found to have a mass lesion in liver on ultrasound while undergoing routine evaluation for dyspepsia. Laboratory investigations including liver biochemical profile, and tumor markers such as alpha feto protein (AFP) were within normal range. On further evaluation with computed tomography scan abdomen she was identified to have 10 × 8 cm 2 lesion in segment IV, V, and VIII [Figure 1]a. There was no previous history of jaundice/blood transfusion. There was no history of oral contraceptive intake. All the relevant investigations done were within normal range. The patient was posted for extended left hepatectomy. On parenchymal transaction only segment 3 was found to be involved by the lesion, so left extended hepatectomy was done. The rest of the liver parenchyma was normal. Rest of the viscera were also normal. The department of pathology received extended left hepatectomy specimen measuring 22 × 15 × 7 cm 3 and weighing 800 g. External surface was unremarkable. Cut surface revealed a well circumscribed grayish white tumor with dark brown to blackish discoloration in the central part. The tumor measured 11.5 × 10 × 6.5 cm 3 [Figure 1]b. The tumor was soft to firm in consistency. Rest of the hepatic parenchyma was unremarkable. The sections showed a well circumscribed tumor composed of polyhedral cells arranged in plates one to two cells in thickness intermixed with variably sized arteries and veins [Figure 1]c. The tumor cells were uniform in size and shape with regular round nuclei, dispersed chromatin, and moderate pale to eosinophilic cytoplasm containing abundant fine to coarse granular brown pigment [Figure 1]d. Occasional foci of mild cytological variation are seen. Mitotic figures were not discernible. Portal tracts were absent. Small foci of large droplet fatty change and clear cell change (probably due to water or glycogen accumulation) were also noted. Hemorrhagic foci were seen. A silver preparation showed an essentially preserved reticulin pattern [Figure 1]e. This pigment stained positive with Masson-Fontana stain [Figure 2]a, faint positive for periodic acid Schiff after diastase (PAS-D) stain [Figure 2]b, negative for iron (Perl's stain), and copper-associated protein (orcein stain). The tumor cells were diffusely positive for Hep-Par 1 [Figure 2]c. CD34 staining shows complete staining pattern (most sinusoidal spaces throughout the mass are CD34-positive) [Figure 2]d. Glypican 3 was negative. Ki67 proliferation index was <0.5%. The surgical resection margin was free of tumor. The section from adjacent liver show maintained architecture with minimal macrovesicular steatosis. We labeled the tumor as pigmented hepatocellular adenoma with diffuse capillarization. We also commented that possibility of extremely well differentiated hepatocellular carcinoma cannot be excluded as mentioned in the report by Hasan et al. [4] Regular follow up was advised and patient is well at 3 months.
Figure 1: CT scan demonstrating large tumor in the liver (a) Gross specimen with gray to black colored central part. (b) Light microscopy showing cords of isomorphic hepatocytes (Hematoxylin and Eosin, ×100). (c) Abundant brown pigment in tumor cells (Hematoxylin and Eosin, ×200). (d) Preserved reticulin pattern (×100) (e)

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Figure 2: Pigments in the hepatocellular adenoma stained black on Masson-Fontana stain (×200) (a) Pigments were reddish brown on Periodic acid Schiff (PAS) reaction after diastase digestion (×100). (b) Positive Hep-par 1 immunostaining (×200). (c) Complete CD34 staining pattern (× 200) (d)

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   Discussion Top


Pigmented hepatic adenomas (PHA) are extremely rare neoplasms. These were first described by Ye et al. in 1999. [3] These lesions are histologically characterized by the presence of extensive Dubin-Johnson pigment within hepatocytic cytoplasm. Recent research suggests that Dubin-Johnson pigment is derived from lipofuscin, atypical bile pigments, or porphyrins and is the result of defective biliary excretion rather than a cause of the disease. The pigment granules can be variably stained with PAS after diastase digestion and by the long Ziehl-Neelsen technique, but are negative with Perls' Prussian blue for hemosiderin and Shikata's orcein for copper-associated protein. [10] The Masson-Fontana technique, highlights Dubin-Johnson pigment. This pigment has been observed in hepatocellular carcinomas and has been thought to be a marker of malignancy. However, eight PHA have been described and all are distinguished by a long and benign natural history.

In eight reported cases of pigmented adenoma, four have been reported in females and four in males with age range of 28- 65 years. [3],[4],[5],[6],[7],[8],[9] Generally, they are solitary lesions, although Ferko et al. reported two lesions occurring simultaneously in a female patient and Bernard et al. reported a male patient with multiple adenomas. [3],[6] No risk factors have been identified for pigmented adenomas in contrast to hepatic adenoma. Ferko et al. reported female patient with long-term phenobarbital use and one case was reported with history long-term oral contraceptive use. [3],[5] The pigment was described as Dubin-Johnson like in most of the hepatic adenomas. Masson-Fontana staining revealed positive results.

The distinction of HCA from well differentiated HCC can be difficult. Features that favor HCC include liver plates more than three cells thick, a marked increase in the nuclear-to-cytoplasmic ratio, mitoses, loss of the reticulin network, and vascular invasion, none of which were identified in the current case. [1] A prominent capillarization of tumor sinusoids shown by a diffuse staining for CD34 has been suggested as evidence of neoplastic angiogenesis in primary liver tumor. Three CD34 expression patterns are observed in hepatic neoplasms. [2] Negative CD34 staining; only blood vessels in portal tracts and/or rare sinusoidal space near portal tracts are CD34-positive. This is seen in normal or cirrhotic liver tissue, and in rare cases of FNH and HCA, but not in HCC. Incomplete CD34 staining pattern in which most of the sinusoidal spaces are positive in some but not in all nodules or many sinusoidal spaces at the periphery of nodules positive, whereas the central sinusoidal spaces are negative. The CD34 staining intensity and positive sinusoidal space is variable in different areas. This pattern is noted occasionally in HCC and in most cases of HCA and FNH. Complete CD34-positive pattern in which most sinusoidal spaces throughout the mass or nodule are CD34-positive with a homogenous staining intensity and staining density. Virtually all HCCs and occasional cases of HCA show this pattern. The present was unusual as it shows pigment deposition as well as complete CD34 pattern both more commonly seen in HCC. However, histomorphology observed in present case favor the diagnosis of hepatocellular adenoma.

In conclusion, pigment deposition can occur in HCA and it should not be considered as marker of malignancy, if histologic criteria of malignancy are not there. Also the prolonged survival following surgical resection in the reported cases indicates that these lesions are unlikely to represent well differentiated hepatocellular carcinomas.

 
   References Top

1.Hirohashi S, Blum HE, Ishak KG, Deugnier Y, Kojiro M, Laurent Puig P, et al. Hepatocellular carcinoma. In: Hamilton SR, Aaltonen LA, editors. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. Lyon: IARC Press; 2000. p. 159-72.  Back to cited text no. 1
    
2.Coston WM, Loera S, Lau SK, Ishizawa S, Jiang Z, Wu CL, et al. Distinction of hepatocellular carcinoma from benign hepatic mimickers using Glypican-3 and CD34 immunohistochemistry. Am J Surg Pathol 2008;32:433-44.  Back to cited text no. 2
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3.Ye MQ, Suriawinata A, Ben Haim M, Parsons R, Schwartz ME. A 42-year-old woman with liver masses and long-term use of oral contraceptives. Semin Liver Dis 1999;19:339-44.  Back to cited text no. 3
[PUBMED]    
4.Hasan N, Coutts M, Portmann B. Pigmented liver cell adenoma in two male patients. Am J Surg Pathol 2000;24:1429-32.  Back to cited text no. 4
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5.Ferko A, Bedrna J, Nozicka J. Pimented hepatocellular adenoma of the liver caused by long-term use of phenobarbital (Czech). Rozhl Chir 2003;83:192-5.  Back to cited text no. 5
    
6.Bernard PH, Blanc JF, Paulusma C, Le Bail B, Carles J, Balabaud C, et al. Multiple black hepatocellular adenomas in a male patient. Eur J Gastroenterol Hepatol 2000;12:1253-7.  Back to cited text no. 6
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7.Koea JB, Kua H. Pigmented liver cell adenoma: Rare but benign. ANZ J Surg 2012;82:86-7.  Back to cited text no. 7
    
8.Masuda T, Beppu T, Ikeda K, Ishiko T, Chikamoto A, Hayashi H, et al. Pigmented hepatocellular adenoma: Report of a case. Surg Today 2011;41:881-3.  Back to cited text no. 8
    
9.Hechtman JF, Raoufi M, Fiel MI, Taouli B, Facciuto M, Schiano TD, et al. Hepatocellular carcinoma arising in a pigmented telangiectatic adenoma with nuclear β-catenin and glutamine synthetase positivity: Case report and review of the literature. Am J Surg Pathol 2011;35:927-32.  Back to cited text no. 9
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10.Bancroft JD, Stevens A. Theory and practice of histologic staining techniques. Edinburgh: Churchill Livingstone; 1990. p. 250-6.  Back to cited text no. 10
    

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Correspondence Address:
Sushma Patra
Department of Pathology, Global Hospital and Health City, Chennai - 600 100, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.107801

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