Hepatocellular carcinoma metastatic to the kidney mimicking renal oncocytoma

Antonio D'Antonio, Alessia Caleo, Oliviero Caleo, Maria Addesso and Amedeo Boscaino

Salerno, Italy

Case Report

Hepatocellular carcinoma metastatic to the kidney mimicking renal oncocytoma

Antonio D'Antonio, Alessia Caleo, Oliviero Caleo, Maria Addesso and Amedeo Boscaino

Salerno, Italy

BACKGROUND:Renal metastases of hepatocellular carcinoma (HCC) are very rare. To our knowledge only five cases have been reported to the present; all had a well-known primary HCC.

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METHODS:We describe the clinico-pathological features of a rare case of HCC metastatic to the kidney in which the renal mass was the clinical debut of disease. The patient was a 54-year-old woman previously submitted to orthotopic liver transplantation, who underwent left nephrectomy for a renal mass.

RESULTS:Histologically, the tumor was composed mainly of epithelioid cells with homogeneous acidophilic cytoplasm resembling oncocytoma or primary renal carcinoma with oncocytic features. A correct diagnosis was made on the basis of positive immunostaining for hepatocyte paraffin 1.

CONCLUSIONS:Metastasis to the kidney is a rare complication that should be considered whenever a renal mass is present in patients with HCC. Since HCC may histologically resemble primary renal tumors such as oncocytoma, pathologists must be aware of this possibility above all in patients referred for liver transplantation and treated with immunosuppressant drugs. Immunohistochemistry is particularly helpful to establish a precise diagnosis in cases of doubt.

(Hepatobiliary Pancreat Dis Int 2010; 9: 550-552)

renal metastasis; hepatocellular carcinoma; immunohistochemistry; differential diagnosis

Introduction

A 54-year-old woman with a clinical history of orthotopic liver transplantation (LT) because of hepatitis C and cirrhosis had received cyclosporine (CsA)-based immunosuppression in association with steroids after LT. Nine months after LT the patient was re-admitted to this hospital because of nausea, fever, and jaundice associated with flank and back pain. Endoscopic retrograde cholangiopancreatography at that time revealed a moderate stricture of the donor duct. The stenosis was endoscopically dilated and treated with antibiotics with a relatively good response. She had further episodes of fever and back pain with a steady decline in her general condition over eleven months. A computerized tomography (CT) scan demonstrated a localized mass in the left kidney with heterogeneous contrast enhancement (Fig. A) in the absence of a hepatic tumor. A nephrectomy was performed. Grossly, the renal tumor was a well-circumscribed encapsulatedmass measuring 3.0×2.5×2.5 cm with a solid, grey to tan cut surface (Fig. B). On microscopic examination, the tumor was composed mainly of epithelioid eosinophilic cells arranged in a trabecular pattern or lined pseudoglandular spaces containing erythrocytes in the lumen reminiscent of glandular differentiation (Fig. C). Immunohistochemical study showed that the tumor cells were negative for CD10, renal cell carcinoma antigen, racemase, and CD117, but positive for cytokeratins, carcinoembryonic antigen, hepatocyte paraffin 1 (HepPar-1), and alpha-fetoprotein (Fig. D). After this diagnosis, the histological material from the cirrhotic transplanted liver was reviewed and examined closely for the presence of previously unrecognized hepatocellular carcinoma (HCC): foci of well-differentiated HCC were seen in a background of liver cell dysplasia. A final diagnosis of renal metastasis of HCC was made. The patient died three months after nephrectomy due to recurrent HCC complicated by sepsis.

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Case report

Although metastatic disease in the kidney is infrequently considered, both autopsy and surgical series indicate the problem is more common than generally thought.[1]Primary tumors of the lung, breast and gastrointestinal tract are the most common sources of renal metastases, but a variable number of other cancers have been reported to metastasize to the kidney synchronously with diagnosis of primary tumour or years after apparently curative treatment.[1]As reflected by the scarcity of descriptions in the medical literature, HCC rarely metastatizes to the kidney.[2-6]In this report we describe two further cases of HCC metastatic to the kidney. In one patient it represented the clinical debut of liver disease.

Fig. A: Coronal multiplanar reconstruction of portal venous phase CT shows a hypodense well-circumscribed mass in the left kidney with heterogeneous contrast enhancement (arrow); B: A well circumscribed, peripheral, solid tumor with a grey to brown color is evident. C: Histological examination reveals a trabecular growth pattern of cells with abundant eosinophilic cytoplasm and central breakdown leading to the formation of pseudoglandular structure with intraductal erythrocytes (hematoxylin-eosin, original magnification ×40); D: Neoplastic cells show an intense immunoexpression for HepPar-1 (immunoperoxidase, original magnification ×20).

Discussion

Ethical approval:Not needed.

A diagnosis of renal metastasis from HCC may be suspected on image studies whenever an antecedent HCC or a liver mass is present. In these cases, as in others with a well-known extrarenal tumor, the use of fine needle aspiration biopsy as a minimally invasive diagnostic procedure, has a high degree of diagnostic accuracy and additionally can be used for staging renal tumors. Histologically, the presence of a neoplastic population composed mainly of epithelioid cells with eosinophilic cytoplasm could be a source of problems in differential diagnosis with oncocytoma, the eosinophilic variants of chromophobe renal cell carcinoma, and papillary renal carcinoma.[7-9]Histologically, metastatic HCC lacks the typical nesting pattern of oncocytoma with epithelial cells admixed in a loose edematous stroma. The presence of a central scar demonstrable on CT scan and grossly has been used for the diagnosis of oncocytoma, but the level of accuracy is poor, as exemplified in the present case. Although histology may allow differentiation in most cases, immunohistochemistry helps in the correct diagnosis. It not only permits a precise diagnosis of HCC but also differentiation among primary and secondary renal neoplasms. Tumor recurrence after LT for HCC is associated with a poor prognosis.[10]Because immunosuppression is a well-known risk factor for tumor growth, the role of cyclosporine-based regimens in the onset of renal metastasis is not a surprise. In fact, previous reports have demonstrated a close relationship between the amount of CsA, one of the most widely used immunosuppressant drugs administered during the first postoperative year, and tumor recurrence in patients who undergo LT for HCC.[10]

6 Mezawa S, Homma H, Doi T, Takada K, Kukitsu T, Kinebuchi M, et al. Re: Spontaneous rupture of renal metastasis of hepatocellular carcinoma: management by emergency transcatheter arterial embolization. Cardiovasc Intervent Radiol 2001;24:143-144.

Funding:None.

HCC is a relatively common malignant epithelial neoplasm histologically composed of hepatocytes with a wide range of differentiation. HCC has a propensity for intravascular spread through the portal venous system and then into the lung or less frequently to other distant sites. HCC metastatic to the kidney is rare, as reflected by the few cases described in the medical literature.[1-6]In these previously described cases, the liver tumor and renal metastasis were synchronous and the diagnostic challenge was to decide which of the two lesions was primary. To our knowledge, the present case is the first in which a renal metastasis represented the clinical debut of liver disease. For differential diagnosis, a combination of clinical and pathological features is always necessary.

5 Hsu YB, Lee PH, Sheu JC, Chen DS, Hsu HC. Hepatocellular carcinoma with metastasis to the kidney: report of a case. J Formos Med Assoc 1994;93:71-74.

Competing interest:No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

1 Pascal RR. Renal manifestations of extrarenal neoplasms. Hum Pathol 1980;11:7-17.

2 Aron M, Nair M, Hemal AK. Renal metastasis from primary hepatocellular carcinoma. A case report and review of the literature. Urol Int 2004;73:89-91.

3 Sanz Mayayo E, Mayayo Dehesa T, Gómez García I, Sáenz Medina J, Rodríguez-Patrón Rodríguez R, Escudero Barrilero A. Renal metastasis of hepatocellular carcinoma. Actas Urol Esp 2003;27:387-390.

(4)制备矿井填充材料技术。所谓膏体充填，即把物料制备成无需脱水、如同牙膏状的浆体，通过泵压或重力作用，经管道输送到井下，适时填充采空区。使用大量破碎后的页岩废渣作为骨料，粉磨后的粉料添加石灰质原料及废碱激发剂作为胶凝材料，成为具有可泵送性和稳定性的膏体充填材料。制备流程见图9。

4 Fukushima M, Isoyama E, Sakaridani N, Sanematsu H, Kadowaki H, Hirakawa S, et al. Renal metastasis originating from liver cancer. Nippon Hinyokika Gakkai Zasshi 1996;87: 710-713.

Contributors:DA and CA wrote the first draft of this commentary. All authors contributed to the intellectual context and approved the final version. DA is the guarantor.

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In conclusion, we stress the importance of considering HCC in the differential diagnosis of an extra-hepatic mass arising in patients referred for LT and treated with immunosuppressants.

2.当前存在 “奢侈化”包装设计的现象，包装设计过于高端，甚至包装的投入远远大于产品本身。企业并未形成独立化、人文化的设计机制，因此设计活动未能实现其应有价值。随着当前人们消费理念的不断成熟，人们在日常消费过程中逐渐倾向于个性化与差异化的消费。因此，若企业不能根据大众的消费需求来进行包装设计，那么其将很难有效实现包装设计的活动价值。

7 Abrahams NA, Tamboli P. Oncocytic renal neoplasms: diagnostic considerations. Clin Lab Med 2005;25:317-339, vi.

8 Kuroda N, Toi M, Hiroi M, Shuin T, Enzan H. Review of renal oncocytoma with focus on clinical and pathobiological aspects. Histol Histopathol 2003;18:935-942.

9 Thoenes W, Storkel S, Rumpelt HJ, Moll R, Baum HP, Werner S. Chromophobe cell renal carcinoma and its variants--a report on 32 cases. J Pathol 1988;155:277-287.

(2)江河漂流生态游。张家界的茅岩河发源于湖南四大水系之一澧水，该水系从湖北流出，湍急回旋地奔腾在山峡里，到永定区温塘镇后，再流入较为开阔的盆谷里，非常适合开展漂流活动。除此之外，慈利县江垭镇的娄江也有着“小三峡”之称，距离武陵源风景区约20 km，距张家界永定区约70 km，该地是典型的喀斯特岩溶地貌，由于地形奇异，悬崖峭立，形成了滩多浪急的水势，在江上漂流的市民众多，惊险刺激。产品的开发离不开宣传，当地政府可以联合开发商举办漂流赛事，邀请媒体发布新闻，吸引更多的游客参与到漂流运动中。

10 Vivarelli M, Cucchetti A, Piscaglia F, La Barba G, Bolondi L, Cavallari A, et al. Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: key role of immunosuppression. Liver Transpl 2005;11:497-503.

November 5, 2009

Accepted after revision April 7, 2010

Author Affiliations: Department of Pathologic Anatomy, A.O. "San Giovanni di Dio e Ruggi d'Aragona", via S. Leonardo, Salerno, Italy (D'Antonio A and Caleo A); Department of Biomorphological and Functional Science, University of Medicine "Federico II", Naples, Italy (Caleo O); Department of Pathologic Anatomy, ASL SA1, Hospital "Scarlato", Scafati (SA) (Addesso M), and Unit of Pathologic Anatomy, A.O.R.N. "Cardarelli", via A. Cardarelli 9, 80131 Naples, Italy (Boscaino A)

Antonio D'Antonio, MD, PhD, Department of Pathologic Anatomy, A.O. "San Giovanni di Dio e Ruggi d'Aragona", via S. Leonardo, Salerno, Italy (Tel: 0039-089632475; Fax: 0039-0817473550; Email: ada66@inwind.it)

© 2010, Hepatobiliary Pancreat Dis Int. All rights reserved.