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Pathology – Research and Practice 206 (2010) 342–345

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Pathology – Research and Practice

0344-03

doi:10.1

� Corr

Taichun

Taiwan.

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journal homepage: www.elsevier.de/prp

Teaching Case

Synchronous renal cell carcinoma and clear cell hepatocellular carcinomamimicking metastatic disease

Tai-Cheng Hou a, Chen-Chung Wu b, Chi-Re Yang c, John Wang a,d,�

a Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, No. 160, Sec. 3, Chung-Kang Rd., Taichung 407, Taiwanb Division of General Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwanc Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwand College of Medicines and Nursings, Hungkuang University, Taichung, Taiwan

a r t i c l e i n f o

Article history:

Received 7 January 2009

Received in revised form

27 May 2009

Accepted 17 June 2009

Keywords:

Hepatocellular carcinoma

Renal cell carcinoma

Clear cell

Double tumor

38/$ - see front matter & 2009 Elsevier Gmb

016/j.prp.2009.06.008

esponding author at: Department of Patholo

g Veterans General Hospital, No. 160, Sec. 3, C

Tel.: +886 4 23592525x5705; fax: +886 4 237

ail address: tch@vghtc.gov.tw (J. Wang).

a b s t r a c t

Double carcinomas of hepatocellular and renal cell carcinoma (RCC) are extremely rare, and among the

reported cases, none of the hepatocellular carcinomas show clear cell change. We report a case of

synchronous double primary clear cell tumor in the liver and the kidney of a 70-year-old male. The renal

mass was a renal cell carcinoma of mixed clear and granular cell types, and the hepatic mass was a

hepatocellular carcinoma with extensive clear cell change that mimicked a metastatic renal cell

carcinoma. A simple battery of immunohistochemical stains composed of hepatocyte antigen, and CD10

was performed to make a definite diagnosis.

& 2009 Elsevier GmbH. All rights reserved.

Introduction

It could be morphologically impossible to differentiate clearcell hepatocellular carcinoma (HCC-CC) from metastatic con-ventional renal cell carcinoma (RCC). Although some clinicalinformation could be taken as clues, such as the presence ofa renal tumor or a known history of viral hepatitis, immunohis-tochemical staining is still needed to render a reliable diagnosis.The morphology and the immunohistochemical profile regardingthese two diagnoses are well-established. However, no coex-istence of HCC-CC and RCC has been documented. Herein, wereport a unique case of synchronous HCC-CC and RCC.

Case presentation

A 69-year-old man diagnosed with hepatitis C virus-associatedliver cirrhosis had been regularly followed-up in a local hospital.During regular abdominal sonographic examination, a hepaticmass in the right lobe was noted. The non-tumorous part of theliver parenchyma showed coarse echogenesity. In addition, a leftrenal mass was found accidentally. CT also revealed suspected

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gy and Laboratory Medicine,

hung-Kang Rd., Taichung 407,

41244.

tumor thrombi in the inferior vena cava. He was transferred to ourhospital for surgical intervention. The initial laboratory data wereas follows: AST/ALT: 45/49 IU/L, BUN/Creatinine: 28/1.9 mg/dL,alpha-fetoprotein: 64.4 IU/mL. After thorough assessment, heunderwent synchronous left radical nephrectomy and segmentalresection of the liver.

Pathology findings

The received specimens were a totally resected left kidneywith partial ureter and a segment of liver. The renal tumorwas 10�5�5 cm3 in size with a gray-tan and necrotic cut sur-face located in the lower pole. There was a tumor thrombus,2�1.8�1.6 cm3, in the renal vein. The hepatic tumor was3�3�2.8 cm3 in size with a yellow-tan necrotic cut surface em-bedded in liver parenchyma without the involvement of thecapsule.

Microscopically, the renal tumor was composed of polygonalcells with eosinophilic and clear cytoplasm arranged in a compacttubulocystic and focal pseudopapillary pattern (Fig. 1A). Thetumor thrombus in the renal vein exhibited the same feature asthat of the renal tumor. The hepatic tumor was composed of twodifferent cell types: cells with clear cytoplasm and cells withabundant granular eosinophilic cytoplasm. The clear cells werearranged in sheets while the eosinophilic cells were arranged in aclassical trabecular pattern (Fig. 2A). Focal sinusoidal dilatationand congestion were also noted in the clear cell region of the

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Fig. 1. HE and immunological staining of renal tumor: (A) Well-demarcated clear cell tumor with delicate vasculature and hemorrhage in renal parenchyma; (B) CD10

staining demonstrated diffuse positivity among tumor cells; (C) HePar-1 staining of tumor cells is completely negative; and (D) epithelium of renal tubules shows focal mild

positivity to HePar-1 staining.

Fig. 2. HE and immunological staining of hepatic tumor: (A) Low-power view of the tumor with diffuse clear cell change; (B) mix of clear cell tumor with and without

sinusoidal dilatation and congestion; (C) HePar-1 staining in clear cell region demonstrated variable positivity; and (D) CD10 staining is completely negative.

T.-C. Hou et al. / Pathology – Research and Practice 206 (2010) 342–345 343

hepatic tumor (Fig. 2B). Mallory bodies were frequently seen inareas with trabecular pattern, but not in the clear cell region. Thenon-tumorous part of the liver showed cirrhotic change withscattered foci of large-cell dysplasia of hepatocytes.

The CD 10 antibody yielded strong and diffuse surfacemembrane staining in the renal neoplasm and was completely

negative for surface staining in the hepatic tumor (Figs. 1B and2D). Focal canalicular staining pattern was seen in the hepatictumor in regions of classical trabecular type, but not in regions ofclear cell type.

The hepatocyte immunochemical staining (HePar-1) in therenal neoplasm was completely negative while the adjacent non-

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Fig. 3. The resemblance between (A) the clear cell hepatocellular carcinoma with sinusoidal dilatation and congestion and (B) the renal cell carcinoma with hemorrhage.

T.-C. Hou et al. / Pathology – Research and Practice 206 (2010) 342–345344

tumor renal tubules showed focal mild positivity (Fig. 1C and D).In the liver specimen, the tumor cells of the classical trabecularpattern displayed strong and diffuse staining in a coarse granularpattern similar to that of normal hepatocytes. These positivelystained granules were evenly distributed in the cytoplasm. Inregions of clear cell type, the staining result was variable. Someareas showed diffuse positivity in the same granular pattern butwith a patchy distribution due to displacement of the granules byclear cytoplasm. And there were also areas showing almostcomplete negative staining with only a few scattered positivestaining cells, especially in areas with sinusoidal dilatation andcongestion (Fig. 2C).

The immunohistochemical profiles of these two tumors arecompatible with a primary hepatocellular carcinoma and aprimary renal cell carcinoma.

Discussion

Coexistence of renal cell carcinoma and hepatocellular carci-noma is extremely rare, and only a few case reports could befound in the literature [2,4,6–8]. Among these reported cases,none of the hepatocellular carcinomas were of clear cell variant.

HCC-CC is an uncommon variant of hepatocellular carcinomaof which the tumor cells have a ‘‘clear’’ cytoplasm due to thedissolving of their intracytoplasmic fat or glycogen accumulationduring tissue processing. When the clear cell change is diffuse, itis almost impossible to distinguish HCC-CC from RCC merely bymorphological examination. However, when encountering apatient with both hepatic and renal mass, a precise diagnosis iscrucial for tumor staging. In this case, a panel of immunohisto-chemical stains, including CD10 and HePar-1, was performed.

Previous studies regarding HCC-CC have shown some usefuldiagnostic clues such as areas of classical (conventional) trabe-cular and canalicular features, the presence of Mallory bodies,and/or bile production [5]. While in HCC-CC, a ratio of clear cellsexceeding 90% is extremely rare, it is not surprising that foci ofclassical HCC will be present if ample tissue is submitted andadequately sampled [1]. In our case, however, the presence ofrenal mass raises some other considerations. For instance, a

histological picture of mixed classical HCC and HCC-CC could alsobe interpreted as metastasis of an RCC into a HCC. The intra-tumoral sinusoidal dilatation and congestion, which may berelated to venous out-flow obstruction and could mimic thecommon hemorrhagic pattern of an RCC, heightened this suspi-cion even more (Fig. 3) [3].

Even though the IHC panel was adequate for diagnosis in thiscase, certain diagnostic pitfalls still exist regarding needle biopsyspecimens. First, needle sampling of areas of HCC-CC with onlysparsely positive hepatocyte immunostaining may lead to falsenegative interpretations. On the other hand, however, entrapmentof non-tumor renal tubules with positive hepatocyte immunos-taining, although not in a typical coarse granular pattern, in RCCcould be falsely interpreted as focal positivity of tumor cells insmall biopsies. CD10 immunostaining, which shows a character-istic canalicular pattern in HCC, may occasionally intensely stainthe HCC in a less common canalicular–membranous pattern, thusmaking it difficult to distinguish it from the membranous stainingpattern of RCC.

In summary, the differential diagnosis between RCC and HCC-CC is not problematic if the specimen is adequate and a proper IHCpanel is used. However, it could still be a diagnostic pitfall if thediagnosis is based only on needle biopsy or radiological study. It isvery important that the clinicians and the pathologists remainimpartial and non-prejudiced when interpreting the histology andthe IHC results. And through this case, we would like to point outthat the option of two primary tumors should always be takeninto consideration in addition to a primary tumor and itsmetastatic counterpart in spite of their morphological likeness.

Conflict of interest disclosure

The authors declare that they have no conflict of interest.

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