J Cancer Res Clin Oncol (2012) 138:451–454

DOI 10.1007/s00432-011-1112-z

ORIGINAL PAPER

Chromophobe renal cell carcinoma: analysis of 53 cases

Peng-Ju Zhao · Xiao-Peng Chen · Xue-Song Li · Lin Yao · Cui-Jian Zhang · Wei Yu · Qun He · Zhi-Song He · Li-Qun Zhou

Received: 1 July 2011 / Accepted: 5 December 2011 / Published online: 18 December 2011© Springer-Verlag 2011

AbstractPurpose To discuss the pathological and clinical charac-teristics, treatments and prognosis of chromophobe renalcell carcinoma (CRCC).Methods We developed a database that contained 1,870patients who were diagnosed with renal cell carcinoma(RCC) and who underwent surgery in our hospital between2002 and 2010. Afterward, the clinical and pathologicaldata of 53 CRCC cases were extracted and analyzed.Results The mean age of the 53 patients at diagnosis was50.2 years (range, 21–88 years), and the ratio of male tofemale was 1:1. All tumors were unilateral and a majority ofthem (69.8%) were discovered incidentally. The mean tumorsize was 5.8 § 3.2 cm (range, 2–20 cm). Stage T1, T2, andT3 tumors, in accordance with 2004 TNM classiWcation,accounted for 75.5, 13.2 and 11.3% of all cases, respectively.By histologic grading, 11.3, 73.6 and 15.1% of the tumorswere G1, G2, and G3, respectively. Forty-one (77.4%)patients underwent radical nephrectomy, 12 (22.6%) under-went partial nephrectomy. Forty-Wve (84.9%) patients withfollow-up results were alive after a mean follow-up of34 months (range, 4–79 months). Tumor metastasis was dis-covered in 2 patients: one tumor metastasis was found in theliver 4 months postoperation, and the other was found in thelumbar vertebrae 47 months postoperation. No local recur-rence was found. The overall survival rate was 100%.

Conclusions CRCC is an uncommon subtype of RCC,with a favorable prognosis. Chinese patients are seeminglyyounger at diagnosis. Prediction of prognosis is still diYcult.

Keywords Chromophobe renal cell carcinoma · Analysis · Surgery · Metastasis · Racial diVerence

Introduction

Renal cell carcinoma (RCC) is a common category ofhuman malignancies. According to the criterion of the 2004WHO pathological classiWcation, there are 9 subtypes ofRCC, which include clear cell renal cell carcinoma, papil-lary renal cell carcinoma, chromophobe renal cell carci-noma (CRCC), multilocular cystic renal cell carcinoma.CRCC was Wrst described by Thoenes et al. (1985) andconstitutes only 3.6–10.4% of RCC (Cindolo et al. 2005).

CRCC has its own histological, immunohistochemical,and cytogenetic characteristics (Yusenko 2010). By lightmicroscopy, the tumor cells have a compact growth patternand the cytoplasm stains lightly with hematoxylin and eosinstaining. There are two types of CRCC tumor cells: the typ-ical type and the eosinophilic type. Generally, CRCC canbe distinguished from other types of renal tumor withoutdiYculty. However, the eosinophilic cells make it diYcultto distinguish CRCC from renal oncocytoma, even withHale’s colloidal iron staining.

CRCC is known for its low malignancy and favorableprognosis when compared with clear cell renal carcinoma.Although eVorts have been made to Wnd prognostic factors,recurrence and metastasis is still unpredictable since only asmall portion of patients would experience disease progres-sion. As CRCC is an uncommon subtype of RCC, the num-ber of published series on CRCC is very limited. In our

P.-J. Zhao · X.-P. Chen · X.-S. Li (&) · L. Yao · C.-J. Zhang · W. Yu · Q. He · Z.-S. He · L.-Q. Zhou (&)Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, No. 8 Xishiku St, Xicheng District, Beijing 100034, Chinae-mail: pineneedle@sina.com

L.-Q. Zhoue-mail: zhoulqmail@china.com

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452 J Cancer Res Clin Oncol (2012) 138:451–454

study, we report our experience with CRCC, and this clini-cal and pathological study of 53 cases may enrich theCRCC literature.

Patients and methods

Between February 2002 and June 2010, 1,870 patients weretreated in our hospital (Peking University First Hospital)for RCC; 55 of whom were diagnosed with CRCC. We ret-rospectively reviewed the medical records of the 55patients; and since the records of 2 patients were not avail-able, we analyzed the data of 53 patients who were treatedfor CRCC in this study.

The following parameters are discussed herein: age, gen-der, presenting symptoms, tumor size, laterality, TNMstage (in accordance with the 2002 TNM issue), and Fuhr-man nuclear grade. Several microscopic features were alsodescribed: tumor necrosis, hemorrhage, vascular-nerveinvolvement, and sarcomatoid component.

Patient complaints were classiWed as symptomatic orincidental. Routine laboratory test, physical examination,chest X-ray, abdominal ultrasonography, and CT scan wereperformed on all patients preoperatively.

Patient outcomes were evaluated by BUS every 3 or6 months and CT scan every 6 or 12 months. Survival state-ments were determined by Wnal follow-up.

Results

Of all the 53 patients, 26 (49.1%) were male, and 27(50.9%) were female, with a male to female ratio of 1:1.The mean patient age was 50.2 years (range, 21–88 years).Seventeen (32.1%) patients suVered from tumors locatedin the left kidney, while 36 (67.9%) patients suVeredfrom tumors located in the right kidney. All tumors wereunilateral.

Sixteen patients (30.2%) presented with local or sys-temic symptoms. Local symptoms, such as hematuria, Xankpain, and Xank discomfort, appeared in 13 (24.5%) patients.Systemic symptoms, such as edema, loss of body weight,and loss of appetite, appeared in 3 (5.7%) patients. Mostpatients (69.8%) were asymptomatic at diagnosis, and theirtumors were detected by ultrasonography or CT scan inci-dentally.

Forty-one (77.4%) patients underwent radical nephrec-tomy, and 12 (22.6%) patients underwent nephron-sparingnephrectomy. No patient received adjuvant therapy.

The mean tumor size was 5.8 § 3.2 cm (range, 2–20 cm).All tumors were unifocal. By Fuhrman histologic grading,the percentage for G1, G2, and G3 tumors was 11.3, 73.6,and 15.1%, respectively. Necrosis, hemorrhage, vascular-

nerve invasion, and sarcomatoid component were found in14 (26.4%), 23 (43.4%), 13 (24.5%), and 1 (1.9%) tumors,respectively. At diagnosis, tumor stage pT1 was found in 40(75.5%), pT2 in 7 (13.2%), pT3a in 4 (7.5%), and pT3b in 2(3.8%) tumors. No pT4 tumors, lymph node involvement, ormetastasis were found.

In our series, 8 patients were not available for follow-up.The mean follow-up time of the other 45 (84.9%) patientswas 34 months (range, 4–79 months). During this period,all of the 45 patients were alive, but 2 of the patients experi-enced metastasis: one of the 2 patients was found to havemetastasis in the liver 4 months postoperation, and theother patient had metastasis in the lumbar vertebrae47 months postoperation.

Discussion

CRCC is known for its low malignancy and favorable prog-nosis compared with clear cell RCC. In a retrospectivestudy of 2385 RCC cases, Cheville et al. (2003) found thatthe 5-year tumor-speciWc survival rate was 86.7 and 68.9%(P < 0.001) for CRCC and clear cell RCC, respectively. Inthe series of Cindolo et al. (2005), 8.6% of CRCC patientsdied after a median follow-up of 38 months, while for clearcell RCC, the mortality rate was 22%. In their study, the3- and 5-year survival rate for CRCC was 94 and 81%, respec-tively. Our study showed an even more encouraging result: theoverall survival rate was 100%, after a mean follow-up of34 months. There were also other published series thatreported a 100% survival rate (Akhtar et al. 1995; Peyromaureet al. 2004).

It appeared that in China patients were diagnosed withCRCC at a younger age (Tables 1 and 2), although healthexaminations were not as widely performed in China as indeveloped countries. This might indicate some racial diVer-ence, which prior to this study had never been mentionedfor CRCC. At presentation, most (69.8%) CRCC patientswere asymptomatic. Tumors were often detected by ultra-sonography or CT scan during the health examination. Forpatients who had symptoms, the complaints included hema-turia, Xank pain or discomfort, loss of weight and appetite,and so on. Systemic symptoms were not common (5.7%).

Table 1 Mean age of 4 non-Chinese series

Investigator (year)

Patients (n)

Mean age (years)

Peyromaure et al. (2004) 60 58

Cindolo et al. (2005) 104 57.6

Klatte et al. (2008) 124 61.1

Amin et al. (2008) 145 59

Total/mean (–) 433 59.1

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Although CRCC has some imaging features in ultraso-nography, CT, and MRI, none of those features werespeciWc, and the Wnal diagnosis can only be made bypathological examinations. Macroscopically, the grossappearances of surgical specimens have gray cut surfaces,while spots of bleeding, necrosis, and scar could be seenoccasionally. Microscopically, there are two types ofCRCC cells: clear cells and eosinophilic cells, which couldoccur simultaneously in the same tumor. Eosinophilic cellsare diYcult to diVerentiate from oncocytoma cells. Oncocy-toma is a benign tumor, and its prognosis is completelydiVerent from CRCC. Consequently, it is important to dis-tinguish oncocytoma from CRCC which is mainly com-posed of eosinophilic cells. In Hale’s colloidal ironstaining, CRCC demonstrates diVuse positive, which is adistinguishing feature. A loss of 1, 2, 6, 10, 17, and 21 chro-mosome could be detected by genetic tests (Yusenko et al.2009; Furge et al. 2004). Further, some biomarkers, such asKsp-cadherin (Mazal et al. 2005), claudin-7, and claudin-8(Osunkoya et al. 2009), were believed to be helpful fordiagnosis.

CRCC grows slowly, and most of the tumors are wellcircumscribed when detected. CRCC is less aggressive thanclear cell RCC, and inWltrative growth pattern is rare. Mosttumors are at a low TNM stage at diagnosis. T1–T2 tumorscould take up a percentage of more than 80% (Wu et al.2010). In our study, 88.7% tumors were at pT1–pT2 stage.No lymph node invasion was detected. At the same time,nuclear grade was mostly G1–G2 (83%). These featuresmight be the foundation of a favorable prognosis forCRCC.

Although the outcome for CRCC patients is encourag-ing, some patients do experience recurrence or metastasis.Amin et al. (2008) published a series of studies and foundthat 7% of CRCC patients experienced recurrence or metas-tasis during follow-up, and 6% of CRCC patients died. Atthe time of their research of 145 CRCC cases, they foundthat TNM stage, necrosis, and sarcomatoid change weresigniWcantly associated with prognosis. Klatte et al. (2008)reported 124 CRCC cases and concluded that TNM stage,nuclear grade, and sarcomatoid changes were associatedwith tumor-speciWc survival. Cheville et al. (2003) ana-lyzed 102 CRCC cases out of 1985 RCC cases and foundthat TNM stage, nuclear grade, tumor size, sarcomatoid

change, and necrosis were associated with mortality rate.Zini et al. (2008) believed that tumor size, nuclear grade,and necrosis were associated with tumor aggressiveness.And yet, there was also a study that denied the relationshipbetween nuclear grade and prognosis (Delahunt et al.2007). Until now, no eVective prediction had been made. Inour study, no local recurrence was found and only twopatients experienced metastasis. As a result, we were notable to evaluate the predicting values of TNM stage, sarco-matoid changes, or tumor size.

Surgical resection is the best treatment for CRCC. In thepast, radical nephrectomy was the gold standard, whilenephron-sparing nephrectomy was applied only to solitarykidney, bilateral RCC or contralateral renal inadequatepatients. Even so, along with the development of medicaltechniques and the subsequent increment of small RCCdetection, nephron-sparing nephrectomy is becoming moreand more popular. Huang et al. (2009) retrospectively ana-lyzed 2991 RCC patients who were all over 65 years-oldand found that patients who received radical nephrectomyhad higher chances of developing cardiovascular eventsand chronic kidney diseases. Their mortality rate was alsosigniWcantly higher, compared with patients undergoingnephron-sparing nephrectomy. In another study of 648surgically treated RCC cases by Thompson et al. (2008),radical nephrectomy was signiWcantly associated with ahigher mortality rate. The 12 patients who received nephron-sparing nephrectomy in our study were all alive and had noevidence of tumor recurrence or metastasis.

Conclusions

CRCC is an uncommon, but not rare subtype of RCC. Themean age of Chinese patients at diagnosis might be youngerthan other nationalities. Surgical resection can cure CRCCeVectively, and nephron-sparing nephrectomy is performedmore and more frequently now. Although its excellentprognosis has been conWrmed by our results, it is still diY-cult to predict tumor recurrence or metastasis.

ConXict of interest The authors report no relevant Wnancial conXictsof interest.

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Zhang et al. (2007) 25 46.5

Rao et al. (2007) 19 47.9

Our study (2011) 53 50.2

Total/mean (–) 97 48.8

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