International Urology and Nephrology 35: 15–17, 2003.© 2003 Kluwer Academic Publishers. Printed in the Netherlands.

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Metastatic renal clear cell carcinoma mimicking stage IV lung cancer

J. Griniatsos, P.O. Michail, C. Menenakos, D. Hatzianastasiou, C. Koufos & E. BastounisSurgical Department, Pathology Department and Pathologic Physiology Department, University of Athens,“Laiko” Hospital, Athens, 115-27, Greece

Abstract. We present a 63-year-old man who was investigated for a lesion in the apex of the left lung and acoexisting osteolytic lesion in the right major trochanter. FNA of the thoracic mass was suggestive for malignancyyet not diagnostic regarding the tumor type and the site of the primary tumor. A diagnosis of a stage IV lungcancer was favored and he underwent a left exploratory thoracotomy in view to resect the primary tumor. Anextrapulmonary mass localized to the pleura not involving the ipsilateral lung was disclosed. Multiple biopsiesrevealed metastatic clear cell RCC. A 5×7 cm left renal tumor was revealed in a postoperative abdominal CTscan. He was treated with combination of interferon A and vinblastin followed by radical nephrectomy. Twenty-four months after the diagnosis he is alive without evidence of local or distant recurrence. Pleural metastasesfrom RCC are mainly presented as malignant pleural effusions. Thoracic metastatic lesions localized to the pleura,forming solitary or multiple mass(es) have been rarely reported. We review the literature regarding this rare clinicalmanifestation of the disease and we discuss diagnostic and therapeutic options.

Key words: Pleural metastases, Renal cancer, Renal clear-cell carcinoma

Introduction

Renal cancer accounts for 2–3% of all adult cancers,occurring predominantly in the sixth to eighth decadeof life and being nearly twice as frequent in men aswomen [1].

Malignant renal epithelial tumors are mainlyclassified in clear cell, papillary, chromophobe, andcollecting duct carcinoma, with clear cell subtypebeing the commonest (80%) amongst them [2].

The natural history of the disease is unpredictableand generally grave. Approximately, one third of thepatients with renal carcinoma present with metastaticdisease at the time of diagnosis [3], while in 60–70%of them, metastases will develop in the course of thedisease [4]. Metastases to pleura, although have beendescribed [5], are considered as exceptionally rare.

We report a case of synchronous pleural and bonemetastases from “clear cell” renal cell carcinoma(RCC), which at first gave the impression for stage IVlung cancer.

Case report

A 63-year-old man, with a history of diabetes mellitustype II was admitted for investigation of a lesion inthe apex of the left lung, considered suspicious formalignancy.

He first presented with a two-month history ofpersistent pain in the right thigh – of sudden onset– due to which, he was unable to walk. The patienthad consulted an orthopedic surgeon and he had X-rays of lumbar vertebral column, ischium and rightfemur, revealing an osteolytic lesion in the rightmajor trochanter. This finding was supported by ananalogous focal increase in the uptake of Tc-99m-DTPin a bone scan. Chest X-ray revealed a lesion in theapex of the left lung without any evidence of pleuraleffusion. A thoracic CT-scan revealed a solid massmeasuring 7 cm in the same area, extending to the firstand second rib, as well as the supraclavicular fossa;no pleural effusion was detected. He underwent a fineneedle aspiration (FNA) biopsy of the thoracic massunder ultrasound guidance: the result was “suspiciousfor malignancy”.

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Figure 1. Histopathologic findings (H+E stain, original magnification ×100).(a) Pleural lesion: metastatic clear cell RCC. Notice the typical nested architecture, capillary vasculature, and low-grade nuclear features.(b) Nephrectomy specimen: Clear cell RCC, featuring increased eosinophilia, nuclear size, and nucleolar prominence, consistent withFuhrman’s Grade 3. The multinucleated tumor cells (top right) were exceptional.

On admission, the patient did not refer urinarysymptoms (i.e. haematouria), clinical examinationrevealed a palpable firm mass in the left supra-clavicular fossa with no other abnormal findings,while routine laboratory evaluation of serum and urinewas unremarkable, apart from high blood glucosevalue (203 mg/dl).

Based on the history and the results of the imaginginvestigations, a diagnosis of a stage IV lung cancerwas favoured. A brain CT-scan was performed as afinal preoperative staging step and was reported asnormal.

The patient underwent a left exploratory thora-cotomy, which disclosed an extrapulmonary, friable,and hemorrhagic mass localized to the pleura notinvolving the superior lobe of the ipsilateral lung.Multiple biopsies were taken.

On histopathologic examination, both the pleuraand the thorax wall were infiltrated by a highlyvascular, solid tumor with clear cell features, exhibit-ing nested and alveolar architecture, consistent withmetastatic clear cell RCC (Figure 1a).

Because of this histologic finding, an abdominalCT scan had been considered as mandatory and wasperformed in postoperative period. A tumor measuring5×7 cm involving the left kidney, was disclosed.The patient was referred to the Oncology Departmentand he was treated with vinblastin and interferon A.

During that period, he sustained a right transtrochanterfracture that was surgically treated. Tissue samplesfrom the fractured bone were submitted for histologyand disclosed infiltration by clear cell RCC.

After completing chemotherapy, the patient under-went left radical nephrectomy and a diagnosis ofclear renal cell carcinoma, Fuhrman’s grade 3 – pT1was rendered (Figure 1b). Twenty-four months later,the patient is still alive, without clinical evidence ofdisease and remains in good general condition.

Discussion

Histologic subtype is one of the prognostic factors thatdetermine the rate and the distribution of metastaticlesions in the natural course of the RCC. Clear cellRCC has a propensity for vascular invasion and maybe associated with distant metastases at an early stage,while the rest histological types tend to loco-regionalinvasion with lymph node spread [6]. Although clearcell RCC can practically metastasize to any part of thebody, the majority of metastatic lesions are located inthe lung (50%) and bones (49%) [7].

Clinically obvious pleural metastases from RCCare considered as exceptionally rare. Retroperitonealvascular invasion and metastases via Batson’s venousplexous have been proposed as an explanation theory

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for their development [8]. They are mainly presentedas malignant pleural effusions [9, 10], they coexistwith lung metastases [11] and never occur withoutinvolvement of other metastatic site [12].

To the best of our knowledge, thoracic meta-static lesions localized to the pleura, forming solitaryor multiple mass(es) have been reported in only sixcases so far [5, 8, 11]. Such lesions are difficult todifferentiate from mesothelioma [5, 8]. In the presentcase, pleural metastasis was related to clear cell RCCsubtype, and was presented as solitary pleural masswithout effusion, coexisting with bone metastasis.

In cases of pleural effusion aspiration cytology ofthe pleural fluid is a useful diagnostic modality [9],but can not be applied in cases without effusion, likethe present one. The diagnostic role of FNA is welldocumented in metastatic lesions others than pleural.In the majority of metastatic cases, neither the primarysite nor the subclassification of the clear cell tumorscould be accurately determined on the basis of FNAfindings alone, if they are not combined with clinicalhistory [13]. In fact, FNA was diagnostic in a patientwith pleural mass and a known history of nephrectomyfor RCC [5], but the overall experience is generallyminimal. In the present case, because of the absenceof clinical information, FNA was suggestive for malig-nancy, yet not diagnostic regarding the tumor type andthe site of the primary tumor.

In the present case, because FNA’s inconclusiveresult, diagnostic thoracoscopy could be considered asan alternative diagnostic step [14], but the preopera-tive imaging findings were highly suggestive for lungcancer and an attempt to resect the primary tumor wasfavored.

The combination of interferon alpha and vinblastinis a well-established effective medical treatment foradvanced renal cancer [15]. The role and the timingof nephrectomy and cytoreductive surgery in themanagement of metastatic cases are still controver-sial, although recent studies [16] have addressed afavorable outcome. In the present case, we used thecombination of interferon A and vinblastin followedby radical nephrectomy.

The prognosis of pleural metastases in RCC isgenerally poor and the majority of the patients’ diewithin six months from the diagnosis [5, 9].

The present case indicates that: (i) renal cellcarcinoma should be suspected and considered inthe differential diagnosis of a thoracic mass foundin a male patient elder than 60 years-old and (ii)

any diagnostic modality for accurate preoperativediagnosis should also be applied in cases with incon-clusive histology report.

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Address for correspondence: John Griniatsos, MD, 43 TenedouStreet, G.R. 113-61, Athens, GreecePhone: 0030 210 8624627; 0030 6947 828516E-mail: johngrin@hotmail.com