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Laryngeal Metastasis 7 Years After Radical Nephrectomy.

Renal cell carcinoma (RCC) typically metastasizes via the bloodstream and is known to involve almost every organ of the body. Common sites for metastasis include the lungs, bone, lymph nodes, pancreas, adrenal glands, soft tissues, pleura, and brain.[1] However, isolated RCC metastases to the head and neck, especially the larynx, are extremely rare. Although cases of presenting laryngeal metastases leading to the discovery of an underlying RCC have been reported previously,[2-5] there have been only 2 reports in the English literature of metastasis to the larynx occurring years after initial nephrectomy, both of which were not isolated recurrences.[6,7] Review of the literature has revealed only 2 reported cases in the German literature of isolated laryngeal metastasis to the anterior commissure and the false vocal cords, both occurring 6 years after nephrectomy.[8,9] We believe this case to be the first example of an isolated intralaryngeal, supraglottic RCC metastasis, occurring 7 years after potentially curative radical nephrectomy.


A 48-year-old, previously healthy man came to our attention in 1991 after experiencing left flank pain and gross hematuria for 3 weeks. Neither costovertebral angle tenderness nor palpable renal mass was evident on physical examination. Intravenous pyelogram revealed a left renal mass, which was confirmed by abdominal and pelvic computed tomographic scan. A left radical nephrectomy with exploratory laparotomy was performed. All other intra-abdominal organs were grossly free of tumor. The kidney tumor was a clear cell RCC.

The patient's postoperative course and follow-up, including yearly thoracoabdominopelvic computed tomographic scan and urine cytology were all unremarkable. The patient was asymptomatic until 1 year after the last follow-up visit in 1997, when he developed hoarseness. Laryngoscopy revealed a 1.2-cm, tanpink, polypoid, supraglottic mass. The tumor was locally excised and revealed metastatic clear cell RCC.


Tissues from the primary kidney tumor and metastatic nodule were fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin-eosin by routine methods. Histochemistry included periodic acid-Schiff reaction (McManus, Carson, and Pickett) and periodic acid-Schiff reaction with diastase digestion (Luna) for demonstration of glycogen. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections using avidin-biotin-peroxidase technique after enzymatic digestion with proteinase K. Antibodies used were low-molecular-weight anti-human cytokeratin cocktail BA17/MNF116 (Dako Corporation, Carpinteria, Calif), high-molecular-weight anti-human cytokeratin 35BH11 (Dako), and anti-vimentin clone Vim 3B4 (Dako).


The superior pole of the resected left kidney contained a 5.5 x 4-cm, ovoid, yellow-tan tumor with foci of hemorrhage and cystic changes. Histology showed a typical clear cell RCC with sheets of polyhedral cells exhibiting clear cytoplasm and well-defined cell borders (Figure 1). Delicate fibrovascular septae separated these cells into moderately sized lobules. The nuclei were hyperchromatic with mild atypia, rare mitoses, and indistinct nucleoli. Histochemistry showed periodic acid-Schiff--positive and diastase-sensitive intracytoplasmic granules, confirming the presence of glycogen. Immunohistochemical stains showed isolated cells positive for both low-molecular-weight cytokeratin and vimentin. Tumor invaded both the renal capsule and perinephric fat. There was no evidence of vascular invasion. Resection margins around the perinephric fat, renal vessels, and ureter were free of tumor. The tumor was that of a clear cell RCC, American Joint Committee on Cancer stage III, Fuhrman nuclear grade I-II.


The excised laryngeal tumor showed clear cells with distinct cytoplasmic borders displaying architecture similar to that of the RCC removed 7 years earlier (Figure 2). The tumor was distinctly separate from the overlying normal squamous mucosa of the larynx. Histochemical and immunohistochemical staining patterns were identical to those of the original renal tumor, thus confirming the laryngeal mass to be metastatic RCC.



Renal cell carcinoma is one of the great imitators that has an erratic clinical course. Rare involvement of the larynx seems related to the terminal location of the larynx in the lymphatic and vascular circulation.[10] While metastatic neoplasms in the larynx account for only 0.09% to 0.40% of all laryngeal tumors,[10] some studies have shown RCC metastasis to the head and neck to occur in 15.2% of patients with RCC.[4] The potential for RCC to metastasize to the larynx years after nephrectomy necessitates consideration of this entity during workup of a laryngeal lesion, especially given the favorable prognosis after local excision of these isolated metastatic lesions.[7]


[1.] Takashi M, Takagi Y, Sakata T, Shimoji T, Miyake K. Surgical treatment of renal cell carcinoma metastases: prognostic significance. Int Urol Nephrol. 1995; 27:1-8.

[2.] Turner AL. Metastatic malignant tumor of the larynx, secondary to adeno-carcinoma of the right kidney. J Laryngol Otol. 1924;39:181-194.

[3.] Fields JA. Renal carcinoma metastasis to the larynx. Laryngoscope. 1966; 76:99-101.

[4.] Boles R, Cerny J. Head and neck metastases from renal carcinoma. Mich Med. 1971;70:616-618.

[5.] Ferlito A, Caruso G, Recher G. Secondary laryngeal tumors: report of seven cases with review of the literature. Arch Otolaryngol Head Neck Surg. 1988;114: 635-639.

[6.] Miyamoto R, Helmus C. Hypernephroma metastatic to the head and neck. Laryngoscope. 1973;83:898-905.

[7.] Maung R, Burke RC, Hwang WS. Metastatic renal carcinoma to larynx. J Otolaryngol. 1987;16:16-18.

[8.] Hittel JP, Born IA. Ungewohnliche Metastasenlokalisation eines Nierenkarzinoms: ein Fallbericht mit Literaturubersicht [Unusual metastatic site of a kidney carcinoma: a case report with review of the literature]. Laryngorhinootologie. 1995;74:642-644.

[9.] Issing PR, Heermann R, Ernst A, et al. Fernmetastasierung von Nierenzellkarzinomen in den Kopf-hals-bereich [Distant metastasis of renal cell carcinomas to the head-neck area]. Laryngorhinootologie. 1996;75:171-174.

[10.] Nicolai P, Puxeddu R, Cappiello J, et al. Metastatic neoplasms to the larynx: report of three cases. Laryngoscope. 1996;106:851-855.

Accepted for publication May 18, 2000.

From the Departments of Pathology (Dr Dee) and Urology (Drs Eshghi and Otto), New York Medical College, Valhalla, NY.

Reprints: Simpson L. Dee, MD, PO Box 62, Hawthorne, NY 10532-0062.
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Author:Dee, Simpson L.; Eshghi, Majid; Otto, Clifton S.
Publication:Archives of Pathology & Laboratory Medicine
Date:Dec 1, 2000
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