To the Editor:

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare subtype of renal cell carcinoma (RCC).¹ Fewer than 80 cases have been reported in the literature. Patients are usually female, and the mean age of patients in one series was 53 years.² The majority of MTSCCs are indolent, and reports of recurrence and distant metastases are rare.^3–6 Furthermore, almost all cases of nodal or metastatic disease are associated with a high nuclear grade or sarcomatoid element in the primary tumor.^4–6 There are no published reports of systemic treatment in patients with metastatic disease. We describe here a patient with widespread metastatic MTSCC of the kidney treated successfully with sunitinib.

A 61-year-old white female presented with several months of proximal limb myalgia and polyarthralgia. Polymyalgia rheumatica was diagnosed, and prednisone 10 mg daily was commenced. As a result of persistent elevation of inflammatory markers and a lifelong smoking history, chest radiography was undertaken, and a right-sided pulmonary nodule was demonstrated. A computed tomography (CT) scan of chest, abdomen, and pelvis showed a 3-cm right renal mass, a 3-cm left adrenal mass, bulky retroperitoneal adenopathy, a right pulmonary nodule, left hilar adenopathy, and widespread sclerotic bone metastases. Histology from a biopsy of the lower pole renal mass was consistent with an RCC with spindle cell morphology.

Zoledronic acid infusions were initiated. Because of the unusually aggressive presentation, a further biopsy of the renal mass was undertaken at our institution. The biopsy was consistent with an MTSCC of the kidney. Biopsy of the retroperitoneal nodal mass was carried out to exclude a higher grade component or a second pathologic process and confirmed the diagnosis of MTSCC. Immunohistochemical staining for c-KIT was absent, as were mutations in exons 9, 11, 13, and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA. The patient became progressively symptomatic with myalgia, arthralgia, and malaise, and sunitinib was commenced at 50 mg daily on the 4 weeks on/2 weeks off schedule, 7 weeks after the first zoledronic acid infusion. The patient tolerated treatment well, experiencing grade 1 mucositis and diarrhea only. Symptomatic improvement was reported within a few days of starting treatment; a restaging CT at 12 weeks demonstrated a reduction in size of the retroperitoneal nodal mass and left adrenal lesion and stability of other lesions, consistent with a partial response to therapy. At 24 weeks, the patient continues to derive clinical benefit from therapy, and a restaging CT shows stable disease.

This is the first report, to our knowledge, of MSTCC of the kidney treated with sunitinib, and it is noteworthy that both symptomatic and radiologic responses occurred. A limitation of this report is that despite the fact that biopsies of both renal and retroperitoneal lesions were performed, it remains possible that the patient has a second diagnosis such as non–small-cell lung carcinoma. However, it should be noted that tumor shrinkage occurred in response to sunitinib in the biopsy-proven MSTCC retroperitoneal lymph node lesion.

Sunitinib is an oral inhibitor of multiple receptor tyrosine kinases, including vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-KIT, and is a standard of care for the first-line treatment of advanced clear cell renal carcinoma. A pivotal phase III trial demonstrated a progression-free survival benefit of sunitinib versus interferon alfa but included patients with clear cell histology only.⁷ An expanded access trial of sunitinib allowed all histologic subtypes of RCC, but only 13% of patients had non–clear cell histology, and it is not known whether this population included any patients with MSTCC.⁸ The molecular pathology of MSTCC is unknown, and as a consequence, it is impossible to speculate with confidence which of the multiple targets of sunitinib may be implicated in a response to therapy. In light of this report, physicians who treat RCC may wish to consider sunitinib therapy for patients with MSTCC.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultant or Advisory Role: James Larkin, Pfizer (C), Bayer Pharmaceuticals (C), GlaxoSmithKline (C), Novartis (C); Lisa Pickering, Pfizer (C), Novartis (C); Martin Gore, Pfizer (C), Bayer Pharmaceuticals (C), GlaxoSmithKline (C), Novartis (C), Roche (C) Stock Ownership: None Honoraria: James Larkin, Pfizer, Bayer Pharmaceuticals, GlaxoSmithKline, Novartis; Lisa Pickering, Pfizer, Novartis; Martin Gore, Pfizer, Bayer Pharmaceuticals, GlaxoSmithKline, Novartis, Roche Research Funding: James Larkin, Pfizer, Bayer Pharmaceuticals, Novartis; Lisa Pickering, Pfizer Expert Testimony: None Other Remuneration: Lisa Pickering, Pfizer