Michalaki and Gennatas Journal of Medical Case Reports 2012, 6:115 http://www.jmedicalcasereports.com/content/6/1/115 Discussion RCC treatment has been classically derived from clinical trials that incorporated all histologies comprising clear cell, papillary, chromophobe, and other rarer subtypes. Most recently, novel therapies (sunitinib and sorafenib) have shown significant clinical activity in advanced RCC and have changed the standard of care in this disease [1-3]. However, pivotal studies with these drugs were performed exclusively in patients with clear cell histol- ogy. Therefore, the optimal therapy for papillary and chromophobe histologies remains unknown. Overall, ChRCC is considered to portend a good prognosis and is associated with earlier-stage tumors and longer overall survival in comparison with CCRCC. There are conflict- ing reports on prognosis in metastatic disease, and few data on response to treatment exist. Increased VEGF-6 and c-Kit (i.e., mast/stem cell growth factor receptor; proto-oncogene c-Kit; tyrosine-protein kinase Kit; or CD117) expressions have been reported in ChRCC, but the relevance of this to treatment is unknown [4-6]. In an expanded-access trial of sunitinib, 13% of patients had non-clear cell histology, and there was evidence of clinical activity in this group [7]. A large international study reported the outcome of 1001 patients with meta- static RCC (82 of whom had papillary histology). Five- year survival rates of papillary and clear cell subtypes were similar (about 10%). No treatment has proven to be active in papillary RCC, unlike CCRCC. One recently published series illustrated a response rate of only 5% in patients treated with these VEGF-targeted therapies [8]. Both responders received sunitinib, corresponding to an overall response rate of 17% in sunitinib-treated patients. Similarly, progression-free survival seemed to be longer in the patients treated with sunitinib in com- parison with the patients treated with sorafenib (11.9 versus 5.1 months, respectively). IIt is interesting to note that several patients who experienced progression on one anti-VEGF therapy and who were subsequently switched to another anti-VEGF therapy achieved substantial response. Although the overall duration of follow-up was relatively short, the results support the clinical rationale for continued tar- geting of the VEGF and c-Kit signaling pathways in non-clear cell RCC [9,10]. A phase III trial of temsiroli- mus also included patients with non-clear cell histology, and a subgroup analysis demonstrated an improved overall survival on temsirolimus in comparison with interferon and the combination of both drugs [11]. Choueiri and colleagues [12] retrospectively reviewed the efficacies of sunitinib and sorafenib in patients with metastatic papillary RCCs and ChRCCs. Seven patients with ChRCC were treated with sunitinib, and five were treated with sorafenib. A partial response occurred in Page 4 of 5 three patients (25%), and the median progression-free survival time for patients with ChRCC was 10.6 months [12]. In summary, these data suggest that sunitinib and sorafenib have some activity in ChRCC. To the best of our knowledge, there are no published reports of the use of the mTOR inhibitors in this setting. Conclusions In this report, we describe the case of a patient who had ChRCC and who experienced improvement in his gen- eral condition and stable disease on treatment with everolimus after a prolonged response to sunitinib treat- ment. This case report suggests that anti-VEGF agents such as sunitinib and mTOR-targeted agents such as everolimus are effective and appropriate treatments for this RCC tumor subtype. Now that agents directed against these pathways have largely replaced immunotherapy as the standard of care, new questions have emerged and are the subject of ongoing clinical trials. Additional prospective studies and clinical experience with this rare histologic non- clear cell subtype are needed. Consent Written informed consent was obtained from the patient for publication of this manuscript and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Abbreviations CCRCC: clear cell renal cell carcinoma; ChRCC: chromophobe renal cell carcinoma; mTOR: mammalian target of rapamycin; RCC: renal cell carcinoma; VEGF: vascular endothelial growth factor. Authors’ contributions CG analyzed and interpreted the patient data. VM was a major contributor in writing the manuscript. Both authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Received: 15 September 2011 Accepted: 23 April 2012 Published: 23 April 2012 References 1. Motzer RJ, Bacik J, Mariani T, Russo P, Mazumdar M, Reuter V: Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear-cell histology. J Clin Oncol 2002, 20:2376-2381. 2. Cindolo L, de la Taille A, Schips L, Zigeuner RE, Ficarra V, Tostain J, Artibani W, Gallo A, Salzano L, Patard JJ: Chromophobe renal cell carcinoma: comprehensive analysis of 104 cases from multicenter European database. Urology 2005, 65:681-686. 3. Beck SD, Patel MI, Snyder ME, Kattan MW, Motzer RJ, Reuter VE, Russo P: Effect of papillary and chromophobe cell type on disease-free survival after nephrectomy for renal cell carcinoma. Ann Surg Oncol 2004, 11:71-77. 4. Jacobsen J, Grankvist K, Rasmuson T, Bergh A, Landberg G, Ljungberg B: Expression of vascular endothelial growth factor protein in human renal cell carcinoma. BJU Int 2004, 93:297-302.