Renal Cell Carcinoma Presenting as Carcinoma of Unknown Primary Site: Recognition of a Treatable Patient Subset

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Abstract

Micro-Abstract

Using a molecular cancer classifier assay and/or immunohistochemistry, patients with occult renal cell carcinoma can be accurately identified in the carcinoma of unknown primary site population and treated with site-specific therapy.

Background:

Improved diagnostic methods, including gene expression profiling, allow identification of the tissue of origin in most patients with carcinoma of unknown primary site (CUP). Patients with an occult renal cell carcinoma (RCC) are of particular interest, because effective treatment for advanced RCC has no overlap with the empiric chemotherapy used traditionally for CUP. We report the clinical characteristics, pathologic features, and response to RCC-specific treatment in CUP patients identified as RCC using a molecular cancer classifier assay (MCCA).

Patients and Methods:

All CUP patients who had an MCCA performed between 2008 and 2013 at a single institution were reviewed. Patients with an RCC diagnosis using MCCA are reported in this article.

Results:

Twenty-four of 539 CUP patients (4.4%) were diagnosed with RCC using MCCA. None had suspected renal lesions on computed tomography scan; otherwise, clinical characteristics were typical of advanced RCC. Histology was adenocarcinoma or poorly differentiated carcinoma; only 5 of 24 patients had focal features suggestive of RCC (clear-cell 1, papillary 4). Specific MCCA diagnoses included papillary (11) and clear cell (6). Relatively specific renal immunohistochemistry (IHC) stains, when performed, were compatible with RCC in 9 of 11 tumors. Twenty of 24 patients received RCC-specific treatment, and had a median survival of 16 months.

Conclusions:

Patients with occult RCC can be identified in the CUP population using MCCA and/or IHC. Papillary carcinoma is more common in this group than in the larger RCC population. Although confirmation from prospective studies is needed, RCC-specific treatment should be considered for this group of patients.

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