RESUMO
Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt-Hogg-Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the development of an aggressive oncocytic carcinoma from an oncocytoma, leading to aggressive targeted treatment but eventual death 39 months after the diagnosis.
Assuntos
Adenoma Oxífilo/patologia , Neoplasias Renais/patologia , Adenoma Oxífilo/genética , Adenoma Oxífilo/imunologia , Idoso , Progressão da Doença , Inativação Gênica , Componentes Genômicos , Humanos , Imuno-Histoquímica , Cariotipagem , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Masculino , Análise em Microsséries , RNA Mensageiro/análiseRESUMO
OBJECTIVES: To compare the performance of the BD Onclarity HPV Assay (BD Diagnostics, Sparks, MD) in BD SurePath liquid-based cytology media with that of Hybrid Capture 2 (HC2, Qiagen, Germantown, MD) samples co-collected in specimen transport medium in an adjudicated patient cohort. METHODS: The performance of the BD Onclarity HPV Assay using BD SurePath media was compared with that of HC2 samples co-collected in specimen transport medium using 541 archived samples from a multicenter US clinical trial with histologically adjudicated cervical biopsy specimens. RESULTS: The sensitivity for cervical intraepithelial neoplasia (CIN) 2 positivity (n - 104) was 90.4% (95% confidence interval [CI], 83-95) and 93.3% (95% CI, 87-97) and specificity was 76.9% (95% CI, 73-81) and 77.8% (95% CI, 74-82) for the BD assay and HC2, respectively. Nine cases of CIN 2+ had results discordant with the high-risk HPV assay. All were found to have been correctly classified with the BD assay using a novel WAVE denaturing high-performance liquid chromatography double-stranded DNA sequencing method. CONCLUSIONS: The clinical performance of The BD Onclarity HPV Assay with respect to histology end points was similar to HC2. Moreover, discordant analysis revealed improved performance of the BD assay with respect to ability to provide extended genotyping information and lack of cross-reactivity with low-risk HPV types associated with cellular abnormalities. The relative risks for CIN 3 disease for HPV 31 and HPV 33/58 (combined) were comparable to that of HPV 18 in this population, suggesting that these genotypes may warrant monitoring in future studies.