Norman Zambrano

Hereditary and Sporadic Papillary Renal Carcinomas with c-met Mutations Share a Distinct Morphological Phenotype

Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papillary renal cell carcinoma. In addition, c-met mutations were shown to play a role in 13% of patients with papillary renal cell carcinoma and no family history of renal tumors. The histopathology of papillary renal cell carcinoma with c-met mutations has not been previously described. We analyzed the histopathology of 103 bilateral archival papillary renal cell carcinomas and 4 metastases in 29 patients from 6 hereditary papillary renal cell carcinoma families with germline c-met mutations and 6 papillary renal cell carcinomas with c-met mutations from 5 patients with no family history of renal tumors. Twenty-five sporadic renal tumors with prominent papillary architecture and without somatic c-met mutations were evaluated for comparison. All papillary renal cell carcinomas with c-met mutations were 75 to 100% papillary/tubulopapillary in architecture and showed chromophil basophilic, papillary renal cell carcinoma type 1 histology. Fuhrman nuclear grade 1-2 was seen in tumors from 23 patients, and nuclear grade 3 was observed focally in 8 patients. Seventeen patients had multiple papillary adenomas and microscopic papillary lesions in the surrounding renal parenchyma. Clear cells with intracytoplasmic lipid and glycogen were focally present in tumors of 94% papillary renal cell carcinoma patients. Clear cells of papillary renal cell carcinoma had small basophilic nuclei, and clear cell areas lacked a fine vascular network characteristic of conventional (clear) cell renal cell carcinoma. We conclude that papillary renal cell carcinoma patients with c-met mutations develop multiple, bilateral, papillary macroscopic and microscopic renal lesions. Renal tumors with c-met genotype show a distinctive papillary renal cell carcinoma type 1 phenotype and are genetically and histologically different from renal tumors seen in other hereditary renal syndromes and most sporadic renal tumors with papillary architecture. Although all hereditary and sporadic papillary renal cell carcinomas with c-met mutations share papillary renal cell carcinoma type 1 histology, not all type 1 sporadic papillary renal cell carcinomas harbor c-met mutations.

HISTOPATHOLOGY AND MOLECULAR GENETICS OF RENAL TUMORS: TOWARD UNIFICATION OF A CLASSIFICATION SYSTEM

PURPOSE We characterize the genetic abnormalities associated with pathological subtypes of renal tumors, which may help diagnosis or prognostication. MATERIALS AND METHODS A comprehensive literature review of genetic abnormalities associated with different renal tumor subtypes was performed. RESULTS Studies of sporadic and hereditary forms suggest that abnormalities in the von Hippel-Lindau and met genes are the earliest changes in conventional (clear cell) and papillary basophilic renal cancers, respectively. Renal oncocytoma and chromophobe carcinoma have common genetic abnormalities, suggesting a relationship. A similar finding has been observed between papillary adenoma and papillary basophilic renal cancer. CONCLUSIONS These findings suggest that molecular diagnostic testing will help determine histopathological diagnosis, identify tumor types with similar genetic abnormalities suggesting a common origin and indicate potential prognostic markers for future study.

Molecular Genetics of Renal Cell Carcinoma

Renal cell carcinoma can be divided into sporadic and inheritable forms. One of the most common inheritable forms occurs in von Hippel-Lindau disease (VHL). VHL is a multisystem neoplastic disorder in which individuals develop tumors and cysts in multiple organs including the kidneys. Careful linkage analysis and cloning identified the VHL gene on chromosome 3p. In accordance with Knudsons hypothesis and tumor suppression theory, the VHL gene has been shown to have an important role in sporadic renal carcinoma as well. Further understanding of the VHL protein is likely to enhance our understanding of renal carcinogenesis, and clinical implications are beginning to evolve.

¿Es necesario realizar un estudio de etapificación en todos los pacientes con cáncer de próstata? Experiencia de un centro clínico nacional

Background: The role of staging studies in patients with prostate cancer (PCa) is a topic of discussion. Aim: To evaluate the usefulness of imaging studies in patients with prostate cancer. Material and methods: We reviewed the pathology service records to identify patients with prostate cancer diagnosed between 2003 and 2013. We reviewed the electronic medical records of those patients identified as having a prostate cancer. Patients were grouped according D’amico’s classification of cancer dissemination risk. We analized the frequency of imaging studies requested and their efficacy to detect metastases in each risk group. Results: We identified 241 patients with a mean age of 67 years. Fifty two percent of patients were classified as low-risk, 32% as intermediate-risk and 16% as high risk. At least one imaging study was requested to 64% of patients (49, 78 and 87% of patients with low, intermediate and high risk respectively). Among the 155 patients in whom an imaging study was requested, no metastases were found in the low risk group. On the other hand, dissemination was found in 7% of the intermediate-risk group and 62% of the high-risk group. Conclusions: Half of patients with prostate cancer were classified as low risk. In half of this group of low risk patients, staging studies were requested and the probability of detecting metastases was low or nil. The odds of detecting metastases increased in higher risk groups.