title: Renal cell carcinoma with leiomyomatous stroma--further immunohistochemical and molecular genetic characteristics of unusual entity.
abstract: Renal cell carcinoma (RCC) with leiomyomatous stroma (RCCLS) is a recently recognized entity with indolent biological behavior. The diagnostic implication of absence/presence of VHL gene mutation, VHL hypermethylation, or/and loss of heterozygosity of chromosome 3p (LOH 3p) is widely discussed. Criteria for establishing a diagnosis of RCCLS are still lacking. Fifteen RCCLSs were retrieved from our registry. The cases were studied with consideration to the morphology, immunohistochemistry, and molecular genetics. All cases were composed of low-grade epithelial cells with clear cytoplasm arranged in nests intermingled with abundant leiomyomatous stroma. Age range of the patients was 33 to 78 years. The tumor size ranged from 1.5 to 11 cm. Six of the patients were males, and 9, females. Of the 15 tumors sent for molecular genetic testing, only 12 cases were analyzable. All cases were analyzable immunohistochemically. Of 12 of these cases, 5 showed complete absence of VHL gene mutation, VHL hypermethylation, and LOH 3p. Of these 5 cases, 3 were positive for cytokeratin 7 (CK 7). All of the 5 cases were positive for carbonic anhydrase 9, vimentin, and CD10. The remaining 7 of 12 genetically analyzable cases were found to have had VHL hypermethylation, LOH 3p, VHL gene mutation, or a combination of the former 2 characteristics. These 7 cases were positive for vimentin. Variable reactivity was found for CK 7, carbonic anhydrase 9, α-methylacyl-CoA racemase, and CD10. In 1 of these 7 cases, gains on chromosomes 7 and 17 as well as hypermethylation of VHL gene were found. This case was considered as clear cell RCC with aberrant status of chromosomes 7 and 17.
  
  
  CONCLUSIONS
  (1) Leiomyomatous stroma is not specific for the so called RCCLS. It can be seen also in otherwise typical clear cell RCCs. (2) There are no characteristic morphological/immunohistochemical features unique for "RCCLS." (3) Our results indicate that only tumors with the absence of the VHL gene mutation, hypermethylation, and LOH 3p can be diagnosed as RCCLS. (4) Relation of RCCs with a prominent smooth muscle stroma to the renal angiomyoadenomatous tumor/clear cell papillary (tubopapillary) RCC is not clearly evident from our study and has to be further analyzed on larger cohort of the patients.
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Peckova
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Grossmann
authors.affiliation: Department of Pathology, University Hospital Dubrava, Zagreb, Croatia.
authors.forename: Stela
authors.initials: S
authors.lastname: Bulimbasic
authors.affiliation: Department of Pathology, East University Riga, Latvia.
authors.forename: Maris
authors.initials: M
authors.lastname: Sperga
authors.affiliation: Department of Pathology, Institute Nacional de Cancerologia, Mexico City, Mexico.
authors.forename: Delia
authors.initials: D
authors.lastname: Perez Montiel
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Daum
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Rotterova
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Bohuslava
authors.initials: B
authors.lastname: Kokoskova
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Vesela
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Kristyna
authors.initials: K
authors.lastname: Pivovarcikova
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Kevin
authors.initials: K
authors.lastname: Bauleth
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Jindrich
authors.initials: J
authors.lastname: Branzovsky
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dubova
authors.affiliation: Department of Urology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Hora
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
authors.affiliation: Department of Pathology, Charles University, Medical Faculty and Charles University Hospital, Plzen, Czech Republic; Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Plzen, Czech Republic. Electronic address: hes@medima.cz.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hes
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
keywords: Clear cell carcinoma; Kidney; LOH 3p; Leiomyomatous stroma; Renal cell carcinoma; VHL gene mutation