title: PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21).
abstract: The reappraisal of genetically defined subsets of renal tumors can help to highlight the key pathologic features of specific neoplastic entities. We report the morphologic, immunophenotypic, ultrastructural, and molecular features of 11 renal carcinomas bearing a t(X;1)(p11.2;q21) and/or the resulting PRCC-TFE3 gene fusion. The male/female ratio was 4:7. Ten patients were in the age range of 9-29 years and one was 64 years old (mean 21.3 years, median 15 years). The predominant histologic pattern was nested, with islands of tumor cells compartmentalized by thin-walled capillary vasculature. Minor variations on this pattern yielded solid, acinar, alveolar, and tubular architecture. Papillary architecture was seen in nine cases, usually as a minor component. Neoplastic cells were typically characterized by irregularly shaped nuclei with vesicular chromatin and small nucleoli not visible with a 10x objective, and cytoplasm that ranged from clear to densely granular and eosinophilic. Mitoses were extremely rare; 5 were found in 900 high power fields examined from the 11 neoplasms. The most distinctive immunohistochemical feature of these neoplasms was moderate to intense nuclear labeling for TFE3 protein. These tumors were also consistently immunoreactive for the RCC antigen (10 of 11) and CD10 (9 of 9), whereas cytokeratin and epithelial membrane antigen were negative in four cases and were positive focally in the others. Ultrastructurally, all of the six neoplasms examined showed features consistent with conventional-type (clear cell) renal carcinoma, although two demonstrated distinctive intracisternal microtubules. Both tumors tested contained PRCC-TFE3 fusion transcripts. The differential diagnosis includes conventional-type papillary renal cell carcinoma, conventional-type (clear cell) renal carcinoma, and the ASPL-TFE3 renal carcinomas associated with the t(X;17)(p11.2;q25), with the latter two being morphologically the most similar to the t(X;1) renal carcinomas. Aside from their distinctive clinicopathologic features described here, there is experimental evidence suggesting that these tumors may show differential sensitivity to certain chemotherapeutic agents.
authors.affiliation: Department of Pathology, Surgical Pathology, Johns Hopkins Hospital, Weinberg Building, Room 2242, 401 N Broadway, Baltimore, MD 21231-2410, USA. pargani@jhmi.edu
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couturier
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Fournet
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Brian
authors.initials: B
authors.lastname: Hutchinson
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Lilliane
authors.initials: L
authors.lastname: Boccon-Gibod
authors.forename: Charles
authors.initials: C
authors.lastname: Timmons
authors.forename: Naiel
authors.initials: N
authors.lastname: Hafez
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
mesh_terms: D000293:Adolescent; D000328:Adult; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D018797:Cell Cycle Proteins; D002648:Child; D002878:Chromosomes, Human, Pair 1; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics*; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C415042:PRCC protein, human; D011506:Proteins; C069203:TFE3 protein, human; D014157:Transcription Factors