Role of Immunohistochemistry (IHC) in the Differential Diagnosis of Invasive Urothelial Carcinoma (UCa) Versus High-Grade Tumors of the Renal Collecting System [Collecting Duct Carcinoma (CDC) and Renal Medullary Carcinoma (RMC)].
Chandrakanth Annaiah, Gladell P Paner, Allen M Gown, Christian Gulmann, Mitual Amin, Adeboye O Osunkoya, Mahesha Vankalakunti, Loren P Herrera, Ruta Gupta, Komal Arora, Mahul B Amin. Cedars-Sinai Medical Center, Los Angeles, CA; University of Chicago, IL; PhenoPath Laboratories, Seattle, WA; William Beaumont Hospital, Detroit, MI; Emory University Hospital, Atlanta, GA
Background: A high-grade infiltrative carcinoma associated with desmoplasia and an inflammatory stromal response in the renal medullary region poses challenging differential diagnostic considerations between invasive UCa, CDC and RMC. The problem is compounded in limited sampling in needle core biopsies of the kidney and at metastatic sites when a primary mass in the kidney (histology not known) is detected.
Design: Twenty-six (26) tumors were analyzed by a focused IHC panel comprised of 8 markers including novel urothelial differentiation-associated markers (S-100p, GATA3), markers frequently positive in urothelial tumors [high molecular weight cytokeratin (HMCK) & p63], metanephric differentiation-associated markers (PAX-2, PAX-8), marker associated with CDC [Ulex Europaeus Agglutanin 1 (UEA-1)] and INI-1/hSNF5, loss of expression of which is reported to occur in RMC with rhabdoid morphology or tumors with aggressive behavior.
Results: UCa (n=11) showed S-100p, GATA3, p63, HMCK positivity and PAX-2, PAX-8 – negativity in 100% of the cases. UEA-1 was positive in 55% of cases and INI-1 expression was positive in all cases. High-grade tumors of the renal collecting system showed greater variability in immunoprofile. Positive markers included UEA-1 (50%), PAX-8 (33%), HMCK and p63 (17% each); 14% showed rare focal positivity for S-100p. Negative markers included GATA3 and PAX-2 (100%). INI-1 was positive in all 9 cases of CDC and negative in all 6 cases of RMC.
Conclusions: 1) The typical immunoprofile for invasive UCa of the kidney is S-100p (+), GATA3 (+) and PAX-8 (-). 2) CDC and RMC have variable immunoprofile which overlaps with UCa in many traditionally used markers: UEA-1, p63 & HMCK; PAX-8 positivity & negativity for GATA3 is supportive of their diagnosis. 3) INI-1 expression is useful in the distinction of RMC versus CDC; it is lost in the former indicating biallelic inactivation of the INI-1/hSNF5 tumor suppressor gene on chromosome 22q11.2. 4) These findings may become even more crucial as specific targeted therapies are developed for each of these tumor types.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 113, Wednesday Morning