[881] Potential Utility of GATA3 Immunoexpression and HPV Status in the Differential Diagnosis of Urothelial vs Squamous Cell Carcinomas of Distal Penile Urethra

Jeong S Han, George J Netto, Stephen Lee, Nilda Gonzalez-Roibon, Hillary Ross, Rajni Sharma, Antonio L Cubilla, Alcides Chaux. Johns Hopkins University, Baltimore, MD; Instituto de Patologia e Investigacion, Asuncion, Paraguay

Background: Squamous cell carcinoma (SCC) and urothelial carcinoma (UC) occur as primary tumors of the distal penile urethra, possibly reflecting histogenesis from the native squamous or urothelial mucosa at this site. As there may be a considerable morphologic overlap between the two tumor types, the utility of GATA3, a transcription factor that has been rencently used as a marker of urothelial differentiation, and human papillomavirus (HPV) status was evaluated in the differential diagnosis of the two entities.
Design: We retrieved 6 cases originally classified as primary urothelial carcinoma of distal urethra from our surgical pathology archives. All H&E sections were retrieved and reviewed by 2 urologic pathologists on the study. Medical records were also reviewed. Extension from other urologic sites was clinically excluded in all cases. Whole routine representative sections were stained for GATA3 (BioCare, GATA3 clone L50-823) using standard immunohistochemistry techniques. In situ hybridization for high-risk HPV (HR-HPV) was also performed in all cases. In addition, GATA3 immunoexpression was evaluated in a tissue microarray (TMA) containing 38 cases of SCC of the penile glans.
Results: In the TMA section, all 38 cases of penile glans SCC were negative for GATA3. Based on the morphologic review, GATA3 immunohistochemistry, and HR-HPV in situ hybridization, the 6 distal urethral tumors were reclassified as shown in Table 1.

GATA3 and HR-HPV in 6 distal urethral carcinomas originally diagnosed as UC
Case No.AgeReclassified DiagnosisGATA3HR-HPV
148Basaloid SCCNegativePositive
269Invasive UCPositiveNegative
370Invasive UCPositiveNegative
473Invasive UCPositiveNegative
560Warty-Basaloid SCCNegativeNegative
673Warty-Basaloid SCC*NegativePositive
* A noninvasive UC component was positive for GATA3 and negative for HR-HPV

The original diagnosis of invasive urothelial carcinoma was confirmed in 3 cases. The 3 additional cases that were reclassified as SCCs were of basaloid or warty-basaloid subtype. One of the latter revelead a noninvasive component that displayed urothelial differentiation, as suggested by its GATA3 positivity and lack of HR-HPV.
Conclusions: We found no expression of GATA3 in bona fide penile glans SCC. In difficult distal urethral carcinoma tumors displaying ambiguous urothelial/squamous features, GATA3 and HR-HPV detection may aid in differetiating SCC from UC.
Category: Genitourinary (including renal tumors)

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 86, Tuesday Afternoon


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