False Immunohistochemical Results for Herpesviridae and Other Clusters of Differentiation Due To Biotin Intranuclear Inclusions in the Gestational Endometrium

Abstract

Francesco Rivasi, Luca Roncati, Giuseppe Barbolini, Elisabetta Petrella, RenzoBoldorini

Objective: There are now eight known human herpes viruses (HHV) containing a double-stranded DNA genome: Herpes Simplex Virus 1 (HSV1, HHV1), Herpes Simplex Virus 2 (HSV2, HHV2), Varicella-Zoster Virus (VZV, HHV3), Epstein-Barr Virus (EBV, HHV4), Cytomegalovirus (CMV, HHV5), Herpes Virus 6 (HHV6-a, HHV6-b), Herpes Virus 7 (HHV7) and Herpes Virus 8 (HHV8, KSHV - Kaposi’s sarcoma associated herpes virus). The highest risk of maternal-fetal HSV transmission is among women who acquire a genital infection during pregnancy. Congenital HHV6 infection occurs in 1% of births, a rate similar to that for CMV infection. Congenital HHV6-a infections are asymptomatic, whereas postnatal HHV6-b infections present with acute febrile states. The purpose of this study was to eliminate false positive results in order to achieve an accurate pathological diagnosis for herpes virus infections to the gestational endometrium. Methods: The biopsies of three suspected cases of gestational herpetic endometritis were submitted to immunohistochemical tests for HHV1+2, HHV5, HHV6-a, HHV6- b, HHV8 and for other clusters of differentiation (CD4, CD8, and CD20) in compliance with the ABC method protocol. Samples from the three cases under study were submitted to a real-time polymerase chain reaction (PCR). Results: All three cases exhibited false intranuclear immunohistochemical positivity to the antibodies being used. Conversely, all three reactions tested negative with biotin inactivation. The PCR for herpesviridae, which was positive in the known herpetic controls, showed negative in all three cases. Conclusions: Immunohistochemical investigations of the gestational endometrium (particularly in pregnancies near to term) may yield false results for several herpes viruses, as well as for other immunohistochemical reactions obtained using the ABC method without prior biotin inactivation.