A 32-year-old primigravida woman presented to the hospital with inevitable abortion at 15 weeks' gestation. Prenatal care had been adequate, and her prenatal course had been uneventful. She had no history of remote or recent human herpesvirus (HHV) infection, or signs of current genital lesions. On admission, fetal heart tones were absent; subsequently, 2 female stillbirths were spontaneously delivered.

The 120-g, monoamniotic, monochorionic placenta had scant, thick, and opaque membranes; pale friable parenchyma; and no grossly identifiable focal lesions. Microscopically, the placenta showed scattered foci of bland villous necrosis (Figure, A; original magnification ×400) and bland decidual necrosis of placental membranes. No cytopathologic nuclear features suggesting HHV infection were identified. The areas of necrosis were positive for HHV both by immunohistochemistry (Figure, B; original magnification ×400) and by in situ hybridization (Figure, C; original magnification ×400). Polymerase chain reaction studies performed at the molecular pathology laboratory of Cincinnati Children's Hospital Medical Center demonstrated the presence of HHV-2 DNA within paraffin-embedded placental tissue.

Because of these findings, we checked the results of maternal serology, which demonstrated HHV-1/2 immunoglobulin M of 6.65 enzyme immunoassay units (negative, <0.91). Serum titers for cytomegalovirus, toxoplasmosis, and rubella were within the reference ranges.

Consequently, we requested and obtained permission for pathologic examination of the fetuses. Both fetuses were female, consistent with the monozygosity diagnosed on placental examination. The fetuses showed advanced maceration and development consistent with the clinical estimate of gestational age of 15 weeks. No congenital anomalies were noted. Microscopic examination of partially autolyzed fetal organs demonstrated patchy necrosis involving brain, heart, lungs, liver, and adrenal glands in both fetuses, and were positive for HHV by immunohistochemistry and in situ hybridization.

To our knowledge, this is the first report of lethal generalized intrauterine HHV infection in a monozygotic twin pregnancy manifesting with extensive necrosis of fetal organs and placenta. We found only 1 documented description of multifocal bland villous necrosis with possible viral inclusions in necrotic syncytiotrophoblast, probably acquired via a hematogenous route.1 Bland patchy necrosis of fetal organs is a classic microscopic feature of systemic HHV infection. This histologic pattern, however, is ex tremely rare in the placenta, where necrotizing deciduitis or subacute necrotizing funisitis are more common and typical features of HHV-ascending infection.2 With prolonged rupture of membranes, exudative inflammation from secondary bacterial infection may mask the bland necrosis typical of the HHV involvement. The apparently nonspecific microscopic pattern of the hematogenous HHV infection is probably responsible for the low reported frequency of intrauterine infection in babies with neonatal HHV infection.3 In our case, patchy villous and fetal organ necrosis in the absence of clinical HHV lesions on the uterine cervix and only nonspecific necrotizing deciduitis is therefore indicative of the hematogenous route of HHV infection.

In summary, the bland villous necrosis caused by HHV, particularly in the absence of viral inclusions and in the presence of maceration-associated autolysis, may be easily overlooked on routine placental examination. As our case illustrates, placental examination may be the only clue for diagnosing such cases.

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The authors have no relevant financial interest in the products or companies described in this article.

Author notes

Reprints: Jerzy Stanek, MD, PhD, Department of Pathology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267 (jerzy.w.stanek@uc.edu)