Case History

Placenta. 19yo G3P2002 at 22 weeks with PPROM and intrauterine fetal demise. Routine prenatal labs and vaginal exam unremarkable.

Most likely etiology?

A. Chorio w/ fetal sepsis

B. Herpesvirus infection

C. Listeria monocytogenes

D. Parvovirus B-19

E. Treponema pallidum


Unknown  Unknown 1

Unknown 2  Unknown 3


Answer: B. Herpesvirus infection


This case illustrates herpes simplex virus (HSV) placentitis. Placental findings included patchy necrotizing chronic villitis. Immunohistochemical stains for HSVI/II showed strong dense staining of large numbers of infected stromal cells in the necrotic villi. Extraplacental membranes showed extensive amnionecrosis but only rare foci of necrotizing subchorionic and chorionic necrotizing chronic inflammation, with rare positive HSVI/II immunostaining (not pictured). Umbilical cord sections were without inflammation.

Most congenital HSV is acquired via transvaginal transmission in later gestation fetuses as they traverse viral-shedding mucosal surfaces of the birth canal. In these cases, placental findings are usually normal.

Ascending HSV infection may also occur and cause in utero infection prior to delivery. In these cases, the amniochorion and umbilical cord typically show the predominant pathology, without villitis. Findings in these cases can be variable, and include chronic lymphoplasmacytic chorioamnionitis and chronic chorionic vasculitis.  Amnion degeneration and chorionic viral cytopathic changes may be seen.

Transplacental transmission is the least common (estimated 5% of congenital HSV infection), occurs more frequently earlier in gestation, and is associated with poor fetal outcome.

The differential diagnosis for necrotizing villitis with chronic inflammatory infiltrate includes a variety of viral, spirochete, and parasitic infections, grouped under the acronym “TORCH” (Toxoplasma, “Other” including syphilis, Rubella, Cytomegalovirus (CMV), Herpesvirus.)

CMV is the most common perinatal TORCH viral infection. CMV placentitis is characterized by lymphoplasmacytic villitis, villous capillary dissolution with hemosiderin deposition, and large Hoffbauer and/or endothelial cells containing intranuclear viral inclusions of the typical “owls eye” morphology. Intracytoplasmic granular inclusions may also be seen.

In Treponema pallidum placentitis, the most common placental finding is severe necrotizing funisitis, but chronic lymphoplasmacytic villitis may rarely be seen. Infections typically occur in the setting of untreated maternal syphilis. Warthin starry stain or specific immunohistochemical stains can be helpful.

Parvovirus B19 can also be associated with fetal demise, but does not cause placental inflammation. Findings in severe cases include a hydropic placenta and marked fetal erythroblastosis with characteristic intranuclear viral inclusions in intracapillary fetal erythroblasts.

Placental infection by the bacterium Listeria monocytogenes is typically characterized by an acute (rather than chronic) necrotizing intervillositis due to hematogenous spread of the organism. Inflammation is often florid and bacterial organisms may be seen on routine stains.

Ascending bacterial infection usually causes acute inflammation limited to the chorioamnion, sparing the villi. When villitis is present, it likely indicates fetal sepsis. Villitis in these cases is typically neutrophilic, and may be accompanied by villous intracapillary bacterial organisms. This finding carries a particularly poor prognosis for the fetus.



Bedolla G, Stanek J. Intrauterine hematogenous herpetic infection. Arch Pathol Lab Med. 2004 Oct;128(10):1189-90.

Shi TL, Huang LJ, Xiong YQ, Zhong YY, Yang JJ, Fu T, Lei XF, Chen Q. The risk of herpes simplex virus and human cytomegalovirus infection during pregnancy upon adverse pregnancy outcomes: A meta-analysis. J Clin Virol. 2018 Jul;104:48-55.


Case contributed by: Virginia Duncan, M.D., Assistant Professor, Anatomic Pathology, Perinatal Section Head