Diffuse Subamniotic Calcification: A Novel Pattern Of Placental Calcification

Two primary patterns of placental calcification have been described, each with distinctive pathophysiology and clinical relevance. We report a novel pattern of diffuse subamniotic calcification. It occurred in a 25-week placenta involved by recurrent chronic histiocytic intervillositis (CHI) associated with severe intrauterine growth restriction (IUGR) and intrauterine fetal demise (IUFD). This was the mother's third stillbirth related to CHI, despite treatment with intravenous immunoglobulin (IVIG), prednisone, low-molecular-weight heparin, and acetylsalicylic acid (ASA). On placental examination, the majority of the fetal surface was calcified. This variably formed a continuous band or dispersed calcium microparticles. Electron microscopy demonstrated associated electron dense deposits highly suggestive of immune complex deposition. CHI explains recurrent IUGR and stillbirth, but has not been associated with calcification or immune complex deposition. We hypothesize IVIG therapy may have caused immune complex deposition and subsequent dystrophic calcification, supported by its rare association with immune complex deposition disorders in the kidney. Identification of additional cases with this pattern of calcification, with additional studies on fresh tissue including immunofluorescence, electron microscopy and mass spectrometry, may aid in elucidating the underlying pathophysiology and clinical significance of this unusual lesion.