Heterotopic Nodules in the Placenta, an Immunohistochemical Re-evaluation of the Diagnosis of Adrenocortical Heterotopia

Abstract

Background Rare nodules of heterotopic adrenocortical and hepatic tissue are reported in the placenta. A mechanism for adrenocortical tissue in the placenta has been perplexing, while hepatic tissue is generally considered related to yolk sac primordia. The clear cell morphology of these nodules is similar to the adrenal cortex of the adult; however, the fetal adrenal gland does not usually display clear cells. Methods We stained 9 placental nodules, histologically identical to “adrenocortical” heterotopia of the placenta, to determine whether adrenocortical differentiation could be confirmed. These cases include 3 archival cases initially diagnosed as “adrenocortical” heterotopia. Results Immunohistochemical staining with steroid factor-1 (SF-1), HepPar-1, and Arginase-1 showed that these nodules of clear cells are actually hepatic (SF-1 negative, HepPar-1, and Arginase-1 positive). PAS staining suggests that glycogen accumulation is responsible for the clear cytoplasm. In contrast, a nodule of adrenocortical heterotopia near the testis and the adrenal gland from a 38-week-old neonatal autopsy case confirm SF-1 reactivity as expected. Conclusion We propose that adrenocortical heterotopia in the placenta is a misnomer, and that these subchorionic nodules of clear cells demonstrate hepatic differentiation.

Fetal Origin of Placental Hepatic Nodule

“…1,7,8 Lineage markers for other tissues including renal, adrenal, and melanocytic lineages were negative or nonspecific in all cases in which they were performed. 3,5,8,10 Special stains for reticulin and periodic acid-Schiff (PAS) with and without diastase showed patterns consistent with normal hepatic tissue. 1,2,4,5,8 Electron microscopy showed ultrastructural characteristics consistent with hepatocytes.…”

“…To date, there are 37 reported cases in the literature, ranging from incidentally discovered microscopic nodules to grossly identifiable mass-forming lesions 1-18 . Notably, 10 of these cases 11-17 were initially thought to be of adrenocortical derivation; a recent paper 10 elucidated the likely hepatocellular origin of these nodules through comprehensive immunohistochemical profiling. The gestational age ranged from the first trimester to 37 weeks, and where the status was known, all but 1 case (at 16 weeks) resulted in a liveborn delivery.…”

“…Positivity for HepPar1 (hepatocyte-specific antibody) was noted in all reported cases where the immunohistochemical stain was performed, 1,3,7-10 including this case. The nodules were positive for arginase-1 3,10 and showed variable reactivity for other lineage-specific markers including alpha-1-antitrypsin, 2-4,7-9 AFP, 1-5,8,9 glypican-3, 3,9 and carcinoembryonic antigen. 1,3,5,8 Glutamine synthetase and nuclear beta-catenin were minimally positive and negative, respectively, suggesting a benign process.…”

Heterotopic Adipose Tissue in the Placental Parenchyma: Case Report

“…4 Schaumann and Hussein 5 recently linked hepatic and adrenocortical choristomas to chorangiomas, fetal malformations, and multiple pregnancies. Heerema-McKenney et al 6 suggest using immunohistochemistry to differentiate between hepatic versus adrenal origin and describe localization of heterotopic adrenal and hepatic tissue as being, “within the confines of a stem villus, demonstrating branching chorionic villi extending from the surface of some, and muscular vessels in others”. 6 In the present case, our description coincided with that of other authors who classify intervillous localization as “ectopic intervilli”.…”

“…Heerema-McKenney et al 6 suggest using immunohistochemistry to differentiate between hepatic versus adrenal origin and describe localization of heterotopic adrenal and hepatic tissue as being, “within the confines of a stem villus, demonstrating branching chorionic villi extending from the surface of some, and muscular vessels in others”. 6 In the present case, our description coincided with that of other authors who classify intervillous localization as “ectopic intervilli”. 2 As far as we could find, no reports exist on heterotopic adipose tissue in the literature.…”