Placenta

This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2018, Case 35, and is amnion nodosum of the placenta.

Sections of placental disc demonstrate the characteristic features of amnion nodosum: collections of fetal squamous cells, keratin, sebum, hair, and proteinaceous debris on the fetal surface, with erosion and/or attenuation of the amniotic epithelium. There is no associated inflammatory response. Occasionally, nodules can be embedded in amniotic mesoderm, or dissect through the amnion into the spongy tissue plane between the amnion and chorion (not seen in the submitted case). The involved portion of amnion is identical to that of the uninvolved adjacent amnion but can show hyperplastic changes. Amnion nodosum is found in 1% of placentas and is associated with severe fetal anomalies in 30% of cases. Amnion nodosum was first described in 1912 and is the result of significant, prolonged oligohydramnios. It has since been found to occur in cases of renal agenesis, premature rupture of the membranes, twin-twin transfusion syndrome (donor twin’s placenta), diamnionic acardiac twins, and sirenomelia, among others. Amnion nodosum has been observed in 9- and 16-week-old fetuses, and when oligohydramnios occurs late in pregnancy, amnion nodosum does not develop, with only minimal degenerative changes seen in the amnion.

Amnion nodosum is therefore an important placental lesion associated with high perinatal mortality (up to 35%), not only due to the anomalies described above, but also due to pulmonary prematurity that results from the lack of fetal swallowing of amniotic fluid. This lesion has been described as the equivalent of a “critical result,” requiring an immediate discussion with the treating neonatologist.

Grossly, examination under oblique light shows fine 0.1 to 0.5 cm granules on the fetal surface of the membranes. Nodules may be translucent or opaque brown-yellow, and do not involve the surface of the umbilical cord. In severe cases, nodules may be so plentiful as to create a “cobblestone” appearance of the amnion.

Squamous metaplasia is a benign amniotic change found in up to 60% of term placentas and may mimic amnion nodosum on gross examination. A key observation is that the nodules in squamous metaplasia cannot be scraped from the fetal surface, whereas the nodules in amnion nodosum can be scraped off. A second distinguishing feature is the focality and proximity to the umbilical cord insertion point in squamous metaplasia, in contrast to amnion nodosum, which can be found anywhere on the amnion. Squamous metaplasia is a misnomer in that amnion itself is squamous epithelium, albeit premature, and is continuous with the fetal skin. Microscopically, squamous metaplasia demonstrates maturation of the amniotic epithelium with obvious recapitulation of normal epidermis (stratification, cellular flattening, keratohyaline granules, melanin, and focal keratinization), distinguishing it from the nodules of amnion nodosum. Squamous metaplasia is of no clinical significance.

Subchorionic fibrin deposition may grossly mimic amnion nodosum. A key gross observation is that the amnion can slide over the deposits in cases of subchorionic fibrin deposition, whereas the nodules in amnion nodosum move with the amnion.

Accumulation and degeneration of amniotic debris in cases of prolonged fetal demise may mimic amnion nodosum both grossly and microscopically; however, these are distinguishable with keratin immunostains. Fetal skin is CK14+/CK13-, while amniotic epithelium is CK13+/CK14-.

1. Which of the following gross observations is true?
   
   
   1. The amnion can slide over the nodules of squamous metaplasia.
   2. The nodules in squamous metaplasia are found anywhere on the amnion.
   3. The nodules in subchorionic fibrin deposition can be scraped off the fetal surface.
   4. The nodules of amnion nodosum can be scraped off the fetal surface.
   5. The chorion can slide over the nodules of squamous metaplasia.
2. Which of the following descriptions is true?
   
   
   1. The amniotic nodules in cases of prolonged fetal demise are grossly, microscopically, and immunophenotypically identical to those of amnion nodosum.
   2. The nodules in amnion nodosum are limited to the surface of the amnion.
   3. The nodules in amnion nodosum may burrow into the spongy cleft between the amnion and chorion.
   4. The nodules in amnion nodosum show metaplastic changes.
   5. The nodules in squamous metaplasia show metaplastic changes.
3. Which of the following immunophenotype characterizes fetal skin?
   
   
   1. CK13+/CK14+
   2. CK13+/CK14-
   3. CK13-/CK14-
   4. CK13-/CK14+
   5. CK13 variable/CK14+

1. Adeniran AJ, Stanek J. Amnion nodosum revisited: clinicopathologic and placental correlations. Arch Path Lab Med. 2007;131(12):1829-1833.
2. Baergen RN. Manual of Benirschke and Kaufmann’s Pathology of the Human Placenta. New York, NY: Springer Science Business Media; 2005:223-248.
3. Bartman J, Driscoll SG. Amnion nodosum and hypoplastic kidneys. An electron microscopic and microdissection study. Obstet Gynecol. 1968;32(5):700-705.
4. Kraus FT, Redline RW, Gersell DJ, Nelson DM, Dicke JM. Atlas of Nontumor Pathology: Placental Pathology. Washington DC: Armed Forces Institute of Pathology and American Registry of Pathology, 2004;163-178.
5. Scott JS, Bain AD. Amnion nodosum. Proc R Soc Med. 1958;51(7):512-513.
6. Thompson VM. Amnion Nodosum. J Obstet Gynaecol Br Emp. 1960;67:611-614.

Sabrina C. Sopha, MD, FCAP
Surgical Pathology Committee
Baltimore Washington Medical Center
Glen Burnie, MD

1. The nodules of amnion nodosum can be scraped off the fetal surface. (d)
2. The nodules in amnion nodosum may burrow into the spongy cleft between the amnion and chorion. (c)
3. CK13-/CK14+ (d)