TROPHOBLAST INCLUSIONS ARE ASSOCIATED WITH KARYOTYPIC ABNORMALITIES

TROPHOBLAST INCLUSIONS ARE ASSOCIATED WITH KARYOTYPIC ABNORMALITIES

Harvey Kliman MD, PhD Yale University Obstetrics & Gynecology School of Medicine 312 FMB Reproductive and Placental Research Unit Yale University School of Medicine 333 Cedar Street New Haven, Connecticut United States 06520-8063

Lesley French Yale University Ob/Gyn 312 FMB Yale University School of Medicine 333 Cedar Street New Haven, CT USA 06520-8063

OBJECTIVE: The normal placental villous is covered with two regular layers of trophoblasts (Fig. 1). Normally these layers form a smooth surface on the villi. Occasionally scalloping and deep invaginations of the trophoblast layers can be seen. If cut appropriately, these invaginations appear as islands of trophoblasts within the villi—trophoblast inclusions (TI). We sought to determine if these TI are associated with chromosomal abnormalities.

STUDY DESIGN: 77 patients with abnormal fetal karyotypes were identified in our CVS logs from 1/10/94 to 8/16/98. 15 patients were found who also had pathology slides available for examination. Scalloping and invaginations (Fig. 2) were graded from 0 (none) to 3 (many). The number of TI were counted per slide (Fig. 3).

RESULTS: 14/15 (93%) of the cases had trophoblast inclusions. The female trisomy 21 fetuses had the highest average number of trophoblast inclusions (13.25), followed by 47, XXX with 9.5 inclusions, and females with trisomy 18 with 6 inclusions (see Table).

CONCLUSION: Our study demonstrates that trophoblast inclusions are commonly found in the placentas of fetuses with known chromosomal abnormalities suggesting that TI are a marker of a developmental abnormality in the placenta and fetus. However, one of the limitations of a study based on karyotypic abnormalities alone is that there exists many thousands of potential genetic disorders that may lead to abnormal villous growth patterns in the absence of any apparent karyotypic abnormality. It will therefore be necessary to collect additional specimens from both chromosomally and genetically normal and abnormal cases before we can conclude with certainty that TI are predictive of karyotypic and/or genetic abnormalities.

Figure 2. Examples of trophoblast invaginations. A, B) Trophoblast invaginations forming cleft-like structures. Note the many cytotrophoblasts lining the invaginations (red arrowheads) and the fewer cytotrophoblasts underlying the normal bilayers (orange arrowheads). C) Invagination that ends in an area of increased syncytiotrophoblasts (arrow). Even though the bilayer is invaginated, syncytiotrophoblasts still form. D) Bulb-like prominence of syncytiotrophoblasts at base of invagination (arrow).

Figure 3. Examples of trophoblast inclusions. A) Trophoblast inclusion within the villous core. Note how the cytotrophoblasts of the bilayer (orange arrowheads) and the cytotrophoblasts of the inclusion (red arrowheads) both are adjacent to the villous core. B) Trophoblast inclusion with a prominent syncytiotrophoblast layer and a lone cytotrophoblast (arrowhead). Fetal vessel (V). C) Chorionic villous with four prominent TIs (arrows). D) Trophoblast inclusion with very expanded syncytiotrophoblast component (arrow).

Karyotype	Scalloping (0-3)	Invaginations (0-3)	TI/slide
47, XX, +18	2	2	6
47, XY, +18	0	0.13	1.13
45, X	2	1	1
47, XXY	1	1	2
47, XXX	1	1.5	9.5
47, XX, +21	1.13	1.6	13.25
47, XY, +21	0.67	0.84	1.84
45, XY, -21	1.5	1.5	0.5
47, XX, +13	0	0.2	0.4
69, XXX	1.2	1.2	4.8