Mixed chorangioma and leiomyoma of the placenta,with a brief review of nontrophoblastic placental lesions

Introduction

Chorangiomas are the most common placental tumor, found in about 1% of term placentas. ¹ They are benign hemangiomas or hamartoma-like lesions, which represent an excessive vascular proliferation within the chorionic stem villi. ² Most chorangiomas are solitary, solid nodules, up to several centimeters in size, located in the superficial placental parenchyma near the fetal surface or placental margin. They are thought to be induced by decreased oxygen tension, which is supported by their increased incidence in higher altitudes and their development in areas on the placenta with poorer perfusion, such as the placental margin. ³ On ultrasound, they present as a hypo- or hyperechoic, well-circumscribed mass with cystic areas and vascular channels, seen on color Doppler. ⁴ Leiomyoma of the placenta is an extremely rare benign nonvascular, non-trophoblastic mesenchymal tumor. It may arise from fetoplacental mesenchymal tissue or may be of maternal origin. In most reports, the origin of the tumor is a maternal uterine leiomyoma that becomes entrapped in the placenta, proven by genetic studies. ⁵

Other rare primary non-trophoblastic placental tumors have been reported, such as teratomas and heterotopic lesions such as hepatic adenomas.^6–11 These lesions are usually found incidentally and are unassociated with significant maternal or fetal morbidity. Herein we present a rare case of a placental mass found to be a mix of chorangioma and leiomyoma.

Case Report

A 39-year-old morbidly obese (BMI 43 kg/m²) woman with an extensive smoking history (20 cigarettes per day) was found to have an echogenic placental lesion with a central vascular axis, identified at 33 weeks and 4 days of gestational age by ultrasound. The lesion measured 7 cm in maximum diameter and was suspicious for chorangioma. Five previous scans were normal and done between 18 and 29 weeks. An ultrasound was performed every week thereafter, with a cesarean section planned at 39 weeks of gestational age, due to the concern for fetal growth restriction.

At 39 weeks of gestation, via cesarean section, a healthy female neonate weighing 2,945 grams was delivered without maternal or fetal complications. The placenta weighed 680 grams and measured 24 × 18 × 2 cm. The expected placental size at term is about 450 grams, so the placenta was slightly large for gestational age; however, the mass was not measured separately, so it was included in the overall placental weight. At the periphery of the placenta on the fetal surface, was a brown-red lesion measuring 9 × 5 × 2 cm with a feeding vessel of 6 cm coming from the umbilical cord insertion site: presenting like an accessory lobe (Figure 1). Microscopic examination revealed the portion of the lesion directly under the chorion to show the characteristic features of chorangioma, with abundant thin-walled vessels (Figure 2). Deeper into the lesion, there were bundles of smooth muscle interspersed with the aberrant vessels (Figure 3(A) and (B)), with foci of solid smooth muscle (Figure 3(C)). Nuclear atypia and mitotic activity were absent. Immunohistochemical staining showed a low ki-67, as well as positive CD34 and CD31, highlighting the vascular proliferation. The SMA immunohistochemical stain was also positive, highlighting the proliferation of smooth muscle throughout the neoplasm. Caldesmon immunohistochemical staining was also performed, to verify that the cell type staining positive for SMA was smooth muscle, since myofibroblasts and pericytes may also express SMA. In the chorangioma-like areas, there was either very little caldesmon staining (Figure 4(A)) or scattered muscle fibers (Figure 4(B)). This transitioned to areas of dense muscular bundles (Figure 4(C)). The umbilical cord displayed furcate insertion macroscopically, but the umbilical cord and fetal membranes were without significant histopathology. The remaining placenta was unremarkable with no pathology.

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Figure 1.

The lesion was attached by a broad base to the fetal surface at the edge of the placenta, and a prominent feeding vessel was noted (arrows).

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Figure 2.

The portion of the lesion directly under the chorion showed the characteristic features of chorangioma, with abundant thin-walled vessels (inset, magnification ×2).

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Figure 3.

Deeper into the lesion, there were bundles of smooth muscle interspersed with the aberrant vessels (A, B, magnifications: A ×10, B ×40), with foci of solid smooth muscle (C, magnification ×20).

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Figure 4.

Caldesmon staining. In chorangiomatous areas, there was either very little caldesmon staining (A, magnification ×2) or scattered muscle fibers (B, magnification ×20). This transitioned to areas of dense muscular bundles (C, magnification ×20).

Discussion

Non-trophoblastic tumors of the placenta that have been described include: chorangioma, teratoma, and leiomyoma. Metastatic spread of maternal neoplasms such as melanoma, leukemia/lymphoma, and breast and lung carcinomas have also been reported in the placenta^1,5-7,9,12. Hepatic, adrenocortical, and intestinal heterotopic tissues have also been identified within placental tissue.^8–11,13,14

The histopathology of the placental neoplasm in our case displayed characteristics of a classic angiomatous chorangioma, with vascular proliferation, but with smooth muscle throughout, suggesting a leiomyoma-like component. We only found one previously reported case with similar characteristics; a chorangioma with abundant smooth muscle proliferation within the mass. ¹⁵ In 2010, Miliaras et al. presented a case of a well-circumscribed, solid mass located on the fetal surface, measuring 8 × 6 × 5 cm. Microscopically, the angiomatous part of the tumor formed multiple irregular lobules with numerous capillary blood vessels embedded in a loose stroma. These lobules were separated by multiple, broad interlacing bundles of spindle cells. Thick-walled and capillary-like vessels were also identified within the bundles of spindle cells. Nuclear atypia and mitotic activity were completely absent in their case as well. ¹⁵

The intraplacental leiomyomas that have been reported are usually confirmed to be of maternal origin.^16–18 Leiomyoma of the placenta is extremely rare, with only a few intraplacental lesions being reported.^16–18 It is thought to arise from fetoplacental mesenchymal tissue or be a maternal leiomyoma that becomes entrapped within the placenta. Miliaras et al. also noticed that they tend to occur in placentas with male fetuses. ¹⁵ They were able to determine that their mixed chorangioma-leiomyoma neoplasm was of fetal origin, not maternal origin. Since their neonate was male, they were able to use polymerase chain reaction (PCR) to determine there were X and Y-chromosomes present. Since our neonate was female, we could not readily determine if the mass was of maternal or fetal origin.

We considered other entities as differential diagnoses. Due to the lack of any nuclear atypia or mitoses, as well as lack of maternal clinical history, metastatic disease was considered unlikely. Examination of the tumor failed to reveal other mature tissue elements, such as skin, fat, or cartilage, making the diagnosis of a teratoma also unlikely.

Teratomas are neoplasms that arise from totipotent embryonic germ cells.^6,7 All the reported cases of placental teratoma have been composed of benign mature tissue derived from 2 or more germ cell layers.^6,7 The favored hypothesis is that proposed by Fox and Butler-Manuel, that is, aberrant germ cell migration from the yolk sac. ¹⁹ Teratomas must be differentiated from fetal amorphous. Historically, the diagnosis of teratoma was achieved by the criteria of not having a separate umbilical cord attachment and the tissue being disorganized, without the formation of an axial skeleton/vertebrae. ¹⁹ Recently, however, McHenry et al., reported a case with the criteria of absent axial skeleton and no separate umbilical cord, that had identical genetic profiles between the “teratoma” and the surrounding normal placental tissue. This demonstrated, through molecular genotyping, that the lesion was actually a monozygotic acardiac/amorphous twin rather than a true teratoma. This puts into question the historical criteria being used to diagnose placental teratoma. ⁷ Moreover, it may be speculated that all prior documented cases of placental “teratomas” may also not be true teratomas.

The placental hepatocellular adenoma is another rare neoplasm, which was first described by Chen and colleagues. ¹⁰ Histologically it consists of benign fetal-type liver tissue without portal areas or well-defined canaliculi, with foci of extramedullary hematopoiesis. The histogenesis has been debated, including the possibility of heterotopic tissue, monomorphic teratomas, and fetus amorphous. These hypotheses are primarily based on their usual location in the placenta, beneath the chorion. ¹⁰ Most evidence supports a true adenoma histogenesis, presumably arising from displaced yolk sac elements. ¹¹ Recently, Bu et al. used fluorescence in-situ hybridization and chromosomal microarray to show a male sex chromosome complement (XY) within the nodule, confirming the fetal origin of their placental hepatocellular adenoma. This supports the hypothesis that these may represent an embryonal rest or residual abnormal cell migration. ⁸

Heterotopic adrenocortical tissue has also been reported in the placenta. ¹³ However, Heerema-McKenney et al. recently used Immunohistochemical staining to show that these nodules of clear cells are actually hepatic, due to their negative staining for SF-1 and positive staining with HepPar-1 and Arginase-1. PAS staining suggested that glycogen accumulation was responsible for the clear cytoplasm. They proposed that adrenocortical heterotopia in the placenta is really a misnomer, and that these nodules of clear cells are hepatic in origin. ¹⁴

Despite the histopathological variations of lesions found within the placenta, no previously coined entity has been reported that describes a chorangioma with smooth muscle proliferation, apart from Miliaras et al. ¹⁵ The prominent smooth muscle component supports the hamartomatous nature of chorangioma. If our case is also of fetal origin, it would support the possibility of a hamartoma arising from mesenchyme. We support the naming of this entity as “chorangioleiomyoma.” ¹⁵