Chorangiomas : histopthological, clinical and genetic studies

Chorangioma (CA), although, is the most common non-trophoblastic, vascular, tumor-likelesion of the placenta with incidence approximately 0.5-1% of all examined placentas, the specific etiology and genetic background of these lesions is still poorly understood. However, an increased incidence of CAs has been reported in pregnancies occurring at high altitudes and in relation to the in utero hypoxic status (preeclampsia, multiple gestation). Thus, CAs are suggested to be hypoxia-induced reactive vascular hyperplasias rather than true tumors, although this theory has not been supported by systemic genetic studies, so far. In contrast, the occasional reports of recurrence of CA suggest that genetic factors may play also role in the pathogenesis of these lesions. Further, infantile hemangioma (IH) shares various histochemical and genetic characteristics with placental endothelial cells; notably, a predictable life cycle of initial proliferation followed by apoptotic involution similarly to that of the placenta. These findings suggest the possibility that the placenta could be the origin site of IH.

Our first and second studies characterized 170 CA cases morphologically and clinically providing evidence that CAs are associated with an increased rate of hypoxia related placental morphological changes and more adverse clinical outcome in singleton pregnancies compared with multiple pregnancies.

Our cohort of CAs demonstrated a high incidence of preeclampsia, which could be an invaluable information for clinical placental diagnostics and might lead to a possible recognition of CAs as potential morphologic indicator for placental hypoxia.

The third study of genetic background of CA analyzed eight large CAs using the array comparative genomic hybridization method and revealed no pathogenic copy number variants in the CA samples compared with either standard control DNA or unaffected placenta DNA from the same individual. This lack of association in our pilot study could support a non-tumorous, non-genetic origin of the CAs; however, additional genetic studies of larger sample sets are required to fully exclude a possible genetic contribution.

In our fourth study, we investigated the co-existence of CA and IH using a questionnaire answered by the parents and failed to demonstrate any correlations between CAs and IH. Furthermore, the occurrence of multiple pregnancies or preeclampsia was not associated with an increased incidence of IH. The latter could be explained by the fact that pathogenesis of IH is more complex and several risk factors contributing to its etiology.

List of scientific papers

I. Meeli Sirotkina, Konstantinos Douroudis, Magnus Westgren, Nikos Papadogiannakis. Association of chorangiomas to hypoxia-related placental changes in singleton and multiple pregnancy placentas. Placenta. 2016;39:154-9.
https://doi.org/10.1016/j.placenta.2016.01.020

II. Meeli Sirotkina, Konstantinos Douroudis, Nikos Papadogiannakis, Magnus Westgren. Clinical Outcome in Singleton and Multiple Pregnancies with Placental Chorangioma. PLoS One. 2016;11(11):e0166562.
https://doi.org/10.1371/journal.pone.0166562

III. Meeli Sirotkina, Magnus Westgren, Nikos Papadogiannakis. Genetic analysis of copy number variation in large chorangiomas. [Manuscript]

IV. Meeli Sirotkina, Konstantinos Douroudis, Carl-Fredrik Wahlgren, Magnus Westgren, Nikos Papadogiannakis. Exploring the association between chorangioma and infantile hemangioma in singleton and multiple pregnancies: a case control study in a Swedish tertiary centre. BMJ Open. 2017;7:e015539.
https://doi.org/10.1136/bmjopen-2016-015539