Generalization of cases and mechanisms of metastasis of malignant tumors in the placenta and embryo

Abstract. Placental metastasis is a rare but serious complication of pregnancy. Because of the rarity of the occurrence, there is no described and possible, generally accepted algorithm for the diagnosis and management of such patients, but there are described cases or series of cases that reflect the behavior of different tumors when metastasized into the placenta and embryo. We suggest to consider and generalize from the moment of description of the first case of metastasis of cancer in the placenta, and to present possible mechanisms of occurrence of this pathological process.

It is well known that the placenta of mammals, in particular human beings, is a unique tissue, because in it the cells of two genetically different organisms (mother and fetus) are in direct contact with blood [9 1], i.e. the fetus is an allograft in relation to the mother body. Embryonic lint trophoblasts penetrate the maternal endometrial decidua and are intertwined with each other, while extra lint trophoblasts reconstruct the maternal arteries, replacing endothelial cells. The embryonic cells of the trophblast are "bathing" in the mother's blood. [10 2] Moreover, although there are mechanisms that ensure maternal tolerance of paternal antigens to the cells of the fetus in the placenta, such close interaction between mother and fetus allows the penetration of different cells. For example, it is well known that normal blood cells migrate between mother and fetus and vice versa, resulting in microchimerism. [11, 12 3, 4] It is because of this feature that it is not surprising that tumour cells can also use this path. To date, the placenta is the only means of natural cancer cell transmission between humans, and these examples, found in the literature, we presented below. Friedreich first reported on metastasis of carcinoma in 1866. [5] Alexander et al studied 87 cases of placental and fetal metastasis published between 1918 and 2002. Of the 87 (31%) confirmed cases, 27 were melanomas. [6] Malignant melanomas are the most common among them, accounting for 30 per cent of cases. Lung malignancies, hematological and breast cancer are the second most common malignancies, and stomach cancer is less than 5% of reported cases. [7, 8]. The presence of placental metastases does not imply fetal metastases, although fetal metastases are associated with placental lesions. Of the 27 cases mentioned above, only 6 (22%) have seen transplacental metastases, also referred to as "vertical transmission". The most common metastasis places in the fetus are the skin, most often together with metastasis to the liver. The Alexander et al study describes the only case of metastasis in CNS. Two clinical cases of intravenous melanoma metastasis to the fetus have also been published in the literature: the first to the posterior cranial fossa and the second to the left temporal bone [9, 10]. To date, we have recorded only nine cases of melanoma in the fetus and only three intra-ranial metastases. Another no less interesting metastatic tumor is stomach cancer. Stomach cancer is a global health problem with ~934,000 (8.6%) newly diagnosed cancer cases and 700,349 deaths annually. Nearly two-thirds of cases occur in Eastern Europe, South America and Asia, with 42% in China alone. [11] Only 0.1% of all stomach cancers occur during pregnancy. [7] According to the literature, only seven cases of metastasis of stomach cancer to the placenta have been described. The difficulty of diagnosis is due to the non-specific manifestation of the disease, and complex differentiation of gastrointestinal symptoms. [12] It is noteworthy that despite the presence of the transplacental pathway of cell transmission between mother and fetus, the transmission of directly tumor cells is poorly represented in practice and in literature. The main constraints are immune recognition and lack of pathways to viable cellular traffic. [13] Conclusion: Unfortunately, the study of malignant neoplasms in pregnant women is limited, as it can be clinically difficult to diagnose tumors at an early stage, because of the long duration and small number of pregnancies in humans. In spite of the fact that the literature describes single cases of tumors transplacental transmission from mother to fetus, it is necessary to remember about such possibility, in view of placenta anatomic structure. This is of special interest, as the presence of tumors affects the course of pregnancy, and that is why it is necessary to develop new methods of diagnosis and treatment of this category of patients.