Introduction

The association of cancer and pregnancy is rare, with an incidence of 1 in every 1 000 pregnancies, with breast cancer, melanoma, cervical cancer, lymphomas and acute leukemia being reported in order of frequency^1,2. The diagnosis represents a challenge for the obstetrician due to the low incidence and to the poor maternal-fetal prognosis in the advanced stages of the disease.

Sarcomas are rare primary soft tissue or bone malignant neoplasms. In the period from 2009 to 2015, 404 cases were published in the journal Rare tumors, in which 0.9% corresponded to Ewing sarcoma and 0.6% to rhabdomyosarcoma^3,4.

The presence of Ewing sarcoma in pregnancy is rare. Between 1963 and 2016, only 19 cases associated with pregnancy were reported, including 3 cases of extraskeletal sarcoma. Regarding rhabdomyosarcoma, between 1970 and 2016 only 14 cases associated with pregnancy have been reported⁵.

We present two cases of pregnant women with a diagnosis of Ewing sarcoma and alveolar rhabdomyosarcoma, respectively, treated at the National Institute of Perinatology of Mexico. Its approach, treatment plan and perinatal outcomes are described.

Case Reports

Case 1. A 25-year old female patient, primiparous, without relevant family medical history or associated comorbidities was referred to the National Institute of Perinatology (NIPer) from a second-level hospital with a 23.0-week pregnancy and a 20-cm mass in the left gluteal region, with pain and difficulty walking. Upon admission, magnetic resonance imaging studies were requested, as well as a biopsy of the lesion in the gluteal region, which was reported in pathology as a small cell tumor compatible with extra-skeletal Ewing sarcoma. The study was complemented with a chest x-ray, where multiple pulmonary nodules were seen, the largest of 3.5 cm located in the upper left lung lobe. With a diagnosis of metastatic disease, symptomatic treatment with oxycodone was started, with a poor response.

She was hospitalized with 25 weeks of gestation and disabling left pelvic limb pain. Venous Doppler did not show evidence of thrombosis. In the control chest radiography, an increase in size was observed in the previously observed nodules, and the magnetic resonance imaging visualized tumor in the gluteal region with extensive involvement towards the sacrum and iliac bones with a suggestion of necrosis, loss of border towards the lower and left posterior uterine portion, with a separation of 2.5 cm between the fetus and the tumor. With close maternal-fetal surveillance, at 28.0 weeks hemoglobin 10.7 g/dL, platelets 518 000, aspartate aminotransferase (TGO) 111 U/dL, alanine aminotransferase (TGP) 88 U/dL, lactic dehydrogenase (DHL) 1 202 U/dL were found.

A lung maturity scheme and abdominal pregnancy resolution were indicated, obtaining a live newborn weighing 1 760 grams, height 30 cm, Apgar 7/8, Silverman 2. The patient was referred to an oncology center on the third postoperative day for palliative management, diagnosed with stage IV metastatic Ewing's sarcoma.

Case 2. A 22-year-old female patient with a diagnosis of alveolar rhabdomyosarcoma located on the right forearm, undergoing treatment with radiotherapy and chemotherapy, with recurrence on the armpit. Tumor resection was performed, continuing with a new cycle of radiotherapy, when a 12.0-week pregnancy was diagnosed. She was referred to the National Institute of Perinatology (NIPer) to continue prenatal controls. She was admitted with diagnosis of metastatic medullary syndrome and decompression of T9-11 was performed. She continued with close surveillance; however, at week 18.0 there was evidence of an absence of fetal cardiac activity, for which the medical management of the deferred abortion was initiated, obtaining a fetus of 190-grams without apparent malformations.

Discussion

Ewing sarcoma is an uncommon tumor of neuroectodermal origin, poorly differentiated and highly malignant. An incidence of 1.5 cases per million people is calculated; its presentation is more common in childhood and in young adults^6,7. Clinically, it is aggressive, presenting with intermittent regional pain, predominantly nocturnal, which worsens over time and is accompanied in most cases by palpable fast-growing tumors⁸. It has a high rate of recurrence and metastasizes to the lungs and bone, as the most common sites, as was the case with our patient. At the time of diagnosis, 20 to 25% of patients will present with metastases, with a survival less than 30%^9,10).

The diagnostic approach begins with an adequate anamnesis, inspection and palpation. Biochemically, lactic dehydrogenase is correlated with tumor size. Imaging studies include radiographs, which do not represent fetal harm, since the exposure is less than 50 mGy9, followed by a magnetic resonance imaging, which provides high definition images on the extent of the disease. The definite diagnosis is made by biopsy, which should provide enough material to perform conventional histology and immunohistochemistry^11,12.

Adequate determination of tumor size is a critical factor in planning treatment, since tumors with a volume greater than 200 mL have been associated with a poor prognosis. Local management of Ewing sarcoma includes surgery and/or radiation therapy^13-15.

The WHO recognizes four types of rhabdomyosarcoma: embryonal, alveolar, pleomorphic and sclerosing¹⁶. Alveolar soft tissue sarcomas account for less than 1% of all sarcomas. The most common location is the head, neck and, in 20%, the extremities¹⁷ as in the case of our patient. They occur between 15 and 35 years of age, predominantly in the female sex. The prognosis is typically poor; the survival rate of patients with presence of metastasis is 3 years. Despite the availability of chemotherapy and other therapeutic modalities, radical resection is considered the treatment of choice^18,19.

Hormonal and immune changes during pregnancy can affect tumor progression, which is challenging to manage, as the mother and fetus can be affected²⁰. Staging and treatment should not be different from that of a non-pregnant woman. The prognosis of the neoplasia, as well as survival, will be evaluated, aiming to achieve a full-term pregnancy.

Surgery is the main treatment for musculoskeletal malignant tumors and can be performed relatively safely during pregnancy. So it should not be delayed by pregnancy. However, in the case of major pelvic or abdominal surgery, it can increase morbidity and complications²¹. In the case of chemotherapy during pregnancy, it should be avoided in the first trimester and the last dose should be administered 3 weeks before the planned date of birth, in order to avoid hematological toxicity^22,23. Radiation therapy should be avoided during pregnancy, due to the effects on the fetus, which are dose dependent, observing between 2 and 4 weeks the possibility of abortion with doses of 50 to 100 mGy, presence of congenital anomalies and growth restriction with 200 mGy doses between 4 and 10 weeks, and presence of microcephaly and intellectual impairment when the 200 mGy doses are exceeded between weeks 10 and 17²⁴.

The route of delivery should be based on the obstetric recommendation. However, sometimes cesarean section is the preferred method, since the exact time of birth can be determined. The resolution of the preterm pregnancy should be evaluated, in case this could mean a positive effect for the mother or when the tumor involves the pelvic bones and the uterus, as happened in our first case.

In this group of patients, the majority of pregnancies are unintended and lead to treatment interruption. Counseling on family planning methods is essential for women of childbearing age undergoing cancer treatment, as these do not always decrease the fertility rate. Currently, available data indicate that women with cancer do not consistently use contraception. Recommendations on contraceptive methods should be based on future procreation wishes, discuss types and efficacy of contraceptive methods to be used. Include the husband in the decision, and dispel the myth that the patient will not be fertile during treatment^25,26.

In these types of cancers, there is no universal management strategy during pregnancy. The therapy of choice will be individualized, avoiding radiotherapy, due to the effects it may have on the fetus. Multidisciplinary management is essential in cancer patients, with emphasis on postponing the pregnancy until the treatment is completed and the woman is in remission.