Sarcomatoid carcinoma of the oral cavity during pregnancy

Introduction

Head and neck cancer (HNC) during pregnancy is rare, and the best management is challenging due to the conflict between maternal and fetal benefits [5]. A paucity of information in the medical literature exists regarding outcomes of radiation therapy, chemotherapy, and reported maternal and fetal outcomes. This is the first reported case of a pregnant woman with squamous cell carcinoma of the oral cavity who was successfully treated with neoadjuvant chemotherapy during pregnancy and definitive chemoradiation after delivery with good maternal and fetal outcomes.

Case

A 32-year-old African-American woman, G11 P3 Ab7, at 19 and 6/7 weeks of gestation presented with a large painful oropharyngeal mass which had grown rapidly over 3 months. Physical exam was significant for a 3×4-cm ulcerated mass in the right retromolar region. A magnetic resonance imaging without contrast showed an extensive retromolar mass enveloping the right masticator space with invasion of adjacent buccal space and bilateral level II and III lymph nodes enlargement (Figure 1). Biopsy revealed high-grade squamous cell carcinoma with sarcomatoid features (Figure 2). Immunohistochemical stains were positive for bcl-2 and p53 and negative for S-100, suggesting an association with high-risk human papillomavirus (HPV). Given the involvement of the pterygoids muscles, surgery was not recommended. A regimen of concurrent chemotherapy and high-dose radiation, the usual first-line therapy, was considered, but as the Radiation Oncology Department declined to perform radiation during pregnancy, the patient was sent to the Division of Maternal-Fetal Medicine for counseling regarding possible termination of or treatment during pregnancy.

Figure 1

Magnetic resonance imaging without contrast. Short tau inversion recovery axial non-contrast magnetic resonance image at C2 vertebral body showing a retromolar mass (arrow) enveloping the masticator space and invading the buccal region.

Figure 2

Biopsy of retromolar mass. Spindle-shaped cells with marked nuclear atypia and pleomorphism with numerous mitoses in the background of desmoplastic stroma.

Our state-funded institution allows for termination only in cases of immediate risk to maternal life. As this was absent, the patient was offered continuation of pregnancy or the option of seeking termination at another facility. After multidisciplinary counseling, she decided to continue her pregnancy with a plan for neoadjuvant chemotherapy and concurrent chemoradiation after delivery. This regimen included induction chemotherapy with docetaxel at 75 mg/m², cisplatin at 75 mg/m², and 5-fluorouracil at 750 mg/m² (TPF) for four cycles. She received the first cycle at 21 4/7 weeks of gestation with rapid decrease in tumor size and resolution of pain. The remaining cycles were completed on schedule, and the only chemotherapy-related side effects were mild mucositis and diarrhea. Fetal growth was followed every 4 weeks and remained appropriate for gestational age. At 34 3/7 weeks, she presented with worsening vomiting and diarrhea, increased pain and swelling at the site of the lesion, and oligohydramnios. Labor was induced to allow for progression to further treatment. She delivered a 2090-g female infant with Apgar scores of 7 and 9 via a normal vaginal delivery. The infant was admitted to the neonatal intensive care unit due to gestational age, remained stable on room air, had no hematologic abnormalities, and was discharged home on day 8 of life. The patient underwent tooth extraction on postpartum day 1. She was started on concurrent radiochemotherapy 4 weeks following delivery.

Discussion

Management of head and neck cancer (HNC) presents a unique challenge to clinicians. The decision to perform surgery versus combined radiation and chemotherapy continues to be debated and often requires a multidisciplinary approach. The dilemma is even greater in pregnancy as management requires balancing optimal maternal therapy and fetal well-being. In a case series of six patients with various forms of HNC over 22 years, two cases were treated during pregnancy with surgical debulking and radiotherapy, and five cases were treated post-delivery with a combination of surgery and chemoradiation. Two maternal deaths were reported: one occurred in a patient with squamous cell carcinoma of the tongue treated with radiotherapy during pregnancy (who also experienced a fetal death), and one with anaplastic small cell carcinoma of the maxillary sinus who underwent therapeutic abortion [2].

In our case, surgical excision of HNC tumor was not feasible. Within our multidisciplinary teams, there were differing views; the position of the treating radiation and medical oncologists was focused on maternal benefits and they recommended therapeutic termination of pregnancy to enable delivering therapeutic radiation doses of 90 Gy. Estimated fetal exposure would be 9–20 cGy of radiation with abdominal and pelvic shielding [7, 8]. Maternal-Fetal Medicine assessment was that, at 20 weeks’ gestation, after the embryonic phase of development, there are no teratogenic effects of radiation, and risks of microcephaly and mental retardation are minimal as fetal brain susceptibility to radiation damage is greatest between the 8th and the 15th week of gestation [1].

This is the first report of utilizing neoadjuvant chemotherapy in a case of HNC during pregnancy. The appropriate use of induction chemotherapy in the schema of HNC is still the subject of further investigation. Most experts advocate for neoadjuvant therapy for locally advanced disease [6]. The use of chemotherapy in pregnancy, especially after the first trimester, appears to be safe. In a review of 150 women exposed to chemotherapy in the second trimester, the risk of fetal malformations was 1.3%, equitable to the 3% rate in the general population, but intrauterine growth restriction and low birth weight were seen in approximately 50% of exposed infants [3]. In a separate review of 231 women with malignancy, 157 neonates were exposed to chemotherapy and there was no increase in the rate of intrauterine growth restriction [4]. Neonatal myelosuppression is also reported when chemotherapy is administered after 35 weeks of gestation or within 3 weeks of delivery [3].

In conclusion, ethical dilemmas and professional differences in opinions are an inescapable part of managing HNC during pregnancy. The challenge is centered on setting acceptable levels of fetal risk resulting from maternal treatment. Variations in clinical findings and gestational age at presentation preclude absolutist solutions. Neoadjuvant chemotherapy during pregnancy and chemoradiation therapy after delivery were successfully implemented in our case and can be considered in the management of similar cases. Close maternal follow-up to treat side effects associated with chemotherapy administration, serial ultrasound for surveillance of fetal growth, and timely planned delivery are of paramount importance to achieve favorable outcome in such a challenging condition.