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American Journal of OtolaryngologyHead and Neck Medicine and Surgery 33 (2012) 174 177 www.elsevier.com/locate/amjoto

Hypopharyngeal cancer in a pregnant woman

Leyla Kansu, MD, Erdinc Aydin, MD
Departments of OtolaryngologyHead and Neck Surgery, Baskent University, Ankara, Turkey Received 17 January 2011

Abstract

Cancer in pregnant women is a very difficult clinical condition that profoundly affects patients and their families, as well as the medical staff who provide their care. Diagnostic and therapeutic decisions must balance adequate treatment and fetal risk. In developed societies, cancer in pregnant women has become more common during the last 30 years because of an increase in the number of relatively older women who give birth. The most common malignancies in pregnant women are melanoma; lymphoma; leukemia; and breast, cervical, ovarian, gastrointestinal, and genitourinary cancers. Cancer of the head and neck in pregnant patients is very rare. In this article, we describe a rare case of advanced squamous cell carcinoma of the hypopharyngeal area in a young pregnant woman, and we discuss the diagnosis and treatment of cancers of the head and neck in pregnant patients. 2012 Elsevier Inc. All rights reserved.

1. Introduction Although cancer is the second most frequent cause of death in women during their reproductive years, cancer in pregnant patients is not a common clinical problem [1]. However, the association of cancer and pregnancy has become more common during the last 30 years in developed societies, primarily because of an increase in the number of women who give birth at an older age [2]. In addition, smoking and alcohol consumption are increasing in young women [1,2]. Although to our knowledge there are no satisfactory studies about cancer in pregnant women, that disease is estimated to occur in 1 of 1000 pregnancies in developed societies [2]. The malignant diseases most frequently diagnosed in pregnant women are melanoma; lymphoma; leukemia; and ovarian, brain, breast, cervical, gastrointestinal, and genitourinary cancers [3]. The most common pregnancy-associated head and neck cancers

include those of the larynx and thyroid, melanoma, and lymphoma [1,4]. Malignant tumors of hypopharynx are rare. Hypopharyngeal cancer accounts for less than 1% of all cancers in and represents approximately 8% to 10% of all head and neck cancers [5]. Cancer of the hypopharynx occurs primarily in men who are 50 to 60 years old. A review of the English literature yielded no reports of hypopharyngeal carcinoma during pregnancy. In this article, we describe a rare case of advanced squamous cell carcinoma of the hypopharyngeal area in a young pregnant woman, and we discuss the diagnosis and treatment of cancer of the head and neck in pregnant patients.

2. Case report A 32-year-old woman with the primary complaint of a painless mass of more than 1 month duration on the right side of her neck was accepted as a patient in our otolaryngology department. She had experienced difficulty in swallowing and a sore throat for the 2 prior weeks and hemoptysis for the 2 prior days. She was pregnant at 18 weeks gestation. Indirect laryngoscopic examination revealed a vegetative mass in her hypopharynx (Fig. 1). That mass originated in

Conflicts of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the manuscript. Corresponding author. Department of OtolaryngologyHead and Neck Surgery, Alanya Medical and Research Center, Baskent University, Alanya, Antalya, Turkey. Tel.: +902425112522; fax: +902425112350. E-mail address: leylakansu@hotmail.com (L. Kansu).

0196-0709/$ see front matter 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.amjoto.2011.02.007

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Fig. 1. Endoscopic view of the tumor during the patient's first examination.

the posterior wall of the hypopharynx and obstructed the hypopharyngeal and laryngeal areas. Palpation revealed a hard, painless, fixed lymph node approximately 3 cm in diameter in the right submandibular area. Magnetic resonance imaging (MRI) showed a mass that had infiltrated the bilateral aryepiglottic fold, bilateral sinus pyriformis, laryngeal cartilages, prevertebral muscle, tracheoesophageal junction, and upper third of the esophagus (Fig. 2). A punch biopsy of the hypopharyngeal mass was performed after the patient had received a local anesthetic. The pathology report revealed squamous cell carcinoma (clinical stage T4N2M0). The cancer was considered inoperable. The patient was referred to an obstetrician at which time (18 weeks of gestation) the fetus was found to be healthy. The patient and her husband were informed of the aggressiveness of her disease. After they had met with an oncologist and the patient's obstetrician, chemotherapeutic treatment was selected as the therapy of choice, and the pregnancy was not terminated. Adjuvant chemotherapy, including cisplatin and docetaxel, was initiated and was administered every 21 days. At 30 weeks of gestation, amniocentesis was performed, and neither quantitative nor qualitative chromosomal anomalies were identified. After the fifth cycle of chemotherapeutic treatment, when the fetus was viable, a healthy male infant was delivered via cesarean section at 34 weeks of gestation. He weighed 2325 g, and his Apgar score was 9/10. At that time, the patient's laryngeal mass was smaller than its prechemotherapy size (Fig. 3). Positron emission tomography/computed tomography was performed after the patient had been delivered of her

Fig. 2. Magnetic resonance imaging. A sagittal section of the head and neck shows carcinoma of the posterior wall of the hypopharynx.

infant. There was no evidence of distant metastasis. On endoscopic hypopharyngeal examination, the lesion was again smaller. A 45-day course of radiotherapy was added to the adjuvant chemotherapy, and at the conclusion of radiotherapy, no palpable lymph nodes were detected on the patient's neck, the larynx was edematous, and the size of the mass had decreased further (Fig. 4).

Fig. 3. Endoscopic view of the tumor after delivery.

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Fig. 4. Endoscopic view of the tumor after chemotherapy and radiotherapy.

3. Discussion Tumors of the head and neck are rarely encountered in pregnant patients. No evidence suggests that pregnancy affects the course of tumors of the head and neck or the outcome of treatment [6]. Therefore, all information about this rare cancer must be derived from case reports and small retrospective case-controlled studies. The diagnosis and staging of cancer in a pregnant woman indicate that her exposure to ionizing radiation must be limited and her treatment must be restricted to procedures that do not endanger fetal health. Computed tomographic scanning of the head and neck delivers up to 4.0 cGy of radiation. Magnetic resonance imaging scanning does not involve ionizing radiation and is therefore safer than computed tomography [1,7]. We used MRI for diagnosis and staging in our patient. The management of a malignant disease in a pregnant patient requires balancing optimal maternal therapy and fetal well-being. Ideally, the physician's objectives are to cure the patient of her cancer and to ensure the delivery of a healthy, viable infant. Both objectives, however, cannot always be achieved [3]. Treatment may harm the fetus, and delaying therapy or choosing suboptimal treatment to preserve fetal well-being may worsen maternal outcome [4]. The treatment of choice for hypopharyngeal carcinoma is surgery, if possible. General anesthesia has an adverse effect on the fetus, and that effect varies with gestational age: teratogenicity in the first trimester, spontaneous abortion in trimesters 1 and 2, and preterm labor in the third trimester. The second trimester is the preferred time for surgery because the adverse effects of general anesthesia on the fetus are minimal [4]. Risks to the fetus during surgery are not just associated with anesthesia; however, they include intraoperative complications such as hypoxia and hypotension. Decreased placental perfusion because of the long-term positioning of the mother in the supine position during

surgery is a mechanical problem in late pregnancy [7,8]. We did not recommend surgical therapy because of the inoperable disease in our patient. Radiotherapy can cause structural malformations, organ dysfunction, growth retardation, teratogenesis, and fetal death. It can also predispose the fetus to the development of childhood cancers, germ cell mutations, and sterility later in life. The exposure to radiation for the treatment of tumors of the head and neck during the second trimester of pregnancy increases the risk of postnatal childhood cancer approximately 2 to 5 times over the natural risk [6]. The adverse effects of radiotherapy also cause significant maternal morbidity. If possible, radiotherapy should be delayed until the postpartum period [4]. The effect of chemotherapy varies with gestational age. In the first trimester, chemotherapy is teratogenic and may cause spontaneous abortion. The estimated risk of major fetal malformations is 10% with single chemotherapeutic agents and 25% with combination chemotherapy that is administered between 5 and 10 weeks of gestation [9]. The decision to undergo therapeutic abortion must be made in early pregnancy. As a strict rule, chemotherapy must be avoided, especially during the first trimester of pregnancy [10]. When it is administered during the second and third trimesters, myelotoxicity, organ toxicity, intrauterine growth retardation, and preterm labor may occur [4,11]. Other mediating factors of the effects of chemotherapy are the particular drug or combination of drugs used, the dose given, the duration of action, and genetic variability among patients [1]. Antimetabolites (methotrexate, aminopterin) and alkylators (cyclophosphamide, busulfan, chlorambucil, and dacarbazine) have been reported as having higher teratogenic potential. Other chemotherapeutic agents are relatively less teratogenic [2,11]. Pentheroudakis et al [2] reported that cisplatin was associated with hearing loss and cardiac and cerebral malformations in 5 patients. Cisplatin was used in our patient, but her newborn had no malformations. Organogenesis of the brain and gonads continues into infancy. Chemotherapeutic drugs transmitted to infants in breast milk may lead to their infertility and to impaired neurodevelopment, cognitive capabilities, and sexual development. Therefore, breastfeeding is contraindicated during chemotherapy [1] and is not recommended until at least 2 to 4 weeks after the completion of chemotherapy [2]. The prognosis of the pregnant patient with hypopharyngeal carcinoma is unknown, but in nonpregnant patients, 5-year survival is less than 30% to 35% even if surgery, radiotherapy, and adjuvant chemotherapy are used [5].

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