Thyroid papillary cancer-related pregnancy: a case report

Introduction

Thyroid cancer, the most common endocrine malignancy, is often detected in young patients and more frequently diagnosed in women. The reported incidence rates of differentiated thyroid cancer in pregnancy vary from 3.6 to 14 per 100,000 live births [1]. The majority of thyroid cancers are classified as papillary (88%) or follicular (9%), and these two histological types are grouped as differentiated thyroid cancers. Normal physiological changes in pregnancy include increase in maternal thyroid volume. Pregnancy in thyroid cancer patients is not unusual. About 10% of thyroid cancers are diagnosed during pregnancy or the post-partum period. Some hormonal (TSH and HCG) and metabolic changes affect the thyroid gland during pregnancy. However, such a relationship has not yet been confirmed yet.

The diagnosis of a tumor during pregnancy causes anxiety about the optimal timing of recommended treatments. Management of cancer during pregnancy is a challenge. Based on the currently available clinical data, the American Thyroid Association recommends surgery after delivery for patients diagnosed with thyroid cancer during pregnancy that does not present any aggressive features and surgery during the second trimester if aggressive features are present.

Case report

A 31-year-old woman, gravida 2 para 1, had no symptoms other than a lump on her neck. The patient had been aware of a palpable neck nodule for approximately 3 years, during which time she believed that the nodule had been rapidly growing during pregnancy. There was no family history of thyroid disease, but her son was diagnosed with acute myeloid leukemia 3 years ago. Her physical examination was normal, except for a lump on her neck at week 17 of her pregnancy. No fetal abnormality was identified. Her serum thyroid-stimulating hormone (TSH) level was 0.48 µIU/mL, and the serum free T4 level was 11.52 pmol/liter. Neck ultrasonography identified a calcified solid 33- × 23-mm thyroid nodule in the right lobe of the thyroid gland, with no abnormal lymph nodes in the lateral or central neck compartments. After the suspicious ultrasound findings were discussed with the patient and her family, the patient decided to have an ultrasound-guided fine-needle aspiration biopsy. Pathological findings were compatible with papillary thyroid cancer. After the diagnosis, her therapy choices were discussed in detail. The patient decided to undergo surgery and thyroid hormone replacement therapy after surgery. Total thyroidectomy was performed at week 25 of her pregnancy. After total thyroidectomy, the tumor histology was identified as classic papillary thyroid cancer that showed extrathyroidal extension, invasion into the sternothyroid muscle, and lymph node metastases in the central lymph node compartment. The surgical margins were negative. No complications were associated with surgery or general anesthesia. Fetal heart beat was evaluated with ultrasound before and after surgery. No side effects were observed during perioperative periods. Levothyroxine replacement therapy was begun after surgery. Thyroid function test results returned to normal 1 month after surgery. In week 37 of the pregnancy, uterine contractions occurred and a cesarean section was planned because of a previous cesarean section delivery. No congenital anomalies were identified. After delivery, maternal and fetal thyroid function tests were normal. Four months after delivery, breastfeeding stopped and she received iodine-131 (I-131) therapy.

Discussion

Thyroid cancer during pregnancy is detected in 14 out of every 100,000 live newborns, and it is the second-most frequent cancer detected in pregnant women [2]. About 10% of thyroid cancers occurring during the reproductive years are diagnosed during pregnancy or after delivery [1]. Thyroid nodules during pregnancy are often misdiagnosed because of the physiological enlargement of the thyroid. Ultrasound findings are usually sufficient to suspect malignancy; ultrasound-guided fine-needle aspiration biopsies are also suitable for an accurate diagnosis. Seventy-five percent of these women are diagnosed in the 12-month postpartum period [2]. A meta-analysis showed an association between pregnancy and thyroid cancer that was mostly the differentiated type [3]. According to the findings of the same study, an interval of less than 5 years since the last pregnancy had significantly increased the risk of thyroid carcinoma [3].

A pathophysiological background of increased risk of thyroid cancer development and progression in pregnancy is unknown. Women are four times more likely to be diagnosed with thyroid lesions; it is possible that female hormones and/or the genetic code play a role in the pathogenesis. Przybylik-Mazurek et al. concluded that estrogen might have been modifying the proliferation of thyroid cancer cells [4]. Another study also showed an association between high parity and thyroid cancer [5]. In these experimental studies, it was shown that estrogen receptors may play a role in thyroid reprogramming, oncogenesis, and progression. But the use of exogenous estrogens are not found to be associated with higher risk of thyroid cancer [6].

Most studies have shown that pregnancy did not have an impact on the prognosis of thyroid cancer. According to some studies, no difference was found in thyroid papillary cancer prognosis between pregnant women and non-pregnant women [7], [8], [9]. However, some studies support the contrary: Vannucchi et al. reported a significantly worse outcome in pregnant patients [10] and Ilaria et al. suggested that pregnancy may negatively affect the prognosis of thyroid papillary cancer [11]. Thyroid papillary cancer and thyroidectomy had no significant effect on mortality during pregnancy and was not associated with worse neonatal and maternal outcomes [8]. In a study by Cabezón et al. lymph node metastases were detected in 44.8% and invasion of adjacent extrathyroidal tissue in 6.8% of pregnancies [12]. In the present case, lymph node metastases and invasion of adjacent extrathyroidal tissue were detected. Takashi et al. compared results of surgery during pregnancy and surgery after delivery by means of incidence of lymph node metastasis, incidence of extrathyroidal extension, or tumor size [13].

Radioactive I-131 should only be given after delivery and cessation of breastfeeding is required. Women receiving radioiodine therapy should avoid pregnancy for 6–12 months due to increased risk of infertility, miscarriage, or fetal malformation [14], [15].

There is no consensus about the optimal timing of surgery. Usually, surgery is preferred to be delayed until delivery, except in cases of aggressive pathological or clinical features, compressive symptoms, rapid enlargement of tumor, and patients’ concern. In our case, surgery was preferred during the second trimester. In high-risk patients, surgery should be performed in the second trimester. The Endocrine Society Guidelines recommend that women who are diagnosed with papillary thyroid cancer without evidence of advanced disease should wait for surgery until the postpartum period. After thyroid surgery during pregnancy, levothyroxine therapy is necessary to obtain optimal fetal development.

In conclusion, the management of thyroid cancer during pregnancy is a challenge. These patients should be managed by a multidisciplinary team. Thyroid surgery is safe in the second trimester; post delivery is also an acceptable time for surgery. Survival and disease-free intervals are identical with pregnant and non-pregnant women. I-131 therapy is contraindicated during pregnancy and breastfeeding.