Thyroid Carcinoma on the Side of the Absent Lobe in a Patient with Thyroid Hemiagenesis

Background Thyroid carcinoma complicated by hemiagenesis is very rare, and previous reports have not described this cancer on the side of the absent lobe. Methods and Results We report the case of a 64-year-old woman in whom left thyroid hemiagenesis was discovered incidentally during investigations of abnormal sensation during swallowing. A tumorous 1.4 cm lesion was also found on the side of the absent lobe, left of the isthmus. Fine-needle aspiration biopsy revealed class V papillary carcinoma, but no lymph node metastases. Total thyroidectomy was performed for stage cT1bN0M0 carcinoma. Histopathology revealed normal thyroid tissues in the right lobe and isthmus, while the left lobe was absent. The mostly papillary carcinoma was adjacent to the truncated thyroid tissue, with a portion histologically consistent with poorly differentiated carcinoma. Conclusions All previously reported cases of thyroid cancer complicated by hemiagenesis have represented carcinoma occurring within the present lobe. This case is extremely rare.


Introduction
yroid hemiagenesis is an extremely rare congenital abnormality, with a reported prevalence of 0.02-0.2% [1,2]. is pathology is often discovered during detailed examinations for abnormal thyroid function and thyroid diseases such as goiter. Only 13 previous cases of thyroid cancer concurrent with thyroid hemiagenesis have been reported. Tumors in each of those cases occurred in the remaining thyroid tissue; no previous reports have described thyroid carcinoma occurring on the side of the absent thyroid lobe. We report a case of thyroid carcinoma arising on the side of the absent lobe. To the best of our knowledge, this represents the rst report of its kind. Although the cause of onset is unclear, we discuss our hypotheses regarding the tumorigenic mechanisms of thyroid carcinoma in this case.

Case Presentation
A 64-year-old woman was referred to our department for evaluation of a thyroid mass discovered incidentally during examinations for symptoms of abnormal sensation during swallowing. e patient had no history of previous surgery or radiotherapy to the neck. She had no signi cant past medical history. No family history of thyroid disorders was elicited. Examination of the neck revealed a rm mass with irregular edges and little mobility. No cervical lymphadenopathy was evident. Examination of the oral cavity, pharynx, and larynx showed ndings within normal limits, with mobile vocal cords. Ultrasonography and computed tomography (CT) did not show a left lobe of the thyroid, but the right lobe and isthmus were identi ed. A 0.7 × 0.8 × 1.4 cm hypoechoic nodule with small calci cations and attenuation of posterior echo and a 0.8 × 0.7 cm enhanced nodule with clear borders were identi ed on the left side of the isthmus (Figure 1). Ultrasonography and CT did not reveal enlarged lymph nodes on either side of the neck. CT also did not reveal metastatic tumors in the lungs. Serum thyroid-stimulating hormone (TSH) was 1.35 μIU/mL (normal range: 0.35-4.94 μIU/mL), free triiodothyronine (FT3) was 2.87 pg/mL (normal range: 1.71-3.71 pg/mL), free thyroxine (FT4) was 1.43 ng/dL (normal range: 0.70-1.48 ng/dL), and thyroglobulin was 12.93 ng/mL (normal range: 0-32.7 ng/mL). Ultrasonographyguided ne-needle aspiration cytology identi ed the nodule as papillary thyroid carcinoma. e patient underwent surgery using a standard collar incision. Intraoperative ndings con rmed the presence of the right lobe and isthmus, the absence of the left lobe, and the presence of a rm nodule with in ltration into the muscle tissue surrounding the site of the absent lobe on the left of the isthmus after abduction of the anterior cervical muscles. Total right thyroid lobectomy isthmectomy, resection of the tumor, and central neck dissection were performed concurrently. e tumor had invaded the lateral branch of the recurrent laryngeal nerve, which was also resected, but the medial branch of the recurrent nerve was preserved ( Figure 2). On the side of the absent thyroid, the superior thyroid artery, superior thyroid vein, middle thyroid artery, inferior thyroid artery, inferior thyroid vein, and parathyroid glands were in the normal locations. No abnormality was evident in the pathway of the recurrent laryngeal nerve. Postoperative histopathological examination found that the right lobe and isthmus were present and the left lobe was absent.
e tumor was adjacent to the left side of the isthmus (Figure 3), and a clear demarcation was evident between the thyroid and tumor ( Figure 4). Most of the tumor was consistent with thyroid papillary carcinoma with a funicular-and microfollicular-shaped ductal structure, and nuclear grooves were observed within the tumor cells at high magni cation (Figures 5(a) and 5(e)). A honeycomb structure and necrosis were observed in a section of the in ltrating tumor, and a marked di erence was seen in the sizes of nuclei, indicative of poorly di erentiated thyroid carcinoma ( Figure 5(b)). In addition, immunohistochemical staining showed that both the papillary and poorly di erentiated carcinomas were

Discussion
yroid hemiagenesis was rst reported by Henle in 1866 [3]. e thyroid develops via epithelial cell proliferation from the foramen cecum of the tongue between the tuberculum impar and copula linguae in week 5 of gestation. e gland subsequently descends as a diverticulum dividing into right and left lobes, reaching the anterior of the trachea in week 7 of gestation [4]. yroid hemiagenesis is postulated to be caused by failure of the diverticulum to divide, but some reports have also described associations between a lingual thyroid and hemiagenesis [5,6]. Conrmation that other locations remain free of abnormal accumulation on thyroid scintigraphy is therefore necessary, even if thyroid hemiagenesis is observed on ultrasonography, CT, or other modalities. In this case, thyroid scintigraphy was not performed before surgery. However, no abnormal accumulation was detected at other sites on thyroid scintigraphy performed postoperatively following 131 I ablation.
Only 13 cases of thyroid cancer complicated by thyroid hemiagenesis have been reported [7][8][9][10][11][12][13][14][15][16][17][18]. ese cases included 11 female and two male patients, ranging between 14 and 74 years in age. In eight of these 13 cases, the tumors were discovered by palpation following cervical swelling or nodule detection. Five cases, including ours, were asymptomatic. Papillary carcinoma was the most common histology in 10 cases, with one case of follicular carcinoma, one of medullary carcinoma, and one of combined papillary and follicular carcinoma. Our case showed a combination of papillary and poorly di erentiated carcinomas, representing the rst case in which poorly di erentiated carcinoma was identi ed. Among cases reported to date, the left side of the thyroid was absent in eight patients, and the right side was absent in ve. Tumors in all cases except ours arose in the existing parts of the thyroid (i.e., in the lobe or isthmus). In our case, however, the tumor arose on the side of the absent thyroid. e fact that positive results for TTF-1 were obtained for both the papillary and poorly di erentiated carcinoma sites suggested that the cancer originated in the thyroid. However, checking for thyroid tissues on the side of the absent thyroid was not possible, so the origin of the thyroid cancer in our patient could not be con rmed.
We formulated three hypotheses regarding thyroid carcinogenesis in our patient (Figure 6), as outlined below. eory 1. Hypoplasia of the left thyroid lobe plus thyroid cancer arising on the hypoplastic side.
is hypothesis was ruled out, as the cancer was not contiguous with thyroid gland tissue on histopathological examination. eory 2. yroid hemiagenesis plus thyroid microcancer plus lymph node metastasis.
An extremely small primary lesion could have been present within thyroid tissue in the right lobe, with further lymph node metastasis to the site of the absent gland on the left resulting in the lesion. Multiple reports have described thyroid microcancer and lymph node metastasis to date, as reviewed by Anastasilakis et al. [19] Even a primary as small as 2 mm can lead to cervical lymph node metastasis. In our case, pathological examination of the residual thyroid using 5 mm thick slices found no microcancer. In addition, we were unable to con rm the existence of lymph tissue on the tumor side.
is hypothesis thus does not seem to be supported.
Ectopic noncontiguous thyroid could have been present with residual thyroid on the absent side, where the cancer originated and eventually replaced the ectopic thyroid. is is very rare, as only ve cases have been reported in which thyroid hemiagenesis was complicated by an ectopic thyroid [5,6,13,20,21], and none involved cancer. In addition, ectopic thyroids are mainly observed originating from the tongue, in front of the larynx, or (rarely) at the paratrachea, esophagus, or within the mediastinum [22]. In the present case, the cancer could have developed in an ectopic thyroid arising paratracheally following thyroid hemiagenesis.
However, the lack of thyroid tissue on the tumor side makes this hypothesis di cult to substantiate.
Although we consider Hypothesis 3 as the most likely, the mechanism of onset in this case of thyroid carcinoma on the side of the absent thyroid cannot be con rmed.
In summary, this case report appears to represent the rst to describe thyroid hemiagenesis complicated by thyroid carcinoma occurring on the side of the absent thyroid and is therefore extremely rare.