A Silent Non-thyroidal Adenoma in the Thyroid

Abstract

The surgeon needs to assess clinically significant thyroid nodules as they may represent aggressive forms of thyroid cancer or ectopic parathyroid glands. We discuss one such unusual nodule in the thyroid.

Introduction

Thyroid nodules are extremely common. Studies have shown that 44–77% of nodules are benign colloid nodules, 15–40% are benign follicular adenomas, and 8–17% are differentiated thyroid cancer. Very small percentages of thyroid nodules turn out to be more aggressive forms of thyroid cancer [1] or ectopic intra-thyroid parathyroid glands (ETPG) [2]. Parathyroid hyperplasia or adenoma in normal and ectopic locations results in hyperparathyroidism, which is associated with symptoms of hypercalcemia, such as nausea, vomiting, renal colic or bone pain [3].

Case Report

A 60-year-old woman presented to the outpatient department with a slowly progressing anterior midline neck mass for 3 months. She had no difficulty in swallowing, change in voice, symptoms indicating hypothyroidism, hyperthyroidism, or parathyroid disorder. She was a known diabetic and hypertensive on regular treatment. Physical examination revealed a swelling of 6 × 5 cm in the midline of the neck, more towards the left. It moved with deglutition, was firm in consistency, non-tender. Few more nodules were palpable in the left lobe, largest being 1 × 1 cm.

Ultrasonography (USG) neck showed a large cystic lesion with multiple septae and low-level internal echoes, occupying left lobe (7 × 3.6 cm), extending inferiorly up to suprasternal notch. Left lobe measured 6.3 × 4 × 4.3 cm; right lobe measured 4.8 × 1.5 × 1.6 cm. Few cystic lesions of 3–4 mm were noted scattered in right lobe; no parathyroid abnormality was detected. Fine needle aspiration cytology was inconclusive. Thyroid and renal function tests were normal; parathyroid hormone and calcium levels were not tested.

With a provisional diagnosis of colloid nodule, total thyroidectomy was performed. Intraoperatively, 3 of 4 parathyroid glands were found in normal location, appeared normal, and were preserved. The left inferior parathyroid gland was not visualized. Postoperative period was uneventful. Gross examination revealed a multiloculated cyst measuring 5.5 × 3.5 × 4 cm occupying almost entire left lobe (Fig. 1); adjacent lower pole showed a solid area of 1.3 × 1 cm with papillary excrescences. Cut section of right lobe and isthmus showed colloid filled and colloid depleted areas.

Fig. 1.

Gross specimen of total thyroidectomy showing the right and left lobes with a well encapsulated tumor in the left lobe

Left lobe microscopy showed an encapsulated solid tumour, with clear to eosinophilic cells, occasional mitotic figures, capsular and vascular invasion, but without adjacent thyroid infiltration (Fig. 2). Diffuse Pan cytokeratin, Cyclin D1 immunoreactivity, and Synaptophysin, Chromogranin, Calcitonin non-reactivity, with 1% Ki-67 confirmed the diagnosis of intrathyroidal parathyroid adenoma in multinodular goitre. The patient is being followed-up regularly, with normal levels of serum parathyroid hormone and calcium after one month of surgery. She is on thyroid hormone and calcium supplementation.

Fig. 2.

Microscopic photograph showing tumour cells with clear (single arrow) and eosinophilic (double arrows) cytoplasm (Haematoxylin and Eosin stain, ×10)

Discussion

Parathyroid glands originate from third and fourth pharyngeal pouches [4]. The primordium getting trapped within thyroid during fusion of medial and lateral lobes has been proposed to be the cause of ETPG [5, 6]. ETPG may be missed on imaging due to small volume, lack of clinical experience, rarity, and tissue interference of thyroid parenchyma. It is generally not known to lead to hyperparathyroidism but can transform into ectopic intrathyroidal parathyroid adenoma (IPA) or carcinoma. The mechanism of transformation is still uncertain [2]. As thyroid nodules are common; it is vital to distinguish them from the rarely encountered intrathyroidal parathyroid lesions [7].

Missing parathyroids can be found by dissection of peri-thyroidal loose tissue, or a lateral inferior lobe, and thyroidectomy for missing parathyroid adenoma should seldom be done; ETPG occurs in the lower lateral part of thyroid (90%), near recurrent laryngeal nerve (7%), and superior pole (3%) [5]. Inferior parathyroid is more prone to exist ectopically due to a longer migration during embryogenesis [7]. A yellow, soft, oval, well-demarcated intrathyroidal nodule should be subjected to frozen section examination [2]. Nevertheless, thyroidectomy can lead to hypothyroidism, without relief of symptoms of hyperparathyroidism [7]. Other ectopic sites of parathyroid glands include carotid sheath, thymus, retropharyngeal/retroesophageal space and anterior mediastinum [8].

The incidence of IPA has been reported to be 1–6.7% [5, 6, 8]. Ultrasound can be used as a primary tool for diagnosing parathyroid lesions; it is cost-effective, devoid of radiation, real-time, with 76% sensitivity, provides details regarding sectional anatomy and the surrounding tissue. It further allows classification of IPA as partial or complete, based on degree of envelopment by thyroid gland [8]. However, USG may fail to detect IPA in the setting of multiple thyroid nodules or ectopic sites [6, 7]. Color Doppler can be used to identify a polar feeding vessel in IPA with co-existent thyroid nodule [8]

IPA is hypoechoeic on USG [5, 8] with a hyperechoeic line representing the capsule echo of thyroid and parathyroids. A halo around nodules may be seen due to a rim of blood vessels around the adenoma or compressed surrounding tissue [7]. In this case, IPA was mistaken for thyroid nodule on USG.

Tc-99 m sestamibi-scintigraphy with single photon emission computed tomography (sestamibi-SPECT) has high sensitivity (84%) for intrathyroidal parathyroid lesions. The drawbacks include low specificity, high cost and inability to detail sectional anatomy [6, 7]. A combination of ultrasound and sestamibi-SPECT (91% sensitivity) may be beneficial in diagnosis [4, 7].

The challenge faced by the pathologist is distinguishing between atypical parathyroid adenoma and parathyroid carcinoma. Immunohistochemical markers like synaptophysin, chromogranin-A, keratin, thyroglobulin, parathyroid hormone, Ki-67, galectin-3, PGP9.5, Rb, bcl2, p27, hTERT, mdm2, and APC can be used [9]. Ki-67 is usually above 5% in parathyroid carcinoma and less than 5% in parathyroid adenoma.

IPA may be associated with hyperparathyroidism in 1–3.4% cases [7]. Rarely, acute haemorrhage of preexisting ETPA with abrupt cystic degeneration has been reported, leading to a neck mass with typical symptoms of primary hyperparathyroidism. The lack of familiarity and experience with this entity and its unusual features lead to misdiagnosis as goitre [4].

Treatment options include enucleation of intrathyroidal nodule [4] or hemithyroidectomy [10]. Enucleation of ETPA ensures preservation of thyroid function and reduces damage due to compression. Incidental rupture of cystic fluid must be cleared to decrease parathyroid hormone release into bloodstream. Parathyroid exploration must be performed only ipsilaterally, to prevent damage to vessels and recurrent laryngeal nerve [4]. In our case, total thyroidectomy was done as both lobes showed nodules. Histopathological examination revealed an incidental finding of IPA with coexisting nodular goitre.

Author contributions

Concept, data acquisition—MK, NK; Manuscript writing—MK, NK; Supervision—DD, HK. All authors read and approved the final version of the manuscript.

Funding

No funding was obtained.

Data Availability

Data transparent.

Code Availability

Not applicable.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

Approval was obtained from the Institutional Ethics Committee, KMC Mangalore (IEC KMC MLR 01-2020/50). The report adheres to the tenets of the Declaration of Helsinki.

Consent to Participate

Informed consent was obtained.

Consent for Publication

The patient has consented to the submission of the case report to the journal.