Nodular hyperplasia presenting as a mediastinal mass: Three case reports.

RATIONALE: Based on imaging and biopsy results, surgical removal of mediastinal nodular hyperplasia (MNH) may be unnecessary, and mediastomy may be avoidable. PATIENT CONCERNS: We report three cases of nodular hyperplasia presenting as a mediastinal mass on imaging studies during a health check-up or for the evaluation of known abscess in the right masticator and submandibular spaces.
INTERVENTIONS: In the first two cases, surgical excision was performed, and in the third case, US-guided core needle biopsy was performed. DIAGNOSES: Histopathological examination revealed MNH in the first two cases, and histologic examination suggested MNH. OUTCOMES: In the first two cases, there were no associated complications after successful surgical removal. In the third case, surgery was not performed because of old age and no associated symptoms. LESSONS: MNH may mimic mediastinal tumors on imaging studies. Accordingly, awareness of imaging features, interval changes, associated symptoms, and biopsy results may be necessary for the appropriate management of MNH.

Introduction

Ectopic thyroid is a rare developmental abnormality resulting from aberrant embryogenesis of the thyroid gland during its passage from the floor of the primitive foregut to its final pre-tracheal position.[ The most common location of ectopic thyroid is the lingual area (i.e., tongue base), although the mediastinum can also be involved.[ Intrathoracic ectopic thyroid is another rare condition, accounting for approximately 1% of all mediastinal tumors.[ It has been reported to occur in the mediastinum, lungs, and heart, and it usually presents with dry cough, dyspnea, and hemoptysis.[ Orthotopic thyroid tissue usually coexists with mediastinal ectopic thyroid, and the patients are found to be euthyroid.[ In the majority of cases, ectopic thyroid is located in the anterior mediastinum.[ Mediastinal nodular hyperplasia (MNH) is a very rare condition that may result from intrathoracic extension of nodular hyperplasia in a normally located thyroid gland or the de novo development of nodular hyperplasia in ectopic thyroid tissue located in the mediastinum.[ To our knowledge, however, imaging and therapeutic data concerning MNH is lacking. Furthermore, no appropriate management guidelines have been established.

Here we present 3 cases of MNH, 2 of which were treated by surgical excision, and describe their ultrasonography (US), computed tomography (CT), and radionuclide scan findings.

Case reports

Ethical statement

This study was approved by the institutional review board of Inje University Busan Paik Hospital. Informed consent and ethical approval were waived owing to the retrospective nature of the study and patient anonymity.

Case 1

In December 2017, a 50- to 60-year-old woman underwent thyroid US during a health check-up at a local clinic. A large mass was detected in the infrathyroidal region and superior mediastinum (Fig. 1A and B), and she underwent neck CT for further evaluation at the same hospital (Fig. 1C–E). Subsequently, she was referred to our hospital, where thyroid and parathyroid function tests revealed normal findings (T3, 101.3 ng/dL [normal range, 80–200 ng/dL]; free T4, 1.36 ng/dL [normal range, 0.93–1.71 ng/dL]; thyroid-stimulating hormone, 1.31 mIU/L [normal range, 0.27–4.20 mIU/L]; serum calcium, 9.5 mg/dL [normal range, 8.6–10.4 mg/dL]; serum parathyroid hormone [PTH], 31.64 pg/mL [normal range, 15–65 pg/mL]), and no specific abnormalities were detected during physical examination of the neck. The patient underwent US-guided fine-needle aspiration with PTH measurement performed by a radiologist with 7 years of experience in using a high-resolution US device (iU 22; Philips Medical Systems, Bothell, WA) equipped with a 5 to 12-MHz linear probe. The PTH level in the aspirate was 12.18 pg/mL, and there was inadequate cytology. For further evaluation, thyroid scanning with Tc-99m pertechnetate was performed (Fig. 1F). Even then, the origin of the mass and its diagnosis remained unclear. A head and neck surgeon with 6 years of experience performed surgical excision for diagnosis and treatment. After the placement of a low transverse cervical incision, the large mass was successfully dissected without injury to the adjacent nerves and vessels (Fig. 1G). The mediastinal mass was not connected to the left thyroid lobe, while it was attached to the innominate artery and vein by loose connective tissue. Mediastomy was not performed, and no significant complication was observed after surgery. Histopathological analysis of the surgical specimen confirmed nodular hyperplasia (Fig. 1H).

Figure 1

Imaging findings for a 50- to 60-year-old woman with a large mass in the superior mediastinum. Longitudinal gray-scale (A) and color Doppler (B) sonograms of the infrothyroidal region show a large solid mass (arrows: maximum diameter, 42.7 mm) exhibiting hyperechogenicity, smooth margins, an ovoid shape, and mixed vascularity. On nonenhanced axial (C), contrast-enhanced axial (D), and contrast-enhanced coronal reformatted (E) computed tomography images, this mass (arrows) appears well delineated with smooth margins, a mild mass effect, inhomogeneous enhancement, and separation from the thyroid gland or adjacent structures. Thyroid scan with Tc-99m pertechnetate (F) reveals nearly no radiotracer uptake by the mediastinal mass (arrows). In the operative field (G), the mediastinal mass (marked as MM) is completely isolated from the right thyroid lobe (marked as RTL), and the right recurrent laryngeal nerve (arrow) and right inferior parathyroid gland (arrowhead) are preserved during surgery. Histopathological analysis of the surgical specimen shows a well-circumscribed mass composed of variable-sized thyroid follicles with markedly edematous and fibrotic stroma (hematoxylin and eosin stain, ×40) (H). These features correspond to nodular hyperplasia.

Case 2

In November 2017, a 60- to 65-year-old woman underwent thyroid US during a health check-up at a local clinic, and a large mass was found in the infrathyroidal region and mediastinum (Fig. 2A and B). She was referred to our hospital for further evaluation. Thyroid and parathyroid function tests revealed the following: free T4, 1.28 ng/dL (normal range, 0.93–1.71 ng/dL); thyroid-stimulating hormone, 1.71 mIU/L (normal range, 0.27–4.20 mIU/L); serum calcium, 13 mg/dL (normal range, 8.6–10.4 mg/dL); and serum PTH, 89.25 pg/mL (normal range, 15–65 pg/mL). Thus, while her thyroid function was normal, hyperparathyroidism was suspected. However, no specific abnormalities were detected during physical examination of the neck. The patient underwent US-guided fine-needle aspiration performed by a radiologist with 7 years of experience in using a high-resolution US device (iU 22; Philips Medical Systems, Bothell, WA) equipped with a 5 to 12-MHz linear probe. Cytology revealed a suspicious follicular neoplasm (Fig. 2C and D). On the basis of parathyroid single-photon emission CT (SPECT), a right functional parathyroid adenoma exhibiting intense radiotracer uptake was suspected, while the mediastinal mass showed poor radiotracer uptake (Fig. 2E and F). Before surgery, neck CT was performed to determine anatomical details (Fig. 1G–I). A surgeon with 6 years of experience performed surgical excision for diagnosis and treatment of the right parathyroid adenoma and mediastinal mass. After the placement of a low transverse cervical incision, right inferior parathyroidectomy was performed first, followed by removal of the mediastinal mass. The mediastinal mass was not attached to the left thyroid lobe, whereas strong connective tissue was found between them. Mediastomy was not performed, and no significant complication was observed after surgery. Histopathological analysis of the surgical specimen confirmed nodular hyperplasia (Fig. 2J).

Figure 2

Imaging findings for a 60- to 65-year-old woman with a large mass in the superior mediastinum. Longitudinal gray-scale (A) and color Doppler (B) sonograms of the infrothyroidal region show a large solid mass (arrows: maximum diameter, 46.0 mm) exhibiting hyperechogenicity, smooth margins, an ovoid-to-round shape, and mixed vascularity. On nonenhanced axial (C), contrast-enhanced axial (D), and contrast-enhanced coronal reformatted (E) computed tomography images, this mass (arrows) appears well delineated with smooth margins, a mild mass effect, inhomogeneous enhancement, and separation from the thyroid gland or adjacent structures. Dual-phase planar Tc-99m sestamibi scan (F) and fused coronal single-photon emission computed tomography (G) images show intense radiotracer uptake by the inferior aspect of the right thyroid lobe, with delayed washout (thin arrow, parathyroid adenoma), and increased tracer uptake by the mediastinal mass, with early washout (thick arrow, mediastinal nodular hyperplasia). During surgery, the mediastinal mass is completely isolated from the thyroid gland. Histopathological analysis of the surgical specimen reveals micro- and macrofollicles with cystic dilatation and edematous stroma (hematoxylin and eosin stain, ×40) (H). These features correspond to nodular hyperplasia.

Case 3

In March 2016, a 75- to 80-year-old woman underwent neck CT for the evaluation of known abscess lesions in the right masticator and submandibular spaces at our hospital. The findings incidentally revealed a large mass in the superior mediastinum (Fig. 3A–C). However, she was discharged after treatment of the abscess lesions, and the mediastinal mass was not evaluated further because of no associated symptoms. After 20 months, she underwent chest CT during a health check-up at a local clinic (Fig. 3D–G), and she was referred to our hospital for further evaluation. On comparison of CT images obtained in March 2016 with those obtained in November 2017, we found that the mediastinal had slightly increased in size. Thyroid and parathyroid function tests were not performed, and no specific abnormalities were detected during physical examination of the neck. For diagnosis of the mass, the patient underwent US-guided core needle biopsy performed by a radiologist with 7 years of experience (Fig. 3H–J). Histological analysis of the biopsied specimen suggested nodular hyperplasia (Fig. 3K). However, surgical removal was not performed because of old age, no associated symptoms, and a mild interval change in size.

Figure 3

Imaging findings for a 75- to 80-year-old woman with an incidental mass in superior mediastinum. Nonenhanced axial (A), contrast-enhanced axial (B), and contrast-enhanced coronal reformatted (C) computed tomography images show a well-delineated mass (arrows) with smooth margins, a mild mass effect, inhomogeneous enhancement, and separation from the thyroid gland or adjacent structures (22.4 × 31.4 × 39.4 mm). After 20 months, nonenhanced axial (D), contrast-enhanced axial (E), and contrast-enhanced coronal reformatted (F) computed tomography images exhibit a mild interval increase in the size of the superior mediastinal mass (arrows, 30.2 × 33.7 × 42.3 mm). Neck ultrasonography (US) (G) and US-guided core needle biopsy (H) for this mass were performed at our hospital. The mass (arrows) appears solid, with isoechogenicity, smooth margins, and an ovoid-to-round shape on US, and the biopsy needle (arrowheads) pierces the target precisely. Histopathological analysis of the biopsied specimen reveals proliferated thyroid follicles of variable sizes (hematoxylin and eosin stain, ×100) (I). These features correspond to nodular hyperplasia.

Discussion

In the present report, histopathological analysis after surgical excision confirmed MNH in 2 of the 3 cases. In both cases, there was no connection between the mass and the normal thyroid gland. Therefore, we considered these cases to be those of nodular hyperplasia originating from ectopic thyroid tissue in the mediastinum. However, ectopic thyroid tissue was not found during histopathological analysis of the resected mediastinal masses. In the literature investigation, we found that the CT features of the masses in the present cases were very similar to those of mediastinal ectopic thyroid reported in previous studies.[ US and CT performed in the previous and present reports showed the mediastinal lesions as discrete masses with a mild mass effect. In addition, these lesions showed inhomogeneous enhancement on contrast-enhanced CT images. These findings do not suggest ectopic thyroid, which exhibits the same features as a normally located thyroid gland on US and CT images.[ Ectopic thyroid exhibits homogeneous attenuation and enhancement on CT images in the absence of underlying diffuse thyroid disease.[ Furthermore, ectopic thyroid rarely shows a mass effect.[ Accordingly, the previous reported cases of mediastinal ectopic thyroid could actually be those of MNH. Further studies are required to clarify this issue.

One of the 2 surgically managed cases exhibited hyperparathyroidism (Case 2), and we suspected a right parathyroid adenoma from imaging findings. The third case was asymptomatic with no associated lesions and was considered a controversial case for surgical management, considering that surgery carries a potential risk for injury to vascular or other organs. In general, asymptomatic euthyroid patients with ectopic thyroid do not usually require therapy, although they are kept under observation.[ In particular, Case 3 in the present report was subjected to core needle biopsy without surgical excision, and the mass exhibited no significant interval change in size or feature on CT images obtained 20 months after initial detection. We recommend that interval changes or associated symptoms of MNH should be investigated through further studies. This will aid in the establishment of appropriate management guidelines for MNH.

This study has several limitations. First, the methods used for diagnostic imaging, laboratory tests, and pathological examinations were not uniform. Second, one of the 3 cases did not undergo surgical removal. Finally, whole-body scanning with radioiodine was not performed.

In conclusion, MNH may mimic mediastinal tumors on imaging studies. Accordingly, awareness of imaging features, interval changes, associated symptoms, and biopsy results may be necessary for the appropriate management of MNH. Our findings are expected to provide a foundation for the establishment of appropriate management guidelines.

Author contributions

Conceptualization: Dong Wook Kim.

Investigation: Do Hun Kim, Yoo Jin Lee, Ha Kyoung Park, Tae Kwun Ha, Ji Sun Park, Soo Jin Jung.

Supervision: Gi Won Shin, Yoo Jin Lee, Young Jun Cho, Ha Kyoung Park, Tae Kwun Ha, Ji Sun Park, Soo Jin Jung, Ki Jung Ahn, Sung Ho Moon.

Validation: Gi Won Shin, Young Jun Cho, Sung Ho Moon.

Writing – original draft: Do Hun Kim.

Writing – review & editing: Dong Wook Kim.

Dong Wook Kim: ORCID: 0000-0002-9826-1326.