Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: demonstrating the natural progression of a rare and misunderstood disease

Abstract

Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid in a 46-year-old woman.

Background

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a rare thyroid cancer with 66 cases previously reported in the literature; it has a higher female predominance.^{1 2} Due to the rarity of the disease and scarcity of data, the cancer lacks any specific investigation or treatment guidelines. However, with recent data suggesting SMECE is a more invasive disease than previously thought; with up to 40% of patients having nodal involvement and 20% having distant metastasis,³ the need for timely diagnosis and treatment is paramount.

Case presentation

We report the case of a 46-year-old woman of Indian ethnicity presenting with a 1-year history of increasing neck swelling. She was assessed in a ‘new neck lump’ clinic and on examination a 19 mm large, fixed, firm thyroid lesion most prominent on the left hand side was palpated. No obvious lymphadenopathy was present. An ultrasound-guided fine-needle aspiration cytology (FNAC) took place that raised suspicion for papillary thyroid carcinoma. A total thyroidectomy was offered but the patient declined surgical treatment, instead opting for a trial of ayurvedic herbal supplements in India. She represented 18 months later with further enlargement of her thyroid lesion with progressive dysphonia. She was subsequently referred to the regional thyroid cancer centre for radical surgery and radiotherapy.

The patient had an unremarkable medical history, denied a history of exposure to radiation and reported no personal or family history of thyroid cancer or other malignancies.

Investigations

Radiological investigations

An ultrasound neck on initial presentation showed marked left thyroid lobe enlargement (50×43×18 mm) with a single left level II (8 mm) lymph node.

On representation 18 months later, the patient underwent a repeat ultrasound neck, a staging CT scan of the neck and chest and an MRI neck. The CT/MRI neck scans confirmed an extensive 85×55 mm thyroid mass up to the level of the left submandibular gland, displacing the left carotid sheath, as well as left lateral neck disease. Right-sided tracheal deviation was noted with moderate compression of the anterior–posterior dimension, and posterior extension to the trachea in the postcricoid space. Abnormal lymph nodes were noted in the cervical and supraclavicular chains. No distant metastasis was detected on CT chest imaging. Imaging can be seen in figures 1–4.

Figure 1.

Ultrasound showing hypoechoic thyroid nodule measuring >6 cm in the left lobe of the thyroid at level 5.

Figure 2.

Ultrasound of left level III lymph node chain showing hyperechoic and enlarged lymph node.

Figure 3.

CT neck images showing a large anterior neck mass arising from the thyroid.

Figure 4.

MRI neck showing large thyroid swelling with right-sided tracheal deviation.

Cytology investigations

The FNAC from her first presentation showed atypical cells and was reported as suspicious for papillary thyroid carcinoma, Thy4.

The second FNAC of the thyroid mass 18 months later was reported as showing atypia and given a cytological grading of Thy3a. Because neither FNAC of the mass confirmed a definite malignancy (ie, Thy5), a core biopsy was performed.

A core biopsy of the thyroid nodule showed poorly differentiated carcinoma with ‘gland-like’ structures showing some features suggestive of papillary cancer (nuclear crowding, contour irregularity, occasional inclusions) and positive staining for TTF1 and pax8. Although there were occasional nuclear inclusions within the tumour, definite features of papillary thyroid carcinoma were not identified.

Assessing tracheal and oesophageal compression

Nasolaryngoscopy showed impaired left vocal cord mobility with reduced abduction and normal right vocal cord mobility. Rigid and flexible bronchoscopy was performed and showed extrinsic compression of the posterior trachea from 2.5 cm below the vocal cords, extending for 3 cm, with 45% reduction in tracheal luminal cross-sectional area. No intraluminal tumour was noted in the bronchial tree. A rigid oesophagoscopy showed no oesophageal involvement.

Differential diagnosis

The patient was preoperatively staged with a poorly differentiated thyroid cancer T4aN1bM0,⁴ following discussion at the regional thyroid cancer multidisciplinary team meeting.

Treatment

After representing 18 months later, the patient consented to a total thyroidectomy with left selective II–IV and bilateral-level VI neck dissection. The left recurrent laryngeal nerve was sacrificed due to tumour encasement. The excised material can be seen in figures 5 and 6. The possibility of a laryngectomy was regarded as solely for salvage due the risks involved and paucity in the literature of this being an effective measure for local control in this tumour classification.

Figure 5.

Posterior surface of the thyroid gland where the tumour was present at tracheal margin.

Figure 6.

Cross-section of thyroid showing extensive fibrosis. There is a very small area of residual normal thyroid in the right lobe (top of specimen on the left where the thyroid is red/brown rather than yellow/white).

Histopathology

The thyroid gland was almost entirely replaced by sclerosing mucoepidermoid carcinoma. The tumour had a variety of morphologies that included cords, solid islands, nests of clear cells and squamous differentiation. There was an accompanying infiltrate of lymphocytes, plasma cells, mast cells and eosinophils suggestive of a thyroiditis although the patient’s antibody status was not known. There was direct invasion of one parathyroid gland, and the tumour was present at the tracheal and superficial margins, resulting in an R2 resection. Eight out of 35 lymph nodes were positive in levels III, IV and VI, with extracapsular spread present.

Immunohistochemistry showed that the tumour cells were positive for CK5, p40, TTF1 and galectin3, focally positive for pax8 and HBME1, and negative for CK7, CK19, CK20, CEA, thyroglobulin and calcitonin. DNA sequencing showed the tumour was negative for BRAF V600E after PCR analysis. Mucin and p63 markers were not tested in this specimen. Histological samples can be seen in figures 7–10.

Figure 7.

Glycogen-rich clear epidermoid cells.

Figure 8.

Small nests and cords of epithelial cells infiltrating a sclerotic stroma richly infiltrated by eosinophils and lymphocytes.

Figure 9.

Squamous pearls within strands of tumour.

Figure 10.

Lymph node metastasis.

Radiotherapy treatment

Following the discussion of the histopathology results at the thyroid cancer multidisciplinary meeting the patient commenced postoperative adjuvant radiotherapy to the thyroid bed bilaterally, cervical levels II−VII and upper mediastinum, over a 6-week period in 30 fractions.

Other treatment

The patient was commenced on levothyroxine 100 μg once daily and calci-chew two tablets three times a day as per the endocrinology team. She was also referred for voice therapy to rehabilitate her left vocal cord palsy.

Outcome and follow-up

The patient is being closely followed up by both the surgical and oncology teams. Laryngectomy is still seen as a last resort salvage option, due to the life changing surgery and limited data on its effectiveness in this tumour type. She was last by the oncology team in April 2021.

Discussion

SMECE of the thyroid gland is a rare type of tumour.^{1 2} With an increasing number of published case reports SMECE is now being recognised as having more aggressive features than previously described⁵ including extrathyroidal extension, lymph node and distant metastasis.⁶

The diagnosis of SMECE is similar to the diagnosis of other thyroid cancers. Once a neck mass is identified it and local lymph nodes are visualised using ultrasound, with fine-needle aspiration used to extract cells for cytological analysis. Occasionally core biopsies can also be used to collect a larger amount of material to enable histological analysis.⁷ The morphology and immunohistochemistry of the structures visualised will begin to formulate the likely cancer type, grade and the method of treatment required. These are assisted by CT or MRI scans to help stage the cancer to evaluate if the cancer has spread elsewhere.

Typical morphological patterns for SMECE are a dense fibrohyaline stroma with infiltrating solid or nested squamous tumour cells that show levels of atypia, with notable eosinophil infiltration with keratin pearls debris identified.⁸ While there was no concurrent papillary carcinoma in the resection specimen, SMECE has also been seen in patients with concurrent papillary thyroid cancer³ and one example of concurrent anaplastic thyroid cancer⁹ further complicating the diagnostic and treatment pathways.¹⁰

This case highlights the difficulty in making accurate diagnosis on limited sample material. The correct diagnosis was made only once the resection specimen was examined and while FNAC and core biopsy samples initially suggested possible features of papillary or poorly differentiated thyroid carcinoma, none of these cancers were found in the resection specimen.

This has been a unique opportunity to observe the natural history of a rare cancer, without evidenced-based intervention, over the course of 18 months. During this time, the tumour was seen to increase in size from 50×43 to 85×55 mm representing a 117% increase, not including depth, alongside the invasion of trachea and superficial margins. Supraclavicular lymph node size increased from 10 to 17 mm, a 70% increase.

Since the literature review by Sukumar et al there have been five further cases of SMECE including this case.3 9 11–14 This brings the total number of reported cases in the literature to 67. Of the cases published, 90% were in females with an average age of 55 years and an age range of 26–89 years. Where data were reported, extrathyroidal extension was seen in 53% of cases % (n=30) with 41% having lymph node spread (n=24) and 14% (n=8) having distant metastasis. Where the follow-up was reported, 80% of patients (n=35) were alive either with disease or in total remission. Our case reported the second largest tumour size of 8.5cm compared with the average of 4.6 cm.

There is currently no formal guideline for the investigation and treatment of SCME due to its rarity. However, there has been a call for closer monitoring and follow-up of these patients⁵ and with more cases showing greater invasion and metastasis^{15 16} than previously believed, better management pathways to enable accurate, timely diagnosis and treatment is required to effectively manage these patients.

This report underlines the importance of quick identification and treatment in a patient whose delay in treatment led to worsening symptoms and extensive disease, requiring more radical surgery and radiotherapy.

Learning points.

• An 18-month delay in treatment of sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) can lead to severe clinical and radiological progression requiring extensive surgical and radiological management in a previously believed slow-growing and indolent cancer.

• It is difficult making an accurate diagnosis on limited sample material. Both the sampling method and amount of tissue obtained can have a large impact on the confirmation, diagnosis and treatment of a thyroid cancer.

• Greater awareness, quicker identification and clearer diagnostic and treatment guidance are required to improve outcomes for patients diagnosed with SMECE.

Ethics statements

Patient consent for publication

Obtained.