Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid

Abstract

Sclerosing mucoepidermoid carcinoma of the thyroid was first reported in 1991. This tumour type may develop as associated to Hashimoto thyroiditis. There are two variants of mucoepidermoid carcinoma of thyroid. The conventional and the sclerosing variants. Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid (SCME) has recently been recognised as a separate disease entity by the WHO. We report a case of SCME in a 62-year-old male patient who presented with a painless anterior neck swelling. Total thyroidectomy was performed, and no adjuvant treatment administered. The patient remained disease free up until 10 months of follow-up. Approximately 40 cases are reported in literature. We report the second case of SCME in Asian men. Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid should be differentiated from the conventional mucoepidermoid carcinoma. Patients should also be advised of long-term follow-up for surveillance.

Background

Conventional mucoepidermoid carcinoma of thyroid gland was first described by Rhatigan et al in 1977.¹ Sclerosing variant with eosinophilia (Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid (SMCE)) differs from conventional mucoepidermoid carcinoma of thyroid as suggested by Sim et al.² First described in medical literature by Chan et al ³ as a low grade thyroid malignancy arising in the background of Hashimoto’s thyroiditis. The expression of p63 suggests a solid cell nest origin in comparison with follicular cell origin.⁴

There are approximately 40 reported cases of SMCE in the published medical literature with female gender predominance.^{5 6} Only 4 out of the 40 reported cases are reported in male gender; we report the fifth case of SMCE in male patients and the second case in Asian men.⁵

Case presentation

A 62-year-old male patient presented with a progressively increasing anterior neck swelling for 10 years. On examination, an enlarged nodular thyroid gland was observed, which moved on deglutition. Patient had bilateral mobile vocal cords on flexible laryngoscopy. Patient had no compressive symptoms. He had a history of weight gain over the past 2 years.

Investigations

Patient had a thyroid stimulating hormone (TSH) of 4.58 (range 0.4–4.0). Thyroid scan revealed a dominant cold nodule (1.5×2 cm) in the right lobe of the gland. Fine needle aspiration cytology (FNAC) of the nodule was reported as atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS).

Differential diagnosis

The differential diagnosis is based on atypical cells seen on FNAC, on examination, patient had a multinodular goitre.

Papillary/follicular carcinoma thyroid are among the most common malignancies of the thyroid gland. Papillary carcinoma of thyroid has papilla-like projections and psammoma bodies on histopathology. Nuclear features include Orphan Annie eyed appearance. Follicular carcinoma is diagnosed by capsular or perivascular invasion, which requires open biopsy. Both of the entities could be diagnosed on histopathology in patients with atypical cells seen on FNAC.

Metastasis to thyroid can be from renal cell carcinoma or very rarely squamous cell carcinoma. FNAC of both could report atypical cells. Squamous cell carcinoma will additionally contain keratin pearls.

Composite tumours of thyroid are another rare entity that could be considered in patients with atypia of undetermined significance on FNAC.

Background of Hashimoto’s thyroiditis was revealed on final histology. Hodgkin’s lymphoma can also be a possibility with long-standing Hashimoto’s thyroiditis and should be considered.⁷ (Histological differential)

Treatment

The patient underwent total thyroidectomy. Intraoperatively, the gland was multinodular and was adherent to surrounding structures. Neck dissection was not carried out as there was no clinical involvement of lymph nodes. All four parathyroid glands were identified and preserved.

Histopathology revealed an infiltrating neoplasm in a background of densely sclerotic stroma and randomly scattered nests of relatively uniform polygonal cells with eosinophilic cytoplasm exhibiting mild to moderate nuclear atypia. Foci of squamoid differentiation as well as columnar cells with apical mucin were present. Numerous eosinophils were seen in the stroma. Mucin pools were highlighted on special stain PAS-Alcian blue. Tumour nests demonstrated positivity for immunohistochemical stains CK 5/6 and TTF-1. This was a low-grade tumour with no lymphovascular or perineural invasion. Stromal inflammatory infiltrate contained eosinophils, plasma cells and lymphocytes. Adjacent thyroid tissue showed chronic inflammatory infiltrate predominantly comprising of eosinophils along with plasma cell and lymphocytes (figures 1–3).

Figure 1.

(A) Tumour exhibiting combination of squamoid cells (large arrow), intermediate cells (small arrows) and cystic spaces (stars). (H&E stain, 200×). (B) Cystic spaces lined by mucinous cells (arrows) (H&E stain, 200×). (C) Small nests of tumour cells (small arrows) were seen against sclerotic background stroma. A lymphoid follicle was also seen (large arrow) (H&E stain, 100×). (D) Intervening stroma between tumour cells showed eosinophil rich inflammatory infiltrate (H&E stain, 400×).

Figure 2.

Tumour cells exhibited cytoplasmic and membranous staining for (A) cytokeratin 5/6 and nuclear staining for (B) TTF-1 immunohistochemical stains. (C) Periodic acid-Schiff-alcian Blue special stain highlights intraluminal and intracytoplasmic mucin.

Figure 3.

(A) Interface of tumour nests (arrows) with adjacent thyroid tissue (H&E stain, 200×). (B) Adjacent thyroid tissue exhibited prominent Hurthle cell change (large arrow) and lymphoid aggregate (short arrow) (H&E stain, 400×).

Extrathyroidal extension was present. These features suggested the diagnosis of sclerosing mucoepidermoid carcinoma with eosinophilia arising in the background of Hashimoto’s thyroiditis. Size of nodule was 4.2×3.8×2.5 cm, pathologic staging was pT3 Nx.

Outcome and follow-up

Patient had a CT scan of head, neck and chest 2 weeks postoperatively that revealed no abnormal enhancing lesion in the thyroid bed. Subcentimetre nodular lung opacities were observed. CT scan preformed after 4 months did not reveal any change in size of the right upper and left lower lung opacities.

Nearly a year after surgery, the patient has no signs of disease recurrence is on a close follow-up.

Discussion

Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid gland is a low grade malignancy.⁶ Majority of the reported cases have a long survival time (up to 12 years) postexcision and adjuvant treatment. There are, however, seven reported cases of aggressively behaving SMCE with high early mortality. Most of the patients present with complains of slow growing, painless anterior neck swelling.⁸ Mean age of the patients is 55.2 years.⁵ Regional lymph node metastasis and extrathyroidal extension are not uncommon⁸ later seen in our case. Distant metastasis of SMCE has also been reported in medical literature with the most common site being the lungs followed by bone and liver.⁵ Conventional mucoepidermoid carcinoma of the salivary gland metastasises to skin, lung, liver and bone.^{9 10} Histologically, the conventional mucoepidermoid carcinoma does share similarities with SMCE. They have larger sheets of epidermoid cells, obvious cystic spaces and lack of vascular invasion.⁸

SMCE should be differentiated from primary squamous cell carcinoma of thyroid, which is very rare and is from secondary deposits. Squamous cell carcinoma has prominent atypia and frequent mitosis and lacks sclerosis and eosinophilia. Additionally, SMCE should be differentiated from squamous differentiation of primary thyroid malignancies.⁵ SMCE could also mirror sclerosing Hodgkin’s disease (HD), the absence of Reed-Sternberg cells and absence of CD15, CD30 and CD45 positivity could help differentiate from HD.⁵ This would avoid misclassification of patient’s condition and prevent unnecessary treatment.

Due to the small number of reported cases, there is no consensus on the definitive treatment of SMCE; surgical excision has. however, been carried out in all the cases. It has recently been recognised as a separate thyroid entity by the WHO.¹¹ Significant response to adjuvant treatment such as radio-iodine ablation, external beam radiation and addition of chemotherapeutic agents such as carboplatin and doxorubicin has not been documented.⁶

In our case, the patient had total thyroidectomy without neck dissection and did not receive any postoperative radio-iodine ablation or other adjuvant treatment. Thyroid whole-body scan was performed, and the patient has neither developed any regional or distant metastasis 10 months after initial treatment.

More cases are needed to be reported to identify any prognostic indicator in patients with sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid. We report the fifth case of SMCE in males and the second case in Asian men.

Learning points.

• Sclerosing mucoepidermoid carcinoma with eosinophilia (SCME) of thyroid should be differentiated from the conventional mucoepidermoid carcinoma.

• SCME of thyroid should be remembered while treating patients with Hashimoto’s thyroiditis.

• Close follow-up is suggested in patients with SMCE of thyroid.