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Extensive mucoepidermoid carcinoma-like differentiation in follicular carcinoma of the thyroid

1 Department of Pathology, AIIMS, Bhopal, Madhya Pradesh, India
2 Department of Pathology and Lab Medicine, AIIMS, Bhopal, Madhya Pradesh, India
3 Department of Pathology, AIIMS, Mangalagiri, Andhra Pradesh, India
4 Department of ENT, AIIMS, Bhopal, Madhya Pradesh, India

Date of Submission24-Sep-2020
Date of Decision23-Nov-2020
Date of Acceptance05-Feb-2021
Date of Web Publication22-Jun-2022

Correspondence Address:
Ashwani Tandon,
Department of Pathology and Lab Medicine, AIIMS, Bhopal, Madhya Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_1422_20

 > Abstract 

Mucoepidermoid carcinoma (MEC) is a rare malignant thyroid neoplasm. Cases of MEC with papillary, insular, and anaplastic thyroid carcinoma have been reported. Here, we present a case of follicular carcinoma with extensive MEC-like differentiation. A 62-year-old female presented with complaint of thyroid swelling for 10 years. Cytological features were suggestive of follicular neoplasm. Contrast-enhanced computed tomography showed metastasis to lung and vertebrae. Salivary glands and breasts were normal on examination and imaging. Subtotal thyroidectomy with bilateral neck dissection surgery was performed. The specimen was submitted for histopathological examination. Microscopy showed features of follicular carcinoma with capsular and vascular invasion along with an additional MEC-like morphology. Follicular carcinoma with extensive MEC-like differentiation is a rare observation. Since the tumor was sparing salivary glands and breasts, we considered it as mucoepidermoid differentiation over a collision tumor. However, immunohistochemistry and molecular analysis were the limitations.

Keywords: Follicular carcinoma, mucoepidermoid carcinoma-like differentiation, mucoepidermoid carcinoma

How to cite this URL:
Vijayvergiya G, Tandon A, Panwar H, Santosh T, Gupta V, Kapoor N. Extensive mucoepidermoid carcinoma-like differentiation in follicular carcinoma of the thyroid. J Can Res Ther [Epub ahead of print] [cited 2022 Jul 2]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=347787

 > Introduction Top

Follicular thyroid carcinoma (FTC) is the second most common malignancy of the thyroid gland after papillary thyroid carcinoma (PTC) and comprises between 10% and 15% of all thyroid cancers. FTC is more aggressive than PTC.[1] Mucoepidermoid carcinoma (MEC) of the thyroid is an extremely rare malignant neoplasm. It was first described by Rhatigan et al. in 1977.[2],[3] MEC of the thyroid shows similar histological features as in the salivary gland. Few cases of MEC along with conventional papillary, insular, and anaplastic carcinoma have been reported in the literature. The association of MEC with FTC is extremely rare.[4] Here, we present a case of follicular carcinoma with extensive MEC-like differentiation.

 > Case Report Top

A 62-year-old female presented to our ENT outpatient department with a complaint of anterior neck swelling for the last 10 years, gradually increasing in size. It was associated with the breathlessness and cough for the last 1 week. Serum thyroid profile tests were within normal limit. Contrast-enhanced computed tomography showed multiple well-defined heterogeneously enhancing nodules in the lungs and vertebrae (indicating metastasis). The patient was referred for cytological examination. Bilateral breast and salivary glands were normal both on general examination and on imaging. On examination, the right lobe of the thyroid was enlarged measuring approximately 13 cm × 8 cm. Fine-needle aspiration cytology was performed using 22-gauge needles. FNA smears showed repetitive microfollicular pattern and sheets of thyroid follicular cells with cytoplasmic vacuolations [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. Given the repetitive microfollicular pattern, cytology smears were suspicious of follicular neoplasm (Bethesda category IV). In view of clinical features including large size, hard consistency and recent rapid growth, malignancy of the thyroid was considered as the most probable diagnosis clinically. Cytological diagnosis of Bethesda IV follicular neoplasm further suggested malignancy. A total thyroidectomy with neck node clearance under general anesthesia was planned. Intraoperatively, both the lobes were of large size and were found adhered to the surrounding structures. The right lobe could be separated from large vessels and removed in toto with identification and preservation of recurrent and superior laryngeal nerves. The left lobe was rather indistinguishable from the surrounding structures. It was tightly adhered to trachea and esophagus in the tracheoesophageal groove and could not be dissected off. The lower part of the enlarged left lobe occupying the central compartment was also adhered tightly onto the tracheal surface and could not be dissected off. Complete (R0) resection could not be achieved on the left side. Lymph nodes present on the right and left lateral compartment were removed. Subtotal thyroidectomy with bilateral neck dissection surgery was performed. The specimen was received for histopathological examination in the department of pathology. On gross examination, the right lobe of the thyroid was enlarged and measured 13 cm × 8 cm × 7 cm and the left lobe measured 4.0 cm × 3.5 cm × 2.5 cm [Figure 2]a, [Figure 2]b, [Figure 2]c. Gross examination from the right lobe showed an encapsulated solid cystic variegated mass with mucinous, granular, and necrotic areas [Figure 2]a, [Figure 2]b, [Figure 2]c. The left lobe was solid gray white. A total of 14 lymph nodes were retrieved. Microscopic examination of both the lobes showed an encapsulated tumor composed of follicular epithelial cells arranged in a predominantly microfollicular pattern, with areas displaying solid sheets to insular pattern separated by fibrous septae. The adjacent areas showed a marked transition to additional predominant patterns displayed solid areas with intracellular and extracellular mucin. The focal area showed squamous differentiation; areas of vascular and capsular invasion were present [Figure 3]a, [Figure 3]b, [Figure 3]c along with the peri-thyroidal extension. Special stain Alcian-PAS showed positivity for mucin [Figure 3]d. Given the areas of follicular carcinoma along with squamoid and mucinous areas, diagnosis of follicular carcinoma with extensive MEC-like differentiation was made (pT3bN1bMx). Considering the intraoperative and histopathological findings, the patient was planned for adjuvant treatment in the form of radioiodine ablation and external beam radiotherapy, but the patient declined the adjuvant treatment. The patient succumbed to disease 2 months postdischarge.
Figure 1: (a-d) Photomicrograph showing cytomorphological features of follicular epithelial cells arranged in sheets, with cytoplasmic vacuolations-? intracellular mucin (Giemsa, x10, x40)

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Figure 2: (a-c) Gross photomicrograph showing enlarged thyroid gland with cut section having a variegated appearance. Grossing of grid was given in the case to look for extensive capsular invasion

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Figure 3: (a and b) Photomicrograph showing histomorphological features of follicular carcinoma with areas of mucin and squamous differentiation. (H and E, ×40) (c) Areas of capsular invasion can be seen. (H and E, ×40) (d) Positive for mucin (AB-PAS, ×40)

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 > Discussion Top

MEC is a common neoplasm of the salivary gland. MEC can also occur in other sites such as the esophagus, breast, lung, pancreas, bronchial tree, and thyroid gland.[2],[3] MEC is characterized by a mixed pattern of epidermoid, intermediate cells, and mucus-producing cells.[5] MEC of the thyroid constitutes <0.5% of all thyroid malignancy. Two types of MEC of the thyroid have been reported in the literature: the primary MEC and sclerosing MEC with eosinophilia.[6] As of now, only 47 case reports of primary MEC are published in the literature. In the literature, we found that primary MEC is commonly associated with primary thyroid carcinoma. Most commonly, it is associated with the PTC. Association with other thyroid neoplasms has been reported in the literature.[7]

According to the literature, MEC is more common in the female with bimodal age presentation and associated with the Hashimoto's thyroiditis and previous history of exposure to the radiation.[8] The most common presentation is hypofunctioning palpable neck mass. The extrathyroidal extension is common and lymph node metastasis is usually seen in approximately 40% of cases.[9] Surgical excision with total thyroidectomy is the gold standard.[3] Primary MEC of the thyroid has a very low-grade potential, but few cases associated with the poor prognosis are also reported in the literature. There is so much debate in the literature regarding the histogenesis of MEC.

The theory proposed by the Rhatigan et al. is that MEC was derived from the ectopic salivary gland in the thyroid.[2] Since there is no evidence regarding the finding of ectopic salivary gland in the thyroid, this theory is rejected. Another proposed theory is that it arises from the thyroid follicular epithelial cells and solid cells nests (SCNs). SCN is the remnant of the ultimobranchial apparatus. MEC is usually positive for immunohistochemical markers such as TTF-1, PAX-8, and calcitonin.[3] Some authors proposed its origin from thyroglossal duct remnants because of the presence of mucin and ciliated epithelial within this tumor. Prichard et al. suggested that if MEC is originating from the thyroglossal duct remnant, it should be located in the isthmus of the thyroid gland.[9] Literature review has shown that MEC could arise from de-differentiation of per-existing WDTC (papillary and follicular thyroid cancer) with a probably higher nodal metastases. It is thought that WDTC may undergo mucinous and squamous metaplasia leads to the origin of MEC from preexisting thyroid carcinoma.[2] According to Prichard et al., MEC arises from the metaplastic dedifferentiation of WDTC rather than directly from benign squamous metaplasia, salivary gland rests, SCN, or thyroglossal duct remnants.[9] Histologically, MEC of the thyroid is a well-differentiated tumor and shows the cystic architecture, abundant extra- and intracellular mucin, and obvious squamous differentiation with keratinization.[7] In our case, abundant extra- and intracellular mucin was present along with the areas of squamoid differentiation. Retrospectively, we found these intracellular mucinous areas in cytology smears also. In our case, thyroiditis was present in the adjacent thyroid.

In view of tumor-sparing salivary gland and breasts, we consider it as mucoepidermoid differentiation over a collision tumor. Follicular carcinoma with extensive MEC-like differentiation is very rare. These areas can mimic metastatic epithelial malignancy. Careful evaluation of these areas is a must. Histochemistry is needed to confirm the mucinous areas. Immunohistochemistry is essential to confirm the diagnosis.

Consent for publication

Written consent for publication and any additional related information was taken from the patient involved in the study.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Cipriani NA, Nagar S, Kaplan SP, White MG, Antic T, Sadow PM, et al. Follicular thyroid carcinoma: how have histologic diagnoses changed in the last half-century and what are the prognostic implications? Thyroid 2015;25:1209-16.  Back to cited text no. 1
Rhatigan RM, Roque JL, Bucher RL. Mucoepidermoid carcinoma of the thyroid gland. Cancer 1977;39:210-4.  Back to cited text no. 2
Shindo K, Aishima S, Okido M, Ohshima A. A poor prognostic case of mucoepidermoid carcinoma of the thyroid: A case report. Case Rep Endocrinol 2012;2012:862545. doi:0.1155/2012/862545.  Back to cited text no. 3
Le QV, Ngo DQ, Ngo QX. Primary mucoepidermoid carcinoma of the thyroid: A report of a rare case with bone metastasis and review of the literature. Case Rep Oncol 2019;12:248-59.  Back to cited text no. 4
Boahene DK, Olsen KD, Lewis JE, Pinheiro AD, Pankratz VS, Bagniewski SM. Mucoepidermoid carcinoma of the parotid gland: The Mayo clinic experience. Arch Otolaryngol Head Neck Surg 2004;130:849-56.  Back to cited text no. 5
Obidike S, Aftab F. Rare case of mucoepidermoid carcinoma of the thyroid gland. J Thyroid Disord Ther 2016;5:1-2.  Back to cited text no. 6
Taconet S, Bosq J, Hartl D, Schlumberger M, Leboulleux S, Scoazec JY, et al. Composite mucoepidermoid carcinoma and columnar cell variant of papillary carcinoma of the thyroid: A case report and review of the literature. Int J Surg Pathol 2016;24:336-40.  Back to cited text no. 7
Cameselle-Teijerio J, Weing B, Sobringho-Simmoes M, Albores-Saavedra J. Mucoepidermoid Carcinoma. In: Lloyd RV, Osamura RY, Klöppel G, Rosai J, editors. Pathology & Genetics. Tumors of Endocrine Organs. World Health Organization Classification of Tumors. Vol. 4. Lyon, France: IARC Press; 2017. p. 111-12.  Back to cited text no. 8
Prichard RS, Lee JC, Gill AJ, Sywak MS, Fingleton L, Robinson BG, et al. Mucoepidermoid carcinoma of the thyroid: A report of three cases and postulated histogenesis. Thyroid 2012;22:205-9.  Back to cited text no. 9


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