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Year : 2019  |  Volume : 16  |  Issue : 3  |  Page : 137-139

Extensive squamous metaplasia in papillary carcinoma of the thyroid: A potential diagnostic pitfall

Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Submission16-Jan-2019
Date of Acceptance25-Feb-2019
Date of Web Publication18-Nov-2019

Correspondence Address:
Dr. Rajiv Kumar
Department of Pathology, Tata Memorial Hospital, Ernest Borges Marg, Parel, Mumbai - 400 012, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/trp.trp_2_19

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It is a rare event to find squamous cells in the thyroid gland. Squamous metaplasia (SM) of the thyroid follicular epithelium is one of such conditions. SM can occur in association with nonneoplastic as well as neoplastic thyroid lesions. Here, we report a case of papillary carcinoma of the thyroid in a 26-year-old female showing extensive SM. On immunohistochemistry, squamous as well as papillary carcinoma component expresses CK7 and thyroglobulin. High molecular weight cytokeratin and p63 were positive in only in the squamous area, while TTF-1 was negative in these cells. Extensive SM in the thyroid can be misinterpreted as primary or metastatic squamous cell carcinoma. Further, the tumor may be mislabeled as collision tumors of thyroid. As it might lead to therapeutic implications, the distinction of SM in thyroid is necessary.

Keywords: Collision tumor, papillary carcinoma, squamous metaplasia, thyroid

How to cite this article:
Yadav S, Kumar R, Bal M, Patil A. Extensive squamous metaplasia in papillary carcinoma of the thyroid: A potential diagnostic pitfall. Thyroid Res Pract 2019;16:137-9

How to cite this URL:
Yadav S, Kumar R, Bal M, Patil A. Extensive squamous metaplasia in papillary carcinoma of the thyroid: A potential diagnostic pitfall. Thyroid Res Pract [serial online] 2019 [cited 2022 Jun 30];16:137-9. Available from: https://www.thetrp.net/text.asp?2019/16/3/137/271151

  Introduction Top

Squamous cells in the thyroid gland are seen very rarely, and their presence is usually associated with some pathological processes.[1] Squamous metaplasia (SM) of the thyroid follicular epithelium can occasionally occur in association with nonneoplastic (like Hashimoto's thyroiditis) and neoplastic thyroid lesions, for example, papillary thyroid carcinoma (PTC).[2],[3],[4],[5],[6] It can be misinterpreted as squamous cell carcinoma (SCC) or anaplastic carcinoma, especially on fine-needle aspiration cytology (FNAC).[7] The distinction of SM in PTC from well-differentiated SCC may be difficult in limited sample. SCC tends to have more aggressive behavior compared with PTC and patients generally require postoperative radiation therapy.[8],[9] Further, collision tumors of the thyroid, although rare, yet described in the literature.[10] Therefore, awareness of this lesion will enable pathologists to avoid apprehension, when they see squamous cells within thyroid. We hereby described the histopathological features for a case of PTC with extensive SM.

  Case Report Top

A 26-year-old female, presented with complaints of midline thyroid swelling for the past 6 months. There was no history of dysphagia, odynophagia, or change in voice. Cervical lymph nodes were not enlarged. Thyroid function tests revealed hypothyroidism (T3 = 0.50 ng/ml, T4 = 0.84 ug/dl, and thyroid-stimulating hormone [TSH] >100.00 μIU/ml). Neck ultrasound revealed a nodular lesion with heterogeneous echotexture and increased vascularity measuring 2.5 cm involving the right lobe. FNAC confirmed the neoplastic nature of the lesion. With the diagnosis of PTC, the patient underwent total thyroidectomy. Grossly, thyroid gland was enlarged and a nodular lesion measuring 2 cm × 2 cm × 1.2 cm was seen involving the right lobe, abutting the inked external surface. The cut surface was homogeneous soft gray-white without areas of necrosis. Histopathological examination revealed a differentiated PTC, classical variant in conjunction with multiple foci of squamoid differentiation (SM). There was abrupt transition from papillary to squamous component, and variable-sized nests of squamous cells were seen throughout the tumor. There was no atypia in the squamous cell component. There were neither areas of fibrosis, inflammation, nor hemorrhage around these nests. On immunohistochemistry (IHC), squamous as well as papillary carcinoma component expresses CK7 and thyroglobulin (TG). High molecular weight cytokeratin (HMWCK) and p63 were positive in only in the squamous area, whereas TTF 1 was negative in these cells [Figure 1]. Hence, diagnosis of PTC with extensive SM was established. There was no lesion in adjacent other organs. Positron emission tomography-computed tomography failed to reveal any disease elsewhere. Postoperatively, the patient received radioactive iodine therapy and was doing well 10 months postsurgery.
Figure 1: Classical papillary carcinoma (single head arrow) with abrupt transition to squamoid areas (squamous metaplasia) (double head arrow) (a: H and E, ×200) and focal areas of inflammation and fibrosis around the squamous cell nests, (b: H and E, ×100). Thyroglobulin immunostaining (c: ×200) showing strong positivity in both papillary area and squamous cell area, whereas high molecular weight cytokeratin (d: ×100) was positive only in the squamous areas

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  Discussion Top

SM occurs somewhat frequently in papillary carcinoma (in particular cystic and sclerosing variant) and in inflammatory lesions (in Hashimoto's thyroiditis).[2],[3],[4],[5] In contrast, SM is rare in follicular adenomas and carcinomas.[6] Clinically, massive SM might accompanied by severe hypothyroidism as seen in the current case.

Pathogenesis of its occurrence remained unclear, and many theories were proposed for the origin of squamous cell within the thyroid gland. One theory recommended that squamous cells were derived from various embryonic remnants, such as a thyroglossal duct, thymic epithelium, and ultimobranchial remnants.[11] Another commonly accepted theory suggests that SM occurs in the follicular epithelium as a result of chronic inflammation or scarring in the thyroid gland.[3] Further, SM might be the result of previous FNAC.[7] Nevertheless, the expression of p63 protein consistently expressed in stem cells and basal cells of stratified epithelia, fits well with the theory of squamous differentiation of thyroid-undifferentiated precursor cells.[12]

SM in the thyroid revealed characteristic histopathological findings in the form of intermingled zones of the squamous cell without cytological atypia and classic papillary carcinoma. SM produced intermediate staining pattern for IHC markers between that of PTC and SCC. As noted in the present case, there was no loss of CK7 and TG expression in metaplastic cells; however, at the same time, these cells had acquired expression for p63 and HMWCK. IHC results in the present case were concordant with previous studies except for positive TG expression in SM.[3],[4],[5] IHC results in the current case support the notion that SM arises from the follicular epithelium and also advocates the fact that SM could have facilitated the development of SCC in the thyroid.[8],[9],[10]

Importance of SM lies in the possibility that it can be a potential diagnostic pitfall. Following differential diagnosis needs to consider, while one see squamous cells in malignant thyroid lesion: diffuse sclerosing papillary carcinoma (DSPC), mucoepidermoid carcinoma (MEC), and SCC either in the form of primary tumor, component of collision tumor, or metastatic carcinoma.[3],[4],[5],[8],[9],[10],[13]

DSPC is a distinctive variant of papillary carcinoma characterized by diffuse involvement of thyroid parenchyma and by the presence of numerous psammoma bodies, marked lymphocytic infiltration, and prominent stromal fibrosis. In addition, extensive SM can be seen frequently.[3] Primary MEC of the thyroid is an extremely rare tumor with mysterious histogenesis. Some authors suggest that it could be derived from PTC; however, others suggest that it may originate from remnants of the ultimobranchial bodies.[13]

Extensive SM can be misinterpreted as primary or metastatic SCC. Primary SCC of the thyroid gland is an unusual tumor with only a few reported cases.[8],[9] According to classic literature, it is thought to arise in two settings: first as a primary tumor as a component of an anaplastic or undifferentiated thyroid carcinoma and second as a component of collision tumor.[8],[9],[10] As SCC is the most common metastatic disease in the head-and-neck region, it is important to rule out infiltration of the thyroid gland from an adjacent organ and metastasis from a distant organ before labeling a lesion as SM, especially in a limited sample.

Treatment guidelines for such lesions are poorly defined due to the dearth of literature on this subject. The squamous cells have no affinity for iodine because they do not possess intracellular TSH receptors, and thus, radioactive iodine and TSH suppressive therapy have little impact on the clinical course.[9] The origins of squamous cancer in the thyroid gland must be evaluated to establish the true evolution of a collision tumor and to plan treatment accordingly.[10]

  Conclusion Top

Although uncommon, SM when occurs in thyroid gland represents an important diagnostic pitfall and challenge for the histopathologists. It is a result of stem-cell differentiation from reparative follicular epithelium toward a squamous phenotype. In view of diagnostic and therapeutic implications, it is important to distinguish papillary carcinoma with extensive metaplasia from collision tumor with SCC as the second component. Hence, a pathologist should be aware of the occurrence of SM in the thyroid gland.

Declaration of patient consent

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

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Conflicts of interest

There are no conflicts of interest.

  References Top

LiVolsi VA, Merino MJ. Squamous cells in the human thyroid gland. Am J Surg Pathol 1978;2:133-40.  Back to cited text no. 1
Magro G, Torrisi A, Ippolito O, Torrisi A, Bisceglia M. Unusual non-neoplastic lesions in the “surgical pathology” of the thyroid. Pathologica 2006;98:119-38.  Back to cited text no. 2
Ryska A, Ludvíková M, Rydlová M, Cáp J, Zalud R. Massive squamous metaplasia of the thyroid gland – Report of three cases. Pathol Res Pract 2006;202:99-106.  Back to cited text no. 3
Kunisue H, Mikami Y, Tanaka K, Sonoo H, Udagawa K, Yamamoto Y, et al. Metastatic papillary thyroid carcinoma of the submandibular lymph nodes with extensive squamous metaplasia: Report of a case. Surg Today 2003;33:751-4.  Back to cited text no. 4
Gomi K, Kitagawa N, Usui Y, Tanaka M, Yoshida M, Hirata Y, et al. Papillary carcinoma with extensive squamous metaplasia arising from thyroglossal duct cyst in an 11-year-old girl: Significance of differentiation from squamous cell carcinoma: A case report. J Pediatr Surg 2011;46:e1-4.  Back to cited text no. 5
Bai Y, Mori I, Liu Z, Li Y, Ozaki T, Taniguchi E, et al. Squamous cell components in a thyroid follicular adenoma: Significant evidence of follicular cell origin by histomorphological, immunohistochemical and molecular analyses. Pathol Int 2011;61:577-81.  Back to cited text no. 6
Pellicer DL, Sadow PM, Stephen A, Faquin WC. Atypical squamous metaplasia in a benign cystic thyroid nodule mimicking high-grade carcinoma. Diagn Cytopathol 2013;41:706-9.  Back to cited text no. 7
Tunio MA, Al Asiri M, Fagih M, Akasha R. Primary squamous cell carcinoma of thyroid: A case report and review of literature. Head Neck Oncol 2012;4:8.  Back to cited text no. 8
Lam KY, Lo CY, Liu MC. Primary squamous cell carcinoma of the thyroid gland: An entity with aggressive clinical behaviour and distinctive cytokeratin expression profiles. Histopathology 2001;39:279-86.  Back to cited text no. 9
Eom TI, Koo BY, Kim BS, Kang KH, Jung SK, Jun SY, et al. Coexistence of primary squamous cell carcinoma of thyroid with classic papillary thyroid carcinoma. Pathol Int 2008;58:797-800.  Back to cited text no. 10
Bellevicine C, Ippolito S, Arpaia D, Ciancia G, Pettinato G, Troncone G, et al. Ultimobranchial body remnants (solid cell nests) as a pitfall in thyroid pathology. J Clin Endocrinol Metab 2012;97:2209-10.  Back to cited text no. 11
Burstein DE, Nagi C, Wang BY, Unger P. Immunohistochemical detection of p53 homolog p63 in solid cell nests, papillary thyroid carcinoma, and Hashimoto's thyroiditis: A stem cell hypothesis of papillary carcinoma oncogenesis. Hum Pathol 2004;35:465-73.  Back to cited text no. 12
Wenig BM, Adair CF, Heffess CS. Primary mucoepidermoid carcinoma of the thyroid gland: A report of six cases and a review of the literature of a follicular epithelial-derived tumor. Hum Pathol 1995;26:1099-108.  Back to cited text no. 13


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