Dedifferentiated Squamous Cell Carcinoma Components in Poorly Differentiated Thyroid Carcinoma

Global Journal of Pathology & Laboratory Medicine
Volume 1, Issue 2, April 2021, Pages: 50-58
Received: September 16, 2021; Reviewed: September 17, 2021; Accepted: September 20, 2021; Published: October 05, 2021

Unified Citation Journals, Pathology 2021, 1(2) 1-08;
ISSN 2754-0952

Authors: Dr. Banan Alkhanbishi 1, Dr. Doaa Al Ghamdi 2File:ORCID iD.svg - Wikimedia Commons

  1. Department of Anatomic Pathology and Laboratory Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
  2. Department of Anatomic Pathology and Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
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Keywords: Thyroid Gland, Poorly Differentiated Thyroid Carcinoma, Dedifferentiated Squamous Cell Carcinoma

1. Abstract:
Primary squamous cell carcinoma (PSCC) of the thyroid is a rare type of tumor. These tumors can be pure squamous cell carcinoma (SCC) or associated with other well-differentiated thyroid carcinoma variants. Since 2004, the World Health Organization has classified thyroid PSCC as a discrete thyroid gland tumor. Thyroid SCC is considered an aggressive malignant tumor if it originates from the thyroid. According to the available medical literature, most described cases of SCC involve dedifferentiated components of well-differentiated thyroid carcinoma. The presence of dedifferentiated SCC components with poorly differentiated thyroid carcinoma (PDTC) is unusual. There are no reported cases of PDTC with pure dedifferentiated SCC components in the medical, scientific English-language literature. We described the first case of PDTC with dedifferentiated SCC components in the left thyroid gland mass in a young female patient. The diagnosis of PDTC with dedifferentiated SCC was established through histopathological examination of hemithyroidectomy specimen slides received from a referral/consultation hospital together with ancillary studies. Later, the patient underwent a completion thyroidectomy. Immunohistochemistry showed positivity for markers of squamous components, supporting the presence of dedifferentiated thyroid SCC. Therefore, the significance of SCC components with PDTC is uncertain with disease progression to undifferentiated anaplastic thyroid carcinomas. We have highlighted differences in histological and biological features according to the overexpression of p53 and increase in proliferative index.

2. Introduction:
Squamous cell carcinomas (SCCs) associated with other thyroid carcinomas, such as papillary thyroid carcinoma and anaplastic carcinoma, have been reported in only 117 cases in the medical literature, 95% of which involved papillary thyroid carcinoma and 5% of which involved follicular thyroid carcinoma [1, 2].

When SCC components appear with another thyroid carcinoma, the clinical prognosis worsens [2]. SCC can coexist with anaplastic thyroid carcinoma, in which case, the World Health Organization (WHO) defines it as anaplastic carcinoma with squamous differentiation [2]. The presence of SCC with PDTC has not been previously reported. We describe the first case of PDTC with dedifferentiated SCC in a young woman diagnosed through histopathological examination and immune profiling for both neoplastic cell components.

3. Case Presentation
Patient Information
A 29-year-old woman, without any known medical illnesses, presented with a left-sided thyroid nodule and was referred to King Abdulaziz University Hospital. She had undergone a left hemithyroidectomy in another institution. A macroscopic examination at another institution revealed a capsulated nodule measuring 3.0 × 2.0 × 1 cm, which was preliminarily diagnosed as mucoepidermoid carcinoma. The specimen was sent to our institution for a second evaluation. We received seven paraffin blocks and seven hematoxylin-eosin (H&E) stained slides along with a histopathology report.

Clinical Findings
The patient presented to us 6 weeks post hemithyroidectomy with good general health. The vital signs were within the normal range, and the neck scar was clean.

Diagnostic Assessment
Computed tomography of the neck, performed in our hospital, revealed slightly enhanced signal intensity at the thyroid gland bed; however, this finding could indicate an operative change. The right thyroid lobe was unremarkable, with no lymphadenopathy or definite evidence of residual or recurrent masses.

The thyroid gland measured 4.0 × 3.0 × 2.0 cm, as per the received histopathological report, and showed a well-circumscribed, gray-white solid mass measuring 3.0 × 2 × 2 cm. Microscopic examination of the tumor revealed sections that were well-delineated, partially capsulated, and focally invasive. The solid architecture was predominant, and the tumor was mainly composed of uniform round cells; however, there was a central area of cystic degeneration with hemorrhage and inflammation. There was an area of squamous differentiation showing nuclear atypia (Figure 1A, 1B). Focal follicles were seen in the tumor, and the colloid had a peculiar bluish tinge, but it clearly constituted colloid (rather than myxoid) materials as it showed peripheral scalloping (Figure 1C). Focal myxoid stroma was also seen in the infiltrating areas of the tumor. The tumor cells showed striking nuclear atypia, mitosis (6 mitoses/10 high-power fields [HPF]), and single-cell tumor necrosis. There was no geographic tumor necrosis, although vascular invasion was identified.

(A): An encapsulated, solid, poorly differentiated thyroid carcinoma (H&E, 4× original magnification)           (B): Tumor with an area of squamous components (red circle) (H&E, 4× original magnification)

(A): An encapsulated, solid, poorly differentiated thyroid carcinoma (H&E, 4× original magnification)
(B): Tumor with an area of squamous components (red circle) (H&E, 4× original magnification)

Colloid with peripheral scalloping (black arrow) (H&E, 10× original magnification)          Immunohistochemistry stains: Positivity for TTF1 and PAX8 (10x) in the solid, poorly differentiated part (blue irregular circle) and squamous area (red irregular circle

(C): Colloid with peripheral scalloping (black arrow) (H&E, 10× original magnification)

Immunohistochemistry stains: Positivity for TTF1 and PAX8 (10x) in the solid, poorly differentiated part (blue irregular circle) and squamous area (red irregular circle        Immunohistochemistry stain: Positivity for CK5/6 (10x) in the squamous component (red irregular circle), and negativity for CK5/6 in the area with the poorly differentiated thyroid carcinoma component (blue irregular circle)

(D, E): Immunohistochemistry stains: Positivity for TTF1 and PAX8 (10x) in the solid, poorly differentiated part (blue irregular circle) and squamous area (red irregular circle)
(F): Immunohistochemistry stain: Positivity for CK5/6 (10x) in the squamous component (red irregular circle), and negativity for CK5/6 in the area with the poorly differentiated thyroid carcinoma component (blue irregular circle)

(G): Immunohistochemistry stain: P53 (20x) overexpression in the squamous components.

(G): Immunohistochemistry stain: P53 (20x) overexpression in the squamous components.

A panel of immunohistochemical markers was used; the tumor exhibited variable nuclear positivity for PAX8 (monoclonal) and diffuse TTF1 reactivity (Figure 1D, 1E), as well as focal staining for thyroglobulin. The tumor expressed CK7. The squamous components showed positive staining for p63 and CK5/6 (Figure 1F). There was reduced BCL2 staining compared to that in the normal thyroid tissue, and E-cadherin was displaced from the membranes to the cytoplasm in some areas. Staining for GATA3 and S100 was performed, revealing only inflammatory cells and scattered cells in the squamous components. The rest of the tumor was negative for GATA3 and S100. The squamous component showed overexpression of p53 (Figure 1G). The tumor was negative for SMA, CD99, M-CEA, chromogranin, calcitonin, CD5, CD117, and nuclear beta-catenin. Both the classic morphology and immunohistochemical profile supported the diagnosis of PDTC with dedifferentiated SCC.

Therapeutic Intervention
The patient underwent a completion thyroidectomy. The lobe was oval, measuring 3.1 × 2.3 × 2 cm, and the cut sections revealed a homogenous brown surface without well-defined lesions. The entire lobe was submitted for microscopic examination, revealing palpation thyroiditis without a residual invasive tumor. After completion of thyroidectomy, 30 mCi of I-131 radioactive iodine therapy (RAI) was administered.

Follow-up and Outcomes
Presently, the patient has been followed up for 16 months and is in relatively good health, with no evidence of local or distant metastasis.

4. Discussion:
SCC of the thyroid can present as a primary tumor or a component of another thyroid carcinoma. Primary squamous cell carcinoma (PSCC) is defined by the WHO (as of 2017) as having exclusively squamous elements with no other carcinomas [3].
SCC has reportedly been associated in the literature with well-differentiated thyroid carcinoma [4, 5, 6, 7, 8]. Of the 117 cases found in the medical literature, 112 included papillary thyroid carcinoma (50% of these cases involved tall cell variants), and five involved follicular carcinomas. Among these 117 cases, 49 involved co-existing anaplastic thyroid carcinoma [2]. Poorly differentiated carcinoma with dedifferentiated SCC components, like that in our case, has not been previously reported.
SCC is poorly understood, as the thyroid typically lacks squamous epithelium. There are three theories to explain the pathophysiology. First, the embryonic nest theory postulates the origin of squamous cells from the thyroglossal duct remnants or the thymus’s epithelium. Second, the metaplasia theory suggests that these cells can be present due to environmental stimuli (inflammation and Hashimoto’s thyroiditis). Third, the dedifferentiation theory suggests that existing papillary, follicular, medullary, and anaplastic thyroid carcinoma cells dedifferentiate into SCC cells [9,10].
The dedifferentiated squamous component of thyroid carcinoma can metastasize to different sites, making it challenging to distinguish it from the PSCC of that site. Immunohistochemical features are very important for differentiating between primary and metastatic SCC. Most reported cases to show that positivity for TTF1, PAX8, BRAF, thyroglobulin, the squamous marker p63, and CK5/6 supports the diagnosis of primary thyroid SCC [11,12,13]. The current case involved diffuse positivity for TTF1 and PAX8, which confirmed the primary origin in the thyroid. Squamous differentiation is confirmed by positivity for CK5/6 and p63.
In the current case, p53 overexpression was absent in the poorly differentiated area and present in the dedifferentiated SCC component, similar to that in reported cases of anaplastic thyroid carcinoma and primary thyroid SCC [2].
Notably, the differential diagnosis of PSCC must include carcinoma showing thymus-like elements (CASTLE) of the thyroid gland, mucoepidermoid carcinoma of the salivary gland, anaplastic thyroid carcinoma, and metastasis or direct extension from adjacent upper aerodigestive organs. The presence of squamous components with PDTC in the background and PAX8 positivity support the diagnosis of dedifferentiated components rather than metastasis. Anaplastic thyroid carcinoma usually has different histological patterns than the sarcomatoid, giant cell, and epithelioid cell carcinomas, with some squamous differentiation. No previous cases have been reported involving only anaplastic squamous components.
CASTLE is the other differential diagnosis, as a tumor in the ectopic thymic tissue can become malignant if it constitutes a solid tumor with foci of squamous differentiation. CASTLE usually shows positive CD5 immunostaining, but this did not apply to our case as solid or squamous components were negative for CD5.
Mucoepidermoid carcinoma of the thyroid is a very rare neoplasm, characterized histologically by a combination of mucocytes, epidermoid cysts, and squamous cells; this histological profile also does not fit our case. Furthermore, myxoid areas were absent as per mucicarmine staining.
The significant presence of SCC and the increased proliferative index (Ki-67 index) are hints to dedifferentiation and changes in thyroid cancer behavior, as p53 is overexpressed in squamous cells. Most reported cases had shown an aggressive nature and behavior close to that of anaplastic cancer in the context of clinical aggressiveness and metastatic potential. Ito et al. investigated 10 patients with PTC-SCC who underwent locally curative resection, indicating potential long-term survivors. Of the 10 patients, 7 patients survived for 8–43 months. Two patients with only focal SCC lesions who did not show distant metastasis at diagnosis survived without any further recurrence for 14 and 43 months after diagnosis. They received no adjuvant therapies [14]. In our case, the squamous portion accounted for <10% of the tumor size, and the tumor was limited to the thyroid with no extrathyroidal extension. At the 9-month follow-up after completion of thyroidectomy and RAI, the patient showed no signs of disease recurrence.
In conclusion, the presence of SCC components in thyroid carcinoma is a very rare finding. It can represent a primary tumor or secondary metastasis or extension from adjacent structures. The association of SCC with other thyroid carcinomas is a hint for behavioral changes with respect to tumorigenesis. Careful histopathological examination for features defining the aggressive behavior of thyroid carcinoma is important that can be affect patient management plan and response to the treatment.

Data Availability
Not applicable

Conflicts of Interests
The authors declare that there is no conflict of interest regarding the publication of this article.

Funding Statement
The authors received no financial support for the research, authorship, and/or publication of this article.

We would like to thank Editage ( for English language editing.


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To citation of this article: Dr. Banan Alkhanbishi, Dr. Doaa Al Ghamdi, Dedifferentiated Squamous Cell Carcinoma Components in Poorly Differentiated Thyroid Carcinoma, Global Journal of Pathology & Laboratory Medicine

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Dr. Doaa Alghamdi

Department of Anatomic Pathology and Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia

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