Introduction

Collision tumors are two histologically distinct malignancies with dissimilar cellular or histological features and genetic origins within the same organ often separated by some amount of normal tissues. Collision tumors are extremely rare, with occasional case reports in the colon, lungs, ovaries, liver, stomach, and kidneys. Such collision combinations described in literature are mainly the co-occurring medullary thyroid carcinoma(MTC) and papillary thyroid carcinoma(PTC), follicular thyroid carcinoma(FTC) and papillary thyroid carcinoma and few cases of squamous cell carcinoma with papillary thyroid carcinomas.(1-4)

Case Presentation:

A 54 year old female reported to the outpatient department with a slow growing painless swelling on neck discerned for the last 20 years, which was initially a small asymptomatic swelling increased to present size by time. There was no family or medical history relatable to this condition and neither any history of trauma. Patient was well built and nourished with healthy mental orientation but with comorbidities of hyperthyroidism and hypertension and was under medication for the same. On clinical examination a soft and diffuse enlarged swelling of size 12x10 cm was identified over thyroid. There was no signs of dysphagia and dyspnoea. Endoscopic examination of the upper aerodigestive tract were normal with mobile vocal cords.

On imaging with ultrasound sonography neck, four nodules were identified distributed two in each lobes of thyroid. The left lobe showed a Thyroid Imaging Reporting and Data System (TIRADS) III nodule measuring 4.2x3.5 cm in the lower pole and a TIRADS IV nodule measuring 2.4x2 cm in the upper pole. The right lobe showed a TIRADS III nodule measuring 2.5x2 cm in upper pole and a TIRADS II nodule measuring 2.1x2.9 cm in lower pole. On CECT neck, a heterogenous enhancing lesion was identified on bilateral neck reaching up to skull base right side pushing carotid and internal jugular vein laterally with no evident tracheal invasion (Figure 1).

Figure 1: Photo radiograph showing CECT image of thyroid gland.

The Fine Needle Aspiration Cytology (FNAC) smears submitted by the patient on review showed a cellular smear with monolayered sheets of follicular cells. Few clusters of cells presented pleomorphic bizarre looking cells having hyperchromatic nuclei and irregular nuclear contours suggested a Bethesda III category - Atypia of undetermined significance (The Bethesda system of reporting thyroid cytopathology) warranting a repeated FNAC. The repeated FNAC from left lobe suggested a Bethesda V - Suspicious of Malignancy and right lobe suggested a Bethesda VI- Malignant thyroid neoplasm. Total thyroidectomy with central compartment nodal clearance was done and specimen was sent for final histopathological examination.

Surgical Pathology

Gross examination:

The total thyroidectomy specimen measured 16x10x4 cm, weighing 220gms. The right lobe measured 8x5x4 cm. Serial sectioning of the right lobe showed a tan coloured nodule measuring 5.5x4.7x3 cm on the upper pole denoted as tumor I. Another grey white nodule identified on the right lobe measuring 2.5x2x1.5 cm extending from the isthmus to the lower pole denoted as tumor II. The left lobe measured 8.5x6.5x3 cm. Serial sectioning of the left lobe showed a grey white lesion with infiltrative borders measuring 7.5x5.5x5 cm involving the upper and middle poles of left lobe denoted as tumor III. The lower pole of left lobe showed a grey brown, nodular lesion measuring 1.5x1.2x0.5 cm denoted as tumor IV. The isthmus measured 5x3x1cm and on sectioning showed a circumscribed grey tan nodule measuring 1.6x1.6x1cm denoted as tumor V. The external surface of the thyroid was inked and representative sections from each lesion were submitted (Figure 2).

Figure 2: Photograph showing the gross specimen of thyroid gland

Microscopic examination:

Tumor I: Site Right lobe - Upper pole, Size: 5.5x4.7x3 cm. Multiple sections examined displayed an encapsulated or well circumscribed follicular patterned thyroid neoplasm with areas of questionable capsular invasion. Focally the tumor cells showed partially developed nuclear features of papillary thyroid carcinoma in the form of nucleomegaly, nuclear grooving and chromatin clearing. A focus suspicious of capsular invasion is noted but no lympho-vascular invasion or extra thyroid extension seen. (Figure 3 A,B). A diagnosis of Well-Differentiated Tumour of Uncertain Malignant Potential (WDT-UMP) was made from the sections studied.

Figure 3: Photomicrograph showing histopathology of all five tumors. 3A,B: Well-Differentiated Tumour of Uncertain Malignant Potential (WDT-UMP) showing partially developed nuclear features of papillary thyroid carcinoma (black arrow head) (H&E,40X,400X). 3C,D: Papillary thyroid carcinoma-Classic Variant ,showing features of classical papillary thyroid carcinoma in form of nucleomegaly, nuclear overlapping ,nuclear grooving and chromatin clearing (black arrow head) (H&E 40X,400X). 3E,F: Primary Squamous cell carcinoma(black arrow head) along with adjacent follicular variant of Papillary Thyroid Carcinoma(black arrow head) showing squamous differentiation with vesicular nuclei and prominent nucleoli(H&E 40X,400X). 3G,H:Follicular variant of Papillary Thyroid Carcinoma showing micro as well as macro follicles with nuclear features of conventional papillary thyroid carcinoma(black arrow head) (H&E 40X,400X).. 3I,J:Hurthle Cell Adenoma showing moderate eosinophilic granular cytoplasm with round to oval centrally located nucleus with distinct nucleoli (black arrow head) (H&E 40X,400X).

Tumor II: Site Right lobe – Lower pole, Size 2.5x2x1.5cm. Sections displayed a neoplasm arranged in papillary architecture with fibrocollagenous stalk lined by neoplastic cells. The tumor cells have moderate amount of eosinophilic cytoplasm with nucleus showing features of classical papillary thyroid carcinoma in form of nucleomegaly, nuclear overlapping, nuclear grooving and chromatin clearing. No lympho-vascular invasion and extrathyroidal extension was seen (Figure 3C,D). A diagnosis of Papillary thyroid carcinoma-Classic Variant was made from the sections studied.

Tumor III: Site Left Lobe - upper and middle pole, Size 7.5x6.5x3.5cm. Sections examined displayed an infiltrative neoplasm composed entirely of tumor cells with squamous differentiation with vesicular pleomorphic nuclei with partially condensed chromatin. Areas of keratinisation and focal calcification noted. The tumor showed multiple foci of lympho-vascular invasion. Extrathyroidal extension was not identified (Figure 3E,F). A diagnosis of Primary Squamous cell carcinoma of thyroid was made from the sections studied.

Tumor IV: Site Left lobe - lower lobe, Size 1.5x1.2x0.5 cm. Section examined showed an encapsulated neoplasm arranged in micro as well as macro follicles with nucleomegaly ,nuclear overlapping ,nuclear grooving nuclear pseudoinclusions and chromatin clearing. Focal capsular breach was seen (Figure 3G,H). A diagnosis of Follicular variant of Papillary Thyroid Carcinomawas made from the sections studied.

Tumor V: Site Isthmus, Size 1.6x1.6x1cm.Section examined showed a well encapsulated neoplasm arranged as small follicles as well as in trabeculae. The cells have moderate eosinophilic granular cytoplasm with round to oval centrally located nucleus and distinct nucleoli. No capsular or lympho-vascular invasion was seen (Figure 3I,J). A diagnosis of Follicular variant of Hurthle Cell Adenomawas made from the sections studied.

In present case the patient is under radiotherapy after surgery and is under close follow up till date.

Discussion

The term "collision tumor" refers to coexistent but independent tumors that are histologically distinct. Plauche et al reported the first case of a collision tumor of FTC and PTC in the year 2013.(1) In literature many hypothesis have been proposed for collision tumors.(1-4) The hypothesis of "chance accidental meeting" of two primary tumors suggest the concurrent occurrence of tumor by chance . Another hypothesis of “stem cell theory” proposes that these tumors arise from a single pluripotent precursor cell, while the “neoplastic coercion theory” states that the first formed tumor may alter the microenvironment which facilitate the development of the second primary tumor. The common stem cell hypothesis suggest the possibility of a common origin for the two concurrently occurring tumors. However no single hypothesis in literature could completely explain collision phenomenon.

Previous research has shown that the most common malignancy of the thyroid is papillary thyroid cancer (PTC) (80%), followed by follicular thyroid carcinoma (FTC) (10%), medullary thyroid carcinoma (MTC) (4%), Hurtle cell carcinoma (3%), and anaplastic carcinoma (2%).(1,5) As per the latest thyroid reporting guidelines by International Collaboration on Cancer Reporting (ICCR-2020) each tumor in a multiple presentation is described on basis of individual core and noncore elements . For the purposes of reporting all other pathological data, the full data set only needs to be applied to the dominant resected carcinoma of a particular lineage. The dominant tumor is defined as the most clinically relevant carcinoma because of its aggressiveness or its higher T category.(6)The present case consisted of the benign hurtle cell adenoma, the WDT-UMP and two histological variants of papillary carcinoma thyroid namely the follicular and classical. All five tumors were reported individually and the dominant tumor being the primary squamous cell carcinoma of thyroid gland. Absence of any other lesions in PET scan ruled out chance of metastatic squamous cell carcinomas to thyroid.

The primary squamous cell carcinoma (PSCC) of the thyroid gland is a rare clinical entity. In literature the origin of squamous cell carcinoma within the thyroid gland has many theories. The “embryonic-rest” theory suggests that the persistence of thyroglossal duct or remnant from a branchial pouch or the basaloid cells from the ultimobranchial body, or the thymic epithelium from the third branchial cleft can become the source of squamous cells . Few authors suggest “metaplasia” theory, in which the origin of squamous cell carcinoma is by metaplasia in a pre-existing papillary carcinoma, anaplastic carcinoma, Hashimoto's thyroiditis or other conditions.(3,4,7,8)

The dilemma in thyroid gland SCC is its differentiation between of SCC primarily arising in the thyroid versus secondary SCC metastasis. Primary squamous cancers of the thyroid are extremely rare and account for less than 1% of all thyroid neoplasms.(8) In the present case the clinical and radiological assessment ruled out the occurrence of any other primary tumors elsewhere. Hence the possibility of a metastatic tumor was eluded favouring the diagnosis of primary squamous cell carcinoma of the thyroid. 

Conclusion

Collision tumors of the thyroid are extremely rare and pose a diagnostic as well as therapeutic challenge. Treatment for collision tumors should depend upon the combination of primary tumors involved and each component of the combination should be treated like an independent primary. Till date, due to the rarity of this collision phenomenon, there is no standard management outline that can be used as a guideline for its treatment.

References

1. Abdullah AM, Qaradakhy AJ, Ahmed MM et al. Thyroid collision tumors; a case series with literature review. Annals of Medicine and Surgery. 2022 Mar 3:103444.
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3. Warman M, Lipschitz N, Ikher S, Halperin D. Collision tumor of the thyroid gland: primary squamous cell and papillary thyroid carcinoma. International Scholarly Research Notices. 2011;2011.
4. Alavi MS, Azarpira N. Medullary and papillary carcinoma of the thyroid gland occurring as a collision tumor with lymph node metastasis: A case report. Journal of Medical Case Reports. 2011 Dec;5(1):1-4.
5. Shah JP. Thyroid carcinoma: epidemiology, histology, and diagnosis. Clinical Advances in Hematology & Oncology: H&O. 2015 Apr;13(4 Suppl 4):3.
6. Ghossein R, Barletta JA, Bullock M et al. Data set for reporting carcinoma of the thyroid: Recommendations from the International Collaboration on Cancer Reporting. Human Pathology. 2021 Apr 1;110:62-72.
7. Pishdad R, Cespedes L, Boutin R, Jaloudi M, Raghuwanshi M. Coexistence of Two Different Thyroid Malignancies: A Collision Phenomenon. Cureus. 2020 Apr;12(4).
8. Mohd-Irman-Shah Ibrahim YR, Jusoh NN. Primary squamous cell carcinoma of the thyroid gland. Iranian Journal of Otorhinolaryngology. 2018 Jan;30(96):65.