A Case Report of Metastatic Primary Thyroid Sarcoma Evaluated by ¹⁸F-FDG PET/CT

Introduction

Thyroid cancer is the most common endocrine malignancy.[123] Most common subtypes consist of papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, and anaplastic thyroid cancer (ATC).[3] Rare subtypes include primary thyroid lymphoma (PTL) and sarcomas.[456] Thyroid sarcomas are tumors that arise from transformed cells of mesenchymal origin, which could be primary in origin or metastatic. Primary thyroid sarcoma (PTS) is very rare with reported frequency ranging from 0.01% to 1.5%.[478] This scarcity presents challenges in terms of diagnosis, as clinical experience in imaging and histopathology in such cases is limited.

Thyroid sarcoma carries poor prognosis and the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) has been implicated in ruling out metastatic disease at initial staging or follow-up. The present report adds a new case to the literature on sarcomas of the thyroid gland, with an emphasis of differential diagnosis of spindle cell lesions of thyroid and the role of immunohistochemistry (IHC) and PET/CT.

Case Report

We report the case of a 49-year-old male, after obtaining written consent, who presented with a rapidly progressive anterior neck swelling accompanied by hoarseness of voice and dysphagia. There was no history of previous comorbidities or known addictions.

The patient had an Eastern Cooperative Oncology Group performance status of 1. Neck examination revealed a large irregular, firm, and tender mass in the midline, extending on to the left side [Figure 1a]. Contralateral displacement of the trachea was noted. Cervical lymph nodes were palpable on both sides. Hopkins examination revealed a submucosal bulge in the left pharyngeal wall, pushing the left true vocal cord [Figure 1b]. Contrast-enhanced computed tomography of the neck showed a mass arising from the left lobe of the thyroid, displaying small microcalcifications and enlarged cervical lymph nodes.

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Figure 1 (a) Clinical examination showing a large irregular mass over anterior neck extending onto the left side of neck causing contour bulge. (b) Hopkins endoscopy showing submucosal bulge in left pharyngeal wall pushing left true vocal cord

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Core needle biopsy from the left lobe of the thyroid [Figure 2] showed fibro collagenous tissue with the presence of tumor cells of spindle cell morphology arranged in sheet and short fascicle nuclei and inconspicuous nucleoli suggestive of high-grade spindle cell neoplasm of smooth cell differentiation. IHC showed positivity with vimentin and smooth muscle antigen (SMA) and negativity for desmin, thyroid transcription factor (TTF-1), leukocyte common antigen (LCA), and S-100. A high Ki 67% index of 50%–60% was noted in most proliferative areas [Figure 3].

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Figure 2 H and E (a: ×4 and b: ×40)-Fibrocollagenous tissue showing presence of tumor cells of spindle cell morphology arranged in sheets and fascicles. Adjacent fibromuscular tissue also identified

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Figure 3 Immunohistochemistry images showing (a) Vimentin diffuse positive, (b) Desmin negative, (c) smooth muscle antigen-focal positive, (d) p53 -mutant staining pattern, (e) Ki67 index - 50%–60% in most proliferative areas, (f) S-100 negative, (g) leucocyte common antigen - negative, (h) thyroid transcription factor - negative

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¹⁸F-FDG PET/CT imaging [Figure 4] unveiled a FDG avid mass lesion in the left lobe of the thyroid. The lesion exhibited anterior extension to the subcutaneous plane, posterior proximity to the prevertebral fascia, lateral displacement of the carotid artery, and medial crossing of the midline with tracheal and esophageal displacement. Superiorly, it reached the level of the hyoid bone, and inferiorly, it extended to the sternum. Craniocaudally, the lesion was extending from the second cervical vertebra to the first dorsal vertebra. Multiple FDG-avid bilateral cervical lymph nodes were detected, and multiple FDG-avid nodules of varying sizes were observed in both lung fields.

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Figure 4 (a) ¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) Maximum intensity projection showing abnormal uptake in the neck region and multiple focal lesions in bilateral lung fields. (b) Fused PET/CT image showing ¹⁸F FDG avid mass lesion in thyroid gland. (c) FDG avid prevertebral lymph node at DV2 and left level II lymph node (blue arrow). (d) FDG avid right hilar lymph node (white arrow) and nodules in bilateral lung fields (e) Multiple FDG-avid nodules in both lung fields in lower lobes. MIP: Maximum intensity projection image

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The comprehensive imaging findings depict an intricate and extensive involvement of the thyroid gland, lymph nodes, and lungs, confirming the advanced nature of the disease. Before the initiation of any therapeutic intervention, the patient experienced a progressive decline in clinical status over few months and ultimately succumbed to the illness.

Discussion

Thyroid cancer encompasses a range of subtypes, with ATC, PTL, and PTS being rare forms. The incidence of PTS is around 0.01% to 1.5%.[78] In a systematic review by Surov et al., it was reported that the most common subtype of PTS was angiosarcoma (20.4%), followed by malignant hemangioendothelioma (16.3%), malignant fibrous histiocytoma (14.1%), leiomyosarcoma (11.3%), and fibrosarcoma (9.2%).[4] Latter entities, leiomyosarcoma and fibrosarcoma are tumors arising from smooth muscle cells and fibroblasts, respectively. Both fall under the umbrella of spindle cell sarcomas of the thyroid and are typically aggressive and can metastasize easily.

Spindle cell lesions of the thyroid encompass a variety of conditions characterized by the presence of elongated, spindle-shaped cells. These can be benign or malignant and may arise from reactive or neoplastic process. These tumors can be classified as either primary, arising directly in the thyroid, or metastatic, where the spindle cell morphology reflects a spread from another site. The differential diagnosis of spindle cell lesions of the thyroid is indeed broad and includes several entities, each with distinct histopathological features. It includes anaplastic carcinoma, medullary carcinoma, Reidel’s thyroiditis, intrathyroidal thymoma, metaplastic spindle cell proliferation associated with follicular cell-derived tumors, teratoma of the thyroid, synovial sarcoma, postfine needle aspiration spindle cell nodules of the thyroid, spindle epithelial tumor with thymus like differentiation, and carcinoma showing thymus like differentiation.[9] Each condition has different implications for management and prognosis, making precise diagnosis essential. In our case, IHC showed positivity with vimentin and SMA, pointing toward sarcoma with smooth muscle differentiation. However, it was negative for desmin, making a probable diagnosis of undifferentiated pleomorphic sarcoma or fibrosarcoma and leiomyosarcoma less likely. IHC further showed negativity for TTF-1, LCA, and S-100, ruling out thyroid carcinoma, lymphoma, and malignant peripheral nerve sheath tumor. A high Ki 67% index of 50%–60% was noted in most proliferative areas, making it high-grade neoplasm.[10] Based on this, a diagnosis of high-grade malignant spindle cell sarcoma of thyroid was confirmed and other differentials were ruled out.

Thyroid sarcomas exhibit a predilection for females, predominantly affecting elderly population above the mean age of 65 years, although the etiology for the same remains unknown. The most common clinical presentation is palpable neck mass with or without compressive symptoms.[411] In our report, the patient was a relatively young male who presented with palpable neck mass having compressive symptoms.

The scarcity of data on the metastatic patterns of spindle cell sarcoma of the thyroid highlights the importance of advanced imaging techniques like whole body ¹⁸F-FDG PET/CT. ¹⁸F-FDG is the most commonly used PET tracer in oncology. However, the role of ¹⁸F-FDG PET/CT is limited only to postoperative cases of differentiated thyroid cancers with high serum thyroglobulin and negative 131-Iodine diagnostic whole-body scan as a prognostic marker.[1213] Furthermore, increased tumor FDG uptake has been noted in aggressive pathologies such as anaplastic carcinoma, Hurthle cell carcinoma, thyroid lymphoma, and sarcomas.[14] In addition to the local disease and metastatic sites, the metabolic activity indicated by FDG uptake can help assess the aggressiveness of the tumor.[1415] In our case, the staging PET/CT scan revealed high-grade disease with nodal metastases and distant lung metastases. ¹⁸F-FDG PET/CT provided a comprehensive view of the disease extent, helping to determine the best therapeutic approach and prognosis.

Treatment of PTS is challenging due to its rarity, lack of well-established guidelines, and typically poor prognosis. Management usually requires a multimodal approach involving surgery, radiation therapy, and sometimes chemotherapy. The first-line of treatment is surgery with total thyroidectomy and possible lymph node dissection. Radiation therapy is given as an adjunct to surgery if postoperative margins are positive or surgical resection is incomplete or preoperatively if tumor is unresectable due to location, size, or local invasiveness. Chemotherapy is generally considered for more aggressive sarcomas, especially in cases where the tumor is metastatic or cannot be completely resected. However, chemotherapy for PTS is often of limited benefit, and the specific chemotherapeutic regimens are not well-established for this disease.[161718] In our case, the patient succumbed to his illness before initiation of any therapy.

In conclusion, the presented case report of a 49-year-old male diagnosed with high-grade sarcoma underscores the valuable role of IHC for accurate diagnosis and ¹⁸F-FDG PET/CT in staging this rare manifestation. The findings from the imaging not only facilitate the delineation of the extent of the thyroid sarcoma but also contribute significantly to a comprehensive understanding of its metabolic activity and the potential for metastatic spread. Given the rarity of these sarcomas within the broader landscape of thyroid neoplasms, diagnosing and managing such cases present unique challenges.