Anaplastic Thyroid Carcinoma: The Great Masquerader

Abstract

Anaplastic thyroid carcinoma (ATC) has been regarded as the rarest form of thyroid malignancy, which entails around 2% of thyroid malignancies. It traditionally presents with rapidly enlarging anterior neck swelling with obstructive symptoms. Due to its rich blood supply and lymphatic drainage, the thyroid gland is resistant to infection. Parallel to that, the presentation of thyroid abscess frequently points towards an underlying upper respiratory tract infection. We present a case involving an elderly female presenting with a thyroid abscess, which later turned out to be ATC following a histopathological diagnosis of the thyroid gland. The initial cytology workout was negative for malignancy. We highlight the relatively uncommon presentation along with its management.

Introduction

The prevalence of thyroid abscesses has been reported to be less than 1% of all thyroid-related pathologies [1]. Immunocompromised patients and children with congenital abnormalities are found to be susceptible to thyroid abscesses. Nonetheless, it is worth noting that long-standing thyroid goitre and thyroid malignancy have also been strongly associated with an increased risk of developing thyroid abscess ². Moreover, cases involving papillary thyroid carcinoma (PTC) presenting with suppurative thyroiditis or thyroid abscess have been reported [2]. ATC is an aggressive malignancy that constitutes less than 2% of all thyroid carcinomas [3]. ATC is a highly malignant tumour composed of undifferentiated cells that do not resemble typical thyroid cells, often delaying diagnosis. Although the exact origin of ATC remains unknown, it is hypothesised to arise from the terminal dedifferentiation of pre-existing thyroid follicular cell carcinomas [3]. ATC typically presents as an aggressive thyroid growth accompanied by constitutional or obstructive symptoms. To date, only two cases have been found in patients with ATC presenting with thyroid and neck space abscesses [3].

Case Report

An elderly lady with underlying diabetes mellitus, hypertension and dyslipidemia presented with a persistent cough for two weeks, marked weight loss and enlarged goitre. According to the patient, the anterior neck swelling slowly increased in size with no association with dysphagia, dysphonia, odynophagia or noisy breathing. As for the cough, it was non-productive, with no episodes of shortness of breath or haemoptysis. The patient was unsure of the triggering factor before the cough. The patient denies any obstructive or B-symptoms. In addition, the patient denies any signs and symptoms of hypo or hyperthyroidism. No sick contacts or similar complaints among family members were identified. There was also no association with recurrent nasal or ear symptoms.

Upon examination, the patient appears comfortable under room air with no noisy breathing audible. Bedside ear, nose and throat examinations were unremarkable. The neck examination revealed anterior neck swelling measuring 6 × 8 cm, which was firm with no punctum or skin changes and was not fixed to the underlying structures. The mass appears to move with deglutition.

Laboratory investigations were suggestive of an infective blood picture with elevated white cell count and high Erythrocyte Sedimentation Rate (ESR). Thyroid function test, viral screening, and Mycobacterium Tuberculosis Immunoglobulin G (MTB IgG) were not detected. Computed Tomography (CT) of the neck and upper thorax revealed an enlarged thyroid gland with no clear demarcation with the strap neck muscles. Fine needle aspiration cytology (FNAC) was negative for malignancy. The patient was treated for acute thyroiditis and given antibiotics with a follow-up.

One month later, the patient presented with rapidly increasing anterior neck swelling with no obstructive symptoms. A neck examination revealed a fluctuant anterior neck swelling. Needle aspiration revealed 20 cc thick pus, and the FNAC report showed features of an abscess. Smear Acid Fast Bacilli (AFB) stain was negative, the pus culture was negative, and there was no growth on the AFB culture. The patient was admitted and treated with intravenous Unasyn (Ampicillin and Sulbactam) and oral Levofloxacin. Repeated CT neck showed a bilaterally enlarged thyroid gland with multiple hypodense nodules, with some of the nodules showing calcification, which is consistent with multinodular goitre (Fig. 1). There was also a large lobulated hypodense lesion at the left thyroid lobe consistent with thyroid abscess causing deviation of the trachea to the right side.

Fig. 1.

CT large lobulated lesion at left thyroid

The patient was later planned for total thyroidectomy following recovery from the acute infection.

Intraoperatively, the left lower pole of the thyroid gland was adherent to the overlying strap muscle and posteriorly to the trachea and anterior surface of the oesophageal serosa layer. In addition, there was pus mixed with caseating necrotising tissues (Fig. 2). Following tumour debulking and selective neck dissection at level VI, tracheostomy was performed electively.

Fig. 2.

Bilateral resected thyroid gland

Histopathological examination revealed undifferentiated (anaplastic) thyroid cells with a background of nodular hyperplasia with cystic degeneration suggestive of ATC (Fig. 3). Unfortunately, the patient developed septic shock secondary to hospital-acquired pneumonia post-surgery, and she passed away.

Fig. 3.

HPE showing squamous differentiation

Discussion

ATC is a rare thyroid malignancy which usually affects elderly patients, typically over 60 years [3]. A female preponderance of ATC has been widely reported [3]. ATC has been associated with an aggressive nature with characteristic rapid local invasion and metastatic spread. Traditionally, patients with ATC present with a rapidly enlarging mass at the anterior neck, which is accompanied by compression symptoms such as dysphagia or dyspnoea. In addition to that, ATC typically presents at an advanced stage and has a poor prognosis. Despite intensive treatment, patients usually die within 6–24 months after diagnosis [4]. ATC presenting as a thyroid abscess is rare; to date, only two similar are found in the literature. In this case report, our patient presented with a persistent cough for two weeks, marked weight loss and enlarged goitre with fluctuant anterior neck swelling. Inflammatory markers were elevated, and a large hypodense lesion at the left lower thyroid lobe in the CT scan mimicked a thyroid abscess and masked the underlying primary thyroid tumour. Needle aspiration revealed 20 cc thick pus, and the FNAC report showed features of an abscess. The diagnosis of ATC was suspected intraoperatively and only confirmed after surgery based on the histopathological report.

Early diagnosis is important as ATC follows this entity’s rapid and aggressive nature. Moreover, most patients typically present at an advanced stage of the disease, resulting in significant morbidity and mortality. Diagnosis of ATC can be established with FNAC or/and fine needle aspiration biopsy with a reported accuracy rate of approximately 84% [4]. Histological patterns mainly seen in ATC include sarcomatous(53%), giant cell (50%) and epithelial (19%), which can occur singly or in combination [4]. The epithelial form manifests squamoid or squamous cohesive tumour nests with abundant dense eosinophilic cytoplasm, with occasional keratinisation can be noted. All patterns of ATC have common features of hypercellularity, large foci of necrosis, increased mitosis, marked invasiveness, and angio-tropism with a tendency to infiltrate medium-sized veins and arteries, replacing their muscular wall [4]. Yet, it is worth noting that, in the case of superimposed infection, the initial pathology may not truly represent the actual pathology. In our case, the initial FNAC is a false negative finding, as the inflammatory process, extensive necrosis and cystic degenerations would have obscured the underlying pathology. However, the subsequent histopathological examination of this patient concluded an anaplastic thyroid carcinoma and nodular hyperplasia with cystic degeneration seen in the background. This case mainly demonstrates epithelial morphology with squamous differentiations. Hence, we highlight the importance of early surgical intervention and histopathological confirmation in cases with a high index of malignancy suspicion.

As for imaging, ultrasound is the preferred imaging technique to diagnose thyroid diseases as it can provide useful information to diagnose invasive thyroid disease. Nonetheless, hypoechoic nodules with irregular margins, microcalcification, and central hypervascularisation increase the likelihood of malignancy in up to 80% of cases. Therefore, FNAC with ultrasound guidance is potentially more beneficial to yield the deeply located tumour area/targeted lesion. Additionally, CT scan, magnetic resonance imaging (MRI), and Positron Emission Tomography (PET) scan is used to evaluate the extent of ATC’s loco-regional invasion and exclude the presence of distant metastasis. The CT imaging of ATC consistently manifests a large necrotic mass involving both thyroid lobes with poorly defined margins, extrathyroidal extension, and local invasion [5]. Due to the highly aggressive nature of ATC, metastasis, notably to the lungs, needs to be carefully examined.

Besides imaging, the role of serum thyroid stimulating hormone (TSH) should not be overlooked. Increased TSH levels are associated with an increased risk of malignancy in patients with thyroid nodules [6], although our patient’s thyroid function test was normal. It is worth noting that well-differentiated thyroid malignancies express TSH receptors, and TSH has been reported to act as a cancer stimulus. Previous literature has evaluated preoperative serum thyroglobulin (Tg) values as a possible predictor of malignancy in thyroid nodules but not routinely practised as preoperative serum Tg and TgAb had no definite impacts on the patient’s management or outcome [6, 7]. However, the postoperative serum Tg value is an important prognostic factor in radioiodine ablation treatment, probability of persistent or recurrent disease, distant metastases, and mortality [7].

Treatment for ATC may be therapeutic or palliative, depending on the staging and prognosis of the patient at the time of diagnosis. Multimodality therapy includes a combination of excisional surgery in a resectable disease or debulking, radiotherapy, chemotherapy and/or targeted therapy. Curative resection in anaplastic thyroid cancers is unusual as the disease is often diagnosed at an advanced stage. However, complete radical resection followed by radio-chemotherapy has been shown to confer a substantial benefit [8]. Radiotherapy and chemotherapy are the treatment options in patients with unresectable tumours. Radiation has more significant treatment morbidity, although it has been proven to achieve 68 to 80% local control [9]. External radiotherapy is usually given at a dose between 45 and 85 Gy, and chemotherapy treatment with a doxorubicin dosage of 60 mg / m2 (80 mg) intravenously every three weeks [6, 8, 9]. Tracheostomy in anaplastic thyroid cancer patients is performed in the event of life-threatening asphyxia due to a tumour blocking the airway. Tracheostomy is also performed electively to anticipate compromised airways in patients receiving chemo-radiation therapy, as radiation may cause inflammation of the laryngo-trachea, oedema, and mucus thickening.

Besides conventional chemotherapy and radiotherapy, molecular targeted therapy such as single or multi-kinase receptors and pathways inhibitors have been widely used [10]. It prevents signalling through several molecular pathways involved in tumoral angiogenesis: vascular endothelial growth factor (VEGF) receptor 1–3, fibroblast growth factor receptor (FGFR) 1–4, platelet-derived growth factor receptor (PDGFR) α, and stem cell factor receptor (KIT) [11]. Lenvatinib is mainly used as it provides the best results and is more widely available. Immunotherapy such as Spartalizumab (a humanised monoclonal antibody that binds programmed cell death [PD-1] and blocks interaction with its ligand [PD- L1]) has also been a therapeutic option in patients with advanced ATC. Macrophages and T-cells express PD-1. The binding of PD-1 to its ligands (PD-L1 or PD-L2) inhibits cytotoxic T-cell immune response and leads to an escape of the ATC cells that express these ligands, found in up to 65–90% of ATC cells [11]. All these multimodality approaches are aimed at slowing down the disease’s rapid progression and facilitating better patient quality of life.

Conclusion

We described a rare case of anaplastic thyroid carcinoma in an elderly female who presented with a thyroid abscess. With early surgery, radiotherapy and chemotherapy, multimodality treatment is recommended for ATC. Apart from conventional chemotherapy and radiotherapy, molecular targeted therapy and immunotherapy have been widely used. Although the multimodality approach provides better overall survival, an aggressive treatment, especially in palliative cases, may hinder the patient’s quality of life due to risks of side effects and complications.

Funding

None.

Declarations

Ethics Approval and Consent to Participate

Research involving human participants.

Informed Consent

Informed consent was obtained from the patient’next of kin.

Conflict of Interest

All authors have no conflict of interest.