Rapidly Growing Thyroid Masses in Adults: Urgent Diagnostic Challenges and Effective Management – Single - Centre Experience and Literature Review

  

    
Case 
    
Extent of    thyroidectomy 
    
Extent of CND
    
Extent of    LND 
    
Infltration pattern
    
Resection margin status
    
N status
    
 
  
  

    
1 
    
Total Thyroidectomy 
    
Yes 
    
No 
    
Prethyroid muscles
    
R1 
    
N1a 
    
pT3b pN1a
  
  

    
6 
    
Total    thyroidectomy 
    
No 
    
No 
    
Muscles 
    
R0 
    
Nx 
    
ypT1b 
  
  

    
7 
    
Total thyroidectomy 
    
yes 
    
yes 
    
Muscle, tumour thrombus yugular left vein
    
R1 
    
No 
    
ypT4a ypN0
  

Table 4: Surgical treatment and staging.

Discussion

Rapidly enlarging thyroid masses are defined as a clinically evident enlargement of the anterior compartment of the neck, occurring in less than one month, and usually associated with compressive symptoms. Locally advanced TC, PTL and thyroiditis are the main entities. Differential diagnosis requires rapid and protocolized assessment. In our study, five patients were diagnosed with TC six with PTL and one case was diagnosed with Riedel’s thyroiditis.

An exhaustive initial evaluation is essential to guide subsequent therapeutic interventions. The first step is performing cervical ultrasound, which serves for characterizing the lesion. Furthermore, it allows to obtain tissue samples for pathological and molecular assessments. Whenever feasible, a core needle biopsy (CNB) should be prioritized over fine-needle aspiration (FNAB) due to its significant diagnostic advantages. Ha et al. reported that CNB is a superior diagnostic tool for anaplastic thyroid carcinoma (ATC) and PTL, demonstrating a sensitivity of 87.5% and a positive predictive value of 100%. In this study, PTL was misdiagnosed in one case of CNB compared to 16 cases of FNAB [6]. CNB reduces the need for diagnostic surgeries and provides sufficient tissue for molecular analyses. In cases where a PTL is suspected, the sample must be referred for flow cytometry [6,7]. In the pathological assessment for PDCT, locally advanced PTC and ATC, the first diagnostic approach is the immunohistochemistry study [8]. Subsequently, Next Generation Sequencing (NGS) is recommended to assess BRAF mutations, NTRK fusions, RET alterations (point mutations or fusions), ALK translocation or m-TOR mutations to assess targeted therapies [9]. Within trial specific studies of other therapeutic targets such as TMB, MSI, dMMR, RAS, TERT, STK11, PTEN, TP53 or IDH1 will be considered within specific protocols [10].

Although cervical ultrasonography is considered the primary imaging modality for the evaluation of thyroid masses, additional complementary imaging studies were required [5,11,12]. A total of 54.5% of our patients were classified as TiRADS-5. However, the initial cervical ultrasound did not raise suspicion of PTL or aggressive TC in any of the reported cases.

Several other tools are available for the diagnosis and staging of thyroid masses, particularly in complex cases. These include CT and PET-CT FDG, which provide detailed imaging to assess the extent of disease, and potential metastases. Furthermore, procedures such as laryngoscopy, endobronchial ultrasonography (EBUS) and esophagoscopy or endoscopic ultrasound (EUS), are highly valuable for evaluating local invasion and involvement of adjacent structures [13,14].

Published studies emphasize the critical role of a multidisciplinary approach and the implementation of standardized diagnostic algorithms in the management of thyroid masses [11,15]. The results of our case series show the impact of the absence of standardized protocols, emphasizing their development as a key objective of this study. A rapidly growing thyroid mass should not proceed to surgery without prior diagnosis and staging. This is particularly significant in cases of advanced TC, where the initial surgical intervention plays a pivotal role in patient outcomes [5]. In the present study, four patients were diagnosed following the initial surgical procedure. Of these, two cases were diagnosed intraoperatively, one with PTL and the other with PDTC. The remaining two cases were identified based on the final pathological results.

PTL is a rare tumor (1-5% of all thyroid malignancies). The most common subtype is DLBCL (50-70%) and MALT lymphoma (10-50%) [12,16]. It is known that the main risk factor for PTL is Hashimoto’s thyroiditis [17,18]. Fifty percent of our patients with PTL had a history of this condition. Five patients were women and one man, with a mean age of 68,5 (range: 48-84), similar as describes in the literature. Uptake in FDG-PET is usually higher in CT than in PTL. In aggressive varieties, PET/CT is useful for both staging and response to treatment [12].

The role of surgery is limited [12]. It is often complex due to tumor infiltration that increases the risk of injury to the recurrent laryngeal nerve and other cervical structures [19]. Moreover, various studies have shown that surgery does not improve survival compared to chemotherapy or radiotherapy, stages IE or IIE included [20]. However, in certain cases, a definitive diagnosis is achieved through histopathological analysis of the surgical specimen, either because TC was suspected or due to indeterminate results from FNAB or CNB. In a case series reported by Sakhri et al, all patients underwent surgery without a confirmed prior diagnosis. In our series, two patients underwent surgery, one due to indeterminate FNAB results and other due to suspect TC; another case was operated on to confirm a PTL diagnosis, while one patient presented with compressive symptoms caused by a goiter. Nevertheless, more recent cases have been managed with corticosteroids to relieve compressive symptoms and chemotherapy [21].

Recent studies have highlighted the optimal treatment for PTL, particularly in DLBCL subtype. The standard frontline treatment of DLBCL remains chemo-immunotherapy with R-CHOP with or without radiotherapy according to disease stage and clinical risk factors [6,18,22].

TC is characterized by having a good prognosis. Unfortunately, certain cases debut as a locally advanced disease or aggressive tumor subtypes, such PDTC, ATC or locally advanced medullary cancer [23]. These forms are associated with significant morbidity and mortality, due to cervical structures invasion (airway, great vessels, esophagus) and therapeutic limitations [2,24,25]. In the present study, five cases were diagnosed as TC, including four PDTC and one case of locally advanced PTC. Surgery remains the cornerstone of treatment for TC. However, in locally advanced cases, surgical intervention must be carefully weighed against its potential impact on quality of life, disease control, recurrence rate, and survival benefits [5]. In our series, four cases underwent surgery, one of which was performed following neoadjuvant therapy. However, two cases were deemed unresectable due to extensive infiltration involving the trachea and esophagus. Other therapeutic modalities include radioactive iodine, external beam radiotherapy, and systemic therapies. Neoadjuvant treatment regimens included Lenvatinib (multikinase inhibitor), dabrafenib + trametinib (selective BRAF and MEK inhibitors), selpercatinib (selective RET inhibitor), vandetanib (multikinase inhibitor), crizotinib, and alectinib (both ALK inhibitors). The use of neoadjuvant therapy for inoperable TC is a promising area and currently under investigation [26]. In the study by Iwasaki et al., six initially inoperable cases were treated with lenvatinib, enabling surgical intervention upon completion of the therapy. Similarly, Yeo et al. reported a series of four cases with favorable outcomes, demonstrating that lenvatinib was effective in reducing the extent of the primary tumor, potentially facilitating limited surgical resection by local disease control [27]. Our experience is limited to a single case.

In summary, it is important to protocolize the management of rapidly enlarging neck masses as time is urgent (Figure 1). It is essential to go beyond ultrasound with the performance of a PETCT scan, and to go beyond FNA with the performance of a CNB, in order to obtain a molecular study that will also allow us to direct the treatments. Optimal management of rapidly growing thyroid tumors requires a multidisciplinary team to evaluate diagnostic findings, therapeutic options, and individual patient needs, ensuring the selection of the most appropriate treatment strategy. The development of standardized diagnostic and therapeutic protocols is crucial to improving oncological outcomes.

    

    

    Figure 1: Algorithm for the management of Rapidly Growing Thyroid Masses.