PTC is a common endocrine malignant tumor around the world. On account of the scarce regional infiltration, PTC is generally regarded as a curable disease. Thus, most patients have favorable postoperative survival. The mortality rate of PTC is estimated to be between 11% and 17%. However, in some cases of PTC with regional infiltration, the postoperative outcomes could be considerable morbidity and mortality. The most common metastatic sites of thyroid carcinoma are the lung, bone, mediastinal lymph nodes, pelvic area, brain, and liver. Thyroid cancer rarely invades the trachea, but if it does, airway bleeding and obstruction can lead to death. Here, we report a case of PTC with tracheal invasion in a 61-year-old woman.
2 Case report
A 61-year-old woman incidentally noticed a mass in her neck 3 years ago. Soon after, she began to present haemoptysis for a year. Further, her physical condition extraordinarily worsened over the course of the month prior to her visit and she had difficulty in breathing. Meanwhile, the mass continued to slowly grow before she sought medical care.
When she visited our hospital, we found a solid mass of roughly two centimeters in diameter with unclear boundary on the left lobe of the thyroid gland. And she felt no pain as we palpated the mass. The mass could easily move upward and downward when she swallowed. No enlarged cervical lymph node was noted. According to the ultrasonogram, the left lobe of the thyroid gland was enlarged, and a hypoechoic solid mass with irregular shape could be detected in the middle and lower part of the left lobe of the thyroid gland. The mass appeared to be partially wrapped around the trachea, and its size was 2.8 × 1.8 × 1.9 cm (vertical diameter × transverse diameter × anteroposterior diameter). Not only was the internal echo inhomogeneous but the inner part of the mass showed a cluster distribution of dot-like calcifications, which were accompanied with acoustic shadows. Additionally, the mass had a second-degree blood supply. Thus, the US indicated that there was a solid mass with calcifications on the left lobe of the thyroid gland (Thyroid Imaging Reporting and Data System [TI-RADS] category 5) (Figure 1).
The thyroid CT image showed a well-defined calcified mass on the left lobe of the thyroid gland, and the mass partially protruded into the lumen, resulting in the thickening on the left side of the trachea. The mass also had obvious enhancement (Figure 2). The fiberoptic bronchoscopy showed a mass blocking most of the upper endoluminal trachea (Figure 3). Pathologic features showed a papillary infiltrating growth of the lamina propria of the cricotracheal mucosa, which revealed PTC infiltrating the trachea. Accordingly, the Shin's staging of tracheal invasion was stage IV (Figure 4).
The cervical mass partially wrapped around the trachea resulted in severe tracheostenosis. As this could potentially cause asphyxia at any moment, the thyroid surgeons suggested her to transfer to the Respiratory Medicine Department to receive the appropriate therapy. The respiratory physicians recommended her undergo positron emission tomography-computed tomography (PET-CT) and tracheal reconstruction.
PET-CT revealed a soft-tissue mass with intense radioactivity on the left lobe of the thyroid gland. The maximum values of CT and standardized uptake were 497 U and 26.9, respectively. The size of the mass was 2.5 × 2.5 × 3.0 cm (vertical diameter × transverse diameter × anteroposterior diameter). Hyperdense calcified shadows could be detected in the mass, and part of the mass protruded into the endoluminal trachea, hence the trachea was compressed to the right side and appeared to be obviously stenotic (Figure 5).
Therefore, according to the above imaging findings, respiratory physicians considered that it was necessary for her to receive a bronchoscopic treatment. Tumor resection was performed by bronchoscopy on the upper tracheal segment to alleviate the tracheal obstruction. And the resected tissue was subjected to histopathological examination. Then she was transferred to the Thyroid Surgery Department, and thyroid surgeons took the surgical type of bilateral subtotal thyroidectomy + exploration of bilateral recurrent laryngeal nerve + dissection of the lymph node in neck central area + circumferential sleeve resection + end-to-end anastomosis + tracheotomy in the patient. The operation went smoothly, but she presented with fluid exudation in the cervical incision because of wound infection postoperatively, and the situation improved after changing the wound dressing. After the surgery, she presented secondary hypocalcaemia; therefore calcium was given intravenously during the perioperative period. After she was discharged, surgeons advised her to take calcium, vitamin D and levothyroxine tablets, and receive 131I treatment postoperatively. So far, we have followed up her postoperative recovery for approximately one and a half years, and she recovered well without any local recurrence or distant metastasis during this period.
PTC is well known for its favorable prognosis and survival. Although the upper ADT is close to the thyroid gland, the incidence of invasion by PTC is extremely low. Whereas morbidity and mortality will rise when the upper ADT is invaded. The International Union Against Cancer classifies the upper ADT invasion as the T4a category.
The extrathyroidal extension is the extension of the primary thyroid tumor outside the thyroid capsule, in which the tumor invades the adjacent structures including striated muscles, trachea, larynx, jugular vein, carotid artery, esophagus, and recurrent laryngeal nerve. Extrathyroidal extension is universally considered a conspicuously adverse prognostic factor, and its incidence in PTCs is about 5%–34%. The TNM classification is the most widely-used staging system for extrathyroidal extension worldwide (Table 1).
Failure to control the extrathyroidal extension in thyroid tumors can cause a series of complications and eventual death. In particular, tumors with tracheal invasion can lead to airway obstruction which is the direct cause of most deaths in the case of thyroid tumors. Preoperative clinical manifestations of tracheal invasion include haemoptysis, hoarseness, presence of the cervical mass, and shortness of breath. The worst condition of PTC with tracheal invasion is when the tumor has extended to the endoluminal trachea, with an incidence of 0.5%–1.5%.
McCaffrey assumed that the primary thyroid tumor could directly invade the trachea, but this usually occurred as a result of extension from a metastatically involved paratracheal lymph node. However, Shin et al thought that the direct invasion of PTC is also a significant invasion pathway. They proposed that the penetration of PTC into the trachea was either due to the proximity of the thyroid capsule and the peritracheal fascia or the presence of potential lines of weakness in the tracheal wall where the vessels penetrate perpendicular to the lumen, allowing pathways of invasion by mechanical shearing forces. Once the thyroid tumor transgressed the glandular capsule, it could proceed to invade the trachea, esophagus, and larynx. The upper ADT invasion was described as a gradual process that started off with the outer layer, moving deeper, and finally entering the intraluminal mucosa. Shin et al described a staging of tracheal invasion based on the pathologic features, which were defined by the degree of the cricoid cartilage and intraluminal tracheal invasion (Table 2).
Shimamoto et al revealed that there is no prognostic difference between the invasion of esophagus and trachea, but the aggressiveness of tracheal infiltration seems to be closely related to the degree of esophageal infiltration, and the invasion of larynx indicates that the disease has evolved into an advanced stage. Kim et al showed that the simultaneous involvement of the trachea and esophagus were associated with higher local recurrence, and laryngeal involvement was related to the lower disease-specific survival.
Imaging examinations, including US, CT, and magnetic resonance imaging (MRI), are commonly performed in thyroid tumors with tracheal invasion. US have the unique advantage over the other imaging examinations as it allows the simultaneous evaluation of thyroid tumor invasion and cervical lymph nodes metastasis. Park et al proved that the US performed well in showing the extension of primary thyroid tumors and diagnosing the preoperative staging of thyroid tumors with lymph nodes metastasis. The American Thyroid Association's Management Guidelines declared that clinicians should take the preoperative neck US for patients with differentiated thyroid carcinoma.
Yamamura et al have summarized different types of tracheal resections of 24 patients with differentiated thyroid carcinoma infiltration and retrospectively reviewed the preoperative US features with postoperative histologic findings. They concluded that the US features were consistent with the pathologic findings, and the total accuracy of US was 83.3%. Thus, the US should be the first choice to establish the diagnosis of thyroid tumors with tracheal invasion even at an early stage.
MRI is also a good choice for examining thyroid tumors with tracheal invasion. The high accuracy of MRI is attributed to its superior soft-tissue contrasting characteristic. Features of tracheal infiltration on MRI images include the endoluminal mass and soft-tissue signals in tracheal cartilage. In one study, when thyroid tumors invaded the trachea, esophagus, and carotid artery, the prediction accuracy of MRI was 88%, 94%, and 91%, respectively. Moreover, MRI can diagnose thyroid tumors invading the adjacent structures simply by measuring tumor circumferences on images.
CT is another imaging examination for assessing thyroid tumors with tracheal invasion. Seo et al demonstrated that CT had better accuracy (83.2%–98.8%) and specificity (89.8%–99.4%) for diagnosing thyroid tumors invading adjacent structures. However, the sensitivity of CT was lower than that of US and MRI, which ranged from 28.6% to 78.2%.
The bronchoscopic examination is generally performed in patients suspected of having thyroid tumors with tracheal invasion. The extent of invasion is further assessed by histopathologic analysis on the resected tissue. Bronchoscopy is quite valuable to measure the extent of laryngotracheal invasion and allow the direct observation of the changes in the bronchial mucosa. Randolph et al advocated that the preoperative bronchoscopy should be examined for patients with invasive thyroid tumors or vocal cord paralysis.
Surgical managements of tracheal invasion consist of the shave excision of the affected tissue and full-thickness tracheal resection. Shave excision is only suitable for the cases of superficial invasion of the cricoid cartilage and in which thyroid tumors have not extended to the cricotracheal lumen. Once the intraluminal trachea is invaded, patients will require the full-thickness tracheal resection by means of a window resection or sleeve resection. For patients with involvement of less than four tracheal rings and endotracheal involvement of less than 50% of the tracheal rings, the window resection of trachea can be adopted. In cases of involvement of small areas of the trachea, the section with the removed tracheal wall can be pulled up and closed. After window resection, the defect can be repaired with sternocleidomastoid myoperiosteal, pectoralis major myocutaneous, or anterior cervical flap and artificial stent. Circumferential sleeve resection is adopted for the cases with significant cricotracheal infiltration, for patients with thyroid carcinoma invading more than 50% of the tracheal rings, tracheal involvement of 4–6 cartilage rings and Shin's stage IV, while window resection is not suitable in these cases. At this time, circumferential sleeve resection + end-to-end anastomosis should be considered. This method can ensure adequate resection range and does not require low-level preventive tracheotomy, which is only considered in special conditions such as bilateral vocal cord paralysis, anastomotic dehiscence or dyspnoea.
Therefore, surgery is the first treatment for thyroid tumors infiltrating the trachea. Postoperative complications include the following: secondary wound infection, which can be treated with local debridement and dressing changes; formation of mouth-floor fistula, which can be treated with debridement and pressure dressing; secondary hypocalcaemia, which can be treated by intravenous administration of calcium during the perioperative period, followed by long-term oral administration of calcium tablets and vitamin D; if tracheotomy is performed, extubating may fail due to the small anterior-posterior diameter of the trachea at the upper edge of the tracheotomy. Whether 131I treatment should be performed after surgery and the specific indications for 131I treatment remain controversial. The main question is whether low-risk patients benefit from such treatment. Most scholars still recommend that patients with laryngotracheal invasion by differentiated advanced T4 thyroid cancer receive 131I treatment after surgery if it is tolerable to them. This could be due to the fact that postoperative 131I treatment can reduce the risk of recurrence and improve the survival rate.[23,24]
Overall, the postoperative survival rate of patients with PTC is generally excellent. If patients have the clinical manifestations of tracheal invasion, they should immediately undergo imaging examinations such as US, CT, or MRI. The bronchoscopic treatment must be performed in patients if the imaging examinations reveal the presence of a PTC with tracheal invasion. The subsequent surgical approach depends on the degree of tracheal invasion. Considering that the extent of invasion will dictate the following steps for surgical management as well as prognosis, it is critical to diagnose the PTC with tracheal invasion as early as possible.
Formal analysis: Chao Fu.
Resources: Kefei Cui.
Supervision: Xiao Ma.
Writing – original draft: Jiateng Zhang.
Writing – review & editing: Jiateng Zhang.
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