Healing of Post-Operative Tracheal Disruption in a Patient with Thymic Carcinoma on Adjuvant Immunotherapy

Abstract

Pneumomediastinum from tracheal perforations due to primary repair breakdown can occur as a complication of thymic cancer surgery. Immunotherapy may be a viable adjuvant treatment for thymic carcinoma patients with tracheal perforations.

Background

Pneumomediastinum from tracheal injuries is a rare but often life-threatening condition.^1,2 Common causes of tracheal injuries are typically either traumatic or iatrogenic, while rare cases of spontaneous perforation have also been reported.^1,3 Postoperative tracheal disruption is relatively rare. A 2026 multi-center study of 640 evaluable patients who underwent airway resection observed only 2% of patients with partial dehiscence.⁴ In patients who received radiation to the surgical area, higher rates of dehiscence are expected due to radiation’s effect on wound healing.^5,6

Symptoms of tracheal perforation include respiratory difficulties, subcutaneous emphysema, hemoptysis, and pneumothorax.¹ Bronchoscopy has often been cited as the gold standard for diagnosis and evaluation of tracheal tears and can often identify the location and size of tracheal injuries.^1,3,7 Prognosis depends upon the size of the tracheal injury, time of detection, and clinical condition of the patient.¹ While typically associated with high mortality and morbidity, exact rates are difficult to determine since other severe injuries often co-occur with the tracheal tear.¹ This is especially true in cases of perforations due to trauma, where an estimated 80% of patients with tracheobronchial injuries due to blunt force trauma died before reaching the hospital.¹ In a systematic review of patients with postintubation tracheal rupture, overall mortality was 22%.²

Tumors closely adherent to the trachea can be difficult to manage even after resection with the potential consequence of a post-operative tracheal disruption. The 2026 NCCN guidelines on adjuvant treatment for thymic carcinoma recommend surveillance with possible radiation for R0 resection, postoperative radiation ± chemotherapy for R1 resection, and definitive radiation ± chemotherapy for R2 resection.⁸ Adjuvant radiation and chemotherapy would present challenges to wound healing. Furthermore, current evidence on adjuvant immunotherapy in patients with thymic carcinoma is limited. A landmark prospective study of pembrolizumab treatment in 40 evaluable patients with recurrent thymic carcinoma observed disease control (complete or partial response plus stable disease) in 75% of patients at a median follow-up time of 20 months.⁹ While there is modest data promoting effectiveness of immunotherapy as a subsequent systemic treatment in thymic carcinoma, risk of adverse events is a concern. In the same study, 15% of patients experienced severe autoimmune toxicity.⁹ In the setting of postoperative airway complications, there is further limited evidence for the safety of immune checkpoint inhibitors. Due to the high mortality and the rarity of the condition, patients with successful recoveries, especially in the setting of cancer and systemic therapy, should be documented to determine effective treatment options for future patients with a similar clinical course.

Approval and consent: IRB approval was waived as this is a single patient case report not considered systemic research and did not require IRB (institutional) approval for publication of the case details. The patient involved in this case report provided informed written consent for the publication of their de-identified clinical data.

Case Presentation

A man in his 50s presented with 6 months of shortness of breath, productive cough, difficulty swallowing, and weight loss. He had no major medical or family history. He also has never smoked and denied alcohol or other illicit substances.

A chest X‑ray performed showed a prominent opacification of the right superior mediastinum. The mediastinal mass was later confirmed by CT and found to be compressing his trachea. Endobronchial ultrasound-guided biopsy revealed thymic squamous cell carcinoma with neuroendocrine differentiation. Clinical stage was thought to be at least Masaoka stage IIB. Surgical resection was originally deferred as R0 was deemed challenging due to its location between the trachea and esophagus. Definitive intent concurrent chemoradiation treatment was initiated emergently during his admission given concern for acute airway compromise and completed as outpatient. He received weekly chemotherapy of carboplatin and paclitaxel with 66 Gray/33 Fractions of radiation without any major issues. Subsequent CT and PET scans displayed excellent response to treatment. Repeat bronchoscopy as well as an esophagogastroduodenoscopy confirmed response to systemic treatment and did not show any invasion of the trachea or esophagus.

At this point, the mediastinal mass was deemed amenable for consolidative surgical resection after multi-disciplinary discussion. Consolidative surgery was performed approximately 3 months after completion of chemoradiation. During the procedure, it was noted that the tumor was adherent to the trachea and esophagus requiring careful sharp dissection (Figure 1). A portion of the tracheal sidewall was excised to achieve grossly negative margins, but surgical intervention primarily focused on tracheal repair. The trachea was repaired with suture primarily and buttressed with a right sternocleidomastoid muscle flap. Unfortunately, final pathology reported an R1 resection with a microscopically positive surgical margin. The patient was discharged within a week after surgery with no acute complications.

Figure 1.

Intraoperative photo of the thymic mass dissected off of the trachea, innominate artery and vein. The close adherence to the mediastinal structures is noted.

However, a few days later, the patient presented to the emergency department with a one-day history of neck swelling, facial swelling, dysphonia, and odynophagia. Patient was febrile and tachycardic and was hospitalized for sepsis and pneumomediastinum. Emergent neck exploration and repair with ENT and thoracic surgery revealed a small hole in the trachea and a wound vac was placed over. Furthermore, later exploration revealed a large defect in the posterolateral trachea. This defect was formalized into a tracheocutaneous fistula by placing an uncuffed tracheostomy tube into the defect. The initial reconstruction of the trachea during the patient’s original tumor resection had not healed well and had broken down, likely due to the invasive nature of thymic cancer requiring aggressive resection, complicated by tissue impairment from the initial chemoradiation received.

Within 3 weeks following the neck exploration, the tracheostomy tube was successfully removed. Given positive margins from the original surgery, the patient was evaluated for continuing systemic treatment. He had already had maximal radiation. Due to the breakdown of the original tracheal reconstruction resulting in tracheal disruption and pneumomediastinum, cytotoxic chemotherapy agents were avoided. As the tumor was positive for tumor PDL-1 25%, immunotherapy of pembrolizumab 200mg q3 weeks was chosen.

Flexible bronchoscopy performed 1 week after decannulation showed evidence of the tracheal defect decreasing in size. Approximately 4 months after decannulation, repeat bronchoscopy revealed a well-healed trachea. Currently (over 2 years later), the patient remains on pembrolizumab 200 mg Q3 weeks without notable adverse events and no evidence of disease on imaging. For a summary of key clinical events, see Figure 2.

Figure 2.

Summary of Important Clinical Events.

Discussion

As discussed in the introduction, postoperative tracheal disruption is rare following airway resection and reconstruction.⁴ The more common early complications include glottic swelling and surgical site infections.⁴ Unfortunately, in the setting of chemoradiation, dehiscence is more likely.^5,6,10 Radiation effects are typically local to tissue which received the highest dose of radiation.⁵ Radiation will cause both direct injury to cellular components and indirect injury from generation of reactive oxygen species, which will in turn trigger an inflammatory cytokine cascade, vascular leakage, fibrosis, and ultimately impaired wound healing.⁵ Chemotherapy agents are systemic and meant to target specific stages of the cell cycle and inhibit tumor cell proliferation or blood vessel growth.¹⁰ Unfortunately, chemotherapies also effect non-cancerous cells such as immune cells, fibroblasts, and epithelial cells which are involved in the wound healing process.¹⁰ In contrast, immunotherapy does not directly inhibit cellular regeneration, and its mechanism of action focuses on increasing immune activity.¹¹ The direct impact of immunotherapy on wound healing is unclear, but recent studies have demonstrated that under most circumstances, immunotherapy does not increase the rate of surgical complications or worsen wound outcomes.¹¹ Immunotherapies should still be used with caution due to the risk of immune‑related adverse events, which may cause direct injury.¹¹

After establishment of a secure airway, the ongoing treatment approach for tracheal injuries can be approached either non-operatively or surgically. While surgical repair has been recommended as the traditional approach, recent studies have advocated for the benefits of minimally invasive or non-surgical approaches under specific circumstances.^7,12 No precise guidelines have been developed, but determination of treatment approach may depend on factors such as injury mechanism, clinical condition of the patient, and size of the tracheal tear.^7,12

This patient’s mechanism for tracheal injury was closely related to his cancer. The tumor grew adherent to his trachea despite regression with chemoradiation and imaging which suggested safer margins than what was observed under gross dissection. Despite the risks, surgical resection of thymic tumors is generally preferred due to lower risk of recurrence and survival benefit.¹³ Ultimately, non-operative treatment for the tracheal injury was chosen for this patient following emergent neck exploration and eventual tracheostomy placement through the defect. Given PDL-1 score of 25%, a single‑agent immunotherapy was carefully chosen to help control his cancer and allow his body to heal while avoiding chemotherapy. This systemic therapy strategy likely helped reduce potential chemotherapy‑related side effects, which may further delay wound healing and increase the risk of infectious complications in the setting of tracheal fistula formation. Of note, this investigation was a single case study, and results may not be generalizable to other patients. Further research should be conducted to investigate the use of immunotherapy in thymic carcinoma patients in high-risk settings such as tracheal injury.

Funding Statement

There was no funding allocated for this manuscript.

Abbreviations

CT, computed tomography; ENT, ear nose and throat; IRB, institutional review board; PDL-1, programmed death-ligand 1; PET, positron emission tomography.

Approval and Consent

IRB approval was waived as this is a single-patient case report, not considered systemic research, and did not require IRB (institutional) approval for publication of the case details. The patient involved in this case report provided informed written consent for the publication of their de-identified clinical data.

Disclosure

HK: Consulting for AstraZeneca and Intuitive, speaker for Merck.

JH: Data safety/advisory board participation from UCI DSMB, outside the submitted work, and consulting fees from Novocure.

CP: Honoraria from Johnson and Johnson, BioImmunity and MJH LifeSciences.

ZA: Advisory board for Catalyst, Janssen/JNJ., Rigel, EMD Serono, BI, AZ, Jassen, outside the submitted work.

SO: Reports honorarium from Pfizer and Astra Zeneca, as well as stock/stock options from MBrace Therapeutics, BlossomHill Therapeutics, Nuvalent, Lilly and Nuvation Bio.

MN: Honoraria from AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Genentech, BMS/Mirati, Takeda, Johnson and Johnson, Boehringer Ingelheim, and Regeneron; consulting fees from Caris Life Sciences; travel support from AnHeart Therapeutics/ Nuvation Bio.

The authors report no other conflicts of interest in this work.