Primary adenoid cystic carcinoma of the trachea: an elusive diagnosis of chronic dyspnoea

Abstract

Primary adenoid cystic carcinoma (ACC) of the trachea is a rare entity, with a 5-year survival between 50% and 80% for resectable cases and 30% in case of unresectable disease. We report a case of a primary ACC on a woman in her 70s that presented with a drawn-out history of dyspnoea. She was diagnosed with an unresectable obstructive tumour of the trachea, which required the placement of a Y-shaped stent. The patient underwent concomitant chemoradiotherapy, with partial response, and is still in follow-up, without evidence of disease progression.

Background

Primary tracheal tumours are a rare and slow-growing type of cancer with the majority of tracheal tumours occurring via direct invasion of the trachea from carcinoma of the lung, oesophagus, larynx or thyroid gland. Adenoid cystic carcinomas (ACCs) are the second most common primary tracheal tumours, accounting for approximately 10%–15% of cases and have a better prognosis than squamous cell carcinoma, the most frequent type.^1–4 They are well-differentiated neoplasms of minor salivary gland origin and usually present with three main architectural growth patterns: cribriform (most frequently), tubular and solid. As for the pathological diagnosis, immunohistochemistry (IHC) is usually not necessary. Nevertheless, it is a useful tool to demonstrate the presence of both ductal and myoepithelial phenotypes (cytokeratins and actin), as well as basal membrane components (collagen IV and laminin), in difficult-to-differentiate cases. Exclusion of distant metastasis and morphology are considered essential criteria for this diagnosis; however, testing for MYB-NFIB and MYBL1-NFIB gene fusions by Fluorencence in situ hybridization or Next-Generation Sequencing could be helpful in selected patients.⁵ Tracheal tumours frequently receive a late diagnosis due to non-specific symptoms, which resemble other benign aetiologies. Symptoms might vary based on their location and histologic subtype.⁶ On average, the diagnosis of ACCs is established 18 months after symptomatic presentation and typically consists of wheezing or exertional dyspnoea.^{7 8} Five-year survival of primary ACCs of the trachea is around 75% and the peak incidence occurs in the 4th and 5th decades of life, usually in non-smokers.^{7 8}

Case presentation

A woman in her early 70s with a medical history of arterial hypertension, dyslipidaemia and grade 1 obesity presented with a history of dyspnoea for the previous 8 months. During this period, the patient was evaluated multiple times in the emergency department, performing repeated chest X-rays, without any abnormalities. She was first treated with a bronchodilator and began nocturnal continuous positive airway pressure, as a diagnosis of obstructive sleep apnoea was made, without significant improvement. Due to worsening of dyspnoea and hypoxaemia in a blood gas analysis, a CT scan of the chest was performed, showing an infracarinal prevertebral mass of 65×44 mm, involving the major bronchi bifurcation (figure 1). A rigid bronchoscopy was performed, revealing a tracheal mass located 4 cm distally to the vocal cords, extending throughout the trachea and reducing its lumen to 5%. It further invaded the carina and right and left main bronchus, while maintaining permeable segments in the right and left bronchial tree. A biopsy of the tumour was performed and a Y-shaped stent was placed.

Figure 1.

CT scan images showing an infracarinal prevertebral mass with 65×44 mm, involving the major bronchi bifurcation.

Gross pathological examination revealed a mainly endobronchial tumour, with less than 4 cm of diameter and a firm homogeneous whitish cut surface, unencapsulated with infiltrative contours. Histology confirmed a malignant biphasic salivary gland-type tumour, consisting of epithelial and myoepithelial cells, with three main architectural growth patterns: cribriform, tubular and solid—composed of small, angulated cells with scant cytoplasm and hyperchromatic nuclei; the glandular component was lined by epithelial cells that produce mucins, demonstrated by Alcian blue staining, and the surrounding stromal pseudolumina of basal membrane, evidenced by Periodic acid-Schiff staining (figure 2). Programmed death-ligand 1 (PD-L1) expression in IHC was absent and the Ki67 value was 19%.

Figure 2.

Histological sections of the ACC of the trachea. Beneath the respiratory mucosa, there is infiltration of a biphasic tumour arranged in tubular (A), solid (B) and cribiform (C) patterns, lined by epithelial and myoepithelial cells. These cells are clinged to a thickened basement membrane, which forms pseudolumina (D); focally, there is mucous production (E). AB, Alcian blue; ACC, adenoid cystic carcinoma; PAS/D: Periodic acid-Shiff with diastase.

A staging thoracic CT scan was performed, with no suspicious lesions found. Bone scintigraphy showed two sites of focal uptake on the 9th and 10th right costal arches, probably related to former trauma, and confirmed with the patient. The clinical staging was T4N2M0 (tumour, node, metastases) (8th Edition AJCC Cancer Staging).⁹ The clinical case was discussed in a thoracic tumours multidisciplinary team meeting. Surgical resection of the tumour was considered not feasible, given the location and the extent of the disease into the airways. Treatment with concomitant chemoradiotherapy (CRT) to the tracheal lesion was proposed.

Treatment

The patient underwent concomitant CRT with weekly carboplatin (area under the curve of 2) associated with paclitaxel 50 mg/m² every 21 days and image-guided intensity-modulated radiation therapy to the tracheal lesion with a total dose of 60 Gy divided in 30 fractions over 6 weeks. Dose increment to 66 Gy was not possible given the limiting values reached in the organs at risk. Reported chemotherapy-related adverse events were alopecia (grade 2 Common Terminology Criteria for Adverse Events, V.5.0 (CTCAE 5.0)), fatigue, nausea, anaemia and nail changes (grade 1 CTCAE 5.0). Reported radiotherapy-related adverse events were anorexia, cough (grade 2 CTCAE 5.0), fatigue and dysphagia (grade 1 CTCAE 5.0).¹⁰

Outcome and follow-up

A thoracic CT scan was performed 8 weeks after treatment conclusion, evidencing partial response (RECIST 1.1 criteria)¹¹ (figure 3). To this date, the patient maintains follow-up with close monitoring with minimal symptoms (cough (grade 1 CTCAE 5.0)). The last thoracic CT scan was performed 7 months after treatment conclusion showing stable (RECIST 1.1 criteria) although still unresectable disease (figure 3).

Figure 3.

Post-treatment evaluation thoracic CT scan (performed 8 weeks after treatment conclusion), evidencing an expansive lesion with 43×21 mm involving the posterior tracheal wall, extending to the carina with involvement of the major bronchi bifurcation—partial response (RECIST 1.1 criteria). Follow-up thoracic CT scan performed in March 2022, showing stable (RECIST 1.1 criteria) although still unresectable disease.

Discussion

Treating an unresectable ACC presents as a challenge since there is lack of data concerning the treatment approach in this disease setting. Results on primary RT are inconsistent^{12 13} and reports on concurrent chemotherapy combined with RT in ACC are scarce.^{14 15} Based on experience from ACC of the head and neck, CRT with a platinum-based regimen (carboplatin/paclitaxel) seems to be a valid option and is encouraged.^{16 17}

As for resectable disease, complete removal of the tumour, when possible, is the gold standard in ACC treatment.¹⁸ However, due to the infiltrative growth of the ACCs, incomplete resection margins are often observed following surgery. Resectability often becomes more difficult if there is invasion of adjacent critical tissues, especially in patients with distal tracheal involvement. According to various reports, complete resection rates range from 42% to 57%.¹⁹ In cases of advanced tumour stage (T4), incomplete surgical resection (R1 and R2) or perineural invasion (Pn1), evidence suggests that adjuvant radiotherapy after surgery is the preferred strategy.^{19 20}

We based our approach on the evidence available for ACCs of the head and neck and opted for a combined scheme with CRT given the tumour volume and the symptoms associated. Although a higher RT dose (>60 Gy) seems to be associated with improvement in local control rate,^{12 13 21} in this case, it was not possible to administer the initially planned dose of 66 Gy due to the limiting values reached in the organs at risk.

To this date, there are few reports on unresectable tracheal ACC treated with concomitant CRT and we believe that this case report contributes to further encourage this approach.

Patients perspective.

I felt shortness of breath for several months before my diagnosis, not understanding what was happening to me. Although a cancer diagnosis was a scary thing to be faced with, I felt a tremendous symptom relief after initiating treatment. Since the stent placement, I maintain cough and, sometimes a foreign body sensation on my throat, but my quality of life has been significantly improved since the beginning of treatment. I have a deep appreciation for my doctor and his medical team for taking such good care of me.

Learning points.

• Primary tracheal tumours are a rare and slow-growing entity with non-specific symptoms, leading to late diagnosis.

• Tracheal adenoid cystic carcinomas (ACCs) are the second most common primary tracheal tumours (10%–15%) and are associated with better prognosis than squamous cell carcinoma, the most frequent type.

• Complete resection, when possible, is the gold standard of the treatment of tracheal ACCs, but due to their infiltrative growth, incomplete resection margins are often observed following surgery.

• In cases of T4, R1, R2 or Pn1, multimodality treatment is recommended.

• There are few data on the approach of unresectable disease, but either RT or combined chemoradiotherapy are valid options.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).