Laryngeal adenoid cystic carcinoma

Summary

Adenoid cystic carcinomas are malignant tumours and occur in the major and the minor salivary glands. Laryngeal adenoid cystic carcinomas are rare and account for less than 1% of all malignant tumours in the larynx. Adenoid cystic carcinoma is characterised by slow progression, multiple recurrences and late distant metastasis. The aetiology of adenoid cystic carcinoma remains unknown. They usually originate in the supraglottic or subglottic area. Wide-margin surgery alone or in combination with post-operative radiotherapy is the best tumour management. In this article, the case of laryngeal adenoid cystic carcinoma is described in a 55-year-old male patient who presented with a 3-month history of prelaryngeal pain. The patient underwent total laryngectomy and post-operative radiotherapy. For patients with laryngeal adenoid cystic carcinomas, regular and long-term follow-up is mandatory, in order to detect relapses and metastases.

Introduction

Squamous cell carcinoma accounts for about 99% of laryngeal malignancies. Non-epidermoid malignancies of the larynx include sarcoma, lymphoma, and salivary gland carcinoma. Salivary gland carcinomas of the larynx are rare, and account for < 1% of laryngeal malignancy ^{1 2}.

Minor salivary glands are found in various locations, extending from the paranasal sinuses to the larynx. Minor salivary gland tumours are most commonly located in the oral cavity, particularly the hard palate, and less commonly in the nasal cavity, paranasal sinuses, pharynx, and larynx. In contrast to major salivary gland tumours, which are mainly benign, minor salivary gland tumours are more usually malignant.

Adenoid cystic carcinomas, previously known as cylindromas, are the most common malignant tumours that occur in minor salivary glands. Most tumours present supraglottic or subglottic involvement, possibly because the distribution density of subepithelial glands is higher in the supraglottic and subglottic areas than in the glottic area. Two-thirds of these laryngeal tumours occur in the subglottis ³; however, they also occur in the supraglottis in the false cords, aryepiglottic folds ⁴, and caudal aspect of the epiglottis. In the glottis, they are located in the floor of the sinus of Morgagni and subglottic surface of the anterior commissure.

The aetiology of adenoid cystic carcinomas remains unknown. These tumours are found mainly in the fifth and sixth decades of life with a slight female predominance ⁵.

Adenoid cystic carcinomas arise from subepithelial glands ^{1 6} and most commonly present as submucosal masses. Because they spread in a submucosal fashion, they are difficult to detect earlier. This explains why most patients were diagnosed late, at the advanced stage. They tend to spread by perineural extension and frequently recur after initial treatment. Neck metastasis is rare. The most frequent site of distant metastasis is the lung.

Case report

A 55-year-old male, non-smoker, was referred to our Clinic with a 3-month history of pre-laryngeal pain. The patient had no history of dyspnoea, hoarseness, dysphagia or cough. The patient’s medical history included gastro-oesophageal reflux.

Indirect laryngoscopy detected the anterior left para-median sub-glottic sub-mucosal tumour mass which measured 8 mm in its maximum diameter. The laryngeal mucosa was intact and there was no necrosis in the laryngeal mucosa. The glottic and supra-glottic areas showed a normal appearance. There was no impairment of the laryngeal motion. On physical examination, the patient had no palpable neck mass or lymphadenopathy.

The patient underwent computerized tomography (CT) of the neck with contrast medium which showed the presence of a sub-mucosal mass in the left sub-glottic area which had extended through the thyroid cartilage into the extra-laryngeal soft tissues on the left side of the neck (Fig. 1). Neither the physical examination nor neck CT detected any evidence of node involvement. The findings on chest X-ray were normal.

Fig. 1.

CT scan of larynx showing subglotic submucosal mass and destruction at left side of thyroid cartilage.

During direct microlaryngoscopy, a biopsy was taken from the tumour and the pathologist reported that the specimen had a cribriform pattern and was consistent with an adenoid cystic carcinoma.

The patient underwent total laryngectomy and isthmectomy without neck dissection. The surgical margins were free of tumour.

The final pathology report showed negative margins. Specimen showed intra-luminal (sub-mucosal) and extra-luminal tumour growth with involvement of thyroid cartilage and muscular invasion (Fig. 2). Although there was no lymphatic spreading, perineural invasion (which is a feature of adenoid cystic carcinoma) was present.

Fig. 2.

Histological section of laryngeal adenoid cystic carcinoma (100 x magn., H&E staining).

Ten days post-operatively, the patient was discharged. Since this patient had a large tumour with perineural invasion, he was scheduled for adjuvant radiotherapy. At 6-months’ follow-up, there was no evidence of recurrence or metastasis.

Discussion

Minor salivary gland tumours of the larynx are rare and constitute less than 1% of laryngeal tumours. They are usually malignant and the most common type is adenoid cystic carcinoma. This tumour is characterised by slow progression, multiple recurrences and late distant metastasis.

There are no distinct risk factors that predispose patients to this malignancy ⁵. Smoking does not affect the incidence. Unlike squamous cell carcinoma, for which more than 90% of patients are smokers, only of patients with minor salivary gland tumours are smokers.

According to Dexemble et al. ³, 64% of laryngeal adenoid cystic carcinomas occur in the sub-glottis, 25% in the supra-glottis, 5% in the glottis and 6% in the transglottic area.

The signs and symptoms of laryngeal adenoid cystic carcinoma are related to location and size. Tumours of the supra-glottis present with dysphagia. Hoarseness or even dyspnoea is indicative of glottic involvement. Stridor and airway obstruction are more frequently associated with sub-glottic tumours. However, usually, adenoid cystic carcinoma occurs as a large asymptomatic, non-ulcerated sub-mucosal mass. As a result, diagnosis is often delayed and, in the larynx, sub-glottic tumours have the opportunity to invade deeply before they are diagnosed. Our observation that pre-laryngeal pain was the only symptom in a patient with advanced adenoid cystic carcinoma is an important point to make.

Pre-operative histo-pathological analysis is essential because the symptoms do not differ greatly from squamous cell carcinoma. The histo-pathological pattern of adenoid cystic carcinoma is classified into three distinct subtypes: cribriform, which is the most common; tubular, which has the best prognosis; and solid, which carries the worst prognosis ⁵. In our case, adenoid cystic carcinoma contained sheets of small uniform cells arranged in a classic cribriform growth pattern.

Accurate pre-operative mapping and staging are essential. CT is a very useful imaging procedure in adenoid cystic carcinoma. It is highly valuable in the assessment of primary tumour location, extra-luminal extension, regional and distant metastases. It is, therefore, recommended in the pre-operative evaluation. Albeit, CT can underestimate the extent of the tumour because adenoid cystic carcinoma may grow sub-mucosally without producing a distinct mass. In our case, CT with contrast medium showed the presence of a sub-mucosal mass in the left sub-glottic area with extension through the thyroid cartilage into the extra-laryngeal soft tissues on the left side of the neck. Also, these findings correlated with the histopathologic findings in this patient.

The treatment options of laryngeal adenoid cystic carcinoma are still controversial. Surgery with or without post-operative radiotherapy remains the mainstay treatment modality of laryngeal salivary gland carcinomas. Partial laryngectomy is possible in selected patients with small, well-defined tumours and negative surgical resection margins ⁷. Because of the risk of sub-mucosal spread and peri-neural and lympho-vascular invasion, total laryngectomy is often required and most Authors agree that the treatment of choice is wide-margin local excision ³. In the absence of neck metastasis, elective neck dissection is not recommended ^8–11. Neck dissection should be performed in patients who have clinically or histologically confirmed node metastases ^{3 5 12}.

Radiotherapy alone usually has a minor role in treatment ¹². These tumours have been shown to be radiosensitive but are not usually radiocurable. Therefore, the role of radiotherapy is still open to debate. It may be useful as an adjuvant modality for adenoid cystic carcinoma with positive surgical margins, perineural spread or high-grade tumours.

Chemotherapy may be useful as adjuvant therapy for high-grade lesions, either in conjunction with surgery to prevent distant metastases or with radiotherapy as palliation for patients with distant metastases at initial presentation. However, in unresectable tumours or those with local recurrence after surgery, no efficient treatment strategy has been developed.

Known clinicopathological factors with an unfavourable effect on survival, in adenoid cystic carcinoma, include old age, advanced stage, solid histological subtype, high grade, major nerve involvement and the presence of perineural invasion or a positive surgical margin. The five-year survival rates for patients with laryngeal adenoid cystic carcinoma have been reported to range from only 12-17% ^{3 12}. Regular close and long-term follow-up is mandatory, in order to detect relapses and metastases. Since early perineural and haematological spread is common, local recurrences and distant metastases are common and sometimes occur years after the primary tumour has been diagnosed and treated. Distant metastases may occur in the lungs, liver, abdomen, lymph nodes, and bones.

Conclusions

Laryngeal salivary gland carcinomas are rare and account for < 1% of laryngeal malignancies. Therefore, a high degree of suspicion is essential for early diagnosis. This tumour must be considered when aggressive laryngeal tumours are found, especially if the patient is not at risk for squamous cell carcinomas. They usually originate in the supra-glottic or sub-glottic area with a predominance of old age. Most patients are diagnosed late, at an advanced stage. CT can be used to assess tumour extent and growth patterns. Wide-margin surgery alone or in combination with post-operative radiotherapy for advanced lesions that present peri-neural spread or close or positive margins is the best tumour management. For these patients, regular and long-term follow-up is mandatory, in order to detect relapses and metastases.