Abstract
Mucoepidermoid carcinoma (MEC) accounts for only 5% of all salivary gland tumors and is most often seen in the parotid glands. MEC occurrence in the larynx is, however, rare. The incidence of primary squamous cell carcinoma (SCC) of salivary glands is also scarce and comprises only about 1.6% of all salivary gland malignancies. Hereby, we share our experience in managing two patients with rare and opposite variants of malignancy which were diagnosed at the same time; MEC of the larynx and SCC of the parotid. In MEC tumors, the presence of the intermediate and mucous cells with positivity in mucicarmine stain are the significant features. For SCC tumors, identification of the usual tumor markers (p40, CK 5/6 and p63) are pathognomonic. Although MEC and SCC are common in the head and neck regions, the existence of these malignancies in exceptional locations must be considered. The key features mentioned in our comparison table can help distinguish both these tumors and to deliver the correct treatment modalities. The prevalence of genomic and carcinogenic factors in the occurrence of these tumors in uncommon locations needs to be explored in future studies.
Author Contributions
Copyright© 2020
Rajendran Thilaga, et al.
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Introduction
Mucoepidermoid carcinoma (MEC) is the most frequent malignant tumor of the salivary glands. It accounts for about 5% of salivary gland tumors in general and is most often seen in the parotid gland. The female preponderance is about 3:2 in ratio and is more commonly diagnosed in the 5th decade. Moreover, MEC is the most common salivary gland malignancy in children. However, MEC in the larynx is scarce. In 1963, Arcidiacono and Romeo were the pioneers in detecting these types of neoplasm in the larynx. On the other hand, the incidence of primary SCCs of salivary glands is scarce and comprises only about 1.6% of all salivary gland malignancies. The previous history of radiation therapy has been known to contribute to the development of primary SCC. Hereby, we share our experience in managing two patients with rare and opposite variants of malignancy which were diagnosed at the same time; MEC of the larynx and SCC of the parotid. A 70-year-old gentleman, ex-smoker with no comorbid presented to us with hoarseness for 2 months in duration. He also had occasional shortness of breath. There was no constitutional symptom present. Upon our examination, the patient had soft stridor with hoarseness. There were no palpable neck nodes and laryngeal crepitus was present. On flexible nasopharyngolaryngoscopy, a fungating mass was seen occupying the whole length of the left vocal cord, with the cord in a fixed position. The right vocal cord was mobile. A high tracheostomy was done with direct laryngoscopy showing a supraglottic mass obstructing the laryngeal inlet, which is more confined to the left vocal cord and with extension into the subglottic region. Histopathology reported the mass as in favor of MEC. In microscopy, intraluminal and occasional intracytoplasmic PAS-positive diastase-resistant mucin were demonstrated. [ A 42-year-old gentleman, ex-smoker with underlying diabetes mellitus came to our clinic for right neck swelling for about 10 months. The swelling was gradually increasing in size and was giving occasional pain to the patient. But, there were no obstructive symptoms nor a history of prior exposure to radiation. Upon examination, there was a 2x2cm firm, fixed and non-tender swelling palpable at level II of right neck, with no skin changes seen. The facial nerve was intact and the oral cavity was clear. Proceed with flexible scope, there was no mass seen, and laryngeal structures were normal. Fine needle aspiration revealed normal salivary gland elements. A contrasted-CT scan reported a deep lobe parotid gland mass with non-opacification of the right internal jugular vein which could be from compression or thrombosis. [
Discussion
This article aims to highlight the characteristics of both MEC and SCC tumors which had developed at uncommon locations in the head and neck regions and also the histological key features distinguishing both the malignancies. The highest incidence of MEC in larynx mostly occurs in the supraglottic region (61%), where laryngeal glands are mostly located at. This is as shown in this case reported. The site of occurrence differs from SCC as SCC of larynx usually affects the glottis region. Laryngeal MEC has a wide range of diseases from localized invasion to highly malignant lesions as described in this article. The origin of these lesions is usually from the reserve cells in the excretory ducts of submucosal glands. It can also be from the squamous cells in the laryngeal surface epithelium. However, MEC of the larynx is a rare entity in the literature. There are several reasons for this rarity that are worth mentioning. Sampling errors and interpretation errors of the tumor specimen can occur. It is quite difficult to identify these lesions when occurring at sites other than the salivary glands. Thus, these lesions tend to be diagnosed in a more advanced stage. For low and intermediate-grade MEC tumors, the diagnosis is mostly uncomplicated as one can identify the presence of mucous cells and cystic components in these lesions. But for high-grade MEC neoplasms, the diagnosis is rather tricky and challenging as it can resemble other types of tumors histologically. This is especially true for SCC lesions. High-grade MEC tumors are composed mostly of solid islands of intermediate and epidermoid cells. On the other hand, MEC and SCC lesions are quite similar histologically, which can be tricky to establish the correct diagnosis. The presence of the intermediate and mucous cells in MEC tumors is one of the distinguishing features. The prognosis of the MEC tumors mainly relies on factors such as tumor grading and clinical staging. Grading of the tumors is seen as a significant indicator of its prognosis. Thus, about 80% of the 5-year-survival rate was reported by Ho et al. for MEC of larynx generally. But, a poorer prognosis of about 50% was recorded for high-grade tumors while low-grade tumors had a prognosis of 91-100%. Thus, a good cure rate and prognosis can be achieved if these neoplasms are treated early. The main treatment for MEC tumors is surgery, especially for localized disease, as it is quite radioresistant. This is in contrary to SCC of the larynx, which is more radiosensitive. Meanwhile, for primary SCC lesions, the malignant cells show many cytoplasmic processes and desmosomes. Also, the cells have intermediate filaments in their cytoplasm with no secretory granules. These features usually help differentiate primary SCC from the similar-looking MEC. Moreover, SCC malignancies have distinct tumor markers that help pathologists in differentiating it from the rest of the tumors. These tumor markers are p40, CK 5/6 and p63. The use of these markers is as evident in this article. A primary SCC of the salivary gland is mostly an aggressive tumor which can lead to a much poorer prognosis, compared to the conventional SCC. Some of the contributing factors to the poorer prognosis are age more than 60 years old, deeply fixed tumor, any presence of ulceration, cervical nodal metastasis and facial nerve asymmetry. The management option is total parotidectomy, with radical neck dissection, followed by postoperative radiotherapy. However, the 5-year survival range is still at about 25-30% even with sufficient treatment. Both the patients discussed here did not exhibit any striking similarities to be compared upon. Nonetheless, they were both ex-smokers. The carcinogenesis mechanism involved among smokers and the development of squamous cell carcinoma had already been well established in the literature. No genetic analysis was however performed. Thus, for future studies, genetic analysis could be performed for patients with common tumors in exceptional locations to aid in the diagnosis and prognosis. A study done in Egypt in 2009, reported that the expression of cyclooxygenase isoform (COX-2) was much raised in tumors with positive lymph node involvement than that of node-negative tumors. The more aggressive MEC tumors were also found to have higher expression of COX-2. Another biomarker, Bcl-2, also known as B-cell lymphoma protein 2 alpha was also seen to be increased in MEC tumors. Thus, it was concluded that both COX-2 and BCL-2 have good predictive values to determine cervical lymph node metastasis in MEC tumors. In summary, from the case series reported, we came up with a comparison table to help distinguish both mucoepidermoid carcinoma and squamous cell carcinoma.
In larynx-Supraglottis
In larynx-Glottis
Unknown
Smoking and alcoholRadiation exposure
Female (in salivary glands)
Male
CK 14
p40, CK 5/6, p63
Yes
No
Yes
No
Yes
No
No
Yes
Mainly surgery, if localised disease
Mainly radiotherapy
Depends on grade of tumor
60%