Sinonasal tract mucoepidermoid carcinoma: a clinicopathologic and immunophenotypic study of 19 cases combined with a comprehensive review of the literature

Abstract

Primary sinonasal tract mucoepidermoid carcinomas (MEC) are uncommon tumors that are frequently misclassified, resulting in inappropriate clinical management. The design of this study is retrospective. Nineteen cases of MEC included 10 females and 9 males, aged 15-75 years (mean, 52.7 years); males, on average were younger by a decade than females (47.2 vs. 57.7 years). Patients presented most frequently with a mass, obstructive symptoms, pain, and/or epistaxis present for a mean of 12.6 months. The majority of tumors involved the nasal cavity alone (n=10), maxillary sinus alone (n=6), or a combination of the nasal cavity and paranasal sinuses (n=3) with a mean size of 2.4 cm. Most patients presented at a low clinical stage (n=15, Stage I & II), with only 4 patients presenting with Stage III disease. Histologically, the tumors were often invasive (bone or perineural invasion), with invasion into minor mucoserous glands. Surface involvement was common. The neoplastic cells were composed of a combination of squamoid cells, intermediate cells, and mucocytes. Cystic spaces were occasionally large, but the majority were focal to small. Pleomorphism was generally low grade. Necrosis (n=5) and atypical mitotic figures (n=6) were seen infrequently. Over half of the tumors were classified as low grade (n=11), with intermediate (n=4) and high grade (n=4) comprising the remainder. Mucicarmine was positive in all cases tested. Immunohistochemical studies showed positive reactions for keratin, CK5/6, p63, CK7, EMA, and CEA in all cases tested, while bcl-2 and CD117 were rarely positive. GFAP, MSA, TTF-1, and S100 protein were non-reactive. p53 and Ki-67 were reactive to a variable degree. MEC need to be considered in the differential diagnosis of a number of sinonasal lesions, particularly adenocarcinoma and necrotizing sialometaplasia. The patients were separated into stage I (n=9), stage II (n=6), and stage III (n=4), without any patients in stage IV at presentation. Surgery occasionally accompanied by radiation therapy (n=2) was generally employed. Six patients developed a recurrence, with 5 patients dying with disease (mean, 2.4 years), while 14 patients are either alive (n=9) or had died (n=5) of unrelated causes (mean, 14.6 years). MEC probably arises from the minor mucoserous glands of the upper aerodigestive tract, usually presenting in patients in middle age with a mass. Most patients present with low stage disease (stage I and II), although invasive growth is common. Recurrences develop in about a third of patients, who experience a shorter survival (mean, 6.5 years). The following parameters, when present, suggest an increased incidence of recurrence or dying with disease: size ≥ 4.0 cm (P=0.034), high mitotic count (P=0.041), atypical mitoses (P=0.007), mixed anatomic site (P=0.032), development of recurrence (P=0.041), high tumor grade (P=0.007), and higher stage disease (P=0.027).

Fig. 1

An infiltrative epidermoid neoplasm is noted beneath an intact respiratory epithelium

Fig. 2

Goblet cell formation could be seen within transitional epithelium and forming small, papillary projections

Fig. 3

Heavy sclerosis and a desmoplastic-type stroma is noted between islands of epidermoid-intermediate epithelium and mucocytes. There is a hint of mucin extravasation

Fig. 4

The epidermoid component has a sheet-like distribution of neoplastic cells, immediately juxtaposed with mucocytes (goblet cells)

Fig. 5

Mucocytes contained a basophilic, granular mucus within the cytoplasm and within glandular spaces (left). Mucicarmine highlighted the mucus with a strong magenta reaction (right)

Fig. 6

High grade MEC showing an infiltrating tumor composed by cells with profound pleomorphism. Mucocytes were rare in this neoplasm

Fig. 7

The neoplastic cells were highlighted in the basal zones with CK5/6 (left), while more randomly with CK7 (right)

Fig. 8

The proliferation index was often increased, highlighted with a Ki67 (left). Many of the cell nuclei were p53 positive (right)