Sinonasal tract and nasopharyngeal adenoid cystic carcinoma: a clinicopathologic and immunophenotypic study of 86 cases

Abstract

Primary sinonasal tract and nasopharyngeal adenoid cystic carcinomas (STACC) are uncommon tumors that are frequently misclassified, resulting in inappropriate clinical management. Eighty-six cases of STACC included 45 females and 41 males, aged 12-91 years (mean 54.4 years). Patients presented most frequently with obstructive symptoms (n = 54), followed by epistaxis (n = 23), auditory symptoms (n = 12), nerve symptoms (n = 11), nasal discharge (n = 11), and/or visual symptoms (n = 10), present for a mean of 18.2 months. The tumors involved the nasal cavity alone (n = 25), nasopharynx alone (n = 13), maxillary sinus alone (n = 4), or a combination of the nasal cavity and paranasal sinuses (n = 44), with a mean size of 3.7 cm. Patients presented equally between low and high stage disease: stage I and II (n = 42) or stage III and IV (n = 44) disease. Histologically, the tumors were invasive (bone: n = 66; neural: n = 47; lymphovascular: n = 33), composed of a variety of growth patterns, including cribriform (n = 33), tubular (n = 16), and solid (n = 9), although frequently a combination of these patterns was seen within a single tumor. Pleomorphism was mild with an intermediate N:C ratio in cells containing hyperchromatic nuclei. Reduplicated basement membrane and glycosaminoglycan material was commonly seen. Necrosis (n = 16) and atypical mitotic figures (n = 11) were infrequently present. Pleomorphic adenoma was present in 9 cases; de-differentiation was seen in two patients. Immunohistochemical studies showed positive reactions for pan-cytokeratin, CK7, CK5/6, CAM5.2, and EMA, with myoepithelial reactivity with SMA, p63, calponin, S100 protein and SMMHC. CD117, CEA, GFAP and p16 were variably present. CK20 and HR HPV were negative. STACC needs to be considered in the differential diagnosis of most sinonasal malignancies, particularly poorly differentiated carcinoma, olfactory neuroblastoma and pleomorphic adenoma. Surgery (n = 82), often accompanied by radiation therapy (n = 36), was generally employed. A majority of patients developed a recurrence (n = 52) 2-144 months after initial presentation. Overall mean follow-up was 19.4 years (range 0.4-37.5 years): 46 patients died with disease (mean 6.4 years); 5 were alive with disease (mean 5.4 years), and 35 patients were either alive or had died of unrelated causes (mean 16.3 years). ACC of the SNT is uncommon. Recurrences are common. The following parameters, when present, suggest an increased incidence of either recurrence or dying with disease: mixed site of involvement, high stage disease (stage IV), skull base involvement, tumor recurrence, a solid histology, perineural invasion, bone invasion, and lymphovascular invasion.

Fig. 1

A diagrammatic representation of tumor stage, based on a maxillary sinus primary tumor (AJCC 2010). T1: confined to the sinus with no bone destruction; T2: tumor causing bone erosion into hard palate; T3: tumor invades into the subcutaneous tissues (and middle nasal meatus); T4: tumor invades into anterior orbital content

Fig. 2

An intact surface mucosa overlying the cribriform and cystic patterns of a sinonasal adenoid cystic carcinoma

Fig. 3

Bone invasion (left) and perineural and intraneural invasion (right)

Fig. 4

a Low power of a sinonasal adenoid cystic carcinoma showing various patterns of growth. Palisaded neoplastic cells around areas of glycosaminoglycan material. Hyperchromasia of the nuclei is appreciated. b A solid pattern demonstrated focal clefting around the periphery of the nodules of tumor. The cells had a very high nuclear to cytoplasmic ratio, with heavy nuclear chromatin distribution. c The large cystic spaces were filled with light pink to heavily “blue” stained material. There is an intact surface respiratory epithelium

Fig. 5

“Blue-goo” matrix material could appear eosinophilic and granular (left) while the more characteristically “blue” mucinous material (right) was most common. “Carrot-shaped” nuclei surround the cysts

Fig. 6

A high power illustrating the bland nuclear appearance and an intermediate to high nuclear to cytoplasmic ratio. Note the small gland or tubule formation, in addition to the larger cysts

Fig. 7

Immunohistochemistry was not requisite for the diagnosis. However, the following patterns were present: CD117 (C-kit) was often accentuated around true lumens (left), while the p63 highlighted the basal/myoepithelial cells within the tumor (right)

Fig. 8

Overall actuarial survival of sinonasal tract adenoid cystic carcinoma

Fig. 9

Kaplan-Meier plots based on various statistically significant clinical and histologic parameters. The overall survival of sinonasal tract adenoid cystic carcinoma patients is demonstrated for recurrence, perineural invasion, bone invasion, lymphovascular invasion, epicenter (anatomic site) of the tumor, histologic type, stage and tumor grade