Dedifferentiated Salivary Hybrid Carcinoma of the Maxillary Sinus with Pagetoid Spread to the Overlying Lining Mucosa

Hybrid carcinoma of salivary glands is a very rare subtype of malignant salivary gland neoplasm with a little more than 30 cases documented in the literature [1–20] (See Table 1). Most cases of hybrid carcinoma of salivary glands have been reported in the parotid gland and palate. To date, only a single case of salivary hybrid carcinoma has been observed in the maxillary sinus [14]. Although dedifferentiation/high grade transformation has been described in a variety of malignant salivary gland tumors, this phenomenon has not been reported in salivary hybrid carcinoma [21, 22]. Furthermore, while pagetoid spread of neoplastic cells from a malignant salivary gland tumor to the overlying lining mucosa has been documented in the oral mucosa [21–23], such an incidence has not been reported in the maxillary sinus. Herein, we describe an additional case of hybrid carcinoma of salivary glands in the maxillary sinus that demonstrated simultaneous occurrence of high-grade transformation and intraepithelial pagetoid spread to the overlying sinus mucosa. This rarely reported phenomenon is not only of academic interest but can also pose significant diagnostic difficulties, particularly in distinguishing from a HPV-related carcinoma with adenoid cystic-like features. Table 1 Reports of hybrid salivary gland carcinomas Case Report A 68-year-old male patient was admitted to our hospital with the clinical presentation of a mass in the left maxillary sinus. A previous biopsy performed at an outside institute was diagnosed as squamous cell carcinoma involving a polyp originating in the left maxillary sinus. His clinical history was otherwise significant for hypertension, diabetes mellitus, and coronary artery disease. In May 2013, the patient underwent partial maxillectomy including complete removal all mucosa from the left maxillary sinus as well as the anterior skull base. Secondary to positive surgical margins, a complete maxillectomy and partial resection of the hard palate with left osteocutaneous radial forearm flap was performed in July 2013, followed by radiation therapy. In May 2014, the patient developed lymphadenopathy of the left neck consistent with nodal metastasis. A left neck dissection were performed in June 2014 revealing two positive level II lymph nodes. The partial maxillectomy was composed of a 4.5 × 4 × 1.1 cm aggregate of multiple fragmented pieces of erythematous, pink-grey soft tissue resembling mucosa, partially covering cartilage and bone. The microscopic sections exhibited a peculiar interplay of morphologies: the majority of the tumor displayed typical morphologic features of an adenoid cystic carcinoma characterized by a dual population of relatively low-grade, monotonous basaloid myoepithelial and eosinophilic cuboidal ductal cells arranged in cribiform, solid, and tubular architectures. Basophilic mucoid and collagenous eosinophilic material was observed in the pseudocytsic spaces of the cribiform tumor nests (See Fig. 1a). The adenoid cystic carcinoma comprised approximately 50 % of the total mass. In addition, 20 % of the tumor exhibited distinct areas of solid nests and tubules of polygonal myoepithelial cells with clear cytoplasm in the periphery and central cuboidal eosinophilic ductal cells consistent with an epithelial–myoepithelial carcinoma (See Fig. 1b). The third component of the tumor was composed of high-grade polygonal eosinophilic neoplastic cells that displayed pleomorphic, vesicular nuclei and scattered prominent nucleoli. The high-grade neoplastic cells were arranged either as distinct solid nests (See Fig. 1c) or intimately intermingled with the basaloid cells within the nests of the adenoid cystic carcinoma. Notably, this high-grade component focally filled and expanded superficial ducts that opened directly to the overlying lining mucosa (See Fig. 1d). The surface epithelium was also infiltrated by the high-grade neoplastic cells in a pagetoid spread pattern (See Fig. 1e). The high-grade neoplastic cells were predominantly identified in the upper levels of the surface epithelium, sparing the basal layer of the lining mucosa. Fig. 1 a–f Salivary hybrid carcinoma composed of adenoid-cystic carcinoma (a) and epithelial-myoepithelial carcinoma (b) with foci of high-grade transformation (c). High-grade transformed neoplastic cells expand a secretory duct opening to the surface ... Immunohistochemical studies with a panel of antibodies demonstrated a diverse immunohistochemical-staining pattern between the different neoplastic components as illustrated in Table 2, which supported the spectrum of histologic differentiation in this tumor. Notably, most of the solid nests of high-grade neoplastic cells were surrounded by an intact layer of p63 positive myoepithelial layer (See Fig. 2a),indicative of their predominantly intraductal/in situ growth. In addition, there were significant differences in the expression of Ki-67, p53, and Her2-neu in the high-grade neoplastic cells compared to the low grade components of adenoid cystic carcinoma and epithelial-myoepithelial carcinoma (See Fig. 2b–f). Overall, the histologic and immunohistochemical findings were consistent with those of a salivary hybrid carcinoma composed of adenoid cystic and epithelial-myoepithelial carcinoma, associated with high-grade transformation and pagetoid spread in the lining epithelium. Table 2 Tumor immunophenotypes Fig. 2 a–f Immunohistochemical studies display a layer of p53 positive myoepithelial cells at the periphery of the nests of transformed neoplastic cells (a). There is a significantly higher expression of Ki-67 (b) and p53 in the high grade component ... The re-excision showed predominantly residual adenoid cystic carcinoma and scattered foci of invasive high-grade adenocarcinoma. Interestingly, whereas the adenoid cystic component was mostly confined within the stroma of the respiratory mucosa, the high-grade adenocarcinoma primarily invaded the underlying bone (See Fig. 1f), indicative of the aggressive nature of this component. The lining mucosa still demonstrated focal involvement by high-grade carcinoma in a pagetoid spread pattern. A residual component of epithelial-myoepithelial carcinoma was not identified. The left neck dissection performed 1 year later demonstrated two positive lymph nodes harboring high grade adenoid cystic carcinoma. To evaluate the possibility of high-risk HPV infection, in situ hybridization was performed utilizing primers that can detect high risk HPV genotypes (i.e. 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 66) (methods previously described by Carlson et al. [24]). By in situ hybridization, no high-risk HPV DNAs were detected in any components of the tumor.