Mucoepidermoid Carcinoma of the Lacrimal Sac: Clinical-Pathologic Analysis, Including Molecular Genetics

Abstract

Purpose: The aim of this study was to assess whether mucoepidermoid carcinoma of the lacrimal sac is a counterpart of CRTC1/3-MAML2 gene fusion-related salivary gland mucoepidermoid carcinoma.

Methods: In this retrospective observational case series, pathology records were searched for all cases of lacrimal sac mucoepidermoid carcinoma diagnosed between 1990 and 2018. Data collected included demographics, clinical findings, management, and follow-up. Pathologic parameters assessed included tumor morphology, immunohistochemistry, and MAML2 and EGFR fluorescence in situ hybridization (FISH) studies.

Results: Six patients with mucoepidermoid carcinoma of the lacrimal sac, 5 males and 1 female, with a median age of 63 years (range 24-66) were identified. Five tumors were managed with radical resection and 1 patient underwent orbital exenteration. None of the patients developed recurrence or metastases with an average follow-up of 18 months (range 13-23). All tumors had morphologic and immunohistochemical features of mucoepidermoid carcinoma and overexpressed EGFR. MAML2 FISH was negative for MAML2 rearrangement in all tumors. EGFR FISH demonstrated EGFR amplification in 1 tumor.

Conclusions: Mucoepidermoid carcinoma of the lacrimal sac is not a lacrimal sac counterpart of CRTC1/3-MAML2 gene fusion-related salivary gland mucoepidermoid carcinoma. EGFR pathway activation and EGFR amplification in a subset of these neoplasms suggest the potential role for anti-EGFR agents.

Keywords: Adenosquamous carcinoma; CRTC1/3-MAML2; EGFR; Lacrimal sac carcinoma; Lacrimal sac mucoepidermoid carcinoma; MAML2; Mucoepidermoid carcinoma.

Fig. 1

Clinical and pathologic characteristics of lacrimal sac tumor in patient 3. a Right medial canthal mass, focally situated above the medial canthal tendon (arrow). b Axial post-contrast computed tomography scan demonstrates a mass in the region of the lacrimal sac (arrow), with focal adjacent bony changes and with extension into the medial orbit. c Well-differentiated mucoepidermoid carcinoma is composed of epidermoid cells with intercellular bridges (arrow), mucocytes (arrowheads), and cells with intermediate morphology without appreciable nuclear atypia or mitotic activity, forming mucin-filled cysts (stain, hematoxylin-eosin; original magnification, ×100). dEGFR fluorescence in situ hybridization studies demonstrate amplification of red EGFR signal (arrowheads), which is 2–4 times the size of the green centromeric (Con 7) signal in neoplastic cell nuclei, compatible with an EGFR/Con 7 ratio of >2. In contrast, the cell nucleus without EGFR amplification features EGFR and centromeric signals of similar size (arrow).

Fig. 2

Clinical and pathologic characteristics of lacrimal sac tumor in patient 5. a Right medial canthal mass (arrow). b Axial post-contrast computed tomography scan demonstrates a mass in the region of the lacrimal sac (arrow), with focal bone destruction and with extension into the medial orbit. c Invasive neoplasm, composed predominantly of nonkeratinizing epidermoid cells and intermediate cells, without readily identifiable mucocytes forms solid nests and cysts in a background of markedly desmoplastic stroma. d Alcian blue highlights the intracytoplasmic mucin in mucocytes (arrow). e Intense membranous staining with EGFR (arrow) is present in most neoplastic cells. (stains: a, hematoxylin-eosin; b, Alcian blue; c, EGFR; a–d, original magnification, ×50).