Introduction

Tumors of the lacrimal gland are rare, with an incidence of less than 1 per 1,000,000 individuals per year [1]. They represent 6–12% of all orbital space-occupying lesions. Approximately 22–28% of these are primary epithelial tumors [2,3,4].

Since lacrimal gland tumors generally recapitulate the clinicopathologic features of their salivary gland counterparts, the World Health Organization (WHO) classification of salivary gland tumors can be applied to these tumors as well [5].

Fifty percent of primary epithelial tumors of the lacrimal gland are malignant. The most frequently encountered type is adenoid cystic carcinoma, which comprises approximately 20–30% of malignant neoplasms [6]. However, a variety of malignant tumor types that mirror their salivary gland counterparts have been described including ductal carcinoma, acinic cell carcinoma, primary squamous cell carcinoma, mucoepidermoid carcinoma, oncocytic carcinoma, polymorphous low-grade adenocarcinoma, carcinoma ex pleomorphic adenoma, myoepithelial carcinoma, lymphoepithelial carcinoma, epithelial-myoepithelial carcinoma, cystadenocarcinoma, primary sebaceous adenocarcinoma, and basal cell adenocarcinoma.

On the other hand, the most common benign tumor is pleomorphic adenoma, which comprises around 50% of all epithelial tumors [3, 4]. Other benign salivary type tumors that have been described in lacrimal gland are exceptionally rare [7] and include oncocytoma, cystadenoma, myoepithelioma, and Warthin tumor, also known as papillary cystadenoma lymphomatosum.

Here, we present, to our knowledge, the first description of a case of non-sebaceous lymphadenoma of the lacrimal gland.

Case report

In June 2015, a female, 62-year-old patient underwent a computed tomography (CT) scan of the brain due to an episode of syncope. As an incidental finding, the scan showed a 20 × 13 × 22-mm tumor in the orbital pole of the left lacrimal gland (Fig. 1). The patient was referred to the Department of Ophthalmology of our institution for further evaluation. The clinical examination showed a 3-mm exophthalmos with a 2-mm downward dislocation of the left eyeball, and magnetic resonance imaging (MRI) performed in September 2015 confirmed the initial CT findings.

Fig. 1
figure 1

Radiological presentation in coronal, contrast-enhanced, T1 magnetic resonance imaging (a) and intraoperative presentation (b), demonstrating sharply demarcated tumor mass

Full size image

Although there was no radiologic evidence of progression, the patient complained of increasing pain in the left orbital and temporal region and was referred to the Department of Oral and Maxillofacial Surgery for removal of the mass via lateral orbitotomy. The tumor was removed en-bloc, including the attached periorbit and a cuff of orbital fat.

The tumor was sharply demarcated with a tan cut surface, 1.5 cm in diameter (Fig. 2). No cystic areas were noted grossly or histologically. Microscopically, the tumor demonstrated prominent lymphoid stroma, with scattered germinal centers, and an epithelial component consisting of solid cords and trabeculae, with occasional tubuloglandular structures composed predominantly of basal and low columnar cells (Fig. 2). Tumor cells demonstrated very little atypia, and mitoses were rare. The Ki67 proliferation index was below 2%. Normal adipose tissue and lacrimal gland were noted at the periphery of the tumor capsule. Surgical resection margins were negative. Immunohistochemically, the basal (abluminal) tumor cells demonstrated a clear and strong nuclear reaction with the p63 antibody (Fig. 2), while cytokeratin 7 was positive in luminal cells (Fig. 2). Myoepithelial markers such as calponin and smooth muscle actin were negative, as well as SOX10, p16, and PCR for human papilloma virus (HPV) and Epstein-Barr virus (EBV)-encoded small RNAs. Based on the morphological and immunohistochemical findings, a diagnosis of non-sebaceous lymphadenoma was made.

Fig. 2
figure 2

Whole slide presentation of the tumor tissue (a). Basaloid cells forming clusters and tubuloglandular structures, intermixed with small, bland-looking lymphocytes (b) (hematoxylin and eosin, × 40). Cytokeratin 7 positively stained predominantly luminal cells (c), while strong nuclear positive reaction with the P63 antibody was observed in all tumor cells (d) (immunohistochemistry, × 10) n = 48

Full size image

The postoperative course was uneventful and the patient was discharged 5 days after the operation. A CT scan after 6 months showed no sign of recurrence and the scar was barely visible. The patient is now undergoing routine surveillance.

Discussion

Lymphadenomas are rare benign tumors of the major salivary glands, comprising a biphasic tumor cell population that exhibit groups of epithelial cells with or without sebaceous differentiation admixed with intense, reactive lymphoid proliferation. The clinicopathological features of lymphadenomas are poorly understood and their etiology is unknown. Less than 110 cases have been published since they were first described in 1960 [8].

Lymphadenomas typically occur in adults and usually present as a painless mass of long duration in the parotid gland. They are currently subdivided into sebaceous and non-sebaceous lymphadenomas. Non-sebaceous lymphadenomas are less common constituting only 1/3 of all reported cases [8, 9].

The pathogenesis of non-sebaceous lymphadenoma is poorly understood. The lymphoid component in particular is a subject of debate. Many authors regard the lymphoid component as reactive tumor-associated lymphoid tissue [10, 11] while other authors argue that the lymphoid stroma originates from intraparotid lymph nodes, with the epithelial component originating from salivary gland inclusions [12, 13].

In the present case, there were no histologic features (i.e., subcapsular sinuses) to suggest a pre-existing lymph node. Additionally, lacrimal glands do not generally contain intraglandular lymph nodes, making the nodal hypothesis less plausible, at least in this case. This description of a non-sebaceous lymphadenoma in the lacrimal gland does however further substantiate the validity of applying a similar classification scheme for both lacrimal gland and salivary gland tumors [14].

Differential diagnostic considerations for non-sebaceous lymphadenoma include other salivary tumors with prominent lymphoid stroma, such as mucoepidermoid carcinoma, Warthin’s tumor, and acinic cell carcinoma, as well as metastatic non-keratinizing squamous cell carcinoma or lymphoepithelial carcinoma, either HPV- or EBV-driven. The basaloid nested appearance argues against the aforementioned other tumor types. The absence of atypia, necrosis, and high mitotic counts, and negativity for HPV and EBV argue against a metastatic non-keratinizing squamous cell carcinoma or lymphoepithelial carcinoma.

Since 1991, to the best of our knowledge, only 53 cases of non-sebaceous lymphadenoma of the salivary glands have been reported in the literature [8, 10,11,12,13, 15].

In contrast to sebaceous lymphadenomas, non-sebaceous lymphadenomas are more common in women than in men. All non-sebaceous lymphadenomas involved the salivary glands but, in comparison with sebaceous lymphadenomas, extraparotid localization was evident in 40% of these patients (sebaceous lymphadenomas were intraparotid in nearly 90% of patients). No other demographic, clinical, or pathologic differences are known between these two subtypes. While follow-up data are limited, non-sebaceous lymphadenomas appear to be indolent tumors. Though rare cases of sebaceous lymphadenoma have been reported to undergo malignant transformation, this has not yet been described in non-sebaceous lymphadenoma [12].

We presented a case of a non-sebaceous lymphadenoma of the lacrimal gland, which, to the best of our knowledge, is the first report of such case in the medical literature. Our patient is symptom- and tumor-free more than 2 years after the initial presentation and surgery.