Primary ductal adenocarcinoma of lacrimal gland (PDALG) has emerged as a distinct subtype of lacrimal gland adenocarcinoma [1] that accounts for 2% of all epithelial lacrimal gland tumors [2]. Microscopically, this neoplasm exhibits similar characteristics to ductal carcinoma of salivary gland and breast. It usually arise de novo and in only one case it was found as a malignant component of carcinoma ex pleomorphic adenoma [1,2]. Ductal adenocarcinomas are known to have highly malignant nature with only 13 cases reported of lacrimal gland. Out of the 13 published cases, only one has occurred in a female patient. To understand its biological behavior, management and prognosis, each case needs to be reported. We report a second case of PDALG in female and review of literature to describe the clinical, imaging and immunohistochemical features, management and prognosis of this malignancy.

A 38-year-old female presented with painful mass in the right upper eyelid since 2 months. Visual acuity was 20/20 OU. Hertel exophthalmometry showed 2 mm proptosis with inferior dystopia OD (Figure 1a). Computed tomography showed a relatively well-defined mass with diffuse enhancement in lacrimal gland region associated with erosion of roof of the orbit (Figure 1b).

Figure 1: a: Clinical photograph showing fullness in right lacrimal gland region with inferior dystopia of eyeball. b: CT scan showing an irregular mass with diffuse enhancement in lacrimal gland fossa associated with erosion of roof of the orbit and no intracranial extension.

Patient underwent anterior orbitotomy. Thinning of the orbital roof was noted during surgery; however the tumor was excised in-toto along with periosteum. Histopathological examination revealed that tumor was comprised of duct like structures as main component and trabeculae, sheets, hyalinised stroma as infiltrative component (Figure 2a).

Figure 2: a: Microphotograph shows in situ duct like structures and infiltrative trabeculae, sheets with hyalinization and fibrosis in the stroma (H&E stain 100X). b: High power view shows marked pleomorphism , prominent nucleoli and mitotic figures (H&E stain 400X). c: Poorly differentiated component of the tumor with perineural invasion (arrow) (H&E stain 200X). d: Immunohistochemical staining showing positivity for epithelial membrane antigen (200X).

The tumor cells displayed varying degree of pleomorphism, numerous mitotic figures and prominent nucleoli (Figure 2b). Perineural and intravascular invasion was present (Figure 2c). Invasion into the orbital fat was present. Immunohistochemical analysis showed positivity to cytokeratin-7, 10 and epithelial membrane antigen (Figure 2d). Stains for cytokeratin-20, S-100, proto-oncogene Her-2/neu, p-53 and estrogen receptor were negative. The diagnosis of primary ductal adenocarcinoma of the lacrimal gland was made.

Positron emission tomography scan revealed no systemic metastasis. Patient refused exenteration and was advised radiotherapy in view of invasion into the orbital fat. 8 weeks later, she developed local recurrence with intracranial and maxillary sinus involvement. Palliative radiotherapy was administered however, patient died of progressive disease after 6 months.

Literature review revealed 13 de novo cases of PDALG, out of which 8 had been reported from Japan [4,7,9,11]. Mean age of presentation was 58.6 years (range: 39-78 years). Our patient presented at 38 years and is the youngest case of PDALG reported till date. All the reported cases were males, except two including the present case (M:F=12:1). Most common presentation was painless mass in the upper eyelid of less than 1 year duration. On imaging, 11 cases had irregular mass with ill-defined margins.

Associated bony destruction was seen in 3 cases [7,11] and bone remodeling without destruction was present in one case [5]. Five patients underwent tumor resection with globe-sparing surgery, orbital exenteration was done in 7 cases and post-operative radiotherapy was given in 7 cases (Table 1).

Table 1: Clinical data, management and outcomes of the published cases of primary ductal adenocarcinoma of the lacrimal gland (in chronological order).

The diagnosis was based on histopathology which depicts the in situ ductal component and infiltrative trabeculo-ductular component; the special stains and immunohistochemistry had confirmatory role. In all the reported cases, histopathology was consistent with PDALG except one which was hypothesized to be arising from pre-existing pleomorphic adenoma [12]. In most of the cases including the present case, on immunohistochemistry, tumor displayed strong positivity to cytokeratin-7, epithelial membrane antigen and carcinoembryonic antigen. In an only reported series of 5 patients11, authors also found androgen receptor positivity in all the cases (Table 2). There was a significant resemblance in the immunohistochemical pattern with salivary duct carcinoma, as this tumor was also found to be strongly reactive to cytokeratin-7, epithelial membrane antigen, carcinoembryonic antigen and androgen receptors similar to salivary duct carcinoma [13]. In contrast to the other histologic counterpart, duct carcinoma of the breast, immunoreactivity to estrogen and progesterone receptors was not found in any of the cases. Over expression of proto-oncogene Her-2/neu and p53 was seen in some cases [11], however it could not be correlated with distant metastasis and poorer prognosis unlike, in the breast cancer, where it is a significant predictor of overall survival [14].

Table 2: Imaging and immunohistochemical features of the published cases of primary ductal adenocarcinoma of the lacrimal gland.

Out of 13 reported patients local recurrence was seen in one patient [7,5] patients developed lymph node metastasis and distant metastasis was seen in 7 patients (Table 1). The most common site for metastasis was brain [4,7,11]. Six of 13 patients succumbed to the disease albeit short follow up in most of the alive cases. The clinical behavior in our case was quiet aggressive as the history of illness was of 2 months and recurrence developed within span of 2 months after mass excision, followed by metastasis and death in 6 months. The present case differs from the previously published cases, being the youngest and the one with worst outcome owing to rapid progression of the disease. This report adds to the literature, the highly malignant nature of this lacrimal gland neoplasm and emphasizes on aggressive management to improve the prognosis and life salvage.