Polymorphous Low-Grade Adenocarcinoma of the Lacrimal Gland

Malignancies constitute half of all epithelial tumors of the lacrimalgland, with the majority being adenoid cystic carcinoma. Adenocarcinomas aremuch less common and generally demonstrate a poor prognosis. However, therecent application of histological subtyping to this group is leading to abetter characterization of what appears to be a heterogeneous collection.¹ We present a rare case of polymorphous low-gradeadenocarcinoma (PLA) of the lacrimal gland and discuss the clinical manifestationand prognosis in the context of similar tumors arising within the salivaryglands.

A 67-year-old man was initially seen with painless right upper eyelidswelling and conjunctival hyperemia across a 2-day period. The patient hadbeen previously asymptomatic, and old photographs were not available for review.Examination revealed him to be afebrile with a visual acuity of 6/12 OD and6/9 OS, 6 mm of proptosis, 3-mm inferior globe displacement, temporal conjunctivalhyperemia, and a tender mass in the superotemporal orbit. Extraocular movementswere limited in lateral and up gazes. The erythrocyte sedimentation rate was61 mm/h and white blood cell count, 13 200/µL (13.2 × 10⁹/L). Computed tomography findings showed an ill-defined mass in thelacrimal gland with a central radiolucency, rim enhancement, and no bony changes(Figure 1).

The mass was surgically explored via a skin-crease incision and appearedto consist of an abscess containing yellow-green viscous material. A cultureyielded no growth, but biopsy findings of the cavity wall revealed adenocarcinomathought to represent a primary lacrimal neoplasm rather than metastasis becausethe tumor expressed both cytokeratins (CAM 5.2) and S100 protein immunoreactivity.This immunoprofile, while not diagnostic, is typical of salivary gland tumorsincluding PLA.²

The patient underwent thorough systemic evaluation, including computedtomography of the chest, abdomen, and head. All investigation results werenormal, and a lid-sparing exenteration, including the biopsy track, was performed.

Histopathologic results revealed PLA of the lacrimal gland (Figure 2). The tumor cells were cytologicallybland, showing mild nuclear pleomorphism, and no mitoses were identified.However, there was extensive infiltration of the adjacent tissue, and thetumor displayed a variety of architectural patterns, including cribriform,tubular, and fascicular areas along with solid cell nests. Some necrosis wasseen centrally, and infiltration of the extraocular muscle was present. However,there was no perineural or vascular invasion or evidence of encapsulation,and the residual gland was atrophic with evidence of chronic inflammationand fibrosis. The patient made a good recovery and at last follow-up, 6 yearsafter initial examination, there was no recurrence.

Adenocarcinomas constitute 5% to 7% of epithelial tumors arising inthe lacrimal gland.^3,4 Untilrecently, these neoplasms were considered a single entity, classified underthe rubric of "adenocarcinoma" or "adenocarcinoma not otherwise specified."The advent of the World Health Organization Classification of Salivary GlandAdenocarcinomas⁵ proffered a framework forthe categorization of these uncommon lacrimal tumors. This classificationsystem is of significance because certain subtypes are associated with differingbiologic behaviors and outcomes. Three of these subtypes, salivary duct carcinoma,epithelial-myoepithelial carcinoma, and PLA, have been reported within thelacrimal gland.

The histological subtype of PLA seen in our case occurs almost exclusivelyin the minor salivary glands and is distinguished by cytologically bland,uniform cells with few or no mitoses. These cells assume a variety of growthpatterns including cribriform areas, solid nests, tubular regions, clusters,and "Indian file" columns. The cribriform areas are distinguished from adenoidcystic carcinoma by the relative lack of atypia of the component cells. Incontrast to pleomorphic adenomas, PLAs show infiltration into adjacent tissuesas well as a propensity for perineural invasion.^5,6

Within the lacrimal gland, PLA has only been reported on one previousoccasion. Ni et al⁷ mentioned 3 cases intheir series of 272 epithelial lacrimal tumors but did not document clinicalmanifestation, management, or outcome. The clinical manifestation of our patientwas distinctly unusual for an epithelial malignancy of the lacrimal gland.While inflammatory manifestations have been described in a few benign mixedtumors, usually on the basis of mucinous cyst rupture, such a manifestationfor malignant epithelial tumors is distinctly rare. Mucoepidermoid carcinomasin the lacrimal gland rarely cause inflammation, but with regard to adenocarcinomas,an acute inflammatory process has not previously been described. Heaps etal,⁸ in a series of 13 lacrimal adenocarcinomas,found a palpable mass, proptosis, and pain to be the most common manifestation.

In our case, the constellation of acute inflammation in conjunctionwith the central low-density area on computed tomographic scan was suggestiveof a lacrimal abscess. However, the absence of growth in the necrotic cavitycontents militated against an infective etiology. In addition, the centralarea was neither mucinous nor hemorrhagic, leading us to postulate a mechanismof central necrosis secondary to infarction to account for both the inflammatoryresponse and the radiological appearance.

While microscopic focal necrosis has been described in PLA, the occurrenceof significant central cavitation is unusual behavior in a low-grade tumor.⁹ In fact, within the orbit, central necrosis isgenerally a feature of aggressive, rapidly growing malignancies such as sarcomasor metastases. In comparison, PLA arising in the salivary glands has an indolentgrowth pattern and a relatively low incidence (6.5%) of metastasis to theregional lymph nodes.¹⁰ Local recurrenceoccurs in 22% but can usually be managed by further resection. Distant metastasisor death due to tumor is extremely rare, and as a consequence, PLA has a muchbetter prognosis than other salivary adenocarcinomas.¹⁰

The extrapolation of the course of salivary gland PLA to those originatingin the lacrimal gland was one of the factors considered in treating our patient.Although exenteration followed by radiotherapy has been advocated for lacrimaladenocarcinomas as a group,⁸ we electedto treat with exenteration alone on the basis of the known behavior of thistumor. This was in concordance with the management of salivary PLA, whichcarries an excellent long-term survival rate following local excision alone.Conversely, lacrimal tumors designated as lacrimal adenocarcinomas have, ingeneral, a poor prognosis. In the Heaps et al⁸ seriesof 13 patients, 6 died and 3 had recurrent disease. Of the 4 recurrence-freepatients, all had been treated with exenteration and radiotherapy. There was,however, no elucidation of histological subtypes in this series; thus, theguidelines for treatment of PLA in the lacrimal gland need further delineation.It is possible that given the favorable outcome of local resection for salivarygland PLA, a more conservative local resection with clear margins may havebeen adequate treatment in our patient. Nevertheless, some caution is justifiedin extrapolating management as well as classification from salivary glandtumors to those of the lacrimal gland.

In conclusion, it is evident the difference between the poor outlookascribed to adenocarcinoma of the lacrimal gland and the prognosis of PLA,at least in the salivary glands, justifies further characterization of thisentity within the orbit.

The authors have no relevant financial interest in this article.

Corresponding author: Dinesh Selva, MBBS(Hons), FRACS, FRANZCO, Oculoplasticand Orbital Unit, Department of Ophthalmology, Royal Adelaide Hospital, AdelaideUniversity, Adelaide, South Australia 5000 (e-mail: raheyes@mail.rah.sa.gov.au).