Histopathology Achieves Highest Diagnostic Accuracy of Lacrimal Gland Lesions

3d illustration of tear. A drop of the saline, watery fluid continually secreted by the lacrimal glands between the surface of the eye and the eyelid, 3d illustration
3d illustration of tear. A drop of the saline, watery fluid continually secreted by the lacrimal glands between the surface of the eye and the eyelid, 3d illustration
Most cases stem from nonspecific inflammation and lymphoproliferative disorders, according to the study.

A blood work-up cannot replace conventional histopathology for diagnosing lacrimal gland lesions, according to a report published in Clinical Ophthalmology.

Lacrimal gland swelling can signal many conditions that biopsies may help diagnose. This is the first study to review histopathological outcomes of surgical approaches in lacrimal gland biopsies.

Researchers in Saudi Arabia reviewed charts and lab work of 48 patients (aged 9 to 65 years, 62.5% female) who underwent lacrimal gland biopsy from 2014 to 2021. They assessed the accuracy of diagnoses based on radiological imaging by comparing them with final pathological reports.

They found that women and girls tended to have nonspecific inflammation of the lacrimal gland (76%). Men and boys more frequently had lymphoproliferative lesions (42%). Unilateral lacrimal gland swelling (75%) was more common than bilateral (25%), and the right side (52%) was more frequently impacted compared with the left. Periocular pain (40%), eyelid erythema (44%), and proptosis (31%) were other common signs and symptoms. Bilateral disease was most commonly found in lymphoproliferative lesions (n = 4).

The most common pathologies were nonspecific inflammation (n = 17) and lymphoproliferative lesions (n = 12). B-cell lymphoma was the most frequent lymphoid malignancy of the lacrimal gland. It presented half of lacrimal gland lymphomas. IgG4 was the most common pathology among specific inflammations. 

Most cases of nonspecific inflammation and lymphoproliferative lesion were unilateral (78%). Four lymphoproliferative lesions and 2 non-specific inflammation cases had bilateral presentation.

Patients with lymphoproliferative lesions tended to be older compared with patients with non-specific inflammation. Palpable lymph nodes were only present in the lymphoproliferative group (P =.07).

Blood tests were performed in 22 patients’ cases and diagnosed systemic disease in 18.2% of them (P =.02). Magnetic resonance imaging (MRI) had higher concordance rates with histopathology compared with computerized tomography (CT 42% vs 12%). Concordance was highest for pleomorphic adenoma (100%). Concordance was lower for non-specific inflammation (53%) and lymphoproliferative lesions (42%).

Histopathology produced final diagnosis in 41 of the 48 cases (18 of 22 subperiosteal approach, 15 of 18 transeptal approach, all 5 palpebral lobe biopsy, all 3 lateral orbitotomy for excisional biopsy).

Final diagnosis was achieved in 21 of 22 patients from whom 1 specimen was obtained during biopsy. Obtaining 2 specimens (n=11) provided a histopathological match with final diagnosis in 8 patients. When biopsies collected 3 specimens in 10 patients, there was a 70% match. Collection of 4 specimens (5 cases) all reached final diagnosis.

MRI of the brain and orbit of a patient aged 74 years who presented with 9-month history of lid swelling and proptosis showed right lacrimal gland enlargement and right medial rectus muscle enlargement. Histopathology showed lymphocytic infiltration suggesting chronic dacryoadenitis. Thyroid function test (TFT) signaled hyperthyroidism, prompting a diagnosis of lacrimal gland enlargement following thyroid-related orbitopathy (TRO). 

“Blood work-up should not be used to waive off the need for lacrimal gland biopsy, and the diagnosis should preferably be based on histopathology results,” the researchers report. “The MRI is a useful tool to diagnose lacrimal gland lesions; however, histopathology remains the gold standard method.”

Limitations of the study include the basis of surgical approach on surgeon preference and possibility of referral bias. 


Alturkistany W, Althaqib R, Alsulaiman N, et al. Lacrimal gland lesions biopsied in a tertiary eye center in Saudi Arabia: a clinical, radiological, surgical, and histological review. Clin Ophthalmol. 2022;16:191-200. doi:10.2147/OPTH.S331252