A lacrimal sac tumor is a general term for benign and malignant neoplasms originating in the lacrimal sac, which is part of the lacrimal drainage system. The lacrimal sac is located at the junction of the lacrimal bone and the frontal process of the maxilla, and is lined with pseudostratified columnar epithelium with cilia and goblet cells.
It is an extremely rare tumor with fewer than 1000 cases reported worldwide 3); approximately 55% of all lacrimal sac tumors are malignant. Histologically, they are broadly divided into epithelial tumors (60–94% of all cases) and non-epithelial tumors (about 25%). Historically, epithelial tumors have been considered the most common, but some recent series report lymphoma as the most frequent 3).
Benign tumors are more common in younger individuals, while malignant tumors peak in the 50s. Because they clinically resemble chronic dacryocystitis or nasolacrimal duct obstruction, they are easily misdiagnosed, with a median diagnostic delay of 8–10 months 3). The overall mortality rate for malignant lacrimal sac tumors is about 38%, making early recognition and management essential.
Fewer than 1000 cases have been reported worldwide, making it a particularly rare disease among ocular tumors. Diagnosis is often delayed, with a median delay of 8–10 months.
The initial symptoms of a lacrimal sac tumor are similar to those of chronic dacryocystitis.
Hemolacria is reported in 0–40% of lacrimal sac tumor cases, but only 8% are directly linked to malignancy3). If hemolacria is present, further evaluation including imaging is recommended.
The following factors are involved in the development of lacrimal sac tumors.
Imaging studies are essential for the diagnosis and evaluation of the extent of lacrimal sac tumors.
| Examination Method | Advantages | Main Findings |
|---|---|---|
| CT (contrast-enhanced) | Evaluation of bone changes and invasion | Bone erosion and destruction |
| CT dacryocystography | Identification of lacrimal duct obstruction site | Filling defect |
| MRI | Detailed evaluation of soft tissues | Extent and characteristics of the mass |
CT dacryocystography shows filling defects in the lacrimal sac but provides insufficient depiction of soft tissues. MRI is excellent for evaluating soft tissues, and in cases of melanoma, it shows characteristic signal patterns based on the paramagnetic properties of melanin: high signal on T1-weighted images and low signal on T2-weighted images 2). If sinus disease or tumor is suspected, contrast-enhanced MRI is added.
Lacrimal endoscopy allows direct visualization of the lacrimal lumen, and nasal endoscopy confirms the lower opening of the nasolacrimal duct and the presence of nasal tumors.
Fine-needle aspiration biopsy is not recommended due to difficulty in interpreting results and risks of bleeding, infection, and inadequate sampling. Direct incisional biopsy with sufficient tissue sampling is recommended. Endoscopic transnasal biopsy has been reported to be feasible in 73.9% of cases 3), offering a minimally invasive option.
Fine-needle aspiration biopsy is not recommended; direct incisional biopsy is the standard. Recently, endoscopic transnasal biopsy has been reported to be feasible in 73.9% of cases, providing a minimally invasive alternative 3).
For benign epithelial and mesenchymal tumors, complete surgical resection is the standard, with long-term follow-up for the risk of recurrence or malignant transformation. Papillomas are treated with endoscopic resection or laser thermocoagulation, with a reported 5-year recurrence-free survival rate of 67%. Inverted papillomas are locally aggressive with a high recurrence rate, requiring complete resection including the origin and frequent follow-up (every 3 months in the first year).
Surgery
Complete resection: Complete tumor resection including local periosteal removal is the standard. If there is extension beyond the lacrimal system, resection of the orbital and nasal walls may also be required.
Approach: 58.9% undergo open resection (modified Weber-Ferguson approach), 7.9% combined open and endoscopic, and 1.9% endoscopic alone 3).
Endoscopic-assisted resection: Disease-free survival rate of 84.6% (mean follow-up 58.6 months) 3).
Adjuvant Therapy
Postoperative radiotherapy: Recommended for cases with positive margins or advanced disease. Radiotherapy alone yields a 5-year overall survival rate of 84.7% and progression-free survival of 73.5% 1).
Chemoradiotherapy: Combination of weekly cisplatin 40 mg/m² plus 60 Gy radiation has been reported 1).
Neck dissection: For lymph node-positive cases, neck dissection plus ipsilateral parotidectomy is recommended 3).
The staging system for lacrimal sac malignant tumors (proposed) is as follows 3):
| Stage | Extent |
|---|---|
| Stage I | Limited to the lacrimal sac fossa |
| Stage II | Invasion of the globe, nasolacrimal duct, canaliculi, caruncle, or palpebral conjunctiva |
| Stage III | Invasion of the nasal cavity, paranasal sinuses, bone, or skin |
| Stage IV | Invasion of the orbital apex, meninges, brain, lymph nodes, or distant metastasis |
The recurrence rate of squamous cell carcinoma is reported to be 11–66%, and the 5-year survival rate is 61–88% 3). The overall mortality rate for malignant lacrimal sac tumors is approximately 38%, with transitional cell carcinoma and melanoma having the worst prognosis.
Lymphoproliferative tumors are relatively common among lacrimal sac tumors, with DLBCL accounting for 43% and MALT lymphoma for 24% 3).
Lacrimal sac melanoma is an extremely rare tumor with fewer than 100 reported cases worldwide3). Wide excision including total dacryocystectomy is the standard treatment, and immunohistochemical staining shows positivity for S100, HMB-45, and Melan-A2). In cases with lymph node metastasis, neck dissection is performed. The risk of hematogenous and lymphatic metastasis is high, and the prognosis is poor2).
The overall mortality rate for malignant lacrimal sac tumors is approximately 38%. The 5-year survival rate for squamous cell carcinoma is 61–88%3). Prognosis varies greatly by histologic type, with transitional cell carcinoma and melanoma having the worst prognosis.
The lacrimal sac is lined with pseudostratified columnar epithelium similar to the upper respiratory tract, and epithelial tumors arise from metaplasia of this epithelium. Squamous metaplasia due to pre-existing chronic inflammation provides a basis for papilloma development, and some undergo malignant transformation (mainly squamous cell carcinoma).
Epithelial tumors
Papilloma: The most common benign tumor. Exophytic and endophytic growth patterns. Inverted papilloma carries a risk of malignant transformation.
Squamous cell carcinoma: Typically well-differentiated with keratin pearls. Accounts for 70–81% of epithelial malignancies3).
Transitional cell carcinoma: Papillary growth pattern. Non-keratinizing squamous cell carcinoma.
Adenoid cystic carcinoma: Cribriform pattern. Recurrence rate 70–100%.
Non-epithelial tumors
Lymphoproliferative: Predominantly DLBCL and MALT lymphoma. 2–8% of all cases.
Melanocytic: 4–5% of all cases. Derived from melanocytes of the lacrimal sac epithelium or seeding from conjunctival melanoma.
Mesenchymal: 12–14% of total. Fibrous histiocytoma is the most common.
Molecular biological characteristics: TP53 and CIC mutations and ERBB2 amplification have been reported in lacrimal sac carcinoma 3). In squamous cell carcinoma, FGFR p.G388R mutation (associated with recurrence and poor prognosis), HER2 amplification, and PD-L1 overexpression have been identified 1). In mucoepidermoid carcinoma, MAML2 gene fusion and EGFR amplification are observed, and it has been suggested that the molecular profile may differ from mucoepidermoid carcinoma at other sites 3).
Cemiplimab (anti-PD-1 antibody) combined with cisplatin-docetaxel showed a favorable treatment effect in one case of locally advanced lacrimal sac squamous cell carcinoma 3). The efficacy of PD-1/PD-L1 inhibitors for PD-L1-positive head and neck squamous cell carcinoma has been reported in multiple trials, but the risk of hyperprogression has also been noted 1).
HER2-positive lacrimal sac squamous cell carcinoma was first reported 1), and the efficacy of trastuzumab deruxtecan (T-DXd) for HER2-positive solid tumors (DESTINY-PanTumor02 trial) is attracting attention. For adenoid cystic carcinoma, apatinib (TKI) plus nedaplatin concurrent chemoradiotherapy resulted in complete response and 22-month disease-free survival 3).
Intensity-modulated proton therapy (IMPT) showed favorable treatment results in one case of lacrimal sac squamous cell carcinoma while reducing dose to surrounding normal tissues 3). Additionally, brachytherapy with I-125 seeds was performed in 4 cases of lacrimal sac malignancy, with all patients surviving at a median follow-up of 28 months 3).
In 2024, robot-assisted eye-sparing lacrimal sac tumor resection was performed for the first time in a case of pT1 squamous cell carcinoma 3). Also, MD Anderson reported 7 cases of neoadjuvant chemotherapy with platinum + taxane + cetuximab or pembrolizumab, achieving eye preservation 3).
