The major histologically identified cause of ANDO is non-specific chronic inflammation resulting in a blockage of the lacrimal outflow system. In our study, ANDO was associated with non-specific histological changes in 79.2% of the cases and most often showed a chronic non-granulomatous inflammation. These findings are consistent with those reported in other series. Some studies report no specific histologic features were found in 98% of the ANDO cases [4, 13]. In a study by other authors, chronic inflammation was diagnosed in 95% of specimens, and fibrosis was detected in 3.8% [12]. Other authors reported non-specific pathology in 96.49% of cases [10].
Previous studies have demonstrated that secondary causes, including primary or secondary tumors, tumor-like lesions, inflammatory diseases, and mechanical obstruction of the lacrimal drainage system represent the etiology of ANDO in 0–14.3% of cases [8, 9, 11, 12, 14, 15]. In our study, three specific histological findings associated with ANDO were identified after histopathological analysis of the lacrimal sac wall. They included three neoplastic lesions - an adenoid cystic carcinoma, an eccrine spiradenoma and one small B cell lymphoma case. The prevalence of ANDO caused by neoplastic lesions was 1.1%, which is similar to other studies, although it is lower than 8.2% of the cases of ANDO by other authors [4, 9, 10]. One possible explanation for the difference is that their specimens may have been selected using laboratory findings but not surgical records [9]. Ecrine spiradenomas are rare benign sweat gland tumors, and few cases involving the eyelids have been described [16, 17]. This type of tumor is specific for skin adnexa; therefore, it could be interpreted as a skin tumor with ANDO. The patient with spiradenoma in our study did not complain of pain, which is common for this type of tumor [17]. Lacrimal sac adenoid cystic carcinoma is a rare malignant tumor that can be lethal [18]. Lacrimal sac lymphomas are rare and malignant tumors, that often are left misdiagnosed. They present with symptoms of dacryocystitis and epiphora. There are reports which describe 3 lacrimal sac Leukaemia/Small-Cell Lymphocytic Lymphoma cases [19]. Some authors found only 3 cases of adenocarcinoma among 74 malignant lacrimal sac tumors, and others reported 4 adenocarcinomas among 115 lacrimal sac neoplasms [5, 6]. According to previous studies, positivity for CD117 and CD43 is a sensitive and relatively specific marker of adenoid cystic carcinoma, as demonstrated in our study [20, 21].
Due to neoplastic causes, ANDO is reported to be relatively rare; however, overlooking this potentially lethal etiology can delay diagnosis until an advanced stage [6, 7, 22]. Our study demonstrated that the common clinical symptoms of ANDO, such as epiphora and purulence, did not allow for differentiation between the neoplastic lesions and non-specific etiology, however, a specific sign solid palpable mass helped to suspect the tumor in spiradenoma and small B cell lymphoma cases. Most of the primary tumors of the lacrimal sac are malignant, with mortality as high as 37.5%; thus, prompt diagnosis is important for effective treatment [6, 10]. In a study was made an analysis of 82 cases of dacryocystic tumors showed that primary diagnosis of dacryocystitis was established in 5% of patients; in 55% of patients, diagnosis was confirmed only when the tumor had already invaded the adjacent tissues, and in 18% of patients, the tumor was diagnosed when distant metastases were already present [6]. Another study examined 22 clinical cases of lacrimal sac tumors and found that in 27% of cases, the primary diagnosis was incorrect, and the patients were previously treated for dacryocystitis [7].
Considering the low frequency of cases with this specific etiology, many researchers advocate biopsy of the lacrimal sac wall only when anamnestic, clinical, or intraoperative suspicion is present [4, 8–10]. However, this approach can potentially delay the diagnosis. In a Stage 1 tumor described by some authors, no palpable masses of the lacrimal sac were found, and no symptoms of ANDO were observed [6]. However, according to other authors, only 0.5% of 1294 cases were unsuspected when the specific pathologies of ANDO were diagnosed [14].
In our study, there was no significant difference in the disease history, clinical symptoms, or symptom duration between the cases of ANDO with specific and non-specific pathology or among the histological groups of non-specific inflammation, suggesting that the clinical context does not improve the identification of the cause of ANDO, and a biopsy is required. However, in the cases of eccrine spiradenoma and small B cell lymphoma, the palpation of a hard, subcutaneous mass and the intraoperative appearance of the tissues of the lacrimal sac led us to suspect a neoplastic disease. We did not observe a bloody discharge in any of the cases, as described [23, 24]. No suspicious clinical symptoms or intra-operative observations were noted in the adenocarcinoma of lacrimal sac. On the basis that only one case of preoperatively unsuspected malignant neoplasia were diagnosed histologically out of 275 specimens, the authors of this study recommend the selective biopsy of the lacrimal sac when there is clinical or intraoperative suspicion of a tumor.
The first limitation of the study is the number of cases. Larger sample size could make it possible to more accurately evaluate the frequencies of the secondary changes of ANDO and its associations with the clinical appearance. An insufficient sample size and biopsy specimens only from the medial-posterior wall of the lacrimal sac could be the reason why we did not find any specific inflammatory changes such as sarcoidosis or Wegener granulomatosis in our patients, as described in other studies [9, 10, 14]. Additionally, a larger sample size may have revealed a difference in the symptom duration between tumor group and the non-specific pathology group. Second limitation would be that data on the lacrimal system irrigation would add value to this study by improving the preoperative evaluation of the patients.
The authors conclude that chronic non-granulomatous inflammation of the lacrimal sac wall was the most frequent histological findings in cases associated with ANDO; however, three cases of tumors were diagnosed, and two of them were potentially lethal. The complaints of the patients were non-specific, and no associations between the histological findings, clinical presentation, and history of the disease were observed. Because the rate of malignant neoplasia was low, the authors support that a lacrimal sac biopsy is indicated only in the clinically or intraoperatively suspicious cases of ANDO.