Lacrimal Sac Tumors: A Case Series

Abstract

Objective

The aim of the study was to describe the clinical presentation, management strategies, and outcomes in a case series of primary lacrimal sac tumors.

Methods

This retrospective study was conducted in Sheikh Fajilatunnessa Mujib Eye Hospital and Training Institute, Bangladesh, from July 1 to December 31, 2020, and included all patients who were evaluated, treated, and followed up for at least 6 months from January 2013 to October 2020. One patient developed a recurrence of the adenocarcinoma of the lacrimal sac after 1 year of primary treatment. Patients' demographic data were analyzed and reviewed from published articles on lacrimal sac tumors. We assessed patients clinically, followed by radiological evaluation. We also analyzed the biopsy technique, treatment modality, and recurrence. An oncologist reviewed all patients to prepare a plan for adjuvant treatment.

Results

Ten patients with lacrimal sac tumors were included in this study. Swelling in the medial canthal region was the most common presenting feature (100%), followed by epiphora (60%) and pain (30%). Open biopsy was preferred over fine-needle aspiration biopsy. Incisional biopsy or complete excisional biopsy was performed for all suspected malignancies. Malignant tumors were found in 7 (70%) cases, and benign tumors in 3 (30%) cases. Non-Hodgkin's lymphoma (NHL) (40%) was the most common malignant lacrimal sac tumor. Mucosa-associated lymphoid tissue lymphoma was 75%, and diffuse large B-cell lymphoma was 25% among the cases of NHL. Patients with epithelial malignancy were treated with external beam radiation therapy, while NHL patients were treated with chemotherapy (CHOP regimen). Recurrence was noted in 1 case (10%) of epithelial malignancy after 1 year of treatment.

Conclusion

Successful management of lacrimal sac tumors requires a high index of suspicion, as these are fatal tumors, often misdiagnosed as dacryocystitis. Nonepithelial malignancies are more predominant than epithelial malignancies, and hematolymphoid tumors are most frequent.

Introduction

Although lacrimal sac disorders are relatively common, comprising approximately 3% of clinical ophthalmic cases [1], neoplasms of the lacrimal sac are rare in clinical practice. Lacrimal sac malignant neoplasms can potentially be life-threatening [2, 3, 4, 5, 6, 7, 8]. A case series study reported on 1,264 orbital tumors, of which only 2 originated from the lacrimal sac [2]. A French study found only 2 tumors involving the lacrimal sac out of 1,705 malignant tumors of the eye and adnexa [3]. Lacrimal sac tumors can be classified as primary, secondary, or metastatic, and the majority are primary epithelial tumors.

Secondary lacrimal sac neoplasms arise from invading tumors of surrounding structures. Metastases from cutaneous melanoma, hepatocellular carcinoma, and even renal cell carcinoma have been described in the literature [4, 5, 6]. Approximately 72% are malignant tumors, which tend to be locally invasive and have a high recurrence rate. Benign tumors tend to develop in younger adults, whereas malignant tumors typically occur in the fifth decade, with a reported age range of 22–94 years. Thorough clinical workup and computed tomographic-dacryocystography, computed tomography (CT) scan of the orbit, or magnetic resonance dacryocystography can help in diagnosing a lacrimal sac tumor [9, 10, 11, 12, 13, 14, 15, 16, 17]. Lacrimal sac tumors are classified into 4 main categories including epithelial (71–75%), mesenchymal (12–15%), hematolymphoid (10–12%), and melanocytic (24%). Each lacrimal sac tumor category is further subdivided into benign and malignant. The majority of tumors are primarily epithelial tumors. Among benign tumors, epithelial and mesenchymal origins account for 59.5% and 30.6%, respectively. Among malignant tumors, approximately 72% are of epithelial origin, followed by hematolymphoid (17%), mesenchymal (6.4%), and melanocytic (3.5%) origins. The most common types of benign tumors are squamous papilloma, transitional papilloma, fibrous histiocytoma, oncocytoma, and solitary fibrous tumor (SFT)/hemangiopericytoma (HPC). Common malignant tumors include squamous cell carcinoma (SqCC), nonkeratinizing SqCC, non-Hodgkin's lymphoma (NHL), melanoma, and adenocarcinoma. Malignant melanoma and nonkeratinizing SqCC are associated with a high fatality rate. The most common malignant epithelial tumor is SqCC, accounting for 19–23% of all tumors [2, 3, 4, 5, 6, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27]. In this study, we aimed to report on ten cases of primary lacrimal sac tumor and to present an overview of lacrimal sac tumors.

Methods

This retrospective case series study was conducted at Sheikh Fajilatunnessa Mujib Eye Hospital and Training Institute, Bangladesh, from July 1 to December 31, 2020. The study was approved by the local institutional review board and conducted according to the principles of the 2013 revision of the Declaration of Helsinki. This study included all patients who were evaluated, treated, and followed up for at least 6 months from January 2013 to October 2020, and they all presented with a mass lesion in the lacrimal sac area. All patients underwent a thorough clinical assessment, followed by radiologic examination and histopathological analysis. We also scrutinized the biopsy technique, treatment modality, and recurrence. Open biopsy was preferred over fine-needle aspiration biopsy (FNAB). Excisional biopsy was performed in patients who presented lacrimal outflow obstruction with a clinically evident lacrimal sac tumor. An incisional biopsy was performed on a suspicious lacrimal sac tumor. One patient was diagnosed histologically as the adenocarcinoma of the lacrimal sac and again reported with recurrence in the follow-up time (September 2020). An oncologist reviewed all patients to prepare a plan for neo-adjuvant and or adjuvant treatment. Demographic variables, treatment modalities, and the clinical outcome were also analyzed. In addition, all published articles in the past 30 years that reported on lacrimal sac tumors were reviewed. Written informed consent was obtained from each patient before surgery and research work, and any accompanying images.

Results

Ten patients with lacrimal sac tumors were evaluated. All the cases were unilateral, and the right and left lacrimal sacs were involved in 40% and 60% of cases, respectively. The mean age ± SD was 35.67 ± 11.49 years in patients with benign tumors and 55.85 ± 14.73 years in those with malignant tumors. The age range was 37–70 years. There were 7 (70%) males and 3 (30%) females. Malignant lesions were found in 7 (70%) cases and benign lesions in 3 (30%) cases (Table 1). Swelling in the medial canthal region (Fig. 1) was the most common presenting feature (100%), followed by epiphora (60%), pain (30%), and proptosis (10%). Lymph node metastasis was found in 1 case (10%) with mucoepidermoid carcinoma. The sac patency test showed an obstruction in the lacrimal drainage system in all cases. CT scan of the orbit (Fig. 2) was the preferred imaging technique used to effectively diagnose the lacrimal sac lesion in 9 (90%) cases. One patient could not afford the cost of the imaging modality. Dacryocystectomy (DCT) with complete excision of the lesion was performed in 6 cases (60%), and deep incisional biopsy was performed in 4 cases (40%). FNAB was performed before excisional biopsy in 1 case (10%). Three cases (30%) had a benign tumor, and 7 cases (70%) had a malignant tumor. Benign tumors included squamous cell papilloma (1 case, 10%), reactive lymphoid hyperplasia (RLH) (1 case, 10%), and SFT (HPC) (1 case, 10%). In addition, epithelial tumors accounted for 4 cases (40%) and nonepithelial tumors for 6 cases (60%). Of the 4 epithelial tumor cases, 1 (25%) was benign and 3 (75%) were malignant. Among the nonepithelial tumors, 4 cases (66.7%) were malignant, whereas 2 cases (33.3%) were benign. The most common tumor was a hematolymphoid tumor, which comprised 50% of all tumors. Among the hematolymphoid tumors, the malignant lesion was NHL (4 cases, 80%), and the benign lesion was RLH (1 case, 20%). The most common subtype of NHL was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) (3 cases, 75%), followed by diffuse large B-cell lymphoma (DLBCL) (1 case, 25%). MALT lymphoma accounts for 30% of all tumors. Another nonepithelial tumor was SFT (HPC), which accounts for 10% of all tumors. The diagnosed benign epithelial tumor was squamous cell papilloma (1 case, 10%), and the diagnosed epithelial malignancies were SqCC (1 case, 10%), adenocarcinoma (1 case, 10%), and mucoepidermoid carcinoma (1 case, 10%). Among all the patients, 5 (50%) cases were treated by adjuvant external beam radiation therapy (EBRT), and 2 (20%) cases were treated by adjuvant 6 cycles of chemotherapy (CHOP therapy). EBRT was used to treat patients with malignant epithelial neoplasms, 1 patient with MALT lymphoma, and 1 patient with RLH (Fig. 3). All nonepithelial malignant tumors were diagnosed as NHL. Chemotherapy (CHOP regimen) was the useful treatment modality in 2 (20%) cases: 1 case of DLBCL and another case of MALT lymphoma. One patient (10%) with MALT lymphoma refused adjuvant treatment and was lost to follow-up. However, the patient returned after 2 years without recurrence. In patients with a spectrum of SFT (HPC), complete excision of the lesion was performed, and the patients were followed up for up to 8 months after the primary surgery; complete remission was achieved without recurrence during this period. A modified DCR was performed in a patient 6 months after the histological diagnosis of squamous cell papilloma. Recurrence was noted in 1 case (10%) with adenocarcinoma (Fig. 4) during the follow-up period.

Table 1.

Clinical features, management strategies, and outcome of lacrimal sac tumors of this study patients

Case No.	Age, years/gender (M/F)	Presenting symptoms	Duration, months	Imaging study	Primary surgery	Histopathology	Immunohistochemistry	Definitive treatment	Systemic evaluation	F/up, outcome: recurrence metastasis
01	56/M	Watering, swelling, painless lesion in the right lacrimal sac area	8	CT scan	FNAB followed by excision biopsy (DCT)	SqCC	Mucoepidermoid Ca	EBRT	Right preauricular submandibular lymph node	On follow up lymph node metastasis at diagnosis
02	70/M	Watering, swelling in the left lacrimal sac area	6	CT scan	Incision biopsy	SqCC	SqCC	EBRT	No systemic association	Followed up to 6 months, then lost for follow-up. No recurrence and metastasis
03	36/M	Painful swelling in the left medial canthal region	6	CT scan	Incision biopsy	NHL	MALT lymphoma	CHOP therapy	No systemic association	1½ years, complete remission. No recurrence
04	41/F	Swelling, painless firm lesion in the left lacrimal sac area	5	CT scan	Excision biopsy (DCT)	NHL	MALT lymphoma	−	No systemic association	Lost for F/up and came after 2 years, complete remission. No recurrence
05	21/M	Painless swelling in the right lacrimal sac area	24	CT scan	Excision biopsy (DCT)	SFT (HPC)	−	−	No systemic association	8 months, no recurrence. Complete remission
06	67/M	Watering, swelling, painful lesion in the left lacrimal sac area	9	CT scan	Conservative Rx- → pain regressed but swelling persisted, → excision biopsy (DCT)	NHL	DLBCL	CHOP therapy	No systemic association	3 years, no recurrence, complete remission
07	65/M	Watering, swelling in the left lacrimal sac area	8	CT scan	Excision biopsy (DCT)	Adenocarcinoma		EBRT	No systemic association	1 year, presented with proptosis, dystopia, restricted motility at 1 year, incision biopsy confirmed the recurrence
08	37/F	Watering, swelling in the right lacrimal sac area	10	CT scan	Incision biopsy	NHL	RLH	EBRT	No systemic association	9 months, no recurrence. Complete remission
09	49/F	Swelling in the right lacrimal sac area	12	CT scan	Excision biopsy (DCT)	Squamous papilloma	−	−	No systemic association	1 year follow-up. No recurrence
10	56/M	Watering, swelling in the left medial canthal area	8	−	Incision biopsy	NHL	MALT lymphoma	EBRT	No systemic association	Remission. No recurrence, within 1 year F/up

SqCC, squamous cell carcinoma; FNAB, fine-needle aspiration biopsy; NHL, non-Hodgkin's lymphoma; MALT, mucosa-associated lymphoid tissue; EBRT, external beam radiation therapy; RLH, reactive lymphoid hyperplasia; DCT, dacryocystectomy; CT, computed tomography; DLBCL, diffuse large B-cell lymphoma; SFT, solitary fibrous tumor; HPC, hemangiopericytoma.

Fig. 1.

A 36-year-old male patient presented with a painful nodular lesion involving the left medial canthal area like acute dacryocystitis.

Fig. 2.

A 56-year-old male complained of a nontender lesion of the right lacrimal sac area. Axial CT scan of the orbit showing mild enhanced soft tissue lesion involving the right lacrimal sac area. Incisional biopsy of the lacrimal sac and tumor extracted for histopathological confirmation. CT, computed tomography.

Fig. 3.

A 37-year-old female presented with a progressive swelling of the right lacrimal sac area for 8 months. Coronal CT scan of the orbit demonstrated an enhanced elongated lesion involving the right lacrimal sac. Incision biopsy was done, and histopathological examination led to a diagnosis of low-grade NHL (MALT lymphoma). Immunohistochemistry confirmed the diagnosis of RLH. RLH, reactive lymphoid hyperplasia; CT, computed tomography; MALT, mucosa-associated lymphoid tissue; NHL, non-Hodgkin's lymphoma.

Fig. 4.

A 65-year-old male presented with a palpable mass of the left lacrimal sac area. Axial and coronal CT scan of the orbit demonstrating a moderately enhanced lesion involving the left lacrimal sac area and also infiltrating the left medial rectal rectus muscle. This was a recurrence case of adenocarcinoma. CT, computed tomography.

Discussion

Lacrimal drainage system (LDS) tumors are extremely rare [2, 3, 4, 5, 6, 7, 8, 18, 19, 20, 21, 22, 23, 24, 25, 27]. Malignant tumors of the LDS comprise 55–100%, tend to be locally invasive, have a high recurrence rate, and can potentially be life-threatening. Approximately 894 cases of LDS tumors have been reported in the literature from the 1930s to date [18, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36].

Epithelial and Nonepithelial Tumors

Epithelial tumors accounted for 69–71% of cases, while nonepithelial tumors accounted for only 29–31%. Common benign epithelial neoplasms include squamous cell papilloma and transitional cell papilloma. Benign nonepithelial tumors are fibrous histiocytomas [23, 29, 30, 31, 32, 33, 34, 35, 37]. The others include epithelial oncocytoma and a benign mixed tumor. SqCC, nonkeratinizing SqCC, adenocarcinoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, and eccrine adenocarcinoma are common malignant epithelial tumors. Non-pithelial benign tumors include neurofibroma, fibrous histiocytoma, and a spectrum of SFTs. The reported frequency of malignant tumors ranged from 55% to 100%. The most common malignant epithelial neoplasm was SqCC (Table 2), accounting for 19% of all tumors [4, 20, 28, 33, 34, 35, 36, 38].

Table 2.

A review of demography profile, clinical features, and the pattern of lacrimal sac tumors of few case series study in the past 30 years

Authors	Cases, n, M/F	Mean/median age	Common presenting features	Epithelial/nonepithelial	Benign/malignant	Common benign epithelial tumor	Common benign nonepithelial tumor	Common epithelial malignant tumor	Common nonepithelial malignant tumor
Stefanyszyn et al. [4]	115	52	Epiphora (53%), recurrent dacryocystitis (38%), lacrimal sac mass (36%)	82/33	56/59	Squamous and transitional cell papilloma-32	Fibrous histocytoma-13	Squamous cell Ca-24	Lymphoma-09, melanoma-06
Yip et al. [38]	11 4/7	Median-72	Epiphora (82%)	0/11	0/11	−	−	−	Lymphoid-11
Parmar and Rose [5]	15 4/11	58.5	Epiphora (100%), lacrimal sac mass (66.7%)	9/6	02/13	Tr. papilloma-01	HPC-01	Sq cell Ca-02, Tr. cell Ca-02, mixed-01	Lymphoma-05
Valenzuela et al. [39]	11 7/4	58	Epiphora (82%), palpable mass extending above the MCT (64%), pigmented lesion (27%)	11/0	0/11	−	−	Squamous cell Ca-4	Melanoma-02
Sjö et al. [40]	15 6/11	71	Epiphora (85%), swelling (79%), dacryocystitis (21%)	0/11	0/11	−	−	−	MALT lymphoma-05, DLBCL-05
Bi et al. [29]	96	Median 46	Epiphora and lacrimal sac mass	83/12	05/91	−	Neurilemoma-2	Squamous cell Ca-64	MALT lymphoma-5, melanoma-3
Montalban et al. [6]	07 01/06	53	Epiphora (100%), palpable mass (100%)	6/1	0/7	−	−	Squamous cell Ca-5	Lymphoma-01
Sabundayo et al. [41]	05 2/3	49.8	Epiphora (100%), lacrimal sac mass (80%)	0/5	0/5	0	0	0	Lymphoma-05 (DLBCL-03)
Song et al. [42]	69 43/26	52	Epiphora in (59.4%), a palpable mass (52.2%)	All epithelial	All malignant	−	−	Squamous cell Ca	0
Kuo et al. [43]	65 30/35	Benign-60 Malignant-48	Epiphora (29), palpable mass (18), bloody tear (07)	14/5 (in malignant lesions)	46/19	−	−	Squamous cell Ca-06	DLBCL-03

DLBCL, diffuse large B-cell lymphoma; MALT, mucosa-associated lymphoid tissue.

In our cases, malignant tumors comprised 70% and benign lesions only 30%. In our study, benign tumors included squamous cell papilloma, RLH, and the spectrum of SFT (HPC). Seven cases were diagnosed as malignant tumors of the lacrimal sac; 43% were epithelial and 57% were nonepithelial malignant tumors. Nonepithelial malignant lacrimal sac tumors are NHLs, which comprise 40% of all lacrimal sac tumors. Epithelial malignancies include SqCC, adenocarcinoma, and mucoepidermoid carcinoma, represented as a single case (33.3%). Epithelial malignancy was less predominant than nonepithelial malignancy, which is different from the findings of other studies (Table 3).

Table 3.

A review of histological diagnosis, surgical strategies, and outcome of few case reports of lacrimal sac malignancy in the 21th century

	Katircioglu et al. [22]	de Palma et al. [45]	Pradhan and Custer [46]	Brannan et al. [47]	Vozmediano-Serrano et al. [48]	Altan-Yaycioglu et al. [49]	Bansal et al. [50]	Low et al. [51]	Palamar et al. [52]	Erickson et al. [53]	Iordanous et al. [37]	Ramos et al [54]	McGrath and O'Hagan [55]	Shao et al. [56]
Histological diagnosis	Squamous cell carcinoma	DLBCL	Plasmacytoma	Adenocarcinoma	Metastasis from renal cell carcinoma	Basosquamous carcinoma	Mucus secreting adenocarcinoma	Undifferentiated carcinoma	DLBCL	Tr. cell carcinoma	Muco epidermoid carcinoma	ACC-	Malignant melanoma	Malignant melanoma
Age, years/gender	40/M	72/F	83/F	59/M	56/F	58/F	40/F	55/M	55/F	61/M	44/M	41/F	56/F	50/F
Surgical strategy	FNAB followed by medial orbitotomy with en bloc excision of the tumor	Incision biopsy	Incision biopsy, bone marrow biopsy	Incision biopsy followed by extended orbital exenteration	Excision biopsy	Incision biopsy, after 2 weeks-wide excision frozen section biopsy	Incision biopsy, later-en bloc excision of the tumor	FΝAC, later-medial maxillectomy with medial orbitectomy with total excision of the LDS	Excision of the lacrimal sac, 1/3rd of NLD	Incision biopsy, later wide excision with maxillectomy, inferior turbinectomy, ethmoidectomy, and partial rhinectomy	Incision biopsy, extensive surgical resection with medial maxillectomy	DCT	DCR and tissue biopsy	Incision biopsy, later-excision of the tumor
Definitive Rx	EBRT	CHOP therapy	Chemotherapy-3 cycles + EBRT	EBRT	Denied EBRT	−		IMRT-66 Gy	R-CHOP-8 cycles	EBRT		EBRT-33 sessions	IMRT, + VMAT	Pt was refused for RT, and CT
Recurrence/metastasis, follow up	−	Skin involvement at 18 months	Yes, skin, and orbit involvement after 1 year	No, 2 years	No, 4 years	No, 18 months	;No, 6 months		No, 2 years, by PET-CT scan	No, 1 year	No, 1 month	No, 2 years	No, 6 years	−

VMAT, volumetric modulated arc therapy; EBRT, external beam radiation therapy; IMRT, intensity modulated radiation therapy; CT, computed tomography; DCT, dacryocystectomy; LDS, lacrimal drainage system; DLBCL, diffuse large B-cell lymphoma.

Demographic Profile and Clinical Features

The age range of patients with benign and malignant tumors was 34–60 years and 40–81 years, respectively, in different studies. Malignant tumors usually occur in older patients, and benign tumors are often diagnosed a decade earlier than malignant tumors [4, 5, 21, 34, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51]. In this study, the mean age of patients with benign and malignant tumors was 35.67 years and 55.85 years, respectively. In addition, the male-to-female ratio was 7:3; however, several studies have reported that females are slightly more preponderant than males [5, 39, 44]. Epiphora (53–100%) [4, 5, 39, 40, 41], bloody epiphora (11%) [48], nasal obstruction, and purulent or bloody discharge are common features of lacrimal sac tumors. With large or invasive tumors, the presentation includes a medial canthal or lacrimal sac mass (28–100%) above the medial canthal ligament [4, 5, 33, 34, 42, 43, 44], inflammation, proptosis, dysmotility, and dystopia [16, 36]. A palpable lacrimal sac mass extending above the medial canthal tendon has been noted in 9% of benign lesions and 74% of malignant lesions [52]. Benign epithelial tumors expand in the lacrimal drainage apparatus and are well circumscribed, mobile underneath the skin, and firm lesions on clinical examination [12, 13]. In a clinical study, malignant tumors often present with rapid growth of the lacrimal sac tumor, fixation to the skin, and a firm consistency with irregular borders. Secondary malignant tumors often invade the lacrimal drainage system, causing the same symptoms of LDS tumors in addition to the symptoms of their primary tumors [20, 21, 22]. In our study, common presenting features were epiphora (60%), a palpable mass in the lacrimal sac area (100%), and painful swelling (30%). A detailed history, and meticulous ophthalmic, nasal, and systemic workup with lacrimal probing of the patient are mandatory for patient assessment. Metastasis was found in a few reported cases (1–22%). It is difficult to distinguish between chronic dacryocystitis and lacrimal sac mucocele [3, 4, 5, 17, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 38]. The sac patency test revealed an obstruction in the LDS of this case series.

Imaging Study

Imaging is essential for identifying the location, size, and extent of the lesion; assessing the disease severity; and differentiating tumors from inflammatory and infectious lesions [53]. CT scans of the orbit or paranasal sinuses with axial, coronal, or sagittal images are used to diagnose lacrimal sac tumors, and to assess osteolytic changes and the invaded surrounding tissues [2, 4, 5, 6, 12, 13, 14, 27, 32, 33, 34, 35, 53]. A benign lesion is typically defined as a well-defined lesion without any bone erosion on CT images. Bone erosion indicates a primary osseous lesion or malignant lesion. The lesion involving the lacrimal sac area may look hefty, irregular, and associated with bone destruction, which is highly suggestive of malignancy [11, 12]. Cystic lesions may mimic tumors of the LDS and appear as fluid-filled hypodense masses on CT images [20, 21]. Computed tomographic-dacryocystography and MRI of the orbit can help in assessing lacrimal sac tumors [6, 11, 32, 33, 36, 46]. CT is more sensitive than MRI for the evaluation of bone erosion. Malignant epithelial lesions cause more bone destruction than nonepithelial tumors [53]. A CT scan of the orbit was the preferred imaging technique in 90% of the cases in our study.

Surgical Strategies and Biopsy

FNAB is still more controversial than open biopsy. Open biopsy was the preferred biopsy technique rather than FNAB in this study. Incisional biopsy is helpful for suspicious lacrimal sac tumors [22, 36, 37, 42, 43, 44, 46, 47]. Immunohistochemical analysis is important to confirm malignant cases. In this study, the histopathological report was equivocal in 2 cases, which was later confirmed by immunohistochemistry (Table 1). Excision of the lesion with DCR or DCT is the mainstay treatment modality for benign tumors. Adjuvant radiotherapy or chemotherapy can be added after en bloc surgical excision of the tumor if it is malignant [36, 38, 40]. Aggressive malignant lesions may require the removal of the entire lacrimal drainage system, including the canaliculi, lacrimal sac, and entire nasolacrimal duct with lateral rhinotomy [24, 36]. Orbital exenteration and resection of the paranasal sinus may be needed for extensive primary or secondary malignant lesions [4, 33, 40, 47]. Still, the best management option for suspected lacrimal sac tumor is total excision of lacrimal sac (DCT without osteotomy). A planned modified DCR or reconstruction may occur at a later date after histological confirmation. In this case series study, DCT with excision biopsy was the initial surgical strategy in 60% of cases. We planned a modified DCR for all 6 cases who underwent DCT with complete excision biopsy, 6 months after excision biopsy in the cases of benign tumor and 1 year after excision biopsy with completion of all adjuvant therapy in the cases of malignant tumors. A planned modified DCR was later performed in 1 case of squamous cell papilloma. Deep incisional biopsy was performed in 40% of cases to confirm an accurate diagnosis.

Adjuvant Therapy

Adjuvant treatment modalities include EBRT, local radiation therapy (plaque brachytherapy), and chemotherapy (CHOP regimen) or immunotherapy [22, 24]. In this study, adjuvant EBRT was administered in 5 (62.5%) cases of lacrimal sac tumors, especially in epithelial lacrimal sac carcinoma. Two patients (1 case of MALT lymphoma and 1 case of RLH) with nonepithelial tumors were also treated with radiotherapy. CHOP therapy was recommended for 2 patients (20%) with non-Hodgkin's lymphoma. Adjuvant radiotherapy or chemotherapy can be used as an effective treatment modality to reduce the recurrence rate and complete remission after incomplete resection. Immunotherapy (rituximab) combined with chemotherapy (R-CHOP regimen) is a recent treatment modality for patients with high-grade non-Hodgkin's lymphoma (DLBCL).

Prognosis

Patients with premalignant and malignant tumors showed a decreased recurrence rate with lateral rhinostomy (12.5%) and wide excision compared to those without rhinostomy (43.7%) [16]. Recurrence and mortality rates for lacrimal sac tumors vary [37, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 54, 55, 56]. Benign tumors of the lacrimal sac have a good prognosis if completely excised, but benign papillomas with inverted patterns tend to recur. Recurrence occurred in 1 (10%) case (adenocarcinoma) during the follow-up period in this study. The recurrence rate of invasive epithelial malignancies (squamous cell, mucus-secreting adenocarcinoma, and nonkeratinizing SqCC) appears to be approximately 50%, and mortality is 37–100% with treatment for nonkeratinizing SqCC [3, 4, 5, 36, 38, 40, 47, 52]. Metastasis to the bone and skin has been reported in the literature [5, 15, 26, 28, 29, 30, 31, 34, 35, 36, 38]. Lymph node metastasis (10%) was evaluated in 1 patient with mucoepidermoid carcinoma in our study. In a study of primary lacrimal sac lymphoma, systemic involvement occurred in 33% of cases, and the 5-year overall survival rate was 65% [41, 57]. Malignant melanoma is associated with the worst prognosis despite aggressive treatment [3, 4, 5, 53].

Conclusion

Lymphoproliferative tumors were common lacrimal sac neoplasms in our study. A high index of suspicion is required to successfully manage lacrimal sac tumors, as these are fatal tumors and are often misdiagnosed as recurrent dacryocystitis. CT scan of the orbit or paranasal sinuses is the preferred imaging modality to diagnose lacrimal sac tumors. DCT with tumor excision is the initial surgical strategy for any suspicious lacrimal sac tumor. Early and appropriate workup and multimodality treatment can help complete the tumor resolution and reduce recurrence. Radiotherapy is sensitive to epithelial carcinoma, but chemotherapy (CHOP therapy) is the best option for NHL. It is essential for surgeons to carefully inspect the lacrimal sac during DCR to prevent missing lesions. Careful long-term follow-up is required, as recurrence or metastases may occur even after years of primary treatment.

Statement of Ethics

This study was performed with the highest ethical standards as per the World Medical Association Declaration of Helsinki. The subjects provided their written informed consent to join the study, which included photo documentation and biopsies of their lacrimal sac tumors. The procedures and study protocol were approved by the Institutional Review Board (No. Irb/sfmehti/2020/18). No written informed consent was obtained as this was a retrospective observational study (July 1 to December 31, 2013). The study protocol was approved by the Institutional Review Board (IRB) of Sheikh Fazilatunnessa Mujib Eye Hospital and Training Institute (SFMEH&TI), Bangladesh (Irb/sfmehti/2020/18). The IRB was considered for using all the recorded data and photographs for this research. All subjects gave informed written consent before their surgery and also gave the consent to use their clinical documents and photographs for the study.

Conflict of Interest Statement

The authors declare no potential conflicts of interest.

Funding Sources

The authors declared that this study received no financial support.

Author Contributions

S.M.K. and M.N. designed the research study, procured the samples, performed the experiments, and interpreted the results; S.M.K., R.R., and S.S. designed and performed the statistical analyses; S.S. and M.S.N. provided critical input; S.M.K., R.R., and M.N. wrote the first draft of the manuscript with information from all coauthors; S.M.K., S.S., M.S.N., M.R.M., and G.H. contributed to critical appraisal of the manuscript. All authors reviewed and approved the final version of the manuscript before submission.

Data Availability Statement

Data are available upon request which can be directed to the corresponding author.

Study place: Sheikh Fazilatunnessa Mujib Eye Hospital and Training Institute (SFMEHTI), Gopalgonj, Bangladesh. Study design: case series study.