Prognostic Impact of Notch1 Intracellular Domain, P63, and c-MYC in Lacrimal Gland Adenoid Cystic Carcinoma.

Purpose: We assessed whether NICD1 expression, c-MYC expression, and P63 expression by immunohistochemistry (IHC) correlate with prognosis and high-risk clinicopathological features in lacrimal gland adenoid cystic carcinoma (ACC). Methods: Records of patients with lacrimal gland ACC who underwent surgery between 1998 to 2018 were reviewed. Clinicopathologic and treatment data were collected. Tumor tissues were subjected to light microscopy and IHC. Results: Of 43 patients treated during the study period, 21 had archived tumor tissue available and were included. The median age at diagnosis was 47 years, and 13 patients (62%) were male. Thirteen patients (62%) had T2 disease, and none had nodal or distant metastasis at diagnosis. Tumors were positive for NICD1 expression in eight cases (38%), c-MYC expression in eight (38%), and P63 expression in 11 (52%). Positive NICD1 expression was associated with predominantly solid (vs. cribriform/tubular) pattern (P < 0.001), treatment with orbital exenteration (vs. eye-sparing surgery) (P = 0.008), local recurrence (P = 0.047), and death (P = 0.012). Negative P63 expression was associated with predominantly solid pattern (P = 0.001), local recurrence (P = 0.012), distant metastasis (P = 0.001), and death (P = 0.035). A higher percentage of tumor cells staining for c-MYC was associated with presence of perineural invasion (P = 0.036). Positive NICD1 expression was associated with worse disease-free survival (hazard ratio, 6.27; 95% CI, 1.29-30.46), whereas positive P63 expression was associated with better disease-free survival (hazard ratio, 0.03; 95% CI, 0.0002-0.26). Conclusions: IHC for NICD1 and P63 should be considered in lacrimal gland ACC because of their prognostic value and potential as treatment targets.

Magnetic resonance diffusion-weighted imaging in lacrimal gland lymphoma versus inflammation: A comparative study.

PURPOSE: To determine the role of diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) in differentiating the inflammatory process and malignant lymphoma of the lacrimal gland. METHODS: A retrospective analysis of all subjects who underwent lacrimal gland biopsy and magnetic resonance (MR) imaging with DWI sequences during a 10-year period at the Sheba Medical Center, Israel. The lacrimal glands' ADC values were documented bilaterally by blinded observers and correlated with the final histology verified diagnoses. RESULTS: Twenty-eight patients were included, with 19 females (68%) with a mean ± SD age of 48.1 ± 25.7 years. The right orbit was involved in 14 cases (50%) and the left in 13 (46%); one patient (4%) had bilateral involvement. Seventeen cases (61%) had a final diagnosis of idiopathic inflammation or dacryoadenitis, and six cases (21%) were diagnosed with lymphoma. Additional diagnoses included pleomorphic adenoma in 3 (11%), adenoid cystic carcinoma, and solitary fibrous tumor. Lower mean ADC values were observed in the lymphoma versus inflammatory group (1.03 × 10-3 Vs. 1.45 × 10-3, P = 0.02). CONCLUSION: Restricted diffusion on MR imaging can serve as a diagnostic tool in the differentiation between inflammatory processes of the lacrimal gland and lymphoma.

Bilateral Lacrimal Gland Lymphoma - Case Presentation.

Lacrimal gland lymphomas are rare orbital tumors, constituting a minor fraction of all orbital and ocular adnexal malignancies. This case study presents an 83-year-old male with bilateral lacrimal gland tumors, more prominent in the left orbit, causing decreased visual acuity, red eye, excessive tearing, and diplopia. Initial ophthalmological evaluations and imaging suggested bilateral lacrimal gland lymphoma, confirmed by histopathology as diffuse large B-cell non-Hodgkin lymphoma of the MALT type. Due to the significant tumor size and risk of visual function loss, surgical intervention was performed, followed by corticosteroid therapy. Postoperatively, a marked improvement in symptoms and a reduction in tumor size were observed. This case underscores the importance of comprehensive diagnostic approaches, including clinical, imaging, and histopathological evaluations, highlighting the need for a multidisciplinary approach in managing rare orbital tumors like lacrimal gland lymphoma. The patient's postoperative and follow-up care included oncological management to monitor and ensure long-term disease control and patient well-being. Abbreviations: RE = right eye, LE = left eye, CT = Computer tomography, MRI = Magnetic Resonance Imaging, TOD = intraocular pressure of right eye, TOS = intraocular pressure of left eye, US = ultrasound.

Update on lacrimal apparatus dysfunction associated with differentiated thyroid cancer after I-131 therapy.

PURPOSE: The most prevalent lacrimal apparatus dysfunctions associated with differentiated thyroid cancer(DTC) after I-131 therapy are dry eye and nasolacrimal duct obstruction(NLDO), leading to ocular discomfort and lower quality of life for patients. It is crucial to diagnose and manage lacrimal apparatus dysfunction associated with I-131 therapy for DTC. Therefore, this review aims to comprehensively summarize and analyze the advances in mechanisms and therapeutic options underlying lacrimal apparatus dysfunction induced by I-131 therapy for DTC. METHODS: A comprehensive search of CNKI, PubMed, and Wed of Science was performed from the database to December of 2023. Key search terms were "Thyroid cancer", "I-131", "Complications", "Dry eye", "Epiphora", "Tear", "Nasolacrimal duct" and "NLDO". RESULTS: The research indicates that I-131 therapy for DTC causes damage to the lacrimal glands and nasolacrimal duct system, resulting in symptoms such as dry eye, epiphora, and mucoid secretions. Moreover, recent research has focused on exploring relevant risk factors of the condition and experimental and clinical treatments. However, there is some controversy regarding the mechanisms involved, whether it is due to the passive flow of I-131 in tears, active uptake of I-131 by the sodium-iodide symporter (NIS) in the lacrimal sac and nasolacrimal duct, or secondary metabolic and hormonal disturbances caused by I-131. CONCLUSION: It is crucial for early detection and preventive measures by ophthalmologists and the need for further studies to elucidate the mechanisms underlying the disease.

Presumed Lacrimal Gland Pleomorphic Adenoma With Extensive Ossification and Necrosis.

Calcification within pleomorphic adenomas of the lacrimal gland is well recognized but uncommon, being seen more readily in lacrimal gland carcinomas. Bony formation, ossification, in pleomorphic adenomas of the lacrimal glands is even rarer. Together with extensive sclerosis, or "coagulative necrosis," ossification and necrosis should alert the clinician to the risk of malignant transformation. However, both can mimic carcinomatous change, leading to misinterpretation of malignancy in an otherwise benign lacrimal gland neoplasm. We present 2 case reports of patients with clinically presumed pleomorphic adenomas of the lacrimal gland whose histopathology demonstrated lacrimal gland ossification and necrosis without features of malignancy or invasive disease.

Diagnosis and Treatment of Lacrimal Gland Prolapse: A Narrative Review.

BACKGROUND: Lacrimal gland prolapse (LGP) is considered to be one of the causes for upper eyelid contour abnormality that should be recognized and treated properly to yield satisfactory outcomes in blepharoplasty. To describe current findings about the prevalence, pre- and intraoperative diagnosis of LGP and its treatment options. METHODS: PubMed and Google Scholar were thoroughly searched for articles published describing the diagnosis and treatment of LGP. RESULTS: The reported prevalence of LGP by various authors varies between 10 and 60% based on their preoperative or intraoperative reports. Techniques such as dacryoadenopexy, modified dacryoadenopexy, and dacryoplasty have been described to secure the prolapsed lacrimal gland back into its original position. Additionally, creating a Whitnall's barrier has also been suggested as a method to reposition the gland. While all these surgical procedures have shown promising immediate results, there is a lack of published data on their long-term outcomes. CONCLUSION: Diagnosis and proper treatment of LGP could enhance the cosmetic results of upper eyelid blepharoplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mucosa-associated lymphoid tissue lymphoma of the lacrimal gland: A case report and literature review.

RATIONALE: The most common subtype of primary lymphoma of the ocular adnexa is the mucosa-associated lymphoid tissue (MALT) subtype. MALT lymphoma of the lacrimal gland is relatively rare among the lacrimal gland tumors, and the early clinical symptoms are atypical, which can easily lead to misdiagnosis and missed diagnosis. Here, we report a case of MALT lymphoma of the lacrimal gland and explore its clinical manifestations, pathological characteristics, management, and pathogenesis, with the aim of helping clinicians gain an in-depth understanding of ocular adnexal MALT lymphoma. PATIENT CONCERNS: A 60-year-old man presented to our hospital with proptosis and diplopia. The right eye deviated and shifted toward the lower part of the nose. DIAGNOSIS: Orbital enhanced magnetic resonance imaging suggested a mass with a maximum cross-section of 3.2 × 2.1 cm. T1 weighted image was isointense, and the enhancement was more uniform and obvious. INTERVENTIONS: The right orbital mass was treated surgically, and the final pathology report was MALT lymphoma. After the pathological report was released, the patient was transferred to the hematology department for further diagnosis and no further treatment was given eventually. OUTCOMES: Seven months later, the patient did not complain of discomfort. Whole-body positron emission tomography-computed tomography, superficial lymph node examination and orbital magnetic resonance imaging revealed no abnormal changes. LESSONS: The clinical manifestations of MALT lymphoma are heterogeneous. Imaging examination is important for assessing the size of the tumor and its relationship with adjacent tissues. Postoperative pathological examination may provide further evidence for the evaluation of the patient's surgical efficacy and prognosis. Management of MALT lymphoma of the lacrimal gland requires a multidisciplinary approach involving ophthalmologists, hematologists, and radiotherapists.

A New Patient-reported Outcomes Measure for Surgically Treated Epiphora: Tearing Assessment and Rating Scale-12 (TEARS-12).

BACKGROUND: No widely accepted, validated instrument currently exists to measure clinical outcomes in patients who undergo dacryocystorhinostomy (DCR) for treatment of epiphora. OBJECTIVE: To develop a patient-reported outcome measure applicable to this population. METHODS: Psychometric evaluations, consultation with experts, and review of the literature informed item generation of a 12-question questionnaire to incorporate the most relevant symptoms experienced by patients with nasolacrimal duct obstruction. This questionnaire, known as the Tearing Assessment and Rating Scale-12 (TEARS-12), was administered to 32 patients before and after intervention, in the form of endoscopic DCR. Statistical analysis was performed to measure internal consistency, responsiveness, and test-retest reliability. RESULTS: Pre-operative and post-operative TEARS-12 scores (28.2 [standard error (SE) 3.19] vs 11.8 [SE 3.25], respectively, P = 0.001) demonstrated improved patient outcome within 6 weeks following endoscopic DCR. Cronbach's alpha for the questionnaire was 0.90, indicating high overall reliability. Additionally, each question demonstrated internal reliability, with a corrected item-total correlation greater than 0.30. The intraclass correlation between the two pre-operative scores was 0.858 (P < 0.001), indicating high test-retest reliability. CONCLUSION: TEARS-12 is a statistically valid, easy-to-administer instrument to measure clinical outcomes in patients who undergo endoscopic DCR.

Evaluating the Effectiveness of Lacrimal Gland Botulinum Toxin Using the TEARS Score.

PURPOSE: Botulinum toxin (BoNTA) lacrimal gland injections are one treatment option for managing epiphora. Outcomes for epiphora in existing studies are subjective and lack grading. This study utilized validated grading instruments to evaluate the efficacy of BoNTA lacrimal gland injections. METHODS: Prospective study evaluating the TEARS score and quality of life in patients receiving incobotulinum toxin (Xeomin) lacrimal gland injections for epiphora. Epiphora was graded using the TEARS score. Quality of life was evaluated using the watery eye quality of life score. Etiology, benefit duration, complications and additional injections were recorded. RESULTS: Of the 28 patients, (median age 67.5 years), 19 (68%) had facial palsy gustatory epiphora (GE). Median effect duration was 13 weeks. Improvements in tearing frequency (T), clinical effects (E), and activity limitation (A) were seen in 57%, 57%, and 71% of patients, respectively. Median watery eye quality of life score improved from 42.4/100 ± 10.1 to 10.6 ± 15.5 (p < 0.001). Alongside crocodile tears, reflex tearing R-scores improved in 68% of patients with GE vs. 11% with non-GE causes (p = 0.004618). In total 89% of patients with GE and 56% with non-GE requested repeat injections. Self-reported percentage improvement ranged from 0% to 100% (median 60%, interquartile range 10%-76.25%). CONCLUSIONS: This is the first study reporting the outcomes of BoNTA lacrimal gland injections using validated TEARS and watery eye quality of life scores. Clinical and quality of life improvements are seen in most patients. Patients with GE achieve an additional improvement in dry eye-related reflex tearing alongside crocodile tears which both improve with BoNTA. TEARS data supports using BoNTA in these patients and is a useful validated grading instrument for epiphora.

Comparing the diagnostic accuracy of MR dacryocystography (MRD) and dacryoscintigraphy (DSG) in NLDO-related acquired epiphora.

PROPOSE: This study aimed to compare the diagnostic accuracy of MR dacryocystography (MRD) and dacryoscintigraphy (DSG) in the diagnosis of acquired epiphora related to NLDO. A total of 15 patients with acquired epiphora and suspected NLDO were included in this study. METHODS: All patients underwent MRD and DSG examinations. MRD was performed using a 3-Tesla magnetic resonance imaging (MRI) scanner, while DSG involved injection of a radiotracer into the lacrimal drainage system followed by DSG. The results of both imaging methods were compared with the reference standard that was a combination of clinical examination findings and surgical exploration. RESULTS: The results of this study showed that no abnormal findings were observed in MR-DCG in patients before the Valsalva maneuver. However, after the Valsalva maneuver, stenosis/obstruction at the canal surface was observed in all 15 patients diagnosed by DSG, giving a sensitivity of 100% for canal stenosis. Moreover, the results revealed that among these 15 patients, 9 showed stenosis or simultaneous obstruction at the level of the canal and lacrimal sac, but MR-DCG showed these lesions in only 9 patients, giving a sensitivity of 60%. The specificity of MRD and DSG were 85% and 76.7%, respectively. There was a statistically significant difference in the sensitivity of MRD and DSG (p < 0.05). CONCLUSION: This study demonstrated that MRD has a higher diagnostic accuracy in the diagnosis of acquired epiphora associated with NLDO compared to DSG. MRD showed significantly higher sensitivity and specificity than DSG. Therefore, MRD can be considered as the preferred imaging modality in the diagnosis of acquired epiphora due to NLDO. By accurately identifying the underlying cause of NLDO, MRD can help determine the most appropriate treatment approach for patients and lead to better outcomes.

Lacrimal Gland Adenocarcinoma Clinicopathologic Features and Outcomes Compared With Those of Lacrimal Gland Adenoid Cystic Carcinoma.

PURPOSE: Lacrimal gland (LG) adenocarcinomas (ACs) are rare, with limited data. We compared clinicopathologic features and local recurrence, distant metastasis, and survival rates between LG AC and LG adenoid cystic carcinoma (ACC). METHODS: The records of LG AC patients treated from 2008 to 2022 and LG ACC patients treated from 1998 to 2022 at the same center were retrospectively reviewed. RESULTS: The study included 20 patients with AC; 10 de-novo AC, 10 ex-pleomorphic AC; and 51 ACC patients. The median age at diagnosis was 61 years for de-novo AC, 54 years for ex-pleomorphic AC, and 45 years for ACC. All groups had male predominance. The initial T category was T2 in 50% (5/10) of de-novo ACs; 60% (6/10) of ex-pleomorphic ACs; and 59% (30/51) of ACCs. Perineural invasion was present in 33% (5/15) of ACs and 90% (45/50) of ACCs ( p < 0.001). Of the 20 AC patients, 14 had eye-sparing surgery; 4 had orbital exenteration; and 2 had unresectable disease. All AC patients received postoperative radiotherapy and 15 (75%) received concurrent chemotherapy. Fourteen AC patients were tested for human growth factor receptor 2 expression, and 10 (71%) were human growth factor receptor 2 positive; 5 received human growth factor receptor 2-targeted therapy. AC and ACC had similar 5-year recurrence rates (20% and 33%, respectively, p = 0.31) and metastasis rates (20% and 34%, respectively, p = 0.30). de-novo AC, ex-pleomorphic AC, and ACC had similar 5-year disease-specific survival rates (80%, 79%, and 81%, respectively, p > 0.99). CONCLUSIONS: LG AC and ACC have similar baseline clinicopathologic features, except that perineural invasion is more common in ACC, and similar recurrence, metastasis, and survival rates. Human growth factor receptor 2-targeted therapy may be appropriate in some patients with LG AC.

Repeated Lacrimal Gland Biopsies.

PURPOSE: To examine the indications for repeated lacrimal gland biopsies, and the rate of detection of a new diagnosis. METHODS: A single-center, retrospective review of patients who underwent more than 1 lacrimal gland biopsy, either ipsilateral or contralateral, between 2000 and 2022. RESULTS: One hundred and twenty-three patients (80 female; 65%) had repeated lacrimal gland biopsy. The commonest diagnosis on initial biopsy was chronic nonspecific dacryoadenitis (NSD) (49/123; 40%). Indications for repeated biopsy were uncertainty in making a histopathological diagnosis (16/123; 13%), poorly-responsive or recurrent ipsilateral disease (61/123; 50%), new or continued/worsening contralateral disease (30 patients; 24%), and planned tumor resection after initial biopsy (16/123; 13%). Of the 40 patients (33%) with a different histopathological diagnosis after repeated lacrimal biopsy, 4 (10%) had lymphoma, initially reported as NSD (4/49 with NSD; 8%), and 7/40 (18%) (14% of the 49 NSD patients) were reclassified as having specific inflammations (including 2 with granulomatous polyangiitis); of the 7 having reclassification as a specific dacryoadenitis, 6/7 had ipsilateral disease failing to respond to primary treatment, and 1/7 had new onset or progression of contralateral disease. All histology after the primary biopsy of 16 patients with lacrimal gland malignancies retained the same tissue diagnosis. CONCLUSION: Repeated biopsy for lacrimal gland disease in this study revealed a diagnosis of malignancy in 20%, including lymphoma in 8% of those initially diagnosed with NSD. There was a 14% rate of diagnostic progression from "non-specific" dacryoadenitis to a more specific inflammatory disease.

Lacrimal Sac Characteristics in Patients With Punctal and Canalicular Agenesis: Punctum Update (PUP) Study-Paper 3.

PURPOSE: To explore the endoscopic and histopathologic characteristics of the lacrimal sac (LS) and the nasolacrimal duct in cases with punctal agenesis presenting with LS swellings. METHODS: This is a prospective, interventional study of 13 LSs of 8 patients presenting with punctal agenesis and LS swellings over a 5-year study period (June 2018-July 2023). Complete ophthalmic examination was performed along with CT scans of the orbits. The LS was exposed with an anterior lacrimal crest incision and explored. The exterior and interior of the sac swelling were examined and LS flaps were sent for histopathological analysis. RESULTS: The mean age of the patients was 23 years with a male:female ratio of 5:3. All patients presented with swelling in the LS region. Occasional epiphora was the presenting feature in 6 patients. All patients had both upper and lower punctal agenesis on the affected side with associated LS swelling. CT scans showed a hypodense cystic swelling with expansion of the LS fossa and bony nasolacrimal duct ending abruptly short of the inferior meatus. Intraoperatively, the LS had thin, translucent walls with mucoid secretion and an absence of common canalicular opening. Histopathological analysis showed epithelium consistent with LS with less robust development of the sac walls and poorly structured lacrimal drainage-associated lymphoid tissue with scanty stromal inflammation. CONCLUSIONS: The development of LS and the nasolacrimal duct is structurally affected in patients with punctal agenesis. Retrograde approaches for epiphora resolution are not logical in such cases but conjunctivodacryocystorhinostomy with Jones tube can be a feasible option.

Primary Lacrimal Sac Tumors with Extension into Vicinity: Outcomes with Endoscopy-Assisted Modified Weber-Ferguson's Approach.

PURPOSE: To evaluate the outcomes of endoscopy-assisted modified Weber-Ferguson's approach in the management of primary lacrimal sac tumors with extension into the neighboring tissues. METHODS: A retrospective interventional study was performed on all patients with lacrimal sac tumors treated with the endoscopy-assisted modified Weber-Ferguson approach between January 2010 and June 2022 at the Shanghai Ninth People's Hospital, China. Data assessed include demographics, clinical presentations, imaging features, surgical techniques, histopathology, adjuvant modalities of management, complications, and outcomes. RESULTS: A total of 13 patients were included in the analysis. Epiphora and palpable mass lesion were the presenting complaint in 84.6% (11/13) of the patients. Nearly half of the patients (46.1%, 6/13) were misdiagnosed as lacrimal duct obstruction. All the lacrimal sac tumors in the present series showed uneven enhancement on T1-weighted MRI imaging. Postoperatively, 84.6% (11/13) patients recovered well with excellent esthetics and were disease-free after a mean follow-up of 58.6 months. Two patients who underwent additional exenteration developed recurrence and succumbed (at 41 and 96 months follow up) while they were on palliative chemoradiation. CONCLUSION: The endoscopic-assisted modified Weber-Fergusson surgical approach is effective in providing better visibility and accessibility to lacrimal sac tumors with extension into neighboring tissue.

Long-Term Outcome for Primary Papillomas of the Lacrimal Drainage System.

PURPOSE: To report long-term outcomes after surgery for primary benign papillomas of the lacrimal drainage system. METHODS: Retrospective review of patients with primary lacrimal drainage system papillomas, first seen between 1984 and 2021, but excluding lesions with sino-nasal origin or malignant histology. Patients were categorized by tumor histology (squamous, transitional, and mixed cell) and growth pattern (exophytic, endophytic, or mixed). RESULTS: Thirty patients (18 female; 60%) presented at a mean age of 46.1 years (12-79 years). Over an average follow-up of 10.4 years, 30% of patients experienced recurrence, with rates differing slightly by growth pattern: 25% for exophytic tumors and 40% for endophytic and mixed-pattern tumors ( p = 0.431). The overall 5-year recurrence-free survival was 67% (± 9% standard error), this being slightly higher for exophytic lesions (75% ± 10%) as compared to 48% (± 19%) for tumors with an endophytic component ( p = 0.370). No cases of malignant transformation were observed, and the tumor type at recurrence matched the initial diagnosis. CONCLUSION: Primary benign papillomas of the lacrimal drainage system have a long-term recurrence rate of about one-third, with a higher frequency in those exhibiting an endophytic growth pattern. The study highlights the importance of prolonged surveillance for recurrence, especially for endophytic and mixed growth pattern tumors, and for the potential to undergo malignant transformation. The results support the effectiveness of endoscopic surgical excision or laser thermos-ablation in managing recurrent lacrimal drainage system papillomas after dacryocystorhinostomy.

Application of artificial intelligence in oculoplastics.

Oculoplastics is a subspecialty of ophthalmology/dermatology concerned with eyelid, orbital, and lacrimal diseases. Artificial intelligence (AI), with its powerful ability to analyze large data sets, has dramatically benefited oculoplastics. The cutting-edge AI technology is widely applied to extract ocular parameters and to use these results for further assessment, such as screening and diagnosis of blepharoptosis and predicting the progression of thyroid eye disease. AI also assists in treatment procedures, such as surgical strategy planning in blepharoptosis. High efficiency and high reliability are the most apparent advantages of AI, with promising prospects. The possibilities of AI in oculoplastics may lie in three-dimensional modeling technology and image generation. We retrospectively summarize AI applications involving eyelid, orbital, and lacrimal diseases in oculoplastics, and we also examine the strengths and weaknesses of AI technology in oculoplastics.