Neoadjuvant Intra-arterial Cytoreductive Chemotherapy Improves Outcomes in Lacrimal Gland Adenoid Cystic Carcinoma.

BACKGROUND: Lacrimal gland adenoid cystic carcinoma (LGACC) has historically been associated with a poor prognosis even with localized disease, with a survival of 56% at 5 years. In 1988, we treated the first patient with neoadjuvant intra-arterial cytoreductive chemotherapy (IACC). Since then, we have used this protocol as the standard approach. We aim to analyze the outcomes of patients with LGACC treated with the protocol and compare them to a population-based cohort to assess if IACC can improve survival. METHODS: We prospectively assessed all non-metastatic patients with LGACC treated with IACC at a single institution between 1988 and 2021. For a comparison group, we identified all non-metastatic patients with LGACC treated with excision from the Surveillance, Epidemiology, and End Results (SEER) registry. We calculated disease-specific survival using the Kaplan-Meier and Cox proportional-hazards modeling methods. RESULTS: Thirty-five non-metastatic patients with LGACC treated with IACC were identified at a single institution, and 64 patients with non-metastatic LGACC treated with excision were identified in the SEER database. The 5- and 10-year disease-specific survival rates for patients treated with IACC were 84% (95%CI 71-97) and 76% (95%CI 60-92), respectively. While the 5- and 10-year disease-specific survival rates for the population-based cohort were 72% (95%CI 62-82) and 46% (95%CI 32-60). The survival analysis favored IACC, with a 60% lower risk of death (HR: 0.4; 95%CI 0.2-0.9). CONCLUSION: IACC improves disease-specific survival in comparison to a population-based cohort treated with excision. Additional patients treated with IACC at multiple institutions are required to provide further external validity.

Intravascular papillary endothelial hyperplasia of the maxillary sinus extending into the contralateral nasal cavity.

INTRODUCTION: Intravascular papillary endothelial hyperplasia (IPEH) predominantly occurs in the subcutaneous and dermal regions and rarely originates from the sinonasal mucosa. CASE PRESENTATION: We report on the case of a 58-year-old male patient who presented with progressive bilateral nasal obstruction, left-sided epiphora, and intermittent epistaxis. Computed tomography revealed a soft tissue opacity in the left maxillary sinus with intersinusoidal nasal wall demineralization, extending into the surrounding ethmoid cells and the right nasal cavity through a contralateral deviation of the nasal septum. Contrast-enhanced T1-weighted magnetic resonance imaging further confirmed these findings. The IPEH originating from the maxillary sinus extended into the contralateral nasal cavity, and it was successfully removed using an endoscopic endonasal approach, avoiding overly aggressive treatment. CONCLUSION: This case report highlights the diagnostic challenges of IPEH in the sinonasal region and the importance of considering IPEH as a differential diagnosis in patients presenting with nasal obstruction, epiphora, and intermittent epistaxis.

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.

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.

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.

Recurrence rate of pleomorphic adenoma of the lacrimal gland: systematic review and meta-analysis.

PURPOSE: The aim is to increase the understanding of lacrimal gland pleomorphic adenoma's recurrence rate and the factors that influence it. METHODS: A systematic search of PubMed, SCOPUS, Cochrane Library, and CINAHL was conducted following PRISMA guidelines. The data in the included studies were extracted and analyzed. RESULTS: Twenty-two studies were included representing 963 patients from 12 different countries. The pooled analysis of the recurrence rate was 8.83% (95% CI: 5.08-13.50). In the event of recurrence, there was a 75.17% (95% CI: 65.98-82.94) chance of benign recurrence and a 28.35% (95% CI: 19.66-38.41) chance of malignant recurrences, with malignant recurrence occurring almost exclusively after a benign recurrence. The results showed that 47.09% (95% CI: 24.60 to 70.22) of recurrent tumors had a ruptured pseudocapsule and 6.35% (95% CI: 0.82 to 16.54) had an intact pseudocapsule with a significant difference between the two. Of the recurrent tumors, 51.50% (95% CI: 9.28 to 92.39) were biopsied compared to 8.83% (95% CI: 3.40 to 16.49) of the total; the difference between these two proportions was also found to be significant. CONCLUSION: There was a statistically significant difference in the rates of recurrence between tumors that were either biopsied or had a ruptured pseudocapsule compared to those that did not. This evidence adds additional support for excisional biopsy being the procedure of choice for LGPA and reinforces the importance of keeping the pseudocapsule intact during surgical resection.

[An atypical medial canthal mass: a case of lacrimal sac inverted papilloma with literature review]. / Atypische Schwellung des medialen Augenwinkels: Fallbericht von einem invertierten Papillom des Tränenapparats und Literaturrecherche.

BACKGROUND: Lacrimal sac localization of an Inverted Papilloma is extremely rare and no risk factors are reported in literature. HISTORY: A chemical trauma was followed by a painless, growing mass in the medial canthal area associated with epiphora. FINDINGS: Rhinoendoscopy, Computed Tomography and Magnetic Resonance showed a well-defined mass in left lacrimal fossa extended to the nasolacrimal duct. TREATMENT: An endoscopic resection and a dacryocystorhinostomy were performed. CONCLUSION: The aim of the present study is to show an atypical presentation of a well-known tumor along with a suspicious risk factor and to lead otolaryngologists to consider an inverted papilloma of the lacrimal system among lesions causing lateral nasal swelling.

Stereotactic radiosurgery for recurrent pleomorphic adenoma of the lacrimal gland: a case report.

Lacrimal gland pleomorphic adenomas (LGPAs) are common, benign, and intraorbital tumours that cause exophthalmos, ptosis, and visual disturbances. The curative treatment for LGPAs is gross total resection, and radiotherapy is considered adjunctive for recurrence or an alternative for inoperable LGPAs. Stereotactic radiosurgery (SRS) can be used for precise delivery of high radiation doses to the tumour, crucial in the treatment of intra-and extracranial neoplasms. Here, we present a 95-year-old woman who had a rapidly growing, recurrent LGPA and was successfully treated with SRS. The tumour was controlled without any adverse events over 21 months following SRS. SRS is a potential alternative treatment for recurrent LGPA.

Clinical Analysis of Primary Malignant Lacrimal Sac Tumors: A Case Series Study With a Comparison to the Previously Published Literature.

PURPOSE: To report management of a series of patients with primary malignant lacrimal sac tumors and to compare these results to the previously published literature. MATERIALS AND METHODS: A total of 27 patients with pathologically confirmed primary malignant lacrimal sac lesions were enrolled into this study. Pathological classifications, clinical characteristics, various treatment modalities and follow-up time, including tumor recurrence, were documented. The outcome measures included overall survival, progression-free survival, and median survival time. RESULTS: Among 27 eligible cases, 33.33% (9/27) of the tumor was non-Hodgkin B-cell lymphoma, and 33.33% (9/27) was squamous cell carcinoma; both were the most common tumor in this series, followed by adenocarcinoma 18.52% (5/27), then melanoma 7.41% (2/27). Treatment modalities included surgery, radiotherapy, and/or chemotherapy, the overall survival rate of 27 patients was 70.37%, with a median follow-up of 45 months (range: 7 mo-16 y), 8 patients had died from metastatic disease, but 13 patients remained without evidence of recurrent tumor. The 5-year overall survival and progression-free survival for all cases were 73.33% and 66.67%, respectively. The median survival time for 5 deceased patients with interstitial brachytherapy was 98 months, and 5-year survival rate was 60%. CONCLUSIONS: In this series, among primary malignant lacrimal sac tumors, the proportion of lymphoma had increased when compared with the previously published literature, and multidisciplinary therapy may lead to a good prognosis in the majority of patients with the tumors and patients may benefit more from interstitial brachytherapy than external beam radiotherapy.

Recurrent lacrimal gland pleomorphic adenoma.

Pleomorphic adenoma is the most common tumour of the lacrimal gland. Correct preoperative diagnosis is essential as the tumour should be removed en bloc. Incisional biopsy is contraindicated due to risk of recurrence and subsequent risk of malignancy. We identified 13 patients who were diagnosed with lacrimal gland pleomorphic adenoma in our institution over a 31-year period from 1990 to 2021. Of these, we describe four patients, three males and one female, who underwent incisional biopsy. One of these patients had a number of recurrences and required an orbital exenteration. The other two were treated with radiation to the orbit and experienced severe dry eye post-radiotherapy. All three patients are currently disease-free. The fourth patient underwent an incisional biopsy of his lacrimal gland pleomorphic adenoma (LGPA) within the last 6 months and has been referred for radiotherapy. The reasons for a lack of preoperative diagnosis of LGPA included clinical uncertainty and broad radiologic differential. None of the patients who had an en bloc resection experienced recurrence. We recommend that a fine needle aspirate (FNA) biopsy in lieu of a tissue biopsy should be performed where LGPA is included in the clinical and radiological differential diagnosis. If incisional biopsy is required, the suture track should be marked so that the entire biopsy track is removed with the specimen.

Normative lacrimal gland dimensions by magnetic resonance imaging in an Australian cohort.

PURPOSE: To report the normative dimensions of the lacrimal gland on fat-suppressed contrast-enhanced magnetic resonance imaging (MRI) in an Australian cohort. METHODS: Retrospective review of patients who underwent 3 T orbital MRI is presented. Two hundred eleven orbits were used to conduct lacrimal gland measurements. Orbits were excluded if there was ipsilateral orbital or lacrimal gland disease, prior surgery, or poor image quality. The length and width of the lacrimal gland were measured in axial and coronal sections using the largest image. RESULTS: The mean lacrimal gland axial length was 14.6 mm in the right orbit and 14.3 mm in the left orbit. The mean axial width was 4.9 mm in both orbits. Coronal lengths averaged 16.2 mm in the right orbit and 16.4 mm in the left orbit. The coronal width averaged 4.8 mm in both orbits. A significant negative correlation was found between age and the right axial length (r = -0.26, p < .01) and the left axial length (r = -0.26, p < .01) of the lacrimal gland. No statistically significant difference was found between genders or laterality. CONCLUSION: This study presents the normal lacrimal gland dimensions on fat-suppressed contrast-enhanced MRI in an Australian cohort. An inverse relationship exists between age and the axial length of the lacrimal gland. These data may be used to help diagnose enlargement of the lacrimal gland.

Lymphoproliferative disorders in the lacrimal caruncle: report of three cases and review of literature.

This report included three cases of lymphoproliferative disorders developing from the lacrimal caruncle. The first case was an 11-year-old boy with reactive lymphoid hyperplasia in the left lacrimal caruncle. The second case was an 80-year-old woman with reactive lymphoid hyperplasia in the right lacrimal caruncle. The third case was a 77-year-old man with follicular lymphoma in the left lacrimal caruncle. Our literature review of cases with lacrimal caruncular lesions showed 11 reported cases with reactive lymphoid hyperplasia and 17 with malignant lymphoma. There had been no previous report on follicular lymphoma in the lacrimal caruncle.

A rare case of mucoepidermoid carcinoma ex pleomorphic adenoma of the lacrimal gland.

Carcinoma ex pleomorphic adenoma (CEPA) of the lacrimal gland is a rare malignant tumor that arises from a pre-existing pleomorphic adenoma. Lacrimal gland CEPA with mucoepidermoid histological subtype is exceedingly rare. Diagnosis can be aided by radiographic findings, though the gold standard is histopathological analysis following excisional biopsy. Management options include complete surgical excision with or without adjuvant radiation therapy based on tumor grade and invasiveness. We present a 76-year-old woman with 6 months of diplopia and unilateral proptosis. Her initial exam was remarkable for hypoglobus, proptosis, and limited elevation of the right eye. Computed tomography (CT) scan demonstrated a superior, well-circumscribed, extraconal orbital mass. An excisional biopsy was performed, and histopathological findings were consistent with mucoepidermoid carcinoma ex pleomorphic adenoma with positive margins in the tumor capsule. The patient received radiation therapy and remains markedly improved with no disease recurrence at 5 months post-operatively.

Cutaneous eyelid melanoma with lacrimal sac metastasis: the potential role of lacrimal fluid as a metastatic pathway.

Here we present a patient with cutaneous eyelid melanoma patient with lacrimal sac metastasis. Clinicopathological findings in this case support the theory that lacrimal fluid can be a metastatic pathway for tumour cells. Dermatologists should be aware of the possibility that cutaneous eyelid melanoma may involve the nasolacrimal system and should examine it during the perioperative period and in postoperative follow-up.

Lacrimal Sac Reconstruction Using a Nasal Mucosal Graft.

Iatrogenic lacrimal drainage trauma during surgery is not common. It has been reported during orbital surgeries, medial maxillectomies, post-trauma repairs, excision of adherent lesions in the vicinity, and facial reconstructive procedures. The present case reports a focal loss of the lacrimal sac wall during the excision of an intricate dermoid cyst. The defect was sealed by a nasal mucosal graft harvested from the floor of the ipsilateral nasal cavity. Postoperatively, the epiphora was resolved, and a CT-dacryocystography confirmed the anatomical integrity of the reconstructed lacrimal sac.

Extensive Sclerosis ("mummification") in Lacrimal Gland Pleomorphic Adenoma May Indicate Neighboring Malignant Transformation.

Salivary gland pleomorphic adenomas not uncommonly show extensive sclerosis ("dense hyalinization," "coagulative necrosis," or "mummification"), which arise spontaneously or after prior surgery, and this change is considered a high-risk factor for malignant transformation of benign salivary adenomas. While minor hyalinization is common in lacrimal gland adenomas, massive sclerosis-where almost all (90% or more) of the tumor is replaced by an amorphous hyaline material-is extremely rare. Four patients (2 males) are described in whom, despite not having an acute inflammatory episode, their lacrimal gland tumor showed marked sclerotic necrosis within the majority of either the benign or malignant parts of the tumor. Three tumors had evidence of malignant change, 2 to adenocarcinoma, and 1 to mucoepidermoid carcinoma, but none of the malignant areas showed perineural or endovascular invasion. Extensive sclerosis in association with a lacrimal gland pleomorphic adenoma (LGPA) is rare (4/110 of the cases) and-as with salivary adenomas-appears to be associated with a high chance of associated malignant change. Both the surgeon and the histopathologist should regard extensive sclerotic necrosis as a harbinger for malignant change in association with benign pleomorphic adenomas of the lacrimal gland.

Congenital Aberrant Lacrimal Gland Ductules Presenting as a Nonhealing Upper Eyelid Lesion.

A 2-year-old girl presented with a history of a recurrent painless red and swollen lesion on the right upper eyelid. Examination demonstrated an 8.0-mm erythematous papule with overlying crusting skin in the lateral aspect of the right upper eyelid. Probing under general anesthesia revealed openings in the right temporal brow region and upper eyelid that led to aberrant ductules traveling toward the lacrimal gland. The temporal ductule was surgically excised, whilst the eyelid ductule was redirected to the fornix.

Risk and Lag-time for Development of Lacrimal Gland Carcinoma Expleomorphic Adenoma: Observations and Conjectural Study.

AIMS: To estimate the proportion of de novo lacrimal gland pleomorphic adenomas (PAs) and carcinomas expleomorphic adenomas (CEPAs), together with age at presentation and first symptom. Conjectural models of tumor growth are considered. METHODS: Retrospective review of patients with orbital lobe PA or CEPA. The presenting age was examined for conformation to a Gaussian distribution and the cumulative distribution function derived for both tumor types. The risk of CEPA with age was estimated by logistic regression. RESULTS: About one-sixth (27/172; 16%) of these primary orbital lobe tumors were CEPAs, with 145 PAs (76/145 male; 52%) and 27 CEPAs (12/27 male; 44%). The mean presenting age for PAs was 48.3 years (median 47.7; range 11-84 years) and 57.7 years for CEPAs (median 61.2, range 27-91 years) ( p = 0.0062), and the standard deviations for each group are almost identical (16.3 for PAs, 15.9 for CEPAs; p = 0.92). Five (3.4%) PAs and 1 (3.7%) CEPA were asymptomatic: otherwise, the median symptom duration was 24 months for both PAs and CEPAs ( U test: p = 0.65). The odds of CEPA rises significantly with age, increasing 1.04-fold annually ( p = 0.0079). CONCLUSION: The almost identical measures of dispersion for the presenting ages of PA and CEPA suggests that, once malignant transformation occurs, there might be a relatively constant period before it is evident. CEPAs present about a decade after PAs, this unexpectedly later presentation for the malignancy possibly being explained by a gradual replacement of the PA by the newly arising carcinoma within the preceding benign tumor.

Genome Sequencing and Apoptotic Markers to Assess Treatment Response of Lacrimal Gland Adenoid Cystic Carcinoma to Intra-Arterial Cytoreductive Chemotherapy.

Adenoid cystic carcinoma of the lacrimal gland is an aggressive, malignant epithelial neoplasm. We report the case of a 30-year-old male with lacrimal gland adenoid cystic carcinoma treated with neoadjuvant intra-arterial chemotherapy through the internal carotid artery, followed by orbital exenteration and chemoradiation. Treatment response was evaluated using a novel combination of pre- and posttreatment genome sequencing coupled with immunohistochemical evaluation, which showed diffuse tumor apoptosis. A posttreatment decrease in variant allele frequency of the NOTCH1 mutation, and robust tumor cytoreduction on imaging, supports exploration of NOTCH1 analysis as a potential marker of cisplatin sensitivity. The use of genome sequencing and immunohistochemical evaluation could provide a more targeted therapeutic assessment of neoadjuvant intra-arterial chemotherapy in the management of lacrimal gland adenoid cystic carcinoma.

An Algorithm Recommendation to Detect Specific Pathology of the Lacrimal Sac.

ABSTRACT: We aimed to recommend an efficient algorithm to detect the presence of specific pathologies of the lacrimal sac (LS). The charts of 296 patients who had undergone LS biopsy were reviewed retrospectively. The age, gender, history, examination and radiological findings, sac appearance, and pathology results of the patients were recorded. The power of our data to predict the presence of potential specific pathology was identified by regression analysis. After the causality evaluation of the statistical results, an algorithm was created to differentiate specific LS pathologies from chronic dacryocystitis. Our algorithm was mainly formed by deciding on radiological examination and biopsy according to the risk scoring created by the examination findings. A specific LS pathology was observed in 11 (3.7%) patients. When we applied the recommended algorithm to cases with a suspicion of specific pathology and/or found to have a specific pathology, 36.4% of the patients would not require radiological examination and 29.6% of them would not require a biopsy. On the other hand, 80% of the frozen biopsies had been conducted on cases without a specific pathology. Managing the cases according to our algorithm would mean that frozen biopsy would be recommended in only 1 (12.5%) case without a specific pathology. Besides, the detection of cases with a specific pathology would not be prevented and the necessary diagnostic procedures would continue to be performed. Specific LS pathologies can be detected adequately, whereas decreasing unnecessary examinations and procedures in cases without a specific pathology by using our algorithm.