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.

Iodine-125 interstitial brachytherapy for malignant lacrimal sac tumours: an innovative technique.

OBJECTIVES: Primary malignant tumours of the lacrimal sac are rare, surgery and radiotherapy may induce substantial side effects for patients. Here, this article reports an innovative technique of interstitial brachytherapy developed for the treatment of malignant lacrimal sac tumours. PATIENTS AND METHODS: Four patients (male 3, female 1), with an average age of 52.7 years (range 41-72 years), were individually diagnosed with squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma and lymphoma. All patients received Iodine-125 interstitial brachytherapy after surgical resection for malignant lacrimal sac tumours. Visual function examination (vision, intraocular tension, fundus photography, fluorescein angiography, and optical coherence tomography) and CT/MRI/PET-MRI were performed to look for signs of recurrent tumours or metastasis. RESULTS: Four patients were followed for an average of 28 months (range, 23-37 months). All patients were free from local disease. Their visual function was normal, and CT/MRI did not reveal any tumour recurrence. CONCLUSIONS: Iodine-125 interstitial brachytherapy can be used as an alternative to wide excision or exenteration of these tumours. There was good local control, reasonable maintenance of vision, and good cosmesis.

Outcomes in patients with lacrimal gland carcinoma treated with definitive radiotherapy or eye-sparing surgery followed by adjuvant radiotherapy.

BACKGROUND: The optimal treatment for lacrimal gland cancer remains unclear. Eye-preserving surgery, as opposed to exenteration, followed by adjuvant radiotherapy (RT), has recently been reported to deliver satisfactory outcomes, but evidence is sparse. The aim of the present study was to evaluate outcomes in patients with lacrimal gland cancer treated at two tertiary medical centers. METHODS: We retrospectively examined data from patients with lacrimal gland cancer who had received eye-preserving surgical treatment followed by adjuvant RT with or without chemotherapy, or (if the tumor was inoperable) needle biopsy with definitive RT with or without chemotherapy. Baseline clinical and pathological characteristics were considered. Outcomes of interest included post-treatment complications, overall survival (OS), locoregional progression-free survival (LPFS), and distant metastasis-free survival (DMFS). RESULTS: Eighteen patients were included. Two-year OS, LPFS, and DMFS rates were 69.0, 76.7, and 71.4%, respectively. Patients with early-stage (T1-T2) lacrimal gland cancer had significantly better outcomes than those with advanced-stage disease (T3-T4). Two-year OS, LPFS, and DMFS rates were each 100% in patients with disease stages T1-T2, and 37.5, 50, and 37.5%, respectively, in those with disease stages T3-T4 (P < 0.05). Orbital complications were well tolerated. CONCLUSIONS: Eye-sparing surgery with adjuvant RT can achieve satisfactory results in patients with T1-T2 lacrimal gland carcinoma. Disease stage T3 and above was associated with poor outcomes even with post-operative RT, likely due to distant metastasis. Adding neoadjuvant chemotherapy or adjuvant chemotherapy to current treatment strategies might be a suitable choice for this group of patients.

Effects of radiation therapy on the meibomian glands and dry eye in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Radiation therapy (RT) is the treatment of choice in patients with low-grade ocular adenexal mucosa-associated lymphoid tissue lymphoma (OAML) and many of them experience post-RT dry eye with varying severity. The purpose of the present study was to investigate ocular effects of RT on meibomian glands and dry eye by directly visualizing structural changes. Secondly, we focused on the comparison of two groups of patients according to tumor location and radiation technique. METHODS: Sixty-four eyes with OAML of conjunctiva, orbit, lacrimal gland, or lacrimal sac were grouped into conjunctival lymphoma and "orbital-type" lymphoma (i.e., orbit, lacrimal gland, and lacrimal sac). Subjects were investigated for morphological changes in meibomian glands by meiboscore grading system. Radiation technique was examined and Ocular Surface Disease Index (OSDI) questionnaire, Schirmer's test, tear film break-up time (TBUT), slit lamp examination of corneal surface and lid margin abnormality were conducted before and after RT. RESULTS: The increase in meiboscore was statistically significant over time after RT in both groups (P < 0.001). The extent of increase in meiboscore was significantly greater in the "orbital-type" lymphoma group than in the conjunctival lymphoma group (P < 0.001). The changes in OSDI, TBUT, corneal fluorescein staining score and lid margin abnormality score after RT were significantly different across two groups (P = 0.042, 0.001, 0.035 and 0.001, respectively). Schirmer's value decreased after RT in both groups. Dry eye symptoms were most severe right after RT in both groups, but a gradual resolution was noted in most patients with conjunctival lymphoma, whereas symptoms persisted in "orbital-type" lymphoma patients. The OSDI score and corneal fluorescein staining score were positively correlated with meiboscore in "orbital-type" patients at post-RT 6 months (r = 0.43, P = 0.04; r = 0.39, P = 0.03, respectively). CONCLUSIONS: Patients with OAML had different degrees of morphological changes in meibomian glands according to tumor location and radiation technique. "Orbital-type" lymphoma patients are more likely to experience severe injury to meibomian glands, which eventually leads to persistent dry eye. Patients with "orbital-type" lymphoma should be well informed of post-RT damage on meibomian glands and persistent dry eye.

Radiation-Induced Optic Neuropathy: Clinical and Imaging Profile of Twelve Patients.

BACKGROUND: Radiation-induced optic neuropathy (RON) is a form of delayed radionecrosis of the anterior visual pathways, which develops within months to years after external cranial irradiation and causes severe and irreversible vision loss. Small series reports have adequately documented its clinical features, but imaging characteristics have been less completely described. METHODS: We accrued cases from the University of Michigan Neuro-Ophthalmology Clinic files and from cases coded as "radiation optic neuropathy" at the University of Michigan Medical Center between 1994 and 2017. All patients had undergone 3D-conformal linear accelerator (photon) external beam radiation. We collected clinical details of vision loss, including the temporal relationship to radiation. A single neuroradiologist (E.A.L.) evaluated all available magnetic resonance imaging (MRI) studies, noting the presence of enhancement, expansion, or volume loss of the optic nerves or chiasm, corresponding T2 signal abnormalities, and the absence of demyelination or confounding compressive lesions. RESULTS: Twelve patients (15 eyes) met inclusion criteria. Vision loss was usually monocular at outset, but both optic nerves were eventually involved in 3 (25%) patients. Although usually sudden in onset, vision loss often declined slowly over many months, frequently to finger counting, or worse without recovery. An afferent pupillary defect was always present at the time of presentation. Most affected optic discs were pale at the time of first visual symptoms, indicating that subclinical optic nerve damage had been present for several weeks. The latency from completion of radiation to onset of vision loss ranged from 7 to 48 months (average: 18 months). In 2 patients, radiation was delivered to the whole brain, rather than being limited to the anterior visual pathway. MRI typically displayed a discrete region of enhancement of the affected prechiasmatic optic nerve, often with expansion and high T2 signal in the enhancing segment. In 3 affected eyes, enhancement was apparent on imaging completed 3-6 weeks before the onset of vision loss. In one patient, segmental prechiasmatic enhancement became evident only on repeat MRI completed 7 months after vision loss. The duration of enhancement among 9 eyes with follow-up MRIs was at least 2 months, but in one case, enhancement was still present on a study performed 17 months after treatment. CONCLUSIONS: This study further delineates the profile of RON. Visual loss is often acute, profound, and monocular but may decline slowly after acute onset and later affect both optic nerves. High-resolution MRI of the optic nerves usually will display enhancement of a discrete segment of the intracranial prechiasmatic optic nerve, often with accompanying expansion and T2 hyperintensity. In some cases, these imaging features may precede vision loss. They may be subtle or appear after vision loss. Enhancement lingers for a wide interval, ranging in this study from 2 to at least 17 months. Recognition of these imaging characteristics assists in confirmation of the diagnosis of RON.

Long-term Outcomes of Globe-Preserving Surgery With Proton Beam Radiation for Adenoid Cystic Carcinoma of the Lacrimal Gland.

PURPOSE: To describe outcomes of globe-preserving surgery combined with high-dose proton beam radiation (PBR) in treating primary adenoid cystic carcinoma (ACC) of the lacrimal gland. DESIGN: Retrospective case series. METHODS: Twenty-nine patients with primary ACC of the lacrimal gland were identified in the records of a single institution between 1990 and 2017. Patients with nonorbital primary tumor origins or with inadequate follow-ups were excluded. Eighteen patients met inclusion criteria. Clinical data, imaging studies, histopathology, treatment modality, local recurrences, visual outcomes, metastases, and survivals were assessed. Disease-free survivals for the current patients were measured and compared to those of other studies. RESULTS: The eighteen patients (14 female, 4 male) were followed for a median of 12.9 years (range 0.6-22.3 years) after treatment completion. Their median age was 40 years. Four were children (median age 12 years). All were treated with globe-preserving tumor resection and radiation (median dose of 72 cobalt gray equivalents). Three adult patients died of metastatic disease (median of 4.2 years after treatment). Four had local recurrences. Useful vision (20/40 or better) was retained for a median 3 years (range 1-12.9 years). Radiation morbidity included brain injury, retinopathy, optic neuropathy, keratopathy, and cataract. Overall and disease-free survivals were significantly better compared to historical treatments, but did not differ statistically from other modern approaches. CONCLUSIONS: Globe-preserving surgery with PBR, although imperfect, has a favorable long-term survival compared to other modern modalities, and offers a variable period of useful vision.

Corneal complications after orbital radiotherapy for primary epithelial malignancies of the lacrimal gland.

PURPOSE: To review the long-term corneal complications after high-dose external beam orbital radiotherapy given to patients for lacrimal gland carcinomas. The impact of prophylactic measures to improve long-term ocular surface health is also assessed. DESIGN: Retrospective case series. PARTICIPANTS: Patients under the care of Moorfields Eye Hospital and receiving external beam radiotherapy for primary epithelial lacrimal gland carcinoma between 1975 and 2014. METHODS: Retrospective review of ophthalmic case notes at Moorfields Eye Hospital, and oncology and general physician records. MAIN OUTCOME MEASURES: The occurrence of corneal perforation, and time to perforation. RESULTS: Sixty-seven patients were included in this study, of whom nine (13%) developed corneal perforation at a median time of 10.4 months after radiotherapy (mean 35; range 3.2 months to 14.5 years); the majority (7/9; 78%) perforated within 36 months of radiotherapy. The mean follow-up interval of the whole cohort was 8.2 years (median 4.6; range, 2 months to 30.7 years). CONCLUSIONS: Although most patients with globe-sparing treatment of lacrimal gland carcinoma did not suffer corneal perforation, they usually require long-term therapy to maintain the ocular surface. The high-dose external beam radiotherapy needed for lacrimal gland carcinoma can produce significant ocular surface morbidity, and the 13% incidence of corneal perforation was greatest in the first 3 years after irradiation.

Adult alveolar rhabdomyosarcoma of the lacrimal sac.

Lacrimal sac tumours are rare, but must be considered in the diagnosis of patients presenting with masses in the medial canthal region. We report a single case of lacrimal sac rhabdomyosarcoma in a 31-year-old man. The patient self-presented to the eye department with a 4-week history of discomfort, epiphora and a medial canthal mass. After no response to 1 week of oral antibiotics for a presumed diagnosis of dacryocystitis and the presence of firm mass extending above the medial canthal tendon, surgical exploration was carried out which revealed a lacrimal sac mass. Histologically this showed an alveolar rhabdomyosarcoma, which was confirmed on immunohistochemistry. After 4 rounds of chemotherapy and 50.4Gy of radical radiotherapy, the patient is well with no signs of further local or distant disease at 11-months follow-up and 20 months following initial diagnosis. To our knowledge, there are no previously reported adult cases of lacrimal sac alveolar rhabdomyosarcoma in the peer-reviewed literature. We want to highlight the unique diagnosis in this case as well as drawing attention to the possibility of malignancy in patients responding poorly to management when an initial diagnosis of dacryocystitis is made in the presence of a medial canthal mass.

Primary orbital plasmacytoma mimicking lacrimal gland tumor.

Extramedullary plasmacytoma is a rare plasma cell malignancy, comprising 3% of the whole group. The involvement of orbit is even rarer since 80% of extramedullary plasmacytoma have been reported from upper respiratory tract, followed by gastrointestinal tract. The disease is thrice more common in males than females and is more common in 6th to 7th decade of life, but we are reporting a case of extramedullary plasmacytoma presenting as lacrimal gland tumor in a 59-year-old female. The correct diagnosis is essential since the disease is highly radiosensitive and responds well to radiotherapy unlike other malignancy in this region. A high index of suspicion with imaging and careful use of fine needle aspiration cytology helps in diagnosis and prompt treatment.

Radiation therapy: orbital tumors.

Orbital tumors are rare overall, comprising 0.1% of all tumors and less than 20% of all orbital diseases. Tumors may be benign, locally aggressive, or malignant. Of the malignant tumors, lymphomas and metastases are the most common and are primarily seen in the elderly population. While surgery and chemotherapeutic agents are often employed in the management of these lesions, not all patients are candidates for these therapies. Radiation therapy offers a noninvasive, well-tolerated primary treatment modality, whereby vision-sparing is feasible in many cases. In this chapter, we review an array of non-neoplastic entities and orbital tumors, for which there exists a role for radiation, and the radiotherapeutic techniques and applications in their management.

Neutron radiotherapy for adenoid cystic carcinoma of the lacrimal gland.

PURPOSE: Lacrimal gland adenoid cystic carcinomas are rare, aggressive orbital tumors that share histopathologic similarities with salivary gland malignancies. Neutron radiotherapy may be useful for treatment due to its high biological effectiveness for salivary malignancies. METHODS: The authors retrospectively reviewed the outcomes for 11 lacrimal gland adenoid cystic carcinoma patients treated with neutrons from 1988 to 2011. Most had undergone surgery prior to radiation therapy. However, gross residual disease was present in 8 patients. The most common American Joint Committee on Cancer stage was T4cN0M0. Four patients with skull base involvement received a radiosurgery boost and 1 received a proton therapy boost. RESULTS: Median follow up was 6.2 years. Median overall survival was 11.1 years and median disease-free survival was 6.3 years. Five-year local control was estimated by the Kaplan-Meier method as 80%. Three patients had a local recurrence; 4 developed distant metastases. Six patients died. Seven patients had intact vision in the affected eye before neutron radiation. Two required enucleation for a painful dry eye. Of the 5 who avoided an enucleation, 3 had either severe visual impairment (20/400) or only light perception and 2 were without known vision compromise or complications at the time of their death. One patient developed asymptomatic frontal lobe radionecrosis after 2 courses of radiation therapy. CONCLUSIONS: Neutron radiation therapy achieved excellent 5-year local control in this series of high-risk patients, with most cases having gross residual disease. Late recurrences and distant metastases remain a challenge. Meaningful ipsilateral vision preservation was not possible in most cases in the long term, although only 2 patients required an enucleation for treatment effects.

Retinal angiomatous proliferation occurring after radiotherapy.

PURPOSE: To describe two cases of retinal angiomatous proliferation (RAP)-like lesion following radiation therapy for primary tumor. PATIENTS AND METHODS: Retrospective evaluation of two patients with previous irradiation treatment for a pleomorphic adenoma of the lacrimal gland and a vocal cord carcinoma, respectively. Visual acuity (VA), fluorescein angiography and optical coherence tomography were performed and demonstrated a RAP-like lesion in both cases. Treatment with intravitreal injections of Ranibizumab was performed with a follow-up of 19 and 10 months, respectively. RESULTS: Both the patients had a positive response to the treatment with improvement in VA and reduction of intraretinal fluid. CONCLUSION: RAP-like lesions can develop following radiation treatment for a primary tumor. In patients presenting with idiopathic RAP, a history of prior radiotherapy should be considered.

Ophthalmologic outcomes after chemotherapy and/or radiotherapy in non-conjunctival ocular adnexal MALT lymphoma.

In the present study, we evaluated the ophthalmologic outcomes of 24 patients who received chemotherapy and/or radiotherapy for the treatment of non-conjunctival ocular adnexal mucosa-associated lymphoid tissue-type (MALT) lymphoma. Ophthalmologic outcomes were assessed in patients who received chemotherapy and/or radiotherapy from March 2004 until May 2010. Outcomes were determined according to common symptoms following chemotherapy and/or radiotherapy, which consisted of decreased visual acuity, dry eye symptoms, retinopathy, optic neuropathy, increased intraocular pressure, and blepharitis. Nine patients received chemotherapy alone, eight patients received radiotherapy alone, and seven patients received chemotherapy with additional radiotherapy (chemoradiation therapy). Patients treated by chemotherapy alone showed better ophthalmologic outcome scores (mean score, 1.56) than those treated by radiation alone or chemoradiation therapy (mean score, 4.01). In conclusion, the treatment of ocular adnexal lymphoma including radiotherapy showed poor ophthalmologic outcomes due to radiation-induced complications. Recently, many new treatment options have emerged, such as immunotherapy or radioimmunotherapy. In the future study, to select a better treatment modality with fewer complications, well-designed prospective trials with ophthalmologic outcomes are needed.

Successful radiotherapy treatment of lacrimal gland infiltration in patient with Sjögren΄s syndrome.

OBJECTIVE: To present a single case report on successful radiotherapy treatment of lacrimal gland infiltration in patient with Sjögren΄s syndrome. BACKGROUND: Radiotherapy is occasionally used for the treatment of benign disorders. There is no report on use of radiotherapy for local treatment of the Sjögren΄s syndrome in the literature. METHODS: Female patient with lacrimal gland involvement as a part of Sjögren΄s syndrome with diplopia and visus deterioration was treated by radiotherapy with eye shielding. RESULTS: Regression of the infiltration with full restoration of visus and minimal acute radiation reaction was achieved. CONCLUSION: A case report of successful use of local radiotherapy in the treatment of lacrimal gland affected by Sjögren΄s syndrome is presented (Fig. 3, Ref. 6). Full Text in PDF www.elis.sk.

Basal cell adenocarcinoma of lacrimal gland.

Basal cell adenocarcinoma (BCAC) is a recently described rare salivary gland tumor. They are locally invasive and destructive tumors with rare incidence of metastasis. BCAC most commonly occur in the parotid gland followed by the submandibular and other minor salivary glands. The primary management of these tumors is surgery with or without adjuvant radiotherapy. Lacrimal gland is a very rare location of BCAC; only one case has been reported in English literature. We report a case of recurrent basal cell adenocarcinoma of lacrimal gland in a 75-year-old female. She had past history of local excision of a tumor in the lacrimal gland of same side 10 years back, details of which were not available with the patient. We discuss about the case and review the literature about treatment modality in basal cell adenocarcinoma.

Undifferentiated carcinoma of the lacrimal sac: case report and review of literature.

A 55-year-old man presented with a 2-year history of right-sided epiphora and was referred to the Oculoplastic services for dacryocystorhinostomy. A 3-month progressive growth of a right medial canthal mass was found. MRI revealed an extraconal, lobulated, homogeneously enhancing mass in the lacrimal sac fossa with globe indentation and displacement supero-temporally. Following a transcanalicular needle biopsy which was suggestive of a carcinoma, he underwent medial orbitectomy and maxillectomy, through a lateral rhinotomy, with removal of puncta and canaliculi after ensuring no regional or systemic spread. The lacrimal sac tumor was encapsulated, extending superiorly above the medial canthal tendon and involving the nasolacrimal duct, and posteriorly along the medial orbital wall. After ensuring surgical margins were cleared of tumor infiltration, orbital reconstruction was performed with titanium plate and nasolabial flap. He has completed adjuvant radiotherapy with no evidence of tumor recurrence at 15 months of follow-up.

Clinical significance of tumor-infiltrating FOXP3+ T cells in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma.

We evaluated the association between tumor-infiltrating FOXP3+ T cells and clinical outcomes in patients with ocular adnexal lymphoma of mucosa-associated lymphoid tissue type (OAML). Pretreatment formalin-fixed paraffin-embedded tissues from 42 patients with OAML were stained with 236A/E7 anti-FOXP3 murine monoclonal antibody as well as CD3, CD4 and CD8 antibodies. The amount of FOXP3+ T cells was numerically quantified using an image analysis program. Front-line treatments were as follows: combination chemotherapy (n = 25); radiotherapy (n = 9); doxycycline (n = 6); and wait and see (n = 2). Complete response (CR) was observed in 20 (50%) of 40 evaluable patients. Median progression-free survival (PFS) was 50 months. A high number of FOXP3+ T cells (n = 21, ≥ 180/0.58 mm(2)) showed a higher CR rate (33%vs 71%, P = 0.013) and tendency towards prolonged PFS (48 vs 67 months, P = 0.110). In the combination chemotherapy group, a high number of FOXP3+ T cells was significantly associated with a higher CR rate (29%vs 82%, P = 0.008) and prolonged PFS (17 vs 79 months, P = 0.003). A high number of tumor-infiltrating FOXP3+ T cells correlates with a favorable clinical outcome in OAML patients.

Localized orbital mucosa-associated lymphoma tissue lymphoma managed with primary radiation therapy: efficacy and toxicity.

PURPOSE: To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). METHODS AND MATERIALS: From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. RESULTS: The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade ≥2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). CONCLUSIONS: POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.