Head and neck melanoma: the eyelid region has a better prognosis and easier management: a retrospective survey and systematic review.

Eyelid melanoma (EM) is a malignant neoplasm accounting for around 1% of eyelid malignancies. Because of its rarity, most of our knowledge of EM is currently based on studies of cutaneous melanomas located elsewhere. Accordingly, this study aimed to specifically evaluate EM characteristics, management strategies, and prognosis. A retrospective study was carried out on patients diagnosed with EM at Careggi University Hospital, Florence between May 2012 and May 2022. In addition, a systematic review of relevant literature was conducted, encompassing studies published from 2013 to 2023. Clinical, histopathological, therapeutical, and prognostic data were analyzed to assess the metastasis rate and the 5-year survival rate of patients with EM. Separate data were extracted for in situ and invasive disease. Our original study included 19 patients diagnosed with EM with a 5-year survival rate of 100% for in situ and 83.3% for invasive EM. The literature review identified five poorly detailed large database reviews and 14 original studies on EM with an overall 5-year survival rate of 79.7%. The present research indicates that EM is a challenging malignancy, but has a relatively better prognosis and easier management than other melanomas of the head and neck region. These are probably related to the anatomical location which leads to early diagnosis. Therefore, EM should be considered as a specific disease requiring dedicated treatment. Based on the personal authors' experience and comprehensive overview of the current knowledge, a dedicated protocol is proposed.

Periocular sebaceous carcinoma: updates in the diagnosis, treatment, staging, and management.

Periocular sebaceous carcinoma (PSC) is a rare, aggressive, and potentially metastatic adnexal malignancy. Due to the ability of PSC to resemble several benign and malignant conditions, diagnosis is often delayed or mistaken. In addition, even with a known diagnosis, choosing the right treatment is still an open debate. For this reason, we decided to review the most up-to-date literature on PSC and propose a dedicated procedural protocol to help clinicians when dealing with PSC. A PubMed search was carried out using the terms "Sebaceous Carcinoma", "Adnexal Periocular Cancer", "Sebaceous Carcinoma AND eyelid", "Periocular Sebaceous Carcinoma", and "Ocular Adnexa". Pertinent studies published in English from 1997 up to December 2022 were compared to the selection criteria and if suitable, included in this review. Through the initial search, 84 articles were selected. Of these, 36 were included in the final study. Several papers explored different diagnostic and therapeutic strategies regarding PSC diagnosis and management. In light of the current literature review and the multidisciplinary experience of three clinical centers, a dedicated procedural protocol is proposed. PSC diagnosis may be achieved through accurate clinical evaluation, but it requires histopathologic confirmation, which can be challenging. Dermoscopy, in vivo reflectance confocal microscopy, and optical coherence tomography may facilitate PSC clinical examination, while immunohistochemistry stains may support histological diagnosis. Appropriate disease staging is necessary before choosing the treatment, as local disease requires radically different treatment compared to advanced disease. In addition, recent innovations in nonsurgical treatments, including radio-chemotherapy, immunotherapy, and targeted therapy, may be a viable option in the most challenging cases.

Correction: Mazzini et al. Anatomical and Functional Outcomes after Endoresection and Adjuvant Ruthenium Brachytherapy for Uveal Melanoma: A Single-Center Experience. Life 2023, 13, 902.

There was an error in the original publication [...].

Anatomical and Functional Outcomes after Endoresection and Adjuvant Ruthenium Brachytherapy for Uveal Melanoma: A Single-Center Experience.

PURPOSE: To evaluate the anatomical and functional outcomes of endoresection and adjuvant ruthenium (Ru)-106 brachytherapy for uveal melanoma (UM). METHODS: Retrospective case series of 15 UM patients (15 eyes) treated at our center (Careggi University Hospital, Florence). RESULTS: Six patients (40%) were male and nine were female (60%). The mean age of patients at the time of treatment was 61.6 years (±19.41). The mean BCVA at baseline was 20/50. In all cases UM originated from the choroid. The mean tumor thickness at baseline was 7.14 mm (±2.05), and the mean largest basal diameter was 11.2 mm (±1.92). A concurrent retinal detachment was diagnosed in 11 patients (73.3%). Two patients (13.3%) showed vitreous seeding at baseline. Eleven patients (73.3%) were treated with primary endoresection, while four patients (26.7%) were treated with a "salvage endoresection" after primary treatment failure (previous radiation treatment). The mean follow-up time was 28.9 months (±10.6). Thirteen out of fifteen patients were alive and showed no evidence of local recurrence or distance metastasis at the last follow-up visit. The treatment achieved local control of the disease in 14 out of 15 cases (93.3%). In one case, the patient underwent enucleation for disease recurrence. The overall survival rate at the end of the follow-up was 93.3%. The mean BCVA at last follow-up visit was 20/40. Treatment was well tolerated, without significant complications. CONCLUSIONS: Endoresection and adjuvant Ru-106 brachytherapy is a valuable conservative option for selected UM patients and can be used both as a primary treatment and as a salvage therapy. It can control melanoma and avoid enucleation, reduce radiation-related complications, and provide tumor tissue for chromosomal analysis and prognostic testing.

Orbital Extenteration Defects: Ablative and Reconstructive Flowchart Proposal.

ABSTRACT: Orbital exenteration is a radical and disfiguring operation. It is still under debate the absence of correlation between the term describing the resulting orbital defect and the type of reconstruction. Authors' goal was to propose a consistent and uniform terminology for Orbital Exenteration surgery in anticipation of patients' tailored management. Twenty-five patients who underwent orbital exenteration between 2014 and 2020 were reviewed. A parallel comprehensive literature review was carried on. Five different types of orbital exenteration where outlined. Multiple reconstructive procedures were enclosed. An algorithm for orbital reconstruction was proposed based on anatomic boundaries restoration. Eyelid removal was first considered as an independent reconstructive factor, and both orbital roof and floor were indicated as independent reconstructive goals, which deserve different defect classification. In our opinion, this algorithm could be a useful tool for patient counseling and treatment selection, which might allow a more tailored patient care protocol. LEVEL OF EVIDENCE: Level III.

Bilateral choroidal metastasis from adenoid cystic carcinoma of the submandibular salivary gland.

PURPOSE: A case of bilateral choroidal metastasis from an adenoid cystic carcinoma of the submandibular gland is described. CASE DESCRIPTION: A 45-years-old woman with a history of metastatic adenoid cystic carcinoma presented with visual impairment in both eyes. Fundus images showed bilateral creamy-white choroidal masses. Optical coherence tomography revealed subretinal fluid with high reflective speckles and a "lumpy bumpy" anterior contour of the lesions. Fluorescein angiography showed a hypofluorescent pattern of the lesions in early arterial phases, and progressive late hyperfluorescence. A diagnosis of bilateral choroidal metastasis from adenoid cystic carcinoma was made. The patient was advised to underwent palliative chemotherapy, but she expired a few weeks after the diagnosis. CONCLUSION: Salivary gland carcinoma rarely metastasizes to the choroid, with few cases described in literature. In patients with a history of salivary glands tumor the possibility of choroidal metastatization should always be considered.

Multimodal imaging of optic disc melanocytoma.

PURPOSE: To describe the findings of four patients (four eyes) with optic disc melanocytoma (ODM), using multimodal imaging. METHODS: Retrospective case series. RESULTS: On ocular ultrasonography ODMs appeared as hyperechogenic lesions with moderate-to-high internal reflectivity. On blue-light fundus autofluorescence, ODMs showed total hypoautofluorescence, while, on infrared reflectance images appeared as bright and well-marginated lesions. MultiColor composite images showed reddish-brown lesions with well-defined margins. Swept-source optical coherence tomography revealed elevated lesions covering the optic disc with an irregular hyperreflective surface, dishomogeneous internal structure with hyperreflective dots, and posterior shadowing. In all cases optical coherence tomography angiography detected intratumoral blood vessels which were not detectable with fluorescein angiography. CONCLUSION: Multimodal imaging in ODM might be useful both at presentation, increasing the diagnostic accuracy, and at follow-up, providing helpful details, that can help to rule out the possibility of malignant transformation and other ocular complications.

Combined brachytherapy and vitreoretinal surgery for a large retinal capillary hemangioma with exudative retinal detachment.

INTRODUCTION: We report about a large retinal capillary hemangioma (RCH) with exudative retinal detachment and a macular fold, treated with Ruthenium-106 brachytherapy (Ru-106 BT) and scleral buckling surgery, followed by pars plana vitrectomy (PPV), for the removal of macular tractions. CASE DESCRIPTION: A 17-year-old boy was referred to our Ocular Oncology Unit for a large RCH in the left eye. BCVA was hand motion. The RCH measured 4.9 × 6.85 mm in basal diameters and 4.0 mm in thickness and was located in the mid-peripheral temporal retina. It was surrounded by extensive subretinal exudation, forming an exudative retinal detachment, with a retinal fold that extended from the lesion to the optic disc. We performed Ru-106 BT and at the moment of the plaque removal we placed a radial buckle with the aim to unbend the retinal fold. At 3-months follow-up the exudation decreased, we achieved the opening of the peripheral side of the retinal fold, but the macula was still detached. We decided to perform a lens sparing PPV, macular peeling and air tamponade, to remove the vitreoretinal tractions ab interno and to try to complete the opening of the macular fold. After 1-month BCVA was counting fingers, the retina appeared attached, also in the macular area, but the retinal fold remained partially close in the macular side. After 6 months the tumor was inactivated, the macula remained attached, unfortunately, the macular fold remained partially close. CONCLUSION: Ru-106 BT and scleral buckling concurrent approach can be an effective treatment modality in selected cases of large RCHs, followed by PPV to remove eventual vitreo-retinal tractions.

Clinical outcomes and secondary glaucoma after gamma-knife radiosurgery and Ruthenium-106 brachytherapy for uveal melanoma: a single institution experience.

We retrospectively analyzed data from records of 48 patients (48 eyes) treated with gamma-knife (n = 18) or Ruthenium-106 brachytherapy (n = 30) for uveal melanoma, in our Ocular Oncology Unit between December 2013 and September 2019, with the aim to evaluate treatment outcomes, and incidence and risk factors for secondary glaucoma. Patients demographics and tumor characteristics at diagnosis were recorded. Follow-up data were collected regarding local tumor control, treatment complications, enucleation need, metastases occurrence and survival status. The median follow-up period was 33.7 months in the gamma-knife group and 26.2 months in the brachytherapy group. The mean tumor thickness, the largest basal diameter and the tumor volume were significantly higher in the gamma-knife group than in the brachytherapy group. The local tumor control rate was 100% in the brachytherapy group and 77.8% in the gamma-knife group. In the gamma-knife group, six patients were enucleated, no patient treated with brachytherapy underwent enucleation. The overall survival rate was 96.7% in the brachytherapy group and 94.44% in the gamma-knife group. Secondary glaucoma occurred in 10 patients after gamma-knife and in one patient after brachytherapy: it should be emphasized that larger lesions were treated with gamma-knife, whereas smaller tumors were selected for brachytherapy. We found a significative correlation of tumor thickness (P value = 0.043) and volume (P value = 0.040) with secondary glaucoma occurrence after gamma-knife treatment. Moreover, secondary glaucoma significantly correlated with radiation retinopathy in the gamma-knife group (P value = 0.009). This study shows preliminary clinical results that could be useful for further studies with more patients and longer follow-up.

Treatment of periocular advanced basal cell carcinoma with Hedgehog pathway inhibitors: A single-center study and a new dedicated therapeutic protocol.

The management of difficult-to-treat periocular basal cell carcinoma (BCC) becomes very challenging in cases of delayed diagnosis, leading to the development of locally advanced BCC. The aim of this study was to evaluate the outcomes of Hedgehog pathway inhibitors (vismodegib and sonidegib) treatment in patients affected by periocular locally advanced BCC. We focused on the common adverse events and their correlation with the administration schedule, to determine a management protocol specific for the periocular area. This observational prospective study included a single-center case series with patients who were histologically confirmed to have periocular or orbital locally advanced BCC, treated with Hedgehog pathway inhibitors. All patients benefitted in terms of regression or stabilization of the neoplasm. In the first months of treatment, the HPIs were well tolerated, and the first important side effects appeared after about 5 months of continuous use of the drug. These data could lead to a new type of therapeutic scheme where neoadjuvant therapy could be followed by pulse therapy as an adjuvant to surgery.

Ocular oncology service during the COVID-19 outbreak in Florence (Italy): Practical considerations for the management of patients.

The Coronavirus disease 2019 (COVID-19) outbreak has imposed the adoption of strategies to limit the risk of contagion for cancer patients without compromising their healthcare. As well as cancers of other sites, the treatment of certain ocular and periocular malignancies is considered non-deferrable and should proceed despite the pandemic. Delays in treatment of these patients may result in negative outcomes. Herein, we provide some practical considerations deriving from our experience at the Ocular Oncology Unit of Careggi University Hospital (Florence, Italy).

Extensive conjunctival melanoma successfully treated with surgical resection and pre- and postoperative topical mitomycin C.

PURPOSE: To report a case of a large conjunctival melanoma (CM) successfully treated with surgical resection and pre- and postoperative topical mitomycin C (MMC). METHODS: This is a single observational case report. RESULTS: A 58-year-old man was referred to us for a large pigmented conjunctival lesion of the right eye. Slit lamp examination revealed an extensive pigmented lesion diffusely involving the temporal bulbar conjunctiva, with multifocal intensely dark areas and an elevated limbal component extending on the corneal surface. The remaining bulbar and forniceal conjunctiva was not involved. The lesion was clinically diagnosed as CM. Clinical examination and head and neck ultrasonography did not show regional lymphadenopathy. The patient was treated with neoadjuvant topical MMC 0.04% four times a day for 3 weeks. At the end of MMC therapy we observed a reduction in pigmentation and thickness of the lesion. Subsequently, the patient underwent surgical excision of the lesion with "no touch technique," double freeze-thaw cryotherapy of the margins and reconstruction of the tissue defect with amniotic membrane graft. Histopathologic examination of the specimen confirmed the presence of CM, surrounded by primary acquired melanosis with atypia. The excision margins were positive for tumor involvement, so we decided to perform an adjuvant treatment with other four cycles of topical MMC. CONCLUSIONS: The patient was closely followed-up after the treatment, without any local or distant recurrence at 32 months.

Multimodal imaging of a retinal cavernous hemangioma.

PURPOSE: We describe the characteristics of an isolated retinal cavernous hemangioma in a young female patient using multimodal imaging. CASE DESCRIPTION: Fundus examination of the right eye showed a large vascular mass, composed by clusters of dark red and dilated saccular angiomatous formations with superficial whitish fibroglial tissue and hemorrhages, located in the inferonasal peripheral retina, along the vascular arcade. On green-light fundus autofluorescence the lesion appeared hypoautofluorescent, with moderately hyperautofluorescent areas. On multiColor imaging it showed mainly a green pseudocolor, with knobby surface and well-defined irregular margins. Fundus fluorescein angiography showed early hypofluorescence within the tumor mass and late incomplete staining, without leakage. Ocular ultrasonography documented an elevated well-defined hyperechogenic lesion, with high internal reflectivity, without choroidal excavation, retinal detachment, or acoustic shadowing. Swept source optical coherence tomography showed multilobulated cavernous formations, varying in size, containing for the greatest part hyperreflective material, within an interconnecting fibrous scaffold and with an overlying partially adherent epiretinal membrane. Optical coherence tomography angiography documented a few highly reflective, tortuous and abnormal branching veins extending into the tumor mass, with a root-like appearance, and surrounding nodular changes, corresponding to the angiomatous formations. CONCLUSIONS: Different imaging modalities can be used in combination for a better evaluation of the pathological features of this rare vascular tumor.

Long-term follow-up and "double layer sign" in patients affected by circumscribed choroidal hemangioma.

BACKGROUND: Photodynamic therapy has revolutionised the treatment of circumscribed choroidal hemangiomas. The aim of this report is to report the long-term follow-up of patients affected by circumscribed choroidal hemangioma treated using photodynamic therapy. MATERIALS AND METHODS: We retrospectively reviewed patients affected by circumscribed choroidal hemangioma examined at the Retinal Medical Department at the Eye Clinic in Florence. We studied circumscribed choroidal hemangiomas treated using photodynamic therapy with at least 1 follow-up examination. Verteporfin was administered intravenously for 10 min (6 mg/m2 body surface area). After infusion (5 min), a 689 nm laser was applied with a light dose of 50 J/cm2. RESULTS: Ten eyes of 10 patients with circumscribed choroidal hemangioma who underwent Photodynamic therapy were included in our series (2 females and 8 males; average age at diagnosis 47.8 ± 9.3 yrs.; age range: 27-56 years). Five patients (5/10; 50 %) received only the photodynamic treatment whereas 5 patients (5/10; 50 %) also received other treatments (laser photocoagulation, intravitreal injection). On average, the patients received 2 photodynamic treatments (range 1-4). Four patients (4/10, 40 %) had a > 5-year follow-up; (average 4.5 ± 3.7 yrs. range 6 months - 10 years). In 2 patients we identified the "double layer sign" at the optical coherence tomography examination on circumscribed choroidal hemangioma. CONCLUSIONS: In our series, photodynamic therapy was a safe and effective treatment for circumscribed choroidal hemangioma during long-term follow-up. The double layer sign, which can be detected in several choroidal pathologies, suggests common pathogenetic mechanisms for circumscribed choroidal hemangiomas and central serous chorioretinopathy/polypoidal choroidopathy spectrum disease.

Large choroidal metastasis with exudative retinal detachment as presenting manifestation of small cell lung cancer: A case report.

A 64-year-old man, diagnosed with a retinal detachment of his left eye, was sent to our hospital to evaluate vitreoretinal surgery. Left eye best-corrected visual acuity was hand motion. Fundus examination showed a voluminous slightly pigmented choroidal neoformation with secondary retinal detachment. Ultrasonography revealed a large hyperechogenic choroidal mass with retinal detachment, initial choroidal excavation, and low-to-medium internal reflectivity. The clinical-instrumental aspects of the lesion suggested a primary malignancy. The patient underwent chest radiography, which showed a large mass located in the right lung. Contrast-enhanced computed tomography of chest and abdomen showed a voluminous lung lesion, another gross lesion of the liver, and other abdominal localizations. The patient underwent biopsies of the pulmonary and hepatic lesions and both samples showed an epithelial malignancy with neuroendocrine differentiation, compatible with metastatic small cell lung cancer. The patient's clinical condition declined within one month from presentation. In the interim, a contrast-enhanced brain computed tomography documented the presence of cerebellar metastases. The patient was admitted to the oncology department and started chemotherapy and supportive care, but unfortunately he died during the course of the treatment, 5 months after his initial presentation. This case is peculiar both for the unusual presentation of small cell lung cancer and for the morphological appearance of the choroidal lesion that suggested a primary tumor.

Incidence and Survival of Patients With Conjunctival Melanoma in Europe.

Importance: Conjunctival melanoma (CM) is a rare ocular tumor. Estimates of incidence and survival of patients with CM are important to researchers and policy makers. Objective: To estimate incidence and survival of patients with CM in Europe. Design, Setting, and Participants: This population-based cohort study used data from 41 European cancer registries adhering to the RARECAREnet project. All individuals diagnosed as having malignant CM from January 1995 to December 2007 coded according to the International Classification of Diseases for Oncology, Third Edition codes C69.0 (conjunctiva) and 8720-8780 (melanoma) were included. Analysis began March 2019. Main Outcomes and Measures: Trend estimates for incidence and for 5-year relative survival (the ratio of the measured survival of patients to the expected survival in the general population for the same country, age, sex, and calendar year). Crude, age-standardized, and bayesian incidence rates were calculated. Five-year relative survival was calculated by the Ederer II method with the cohort and period approach. Results: A total of 724 patients 15 years or older (512 [70.7%] were 55 years or older; 366 [50.6%] were female) were analyzed with an overall crude incidence of CM (per 1 000 000 person/y) of 0.46 (95% CI, 0.42-0.49). Crude incidence was similar in men and women (0.48; 95% CI, 0.44-0.54 and 0.46; 95% CI, 0.41-0.51, respectively) and increased with age. Age-standardized incidence increased over time only in men and was the highest in Norway and the Netherlands (more than 0.70). Only 1 case in 14 years was estimated to occur in Iceland vs about 20 cases per year in large countries such as France and Germany. Percentage of 5-year survival (83.5 overall; 95% CI, 78.6-87.3) was not different between adult and elderly patients but showed large geographical disparities across European regions (range, 66-89) and improved markedly in male patients (from 76 in 1995-1998 to 86 in 2003-2007, with a difference of 10.2 [95% CI, 1.3-19.2]; P < .05) becoming similar to that of women in the last period. Conclusions and Relevance: Although these data are only available through 2007 and based on registries not uniformly covering the European population, the study provides the first Europe-wide estimates of the incidence and relative survival of patients with CM using population-based data. Geographical differences in survival indicate room for outcome improvement in Southern, Northern, and Eastern European countries.

A rare case of non-small cell lung cancer choroidal metastasis responding to ALK tyrosine kinase inhibitors.

Choroidal localization from non-small cell lung cancer is rare and when it occurs may cause visual alterations. Targeted therapy against actionable gene mutations represents the standard of care in advanced non-small cell lung cancer. We report the case of a 53-year-old woman affected by metastatic anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer who received ALK tyrosine kinase inhibitors, from January 2017. The patient had a complete response of choroidal metastasis after therapy with ALK tyrosine kinase inhibitors. She recovered a complete visus and actually she still continue therapy with alectinib. The patient had a complete recovery of visus in addiction to a long response on treatment.

Adenocarcinoma Arising in the Conjunctiva With Periparotid Lymph Node Metastases.

PURPOSE: To report a rare case of adenocarcinoma (ADC) arising in the conjunctiva which locally recurred and metastasized to the periparotid lymph nodes. METHODS: This is a single observational case report. RESULTS: A 79-year-old male patient was referred to us for a suspected recurrence of conjunctival carcinoma of the right eye. At presentation, we observed an elevated conjunctival lesion with corneal involvement. He was treated with neoadjuvant mitomycin C 0.04% eye drops, followed by surgical excision of the lesion, cryotherapy of the excision margins, and reconstruction with amniotic membrane graft. The tumor was histologically diagnosed as ADC. The negative systemic evaluation and the immunoprofile led us to believe the primitive nature of the tumor. The excision margins were positive, and the patient was lost to follow up for 7 months, and when he came back, a new local recurrence was diagnosed. Then, he received rescue treatment with mitomycin C 0.04% eye drops with complete regression of the lesion. No local recurrence was observed until the 14-month follow-up visit, during which the patient complained of swelling in the right parotid region. Subsequently, he underwent total parotidectomy with neck dissection. Metastasis was found in 3 periparotid lymph nodes. The patient did not receive further treatments, and no recurrences were observed over the following 20 months. CONCLUSIONS: ADC arising in the conjunctiva is a very rare occurrence. Additional observation is required for the management of this rare conjunctival tumor.

Primary Orbital Synovial Sarcoma Mimicking a Periocular Cyst.

Synovial sarcoma (SS) is a high-grade soft-tissue sarcoma occurring predominantly in older children and young adults. Only approximately 7% occur in the head and neck region, with SS representing less than 0.1% of all head and neck cancers. Orbital location is exceedingly rare with only 8 cases reported so far in the literature. It is noted for its propensity for late local recurrences and metastases. Histologically, SS is monophasic, biphasic, or poorly differentiated and harbors a specific chromosomal translocation t(X;18)(p11.2;q11.2) in >95% of cases. In this article, we describe a case of monophasic SS primarily arising in the left supero-nasal orbital region in a 24-year-old woman, clinically mistaken for a periocular cyst. The case is peculiar for its highly unusual location and for its clinical deceptively benign appearance.