Beneath the surface: a case report of metastatic iridociliary ring melanoma treated with pembrolizumab / Abaixo da superfície: relato de caso de melanoma metastático iridociliar em anel tratado com pembrolizumabe

ABSTRACT Iridociliary ring melanoma is an uncommon type of uveal melanoma. Clinical manifestation varies from asymptomatic cases to masquerade syndromes mimicking refractory glaucoma. Treatment options include radiotherapy and enucleation. Management of metastatic uveal melanoma remains discouraging. Novel therapies using immune checkpoint inhibitors are currently under study. We present a case of a 54-year-old Hispanic woman with progressive vision loss due to metastatic ring melanoma with anterior chamber seeding treated with pembrolizumab.

RESUMO O melanoma iridociliar em anel é um tipo incomum de melanoma uveal. As manifestações clínicas variam desde casos assintomáticos até síndromes mascaradas que mimetizam um glaucoma refratário. As opções de tratamento incluem radioterapia e enucleação. O manejo do melanoma uveal metastático continua desanimador. Novas terapias usando inibidores de checkpoint imunológico estão atualmente em estudo. Apresentamos o caso de uma mulher hispânica de 54 anos com perda progressiva da visão por um melanoma metastático em anel, com semeadura de câmara anterior, tratada com pembrolizumabe.

Rosai-Dorfman Disease involving the eye and ocular adnexa. Clinicopathologic series of 17 patients.

PURPOSE: To describe the clinical features and histopathologic findings of Rosai-Dorfman disease (RDD) with ophthalmic involvement diagnosed at a Mexican ophthalmologic referral center in a period of 62 years. RESULTS: A total of 17 cases of RDD with ophthalmologic manifestations in Mexican-mestizo patients were collected. Female predominance was observed in 12 of 17 patients. The mean age was 36 years with a range of 12-76 years. The median age at presentation was 32 years. The orbit was the most affected location with 15 cases. Conjunctival disease was seen in 4 cases: two as isolated lesions, the rest with orbital or uveal involvement . One case suggested choroidal RDD associated to conjunctival and orbital lesion. Three cases presented multifocal disease. A patient with orbital affection developed extranodal disease elsewhere. No concurrent lymphadenopathy was observed in any patient.Histopathological examination revealed classic RDD findings in all cases: A polymorphous cellular infiltrate composed by lymphocytes, plasma cells and large histiocytes with emperipolesis hallmark of the disease. Immunohistochemically, histiocytes were positive for S-100 protein and CD68 in 15 cases. CONCLUSION: RDD of the eye and ocular adnexa in Mexican-mestizo patients is common in middle-aged women frequently as an isolated orbital lesion. Histopathology is necessary for accurate diagnosis. Most patients had a favourable outcome after medical and surgical treatment. To the best of our knowledge this is the largest case series of RDD of the eye and ocular adnexa in Latin-American patients.

Beneath the surface: a case report of metastatic iridociliary ring melanoma treated with pembrolizumab.

Iridociliary ring melanoma is an uncommon type of uveal melanoma. Clinical manifestation varies from asymptomatic cases to masquerade syndromes mimicking refractory glaucoma. Treatment options include radiotherapy and enucleation. Management of metastatic uveal melanoma remains discouraging. Novel therapies using immune checkpoint inhibitors are currently under study. We present a case of a 54-year-old Hispanic woman with progressive vision loss due to metastatic ring melanoma with anterior chamber seeding treated with pembrolizumab.

Clinical and histopathological features of conjunctival "Teddy bear" granuloma: A case series.

PURPOSE: To describe the clinical features, histopathological findings, and prognosis of conjunctival Teddy bear granuloma (TBG) diagnosed in a Mexican ophthalmologic referral center in a period of 64 years. METHODS: We reviewed clinical and histopathological material from all patients with documented conjunctival TBG. Patient's age, gender, location, clinical signs and symptoms, duration, treatment and, specimen size, were evaluated. Formalin-fixed paraffin embedded 5 microns hematoxylin-eosin stained slides and periodic acid-Schiff special stain as well as examination under polarized light microscopy were performed in all cases. RESULTS: A total of 5 conjunctival TBG were collected. The ages of the patients ranged between 2 and 11 with a mean of 6 years. Female to male ratio was 4:1. The right inferior fornix was involved in 4 cases (80%) with clinical diagnosis of conjunctival mass of unknown etiology. Treatment consisted of surgical removal by slit-lamp biomicroscopy (3 cases) and in the operating room (2 cases). No complications were informed in a short follow-up period. Histopathologically, numerous cross-sections of synthetic and non-synthetic fibers surrounded by multinucleated foreign body giant cells, epithelioid histiocytes, lymphocytes, plasma cells and sparse neutrophils were seen. Polarization light microscopy demonstrated numerous birefringent colorful foreign fibers. The follow-up period of the patients ranged between 1 and 32 weeks with a mean of 10 weeks. CONCLUSIONS: Most patients with TBG are children with vague, non-specific symptoms troubling precise clinical diagnosis. Treatment of choice involves surgical excision of the foreign body granuloma followed by topical corticosteroids. All surgical specimens obtained must be sent for histopathological examination. Special awareness is recommended during COVID-19 pandemic lockdown to prevent potential exposure to fibers that may cause conjunctival TBG.

Primary Lymphoepithelioma-Like Carcinoma of the Conjunctiva Metastatic to Regional Lymph Nodes and Parotid Gland in a Mexican Patient.

Lymphoepithelioma-like carcinoma (LELC) of the conjunctiva is a rare malignancy in the ocular adnexa. There are no prospective data regarding treatment methods. Complete surgical excision is sufficient in the majority of cases. Radiation therapy is sometimes used in case of recurrence or positive margins after surgery. This case describes an 89-year-old Hispanic female with a 7-month history tumor primarily located on the left lower palpebral conjunctiva. The patient underwent an excisional biopsy of the tumor, and histopathology exam reported an LELC with positive margins. She developed parotid and neck lymph node metastasis treated with concurrent radiotherapy. The patient had remained disease-free for 3 years. According to the available data, there are only five cases of LELC reported in conjunctiva worldwide, so this report increases the differential diagnoses of tumors in the ocular adnexa and supports the effectiveness of radiotherapy.

Conjunctival myxoma: A systematic review of a rare tumor.

Conjunctival myxoma is an uncommon benign tumor that may develop as a localized disease or as part of the Carney complex, in which case it can cause significant morbidity and mortality. Conjunctival myxomas can mimic other pure or mixed tumors and are often overlooked in clinical practice. Histopathological studies are essential for diagnosis; however, controversy regarding their pathological and immunohistochemical features makes the diagnostic process more difficult. Because of the importance of correctly classifying these conjunctival tumors, as well as recognizing when a systematic screening is required owing to the possible association with life-threatening diseases, we comprehensively evaluate the literature on this rare entity based on a systematic approach.

Conjunctival Myxoma: High-Resolution Optical Coherence Tomography Findings of a Rare Tumor.

PURPOSE: The purpose of this study was to describe 2 cases of biopsy-proven conjunctival myxomas and present their optical signs on high-resolution optical coherence tomography (HR-OCT) with clinical and histopathological correlations. METHODS: Two middle-aged female patients with a clinical diagnosis of conjunctival cysts were referred for surgical treatment. Clinical assessment, photographs, ultrasound biomicroscopy, and HR-OCT images were obtained. Excisional biopsies were performed, and specimens were sent for histopathological and immunohistochemical analyses. RESULTS: Clinically, these patients presented with a well-circumscribed, semitranslucent, yellow-pinkish mass. Ultrasound biomicroscopy showed a dome-shaped epibulbar mass with medium-to-high internal reflectivity. No compromise of the underlying sclera was noted. HR-OCT showed a normal conjunctival epithelium, a subepithelial nonhomogeneous mass with hyperreflective and hyporeflective areas lined by a highly hyperreflective band, and mild posterior shadowing. Histopathological findings and immunoreactivity for CD34 and vimentin confirmed the diagnosis of conjunctival myxoma. CONCLUSIONS: The HR-OCT optical signs found in our 2 cases strongly correlated with the microscopic findings. Disclosing the optical signs observed on HR-OCT can help clinicians diagnose and differentiate this lesion, guiding its management. However, more studies with a larger number of patients comparing conjunctival myxoma and other ocular surface tumors are needed to enlighten readers about the unique pattern observed by HR-OCT.

Intravitreal bromfenac liposomal suspension (100 µg / 0.1 ml). A safety study in rabbit eyes.

INTRODUCTION: There is a need to find alternative treatments for MEe. Bromfenac has shown promise in inhibiting the COX-2 enzymatic pathway that partially causes the inflammatory cascade which contributes to the precipitation of ME. However, like other NSAID's, its intraocular half-life is limited. We hypothesize that a delayed-release liposome formulation containing bromfenac might provide a similar anti-inflammatory effect as long-lasting steroid release systems without the well-known steroidal side-effects. We introduced a novel formulation with these characteristics into the vitreous cavity of rabbit eyes in order to evaluate its safety profile. MATERIAL AND METHODS: 10 left eyes of rabbits were injected with the liposome-encapsulated bromfenac suspension (100 µg/0.1 ml). Basal ERG's were recorded. Total follow-up time was 3 months, at which point ERG's were repeated and eyes were enucleated for histopathological study. Total amplitude and implicit times were recorded. A difference of 25% in either recording was considered significant. Significance was assessed using the paired-t test and Wilcoxon matched-pairs signed-rank test. A p-value of <0.05 was considered significant. RESULTS: No significant changes were recorded in ERG measurements after 3 months when compared to basal measurements. Histopathological analysis of retinal specimens found no traces of liposome-induced toxicity. CONCLUSION: The liposome-encapsulated bromfenac suspension (100 µg/0.1 ml) is not toxic and has been proven safe to use in an animal model. Therefore, this formulation shows promise as a possible future alternative treatment for ME and should be further studied to show its biological effect and efficacy.

Conjunctival tattoo with inadvertent ocular globe penetration and vitreous involvement: Clinico-pathological correlation and scanning electron microscopy X-ray microanalysis.

PURPOSE: The aim is to report a case of conjunctival tattooing with inadvertent injection of tattoo ink into the vitreous cavity and its consequences, the scanning electron microscopy X-ray microanalysis of the ink components, and the microscopic findings of the affected conjunctiva and vitreous. METHODS: Descriptive case report. RESULTS: A 32-year-old man complained of ocular pain and blurred vision after undergoing a subconjuctival red ink tattoo in his left eye. Ophthalmologic examination revealed best corrected visual acuity of 20/80 and intraocular pressure of 26 mmHg. Pain was elicited with eye movements. The bulbar conjunctiva was colored intense red. In the anterior chamber, pigment granules and filaments were suspended on the aqueous humor, and lens capsule was also stained red. Ultrasonography showed high-density non-mobile echoes in the conjunctiva; anterior chamber and vitreous cavity revealed high-density mobile echoes corresponding to pigment particles. Conjunctival tattoo with inadvertent globe penetration was the clinical diagnosis. The patient received medical and surgical treatment. Histopathological examination of the conjunctiva showed red pigment globular deposits within the stroma, and neutrophils and sparse histiocytes with similar intracytoplasmic pigment granules were seen. No granulomatous foreign body reaction was noticed. Vitreous material contained pigment granules; no inflammatory cells were observed. Scanning electron microscopy X-ray microanalysis of the tattoo red ink revealed significant signals of iron, barium, and copper. CONCLUSION: Conjunctival tattoo is a new form of body decoration gaining worldwide popularity. This procedure is performed by untrained professionals causing severe ocular complications including blindness. Safety regarding tattoo ink needs further study as the composition varies among colors. Strict regulations on this matter should be considered.

Extraocular myositis as an initial manifestation of polyangiitis granulomatosis / Miositis extraocular como manifestación inicial de granulomatosis con poliangeítis

ABSTRACT Granulomatosis with polyangiitis (GPA) is a systemic vasculitis with multiorgan involvement. Although ocular involvement has frequently been described, there are few reported cases of extraocular myositis in this disease. The case is presented of a Mexican woman with GPA who debuted with extraocular myositis.

RESUMEN La granulomatosis con poliangeítis (GPA) es una vasculitis sistémica con afectación multiorgánica. El compromiso ocular ha sido descrito frecuentemente, sin embargo, existen pocos casos reportados de miositis extraocular en esta enfermedad. Presentamos el caso de una mujer mexicana con GPA que comenzó con miositis extraocular.

Just another metastatic carcinoid tumour to the uveal tract.

We describe the clinic, image, and histopathologic features of a well differentiated neuroendocrine carcinoma (carcinoid tumour) metastatic to choroid and ciliary body in a 52-year-old Mexican Mestizo man. The ophthalmologic examination showed an inferior choroidal mass accompanied by exudative retinal detachment. Ultrasound B-Scan study revealed a diffuse thickened choroid with overlying serous retinal detachment, ultrasound A-Scan revealed a high internal reflectivity solid lesion. Ultrasound biomicroscopy (UBM) evidenced a dome shaped ciliary body mass, presumptive diagnosis was uveal tract metastatic disease. Scleral flap choroidal incisional biopsy was performed. Microscopic evaluation demonstrated a hypercellular lesion replacing choroid, composed by cohesive oval-round cells with finely granular chromatin arranged in organoid pattern. Immunohistochemical reactions were Pankeratin AE1/AE3 (+), Cytokeratin CK5/6 (+), Chromogranin A (+), Ki67 (20%), typical well differentiated neuroendocrine carcinoma (carcinoid tumour) was diagnosed. Patient had a mediastinal carcinoid diagnosed 3 years earlier. Metastatic cancer to the eye is perhaps the leading cause of intraocular tumour, despite this fact metastases are rarely seen by the ophthalmologist while the patient is alive. Intraocular metastasis should be considered in the presence of ciliary body or/and choroidal amelanotic or pigmented mass and serous retinal detachment in a patient with history of carcinoid tumor, althought its low frequency (2.2%).

Primary conjunctival myxoma: case series and review of the literature.

AIMS: Myxomas are benign soft tissue tumours resembling primitive mesenchyme. They rarely involve ocular structures, and have been recognized in the conjunctiva, eyelids, cornea, and orbit. The aim of this study was to investigate the clinicopathological features of seven patients with primary conjunctival myxoma seen at Dr Luis Sánchez Bulnes Hospital, an ophthalmological referral centre in Mexico City. METHODS AND RESULTS: We reviewed the clinical, histochemical and immunohistochemical studies of patients with documented myxoma of the conjunctiva diagnosed in our hospital. Seven conjunctival myxomas were retrieved from 5923 conjunctival biopsies (0.1%). The mean age of patients was 40 years, with a range of 27-51 years. Females were more frequently affected, and none of our patients had systemic disease. The left eye was involved in five cases, and most of the lesions were located in the bulbar conjunctiva. Histopathological examination revealed a benign tumour composed of spindle-shaped and stellate-shaped cells immersed within an abundant mucinous matrix with sparse vessels and reticulin fibres. Immunohistochemistry demonstrated positivity for vimentin and negativity for smooth muscle actin, SOX10 and GLUT1 in myxoma cells of all cases. S100 was found to be positive in four cases, and muscle-specific-actin in three cases. CONCLUSIONS: Conjunctival myxomas are uncommon tumours. For accurate diagnosis, histopathological examination is mandatory. The treatment of choice is surgical removal, and the prognosis is excellent.

Adenoma of the Nonpigmented Ciliary Body and Iris Epithelium in Mexican Mestizo Patients.

The adenoma of the nonpigmented ciliary epithelium is a benign rare tumor, which may present with different clinical characteristics and requires resection along with histopathologic analysis and the identification of specific immunohistochemical markers for an accurate diagnosis. Here, we report a case series of 4 patients in a Mexican mestizo population with this diagnosis, their clinical features, the ultrasound imaging characteristics and the histopathological and immunohistochemical findings.

Periocular myxoma in a child.

Myxomas are locally invasive, benign mesenchymal neoplasms with odontogenic, osteogenic, or soft tissue origin. Facial myxomas probably account for less than 0.5% of all paranasal sinus and nasal tumors. We report a case of a left painless periocular mass in a 11-month-old girl. The lesion was resected with a clinical diagnosis of lacrimal sac tumor. Histopathology and immunohistochemistry proved the tumor to be a myxoma. There has been no recurrence after 4 years of followup. Midfacial myxomas should be differentiated from other benign and malignant tumors such as dermoid, hamartoma, neurofibroma, nasolacrimal duct cyst, and sarcomas in particular embryonal rhabdomyosarcoma. Because of the infiltrative nature of these tumors, a wide surgery is required to achieve clear resection margins and avoid recurrence.

Congenital smooth muscle hamartoma of the palpebral conjunctiva.

Smooth muscle hamartoma is defined as a disorganized focus or an overgrowth of mature smooth muscle, generally with low capacity of autonomous growth and benign behavior. The implicated tissues are mature and proliferate in a disorganized fashion. A healthy 5-day-old Mexican boy was referred to the authors' hospital in México city for evaluation of a "cystic" lesion of the right eye that had been noted since birth. The pregnancy and delivery were unremarkable. On physical examination, there was a reddish-pink soft lesion with a tender "cystic" appearance, which was probably emerging from the upper eyelid conjunctiva, which measured 2.7 cm in its widest diameter and transilluminated. Ultrasound imaging revealed an anterior "cystic" lesion with normally formed phakic eye. An excisional biopsy was performed, and the lesion was dissected from the upper tarsal subconjunctival space. Subsequent histologic and immunohistochemical findings were consistent with the diagnosis of congenital smooth muscle hamartoma (CSMH) of the tarsal conjunctiva. The authors' research revealed that only one case of CSMH localized in the conjunctiva (Roper GJ, Smith MS, Lueder GT. Congenital smooth muscle hamartoma of the conjunctival fornix. Am J Ophthalmol. 1999;128:643-4) has been reported to date in the literature. To the best of the authors' knowledge, this current case would be the second case reported of CSMH in this anatomic location. Therefore, the authors' recommendation is to include CSMH in the differential diagnosis of a cystic mass that presents in the fornix and palpebral conjunctiva.

Choroidal malignant melanoma in a 6-year-old girl without melanocytosis.

PURPOSE: To describe a case of choroidal malignant melanoma in a child without ocular melanocytosis. METHODS: A 6-year-old girl presented with misalignment of the right eye of a few weeks' duration. Visual acuity was counting fingers in the right eye and 20/20 in the left eye. Ophthalmoscopy of the right eye revealed a well defined choroidal mass in the macular region measuring 10 mm in diameter with overlying subretinal fluid. Ultrasonography revealed that the mass was 10.1 mm thick with choroidal excavation. On the basis of clinical and ultrasonographic findings, the diagnosis was choroidal melanoma without ocular melanocytosis. The eye was enucleated. RESULTS: Histopathologic examination revealed malignant melanoma of the choroid. There was not extrascleral extension. CONCLUSION: Choroidal malignant melanoma can occur in young patients, even in the absence of melanocytosis.

Angiolymphoid hyperplasia with eosinophilia of the lacrimal gland: a case report.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare clinicopathologic entity that has been the subject of considerable confusion and debate. ALHE shares both clinical and histopathologic features with Kimura disease (KD). Because of this overlap, ALHE and KD have been used synonymously in the Western medical literature, as they were thought to represent variations of the same disease. Some pathologic reports have called for distinguishing ALHE and KD as two separate nosological entities, based on their clinical, laboratory, and especially histopathologic findings. ALHE commonly affects women in the third and fourth decades, with head and neck involvement. ALHE has been described rarely in the orbit, eyelids, and lacrimal gland. We report a case of ALHE involving the left lacrimal gland in a 40-year-old Mexican woman. Because ALHE can cause proptosis, lid swelling, ocular dysmotility, or a palpable mass, it should be considered in the differential diagnosis of orbital lesions occurring in adults.