Topical 5-Fluorouracil 0.5% as primary treatment for Ocular Surface Squamous Neoplasia.

PURPOSE: To evaluate the efficacy of topical treatment with 5-Fluorouracil (5-FU) 0.5% in cases of Ocular Surface Squamous Neoplasia (OSSN), and to assess the tolerance of patients undergoing treatment. METHODS: Patients with clinical diagnosis of OSSN referred to the Ocular Oncology division from the Federal University of Sao Paulo, Brazil, were recruited for the current study. Patients were treated with topical 5-FU 0.5% using a regimen of 4 times daily for 10 days, followed by a 3-week drug holiday, continued up to 3 cycles before an alternative treatment. Lesions were evaluated at baseline and throughout treatment. Treatment adherence was assessed using the Morisky Medication Adherence scale. Any adverse events along the treatment were noted. RESULTS: A total of 30 eyes of 30 patients adherent to the treatment were included in the study. Among the total cases treated with 5-FU 0.5%, 24 patients achieved therapeutic success after a mean treatment duration of 21.71 ± 7.77 days, representing a success rate of 80.00% (95% CI: 60.75-91.18%). For each 1 mm2 increase in the lesion area, the odds of treatment success decrease by 6% (OR: 0.94; 95%CI: 0.88-0.99; p = 0.033). Only mild adverse events such as ocular discomfort, ocular burning and tearing were observed along the treatment in 8 patients. CONCLUSIONS: Topical 5-FU 0.5% is an effective therapeutic option in the treatment of OSSN, with an 80% therapeutic success rate, showing good tolerability. The size of the lesion was identified as a factor influencing treatment success, therefore it should be taken into consideration when defining treatment approaches.

[Evaluation of the accuracy of clinical diagnosis of conjunctival neoplasms : Comparison with histological findings after excision]. / Untersuchung der Genauigkeit klinischer Diagnosen von Neoplasien der Konjunktiva : Vergleich mit den histologischen Befunden nach Exzision.

BACKGROUND: Neoplasms of the conjunctiva include many different entities with a broad variety of clinical presentations. This can make a precise clinical diagnosis difficult. R0 resection is the gold standard treatment for most malignant conjunctival neoplasms, but not every benign lesions must treated by excision. In clinical practice it is important to make an accurate clinical diagnosis to enable the best possible management of conjunctival neoplasms. OBJECTIVE: The aim of this study was to determine the accuracy of clinical diagnosis of neoplasms of the conjunctiva. MATERIALS AND METHODS: Within a retrospective design, the data from all patients with excision of a conjunctival lesion between 2011 and 2020 in the Department of Ophthalmology of the UKSH Campus Kiel were extracted and analyzed. The specificity, sensitivity, and positive and negative predictive value for the preoperative clinical rating of dignity and diagnosis were evaluated based on the histological diagnostic findings. RESULTS: Of 220 included cases, 75% were benign and 25% malignant. The most frequent neoplasm of the conjunctiva was benign conjunctival nevus. The sensitivity for clinical prediction of a benign lesion was 0.86 (95% confidence interval [CI] 0.59-0.92), the specificity 0.95 (CI 0.85-0.99), and the positive predictive value 0.98 (CI 0.94-1.0). The sensitivity for clinical prediction of malign dignity was 0.95 (CI 0.85-0.99), the specificity 0.88 (CI 0.83-0.93), and the positive predictive value 0.73 (CI 0.61-0.83). CONCLUSION: The derived values for clinical diagnosis of conjunctival neoplasms can be rated as good. However, in clinical practice, untypical lesions can be hard to diagnose correctly, and the clinical diagnosis should be carefully reviewed; if in doubt, excision should be preferred.

Primary bulbar conjunctival basal cell carcinoma: A clinical-pathologic report and literature review.

Purpose: To enhance the characterization of primary bulbar conjunctival basal cell carcinoma (BCC) clinically and histologically, via report of a case and review of the relevant medical literature. Observations: We report the case of a 73-year-old man with no history of skin cancer who presented with a bulbar conjunctival nodule without connection to the eyelid or caruncle, originally thought to represent a pyogenic granuloma. After one month without improvement on topical prednisolone, excisional biopsy was performed, with routine histopathology and immunohistochemistry. The tumor was found histologically to be primary conjunctival BCC. Immunostaining exhibited negative Ber-EP4 and S100, mostly negative CK7 and EMA, and positive p63. Margins were negative, and the patient had no recurrence six months after excision. Conclusions and Importance: Primary conjunctival BCC must be considered in the differential diagnosis of a conjunctival lesion which may initially appear benign but does not behave as expected clinically. The location of the tumor in the case presented here refutes a prior postulate that primary conjunctival BCC arises from basal adnexal epithelium in the caruncle. Of the immunohistochemical findings, only the Ber-EP4 result differed from the typical immunostaining profile of cutaneous BCC. Further study is needed to determine the frequency of Ber-EP4 positivity in primary conjunctival BCC.

[Conjunctival tumors in children : Histopathological diagnoses in 262 cases]. / Bindehauttumoren bei Kindern : Histopathologische Diagnosen in 262 Fällen.

BACKGROUND: The spectrum of conjunctival tumors in children and adolescents significantly differs from that of adults. OBJECTIVE: The aim of this study was to show the distribution of histopathological diagnoses of pediatric conjunctival tumors. MATERIAL AND METHODS: Retrospective case series including all conjunctival tumors of children and adolescents under 18 years of age examined histologically over a period of 25 years (1990-2015) at the Eye Center in Freiburg, Germany. RESULTS: Among the 262 conjunctival specimens, the most common diagnoses were conjunctival nevi (148, [56%]), most often with junctional activity (106/148, [72%]), pyogenic granulomas (26, [10%]), and dermolipomas (18, [7%]). In one case a malignant tumor (conjunctival melanoma) was detected (1, < 1%). CONCLUSION: The results suggest that pediatric conjunctival tumors are benign in most cases. Most of them were of melanocytic origin, with a junctional conjunctival nevus being the most common diagnosis.

Squamous Cell Carcinoma of the Conjunctiva in a Patient With Previous Squamous Cell Carcinoma of the Lower Lip.

Squamous cell carcinoma (SCC) of the conjunctiva is a rare malignancy that is part of the spectrum of ocular surface squamous neoplasia (OSSN). Numerous non-modifiable and modifiable risk factors, such as male sex, age, cigarette smoking, and immunosuppression, have been identified. Any lesion of the conjunctiva requires a differential diagnosis between benign and malignant diseases, and all suspicious lesions should be biopsied. We present a case of SCC of the conjunctiva in a former smoker with multiple risk factors, including a previous SCC of the lower lip. Metastatic tumors rarely occur in the conjunctiva, but due to our patient's medical history, the exclusion of metastasis from the previous primary tumor was performed through whole-body imaging restaging.  The patient underwent a no-touch wide resection, followed by adjuvant topical chemotherapy with 5-fluorouracil (5-FU). After finishing treatment, the patient continues to attend regular ophthalmology and oncology appointments. Increasing population awareness of modifiable risk factors for OSSN is essential. Misdiagnosis can lead to a loss of time in treatment and progression of the disease.

Long term study of topical interferon α-2b eye drops as primary treatment of ocular surface squamous neoplasia.

PURPOSE: To assess the efficacy of topical interferon α-2ß(IFN) eye drops as a primary treatment for ocular surface squamous neoplasia(OSSN) and evaluate factors that impact response to treatment and recurrence of OSSN. METHOD: A retrospective study of 143 OSSN patients treated with topical IFN(1MIU/ml) from January 1998 to June 2021. The diagnosis was based on clinical examination and anterior segment optical coherence tomography, with histologic confirmation was present in 46.2% of patients. Data on demographic, tumor characteristics, treatment outcome, and side effects were collected. The primary outcomes were tumor resolution frequency and recurrence rate. Secondary outcomes were predictive factors for resolution and recurrence and side effects of treatment. RESULT: Participants were mostly older (mean age, 69 years, SD 12.9, range 29-97), white(89%) males (74%). Complete tumor resolution was achieved in 80.4% of individuals with a mean time to resolution of 4.2 months (SD 2, range 0.5-12.3 months). On multivariable analysis, history of skin cancer (HR: 0.66, p = 0.05, 95%CI: 0.44-0.99) and immune system abnormalities (HR: 0.37, p = 0.009, 95%CI: 0.18-0.79) reduced the risk of tumor resolution, while a prior history of OSSN (HR: 3.49, p < 0.001, 95%CI: 1.76-6.93) increased the risk of resolution. With a mean follow-up time of 44.3 months (SD 50.9, 0-290 months), the recurrence rate was 0%, 2.3% and 3.1% at 1, 2, and 5 years respectively. Mild hyperemia(18.9%) and pain(10.6%) were the two most common side effects. CONCLUSION: Topical IFN eye drops are a safe and effective primary treatment modality for OSSN with a reasonable side effect profile.

Epidemiology and clinical characteristics of congenital choristomas in the ocular adnexa of pediatric patients.

PURPOSE: To investigate the epidemiology and clinical characteristics of infants presenting with conjunctival, palpebral, or orbital congenital choristomas (dermolipomas, epidermoids, and dermoid cysts) and children undergoing surgery for congenital choristomas in the ocular adnexa. METHODS: We reviewed the medical files of congenital choristomas in children seen in The Capital Region of Denmark during a 5-year period (2014-2018). Children (< 18 years) were divided into two groups: those referred < 1 year of age (Group I) and those undergoing surgery to remove the lesion (Group II). Group I was used to calculate a population-based incidence of congenital choristomas by comparing our data to birth statistics from the Danish Medical Birth Registry. RESULTS: A total of 97 children were included, 43 in Group I and 70 in Group II (including 16 patients from Group I). The total incidence of congenital choristomas was 1 in 2537 live born children. Most lesions were palpebral choristomas (27/43, 63%) located in the superotemporal region (17/27, 63%), followed by the superonasal region (7/27, 26%). The main reasons for surgical removal of a congenital choristoma were growth (28/70, 40%) or cosmesis (25/70, 36%). CONCLUSION: The total incidence of congenital choristomas in the ocular adnexa of infants < 1 year of age, including both conjunctival and palpebral congenital choristomas, is about 1 in 2537 live born children in The Capital Region of Denmark. Hence, congenital choristomas are common masses found in the ocular adnexa.

Interventional Radiotherapy (Brachytherapy) in Eyelid and Ocular Surface Tumors: A Review for Treatment of Naïve and Recurrent Malignancies.

The goal of radiotherapy in the treatment of eyelid and ocular surface tumors is to eradicate tumor burden in a manner that maintains visual function and preserve surrounding sensitive ocular tissue. Interventional radiotherapy (IRT-brachytherapy) is a radiotherapy technique associated with a highly focal dose distribution, with the advantage of boosting limited size target volumes to very high dose while sparing normal tissue. The reduction in the ocular and adnexal complications that result from this form of therapy, has led in recent years, to an increase in the use of IRT for the treatment of eyelid and ocular surface tumors. For eyelid malignancies, IRT is used as an independent treatment in small eyelids tumors, in postoperative treatment of high-risk patients and as well as salvage therapy in local recurrences. In the treatment of conjunctival malignancies, due to the high risk of local recurrence, the use of adjuvant therapies as IRT has shown to improve outcomes. In this review, we focus on eyelid and ocular surface IRT techniques and provide an overview of indication, outcomes and toxicity of IRT for the treatment of naïve and recurrent eyelid and conjunctival tumors.

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.

Case of Rapidly Expanding Conjunctival Malignant Melanoma Initially from Primary Acquired Melanosis Diagnosed 14 Years Earlier.

Primary acquired melanosis (PAM) of the conjunctiva is a potentially serious melanocytic lesion that can lead to the development of a melanoma. A 60-year-old woman noticed pigmentation of the conjunctiva of her left eye for more than 10 years. She underwent excisional biopsy combined with cryotherapy and was diagnosed with PAM without atypia by intraoperative consultation. She was followed for 7 years, and no changes were observed. Fourteen years after the initial biopsy, she noted a growing conjunctival tumor, and a melanoma was suspected. She underwent orbital exenteration and skin grafting procedures. Histopathological examination of the specimen led to a diagnosis of conjunctival malignant melanoma. Re-examination of the initial biopsy specimen revealed that there was a proliferation of melanocytes that partially expanded over the basal layer of the conjunctiva which had been diagnosed as PAM with moderate atypia. We conclude that this case of conjunctival PAM had progressed to a conjunctival malignant melanoma after 14 years. Pathological evaluation of intraepithelial lesions has its limitations; thus, cases of PAM, even in the absence of obvious atypia, require careful follow-up.

Ocular Oncology-Primary and Metastatic Malignancies.

Several neoplastic processes can involve the eye, either primarily or secondary to a systemic malignancy. The most common primary tumors of the eye include conjunctival and uveal melanoma, retinoblastoma, conjunctival and intraocular lymphoma, and ocular surface squamous neoplasia. Metastatic spread from systemic malignancies, especially of the breast and lung, also can involve the eye. A combination of ophthalmologic examination, ancillary testing, and cytologic/histopathologic evaluation leads to accurate diagnosis. Management consists of surgery, radiotherapy, chemotherapy, and immunotherapy delivered in various forms.

[Dermolipoma: intraoperative features]. / Dermolipome: aspect per-opératoire.

Dermolipoma is an ectopic skin formation with a greasy component which develops at the level of the fornix of the external canthus. Surgery for dermolipoma is not devoid of dangers. There is essentially a risk of causing damage to the right external muscle and levator muscle of the upper eyelid because there is no cleavage plane between the lesion and the adjacent normal tissues to which it adheres. The anterior surface of the dermolipoma is inseparable from the temporal bulbar conjunctiva. Its posterior surface is adjacent to the right lateralis muscle and can extend up to the levator Müller's muscle complex of the upper eyelid and toward the lachrymal gland. We report the case of a 56-year old patient presenting with a yellowish white lesion of the external canthus of the right eye. The patient underwent orbital scanner in order to exclude the possibility of orbital extension and to establish the relationship with the different ocular structures. Given the aesthetic discomfort, the patient underwent surgical resection of the orbital grease in front of the orbital rim. The main differential diagnoses included conjunctival cyst, complex choristoma and dermoid cyst. Anatomopathological examination confirmed the diagnosis of dermolipoma. The postoperative course was uneventful.

Conjunctival Leiomyosarcoma, a Rare Neoplasm Always Originating at the Limbus? Report of a New Case and Review of 11 Published Cases.

PURPOSE OF THE STUDY: To describe the differential diagnosis and management of a rare conjunctival malignancy. PROCEDURES: A 79-year-old man presented with a conjunctival mass at the limbus. Excisional biopsy revealed a malignant mesenchymal tumor with myogenic differentiation. Six months later, three suspect lesions developed at the border of the previous excision. Pathological diagnosis pointed to a leiomyosarcoma. Adjuvant radiotherapy with strontium-90 brachytherapy was applied. After 3 years, there was neither recurrence nor distant metastases. A literature review revealed 11 cases of conjunctival leiomyosarcoma. RESULTS: All 12 cases seemed to originate at the limbal conjunctiva. Scleral invasion was found only in one patient with multiple previous resections. Corneal invasion was reported in two patients. Four patients had a globe-sparing resection. In two of them, margins were not tumor free and additional brachytherapy gave a tumor-free follow-up of 1 and 3 years. Four cases underwent an exenteration. CONCLUSION AND MESSAGE: Primary conjunctival leiomyosarcoma is a rare tumor with a favorable prognosis due to early detection and consequently limited size. Diagnosis involves histopathological investigation including immunohistochemistry. If possible, complete resection has the best prognosis. Adjunctive radiotherapy can be effective when the margins are not free and should be considered.

Bilateral benign reactive lymphoid hyperplasia of the conjunctiva: a case treated with oral doxycycline and review of the literature.

BACKGROUND: To report a case of bilateral benign reactive lymphoid hyperplasia (BRLH) of the conjunctiva treated with oral doxycycline and perform review of the literature evaluating the presentation, treatment and risk of transformation to lymphoma. CASE PRESENTATION: A case report is described and review of the literature from January 1975 to January 2019 was performed. A 30-year-old man presented with bilateral enlarging fleshy pink medial canthal conjunctival lesions. Incisional biopsy revealed BRLH. Oral doxycycline was initiated (100 mg two times a day) for a total of 2 months. Both lesions decreased in size significantly at the patient's two-month follow up visit. The residual lesion in the right eye was excised along with an adjacent pterygium and the patient has been free of recurrence for the past 1.5 years. The lesion in the left eye has remained stable in size after cessation of the oral doxycycline. A total of 235 cases of conjunctival BRLH were identified in our literature search. The mean age at diagnosis was 35.2 years (range, 5 to 91 years). BRLH lesions were unilateral in 75% of patients and bilateral in 25% of them. Seven patients (2.9%) had a concurrent Epstein-Barr virus (EBV) infection at the time of lesion appearance. The most common treatments were surgical excision (155/235 or 65.9%) and corticosteroids (30/235 or 12.7%), while 14% (33/235) of the patients were observed and 4.6% (11/235) received external beam radiotherapy alone. Recurrence occurred in ten patients (10/235 or 4.2%), of whom five had undergone surgical excision alone, two excision followed by external beam radiotherapy, one excision and oral corticosteroids, one radiotherapy alone and one had been treated with topical corticosteroids. Overall, only 2 of the 235 reported cases (0.8%) developed malignancy, one localized to the conjunctiva and one systemic. CONCLUSIONS: Benign reactive lymphoid hyperplasia is one of the lymphoproliferative disorders of the conjunctiva and ocular adnexa. Extensive literature review shows that most cases are treated with surgery, steroids or observation. Oral doxycycline may be considered an alternative non-invasive treatment of BRLH conjunctival lesions. BRLH lesions warrant careful follow up as they can rarely transform into conjunctival or systemic lymphoma.

Classification, diagnosis, and management of conjunctival lymphoma.

Lymphoma is a malignant lymphoproliferative tumor that can involve the conjunctiva. Approximately 5-15% of all extranodal lymphomas are found in the ocular adnexal region, with approximately 25% of those involving the conjunctiva. Ninety-eight percent of conjunctival lymphomas arise from B-lymphocytes. The most common subtype of conjunctival lymphoma is extranodal marginal zone lymphoma (80%), followed by follicular lymphoma (8%), diffuse large B-cell lymphoma (3%) and mantle cell lymphoma (3%). Natural killer and T cells (NK/T) are rare causes of lymphoma. While most conjunctival lymphomas are localized to the ocular adnexa at the time of presentation, systemic examination and management are of key importance in the long-term care of the patient. This review outlines the classification, etiology, presentation, diagnosis, and management of conjunctival lymphoma. The novel use of high resolution optical coherence tomography, both as a diagnostic tool and as a means for ongoing evaluation during treatment, is illustrated. Treatment options discussed include external beam radiation, chemotherapy, immunotherapy, antibiotic therapy, and combination regimens. Future investigation of the etiology and pathogenesis of conjunctival lymphoma is expected to reveal opportunities for innovative and individualized therapeutic agents. Collaboration between multiple disciplines is key in the advancement of the field.

Primary Conjunctival Rhabdomyosarcoma in a Pediatric Patient.

Rhabdomyosarcomas are neoplasms with a high degree of malignancy and arise from the embryonic mesenchyme. They represent approximately 5% of all pediatric tumors and their main locations are the head and neck (45%), trunk (40%), and extremities (15%). Twenty-five percent to 30% of the head and neck rhabdomyosarcomas appear in the orbit; however, its origin from the conjunctiva is rare, with few case reports published in the literature. We present the case of a five-year-old girl with a diagnosis of primary embryonic rhabdomyosarcoma of the conjunctiva, treated with surgery and chemotherapy. After completing the treatment, it was followed up with controls for oncological ophthalmology, pediatric hematology-oncology, and radiotherapy oncology every six months with magnetic resonance of the orbits. Two years after the end of treatment, the patient is disease-free. Conjunctiva rhabdomyosarcoma is a rare lesion, with few previously reported cases. In the reported case, the histopathological findings and positivity of the different immunohistochemical markers allowed a definitive diagnosis of rhabdomyosarcoma. The excellent prognosis of this pathology is probably linked to the early diagnosis of the disease and the timely administration of radical treatment. It is essential to be able to identify conjunctival rhabdomyosarcoma from its clinical and histopathological characteristics in order to achieve early diagnosis and provide adequate treatment to patients.

A complex choristoma presenting as a salmon patch lesion in the bulbar conjunctiva.

PURPOSE: We describe a rare case of a complex choristoma appearing as a salmon-patch lesion in the nasal conjunctiva. While benign, complex choristomas are grossly indistinguishable from malignant lesions, and an excisional biopsy is warranted to confirm the diagnosis. OBSERVATIONS: A 31-year-old man presented with an elevated glistening pink mass on the conjunctiva. An excisional biopsy with a "no-touch" technique was performed, followed by placement of an amniotic membrane graft without postoperative complications. No subsequent medical treatment was pursued after the biopsy and histopathologic evaluation. Histopathology confirmed a diagnosis of a complex choristoma with sections consisting of fibroadipose tissue with cartilage, smooth muscle, and nerves. Histopathology was negative for malignant cells without morphologic evidence of a lymphoma. CONCLUSIONS AND IMPORTANCE: Conjunctival tumors are difficult to distinguish clinically, and a differential diagnosis often includes the possibility of a malignancy. Histopathologic diagnosis may be required to distinguish between various entities. In our case, a salmon-patch conjunctival tumor was biopsied and confirmed to be a benign complex choristoma.

Clinicopathological Characteristics of Caruncular Tumors in Koreans

PURPOSE: To investigate the clinical characteristics and histological features of tumors in caruncles. METHODS: We conducted a retrospective chart review of 126 eyes of 126 patients who underwent incisional or excisional biopsy of conjunctival masses between March 2008 and December 2016. RESULTS: Twenty-four patients (19.0%) including 10 males and 14 females had a mass located on the caruncle. The mean age at diagnosis was 41.8 ± 13.4 years (range, 15–67 years). Most patients (75%) visited us for a cosmetically visible mass without other symptoms. The mean duration of symptoms was 73.8 ± 113.0 months (range, 1–240 months). The most common histological diagnosis was a melanocytic tumor (50%) followed by a sebaceous gland tumor (12.5%), an epidermoid cyst (12.5%), and papilloma (12.5%). The symptom duration of the melanocytic tumor was significantly longer than other types of tumors (153.6 ± 139.8 months, p = 0.025). CONCLUSIONS: Caruncular tumors accounted for 19% of all conjunctival tumors. The most common pathological diagnosis of a caruncular tumor was a melanocytic tumor, which had a characteristically long symptom duration.

Granular Cell Tumor Located in the Bulbar Subconjunctival Space.

AIM: To report an unusual case of granular cell tumor. METHODS: Case report. RESULTS: A 14-year-old male presented with a bulbar conjunctival yellowish nonmovable mass, in the left eye. The tumor was removed and histopathologic evaluation revealed a granular cell tumor. CONCLUSION: Granular cell tumor can occur at the bulbar subconjunctival space.