A retrospective study on adjuvant chemotherapy in retinoblastoma: validation of the new recommendation against treatment for pT2a tumors based on the 8th AJCC classification.

BACKGROUND: Retinoblastoma (RB) is an intraocular malignant tumor detected in early childhood with variable global impact. Histopathological classification of the tumor in enucleated globes with RB is the key for the decision of adjuvant chemotherapy use. We aim to validate the use of adjuvant chemotherapy in cases with combined pre-laminar/intralaminar optic nerve (ON) invasion and focal choroidal invasion according to the American Joint Committee on Cancer (AJCC) 8th classification. METHODS: This is a retrospective study conducted at King Abdulaziz University Hospital (KAUH) and King Khalid Eye Specialist Hospital (KKESH) in Riyadh, Saudi Arabia of all RB cases who underwent enucleation over 22 years (2000 to 2021). The histopathological findings were reviewed to identify the enucleated globes classified as pT2a tumors, as an inclusion criterion. Basic demographic and clinical data were collected via chart review Simple descriptive and basic statistical analysis of the data was used where applicable. RESULTS: Thirty-one patients who had an enucleated globe with RB that fit into the above classification were included. Sixteen were males and 15 were females. The median age was 14 months (IQR = 14 months). Most of the patients (93.5%) had no family history of RB. The commonest presentation was leukocoria in 87.1% followed by squint in 32.3%. Fourteen patients (45.2%) were treated by enucleation alone while 17 patients (54.8%) received adjuvant chemotherapy. Out of these, 7 patients had unilateral RB and the remaining 10 patients had bilateral RB. None of our patients developed recurrence or metastatic disease irrespective of the indication for adjuvant chemotherapy use after a maximum period of follow up reaching 17.84 years and a median of 10.6 years (IQR = 5.92). CONCLUSIONS: In patients with 8th AJCC histopathological classification of pT2a, chemotherapy following enucleation might not be justified. The outcome in our untreated group of patients did not differ from the treated group with the absence of metastasis after a relatively long period of follow up with a median exceeding 10 years in both groups. Therefore, the risk and benefit of post enucleation adjuvant chemotherapy in the treatment of unilateral RB should be carefully decided and discussed with the primary caregivers taking into consideration the most recent evidence and recommendations in the literature.

Ophthalmic manifestations of nasopharyngeal carcinoma (NPC): A systematic review of reported cases with and without prior history of nasopharyngeal carcinoma.

PURPOSE: We aimed to study reported cases of nasopharyngeal carcinoma presenting with ophthalmic manifestations with and without a prior diagnosis of nasopharyngeal carcinoma. METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A literature search was conducted using the MEDLINE database in PubMed and Google Scholar. We included patients with a previous diagnosis of nasopharyngeal carcinoma in Group I and those without a prior diagnosis of nasopharyngeal carcinoma in Group II. Data included demographics, clinical presentation, history of nasopharyngeal carcinoma, treatment, histopathological description, World Health Organization classification, and outcome. RESULTS: Fifty-eight patients (26 in Group I and 32 in Group II) were included. The male-to-female ratio was 3:1. The mean age of the patients (53.3 ± 11.7 years and 54.8 ± 16.2 years, respectively) and gender did not differ significantly between the two groups. The most common ocular presentations were diplopia and proptosis in the first group (each in 34.6%), whereas visual disturbance was most common in the second group (46.9%). Treatment options and World Health Organization grading were comparable. The outcome in 38 patients (after a comparable follow-up period) was significantly better in group II (p=0.003). There was no statistically significant difference in the outcome of 23 patients in correlation with World Health Organization grades II versus III irrespective of group (p=0.094). CONCLUSIONS: The demographics of patients with nasopharyngeal carcinoma presenting with ophthalmic manifestations were similar between the two study groups, with a wide age range and male predominance. Patients presenting initially to ophthalmologists with no history of nasopharyngeal carcinoma have a more favorable outcome. World Health Organization grading may have less value as a prognostic indicator.

Ophthalmic manifestations of nasopharyngeal carcinoma (NPC): A systematic review of reported cases with and without prior history of nasopharyngeal carcinoma

ABSTRACT Purpose: We aimed to study reported cases of nasopharyngeal carcinoma presenting with ophthalmic manifestations with and without a prior diagnosis of nasopharyngeal carcinoma. Methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A literature search was conducted using the MEDLINE database in PubMed and Google Scholar. We included patients with a previous diagnosis of nasopharyngeal carcinoma in Group I and those without a prior diagnosis of nasopharyngeal carcinoma in Group II. Data included demographics, clinical presentation, history of nasopharyngeal carcinoma, treatment, histopathological description, World Health Organization classification, and outcome. Results: Fifty-eight patients (26 in Group I and 32 in Group II) were included. The male-to-female ratio was 3:1. The mean age of the patients (53.3 ± 11.7 years and 54.8 ± 16.2 years, respectively) and gender did not differ significantly between the two groups. The most common ocular presentations were diplopia and proptosis in the first group (each in 34.6%), whereas visual disturbance was most common in the second group (46.9%). Treatment options and World Health Organization grading were comparable. The outcome in 38 patients (after a comparable follow-up period) was significantly better in group II (p=0.003). There was no statistically significant difference in the outcome of 23 patients in correlation with World Health Organization grades II versus III irrespective of group (p=0.094). Conclusions: The demographics of patients with nasopharyngeal carcinoma presenting with ophthalmic manifestations were similar between the two study groups, with a wide age range and male predominance. Patients presenting initially to ophthalmologists with no history of nasopharyngeal carcinoma have a more favorable outcome. World Health Organization grading may have less value as a prognostic indicator.

Ophthalmic histiocytic lesions (diseases of the L group): A multicenter clinicopathological study of 18 cases and review of literature.

INTRODUCTION: Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are rare histiocytic disorders in the L (Langerhans) group diseases. They range from self-limited benign diseases to lethal disseminated forms. METHODS: This retrospective study was conducted in 3 tertiary hospitals in Saudi Arabia and Brazil. Histopathological records were searched for all patients diagnosed with ocular and periocular histiocytic disorders from January 1993 to December 2018. Histopathological slides and medical files were reviewed for data collection and simple analysis of demographics, clinical manifestations, and management. The relevant literature is reviewed. RESULTS: Twenty-two eyes of 18 patients with biopsy-proven histiocytic disorders in the L group were included. Female-to-male ratio was 1.25:1. Average age at presentation was 14 years (range, 1-54). LCH was diagnosed in 14 eyes, while eight eyes had ECD. All LCH cases were unilateral and confined to the bone as cases of eosinophilic granuloma (EG), while patients with ECD were bilateral. Commonest presentations in EG and ECD were eyelid swelling (85.7%) and periocular xanthomas (75%), respectively. Orbit was involved in 100% of EG cases, with bony erosion in 54.5%. Relevant systemic involvement was found in 100% of ECD and 21% of EG cases. Surgical intervention was needed in 16 of the 22 eyes (72.7%). All EG and 25% of patients with ECD required surgical excision. CONCLUSIONS: Histiocytic disorders are a rare group of diseases, including the L group. Relevant systemic associations require specific and selective therapy. A high clinical index and multidisciplinary collaboration are essential for the proper evaluation and management of these patients.

Clinicopathological Correlations in Enucleated Globes of Late-Stage Coats Disease with a Review of the Literature.

BACKGROUND: Coats disease may cause diagnostic dilemma because of its variable clinical presentation that can be suspicious of retinoblastoma. Late sequelae of the disease are blinding with possible enucleation. We demonstrate the main histopathological findings of Coats enucleated eyes with literature review. METHODS: This was a retrospective study of all enucleated globes diagnosed as Coats disease over 30 years and were reviewed by two pathologists. The corresponding demographic data, clinical presentation, pre-operative clinical impression, and indication for enucleation were collected. Descriptive analysis of our own series data was performed. Our findings were then correlated to published data that were collected from 1983 to 2021 from the PUBMED database in English-written language. Shields classification was used as an inclusion criterion for the published reports to be analyzed. RESULTS: We had seven enucleated globes with Coats disease. Mean age at presentation was 3.2 years (range 3 months to 9 years). Male predominance was observed in 6 and all cases were unilateral. Strabismus was the most common initial presentation (57%, n = 4), followed by leukocoria (43%, n = 3). Indication for enucleation was mostly suspected retinoblastoma (57%, n = 4). Four eyes were classified as stage 4, and 2 had advanced stage 5 changes. Histopathologically, subretinal fluid with lipid-laden macrophages was seen in all cases, the anterior chamber was shallow in 5/7 with angle neovascularization in 2/7. Telangiectatic vessels were clearly observed in 4/7. CONCLUSION: Coats disease is a potentially visually disabling disease that is mostly unilateral in 95%, has male predominance of 81%, and wide age range with a mean of 17 years. In Saudi Arabia, the disease seems to present at younger age, tends to be more advanced, and may be indistinguishable from retinoblastoma at the time of diagnosis. Shields staging of Coats is highly recommended to be followed clinically to unify the pathways for treatment and to correlate the concluded outcomes.

Periocular intravascular papillary endothelial hyperplasia: A retrospective study.

INTRODUCTION: Intravascular papillary endothelial hyperplasia (IPEH) is a rare proliferation of endothelial cells with uncertain etiology related to thrombus formation. Diagnosis is usually confirmed histopathologically. This condition has been previously described in the periocular region but not in the conjunctiva. METHODS: It is a retrospective case series in which we evaluated seven patients with histopathologically confirmed IPEH cases. Data regarding the demographics, clinical presentation, radiological description, histopathological features including any IHC staining, suspected underlying vascular etiology, management options, and follow up outcome were collected. RESULTS: A total of seven cases of histologically confirmed IPEH were included. Five out of seven patients were male (71.4%). The age range was between 6 and 69 years with a median age of 36 years. Three cases involved the eyelid (42.8%) and another three were found in the conjunctiva (42.8%). Pre-existing underlying vascular lesions were observed in all patients, five malformations (mostly lymphatic-venous) and two conjunctival hemorrhagic lymphangiectasis. All cases were treated with excisional biopsy with no signs of recurrence within an average of 7 months follow up. CONCLUSIONS: Periocular IPEH is a rare tumor that is likely to coexist with underlying vascular lesions and thrombus formation. We are reporting its existence in the conjunctiva for the first time. Therefore, pathologists should be aware of the histopathological spectrum of this lesion.

Intraocular T-cell lymphoma metastasizing from a primary adrenal T-cell lymphoma: Case report.

INTRODUCTION: Most intraocular T-cell lymphomas arise from metastatic source. We are reporting a rare case of intraocular T-cell lymphoma masquerading as pseudo-hypopyon and vitritis. The eye involvement proved to represent a metastatic spread from a co-existing adrenal T-cell lymphoma, which was discovered after the initial ophthalmic presentation. PRESENTATION OF CASE: Our patient was a 71-year-old Saudi man, who was admitted for workup of anemia and weight loss. He also noticed a gradual, painless decline in his vision of both eyes, for which he was referred to the ophthalmology unit. Ocular examination revealed left eye 3 mm pinkish hypopyon. A diagnosis of T-cell lymphoma was made based on careful microscopic examination of the left aqueous fluid, immunohistochemical (IHC) and Flow cytometry analysis. Computerized tomography showed a large invasive left adrenal mass, which has proven to be a primary adrenal lymphoma with multiple metastasis including the intraocular involvement. DISCUSSION: Primary intraocular lymphoma is the most common lymphoma in the eye. Intraocular T-cell lymphoma is rare and is mostly metastatic. On the other hand, primary adrenal lymphoma (especially T-cell lymphoma) is also rare. There are only 5 cases of primary adrenal lymphoma, two of which, resulted in eye metastasis similar to our case. Primary adrenal lymphoma is known to be aggressive. Our patient eventually passed away. CONCLUSION: This report stresses the importance of referring patients with systemic lymphoma to an ophthalmologist to be evaluated for ocular involvement. Even though intraocular metastatic adrenal T cell lymphoma is rare, high clinical suspicion in patients who are presenting with pinkish hypopyon in the presence of other constitutional symptoms is essential.

Adult Orbital Lesions in Saudi Arabia: A Multi-centered Demographic Study with Clinicopathological Correlation.

The demographics, clinical features, and histopathological classification of orbital space-occupying lesions in adults have not been widely described in our part of the world except for the pediatric population. In this retrospective study, we collected 110 consecutive adult patients (18 years and older) with orbital lesions (excluding lacrimal gland lesions) that were diagnosed histopathologically in two tertiary eye centers in Riyadh, Saudi Arabia (January 2000 to July 2017). Patients with thyroid-related orbitopathy, infectious, and inflammatory/pseudo-inflammatory lesions were excluded. We had 60 males (54.5%) and 50 females (45.5%). The mean age at presentation was 51.4 years (range 19-99). Proptosis was the most common clinical presentation (mean duration 15.4 months). The orbital lesions in order of increasing prevalence were: lymphoproliferative lesions in 26.4%; vascular in 21.8%; secondary tumors in 14.6%; neurogenic in 13.6%; structural in 10.0%; soft tissue tumors 8.2%; then metastatic tumors (2.7%) and others (extramedullary leukemia, fibrous dysplasia, and histiocytic lesion: Rosai-Dorfman disease): one case each. Gender distribution was varied in lymphoproliferative disorders compared to vascular lesions. Cavernous hemangioma was the most common vascular lesion (83.3%) and schwannoma was the most common neurogenic tumor (60%). Secondary lesions extended to the orbit mostly from eyelids in nine out of 16 or conjunctiva in four out of 16 cases. A favorable outcome was observed in about 80% of patients who underwent excisional biopsy. The rest encountered local recurrence of the tumors, growing of residual lesions, and recurrence with further invasion to nearby structures. We concluded having a similar demographic pattern of orbital lesions in adults as has been universally reported. We have fewer secondary tumors. We have summarized the pathological profile of adult orbital lesions according to patients' age, gender, symptoms, and location of the lesion as a baseline guide for proper diagnosis of any orbital mass prior to surgical management planning and for future prognostic studies.

Orbital solitary fibrous tumors: a multi-centered histopathological and immunohistochemical analysis with radiological description.

BACKGROUND: Solitary fibrous tumors (SFT), formerly called hemangiopericytoma, are rare tumors derived from mesenchymal cells originally described in the pleura, but these tumors may affect extraserosal tissues including the lacrimal gland and orbit. OBJECTIVE: Conduct a multi-centered clinical, radiological and histopathological analysis of 17 orbital SFT cases. DESIGN: A retrospective case series. SETTING: Three eye centers in two countries. PATIENTS AND METHODS: The data collected from the charts of 17 adult patients presenting with tissue diagnosis of orbital hemangiopericytoma or SFT from January 2003 to December 2018 included demographics, clinical imaging and histopathological information including immunohistochemical (IHC) characteristics. MAIN OUTCOME MEASURES: The demographic characteristics, clinical presentation, and histopathological patterns or variants of SFT were analyzed. SAMPLE SIZE: 17 adult patients. RESULTS: Mean age was 45 years (range 23-80 years). Male to female ratio was 3:1. The right eye was affected in 12 (70.5%) patients. Commonest presentation was proptosis in 13/17 (76% of patients). Other symptoms were impaired motility (29%) and ptosis (11%). Lesions mostly affected the medial orbit (35%), then orbital apex in 11%. The histopathological classic pattern-less variant was the commonest. One case with aggressive behavior, multiple recurrences and atypical features was encountered. Immunohistochemical (IHC) markers used included CD34 expression in all cases, Bcl-2 expression in 10/11, CD99 in 9/9 and Vimentin in 4/4. STAT6 was used in 2 cases. CONCLUSIONS: SFTs are rare tumors affecting the orbit in both genders equally in their mid-forties, but showed male predominance in our analysis with a predominant classic histopathological pattern. Tissue diagnosis is essential and requires IHC studies for confirmation. LIMITATIONS: Sample size is relatively small owing to the rarity of this tumor in the orbit. CONFLICT OF INTEREST: None.

Enucleated globes with choroidal melanoma: A retrospective histopathological study and correlation with cytogenetic profile in 2 eye centers.

BACKGROUND: Uveal melanoma is the commonest intraocular malignant tumor in adults and the choroid is the commonest involved location. It is more prevalent in Caucasians; however, the demographics are widely variable based on ethnicity. Histopathological features have been correlated to the cytogenetic profile, which we intend to report through the study of enucleated eyes with choroidal melanoma (CM). MATERIALS AND METHODS: A retrospective review of 28 enucleated globes with CM in 2 tertiary eye centers (January 2000-December 2017). The tumors were histopathologically classified based on the 8th edition of the American Joint Committee on Cancer (AJCC). The histopathological risk factors and the AJCC classifications were correlated with Fluorescence in situ hybridization (FISH) for chromosomes 3 and 8 available results in 18/28 eyes. RESULTS: We have included 28 patients with a mean age of 56 years, 13 males (46.4%) and 15 females (53.6%). None had lymph node involvement or metastatic disease. The tumor size was categorized as 3 and 4 in 68% of eyes. Half tumors were of spindle cell type and were associated with absent cytogenetic abnormality in chromosomes 3 and 8 (P=0.005). Closed vascular loops presence was significantly associated with abnormal chromosomes 3 and 8 (P=0.027). CONCLUSION: Patients in our area presented late with larger tumor size. The spindle cell CM was the commonest and correlated with negative FISH results, while the presence of closed vascular loops was a risk factor for abnormal FISH results hence expected worse prognosis. AJCC classification did not correlate well with our FISH results.

Enucleated globes with advanced retinoblastoma: correlation of histopathological features and reclassification of tumors according to the 8th edition of the American Joint Committee on Cancer (AJCC).

PURPOSE: We aim to study certain histopathological characteristics of the retinoblastoma (RB) tumors in globes with clinically advanced RB, which can be correlated with the high-risk features including: tumor differentiation, growth pattern and focality. We also aim to reclassify the tumor pathologically in the analyzed cases according to the American Joint Committee on Cancer (AJCC) 8th edition in an attempt to compare the validity of this newest classification. METHODS: Retrospective study of patients diagnosed with clinical RB of groups D and E during the period: January 2013 to December 2017 at King Khaled Eye Specialist Hospital (KKESH) and King Abdulaziz University Hospital (KAUH). Charts were reviewed for demographic and basic clinical data. Histopathological features (tumor differentiation, growth pattern, focality, seeding, and presence of choroidal invasion (focal versus massive), level of optic nerve (ON) invasion, anterior chamber invasion, scleral and extra-scleral extension, and finally the documented pathological tumors (pT) classification based on the AJCC 7th edition were collected. RESULTS: We included 146 eyes with advanced retinoblastoma (groups D and E) from 104 patients. Gender distribution was almost equal with 54 males. Median age was 12 months (range 1-96 months), and a mean age was 17.1 ± 15.1 months. No family history was found in the majority (94.2%). Clinically, the most common presenting symptoms: leukocoria (73.3%), squint (33.6%) and least commonly proptosis (2.7%). A total of 106 enucleation specimens were reviewed. Degree of RB differentiation was: well differentiated (18%), moderate (30%), poor (35%), and undifferentiated (17%). The most common high-risk features were ON invasion (68%) with the majority being prelaminar in nature, choroidal invasion (45%) with more than half being massive, iris/trabecular meshwork (TM)/Schlemm's canal invasion (8.5%), and then intra-scleral/extra-scleral extension (5%). Less tumor differentiation doubles the relative risk of massive choroidal invasion (with 95% CI) with a statistically significant P value (P = 0.030). Endophytic RB was associated with vitreous seeding, while exophytic tumors were associated with subretinal seeding (P = 0.001) each. Ten cases with combined ON invasion (pre-laminar) and focal choroidal invasion were reclassified pT2a in the AJCC 8th edition instead of pT2b in the older 7th edition. CONCLUSIONS: Our demographic and basic clinical data for advanced RB are comparable to other similar reports. The tumor growth pattern correlates well with the type of seeding observed in enucleated globes with RB. Less tumor differentiation is a relative risk of massive choroidal invasion. It is advocated to implement the AJCC 8th edition by ocular pathologists worldwide aiming to histopathologically classify the RB tumor in cases for selective adjuvant chemotherapy.

Epibulbar complex and osseous choristoma: Clinicopathological study with interesting associations.

MATERIALS AND METHODS: A retrospective cohort study of cases with tissue diagnosis of epibulbar choristoma in 2 centers presenting during the period: 2000-2016 with focus on cases of complex and osseous choristoma. Demographic and clinical data were collected by the resident from medical records. The histopathological slides were reviewed by 2 pathologists and cases of complex and osseous choristoma were analyzed by biostatical staff. RESULTS: 120 epibulbar choristomas were identified. 13/120 patients (10.8%) with complex choristoma and 2/120 patients (1.7%) with osseous choristoma. 15 cases were further analyzed: 7 were males and 8 were females. Mean age at presentation was 7.6 year. Commonest location was temporal in 66.6%. The presence of smooth muscle component was associated with a larger size choristoma (p = 0.042). 73.3% had other ophthalmic manifestations (mostly eyelid anomalies) while 9 systemic associations (mostly Goldenhar's syndrome) were found in 8/13 cases of complex choristoma. CONCLUSION: Epibulbar complex and osseous choristomas are rare. Histopathologically, the presence of smooth muscle significantly correlates with the lesion size. Complex choristoma is more likely to be associated with systemic manifestations. Further genetic studies for this condition are recommended.

Halo nevus of the choroid in 150 patients: the 2010 Henry van Dyke Lecture.

OBJECTIVE: To evaluate choroidal halo nevus. METHODS: We performed a retrospective medical record review on all patients with a clinical diagnosis of choroidal halo nevus treated at the Ocular Oncology Service at Wills Eye Institute from April 1, 1974, through June 30, 2008. Their clinical characteristics and natural history were studied. RESULTS: The choroidal halo nevus showed 2 components, including a distinct central pigmented region surrounded by a yellow halo. Of the 150 patients, 107 (71.3%) were women and 43 (28.7%) were men; and 149 (99.3%) were white, with a median age at presentation of 54 years. Autoimmune disorders were found in 4 patients (2.7%), a rate similar to the prevalence in the US population (2.7% vs 3.1%, P = .74). Preexistent cutaneous melanoma was found in 5 patients (3.3%), which was significantly more prevalent than the rate for the US population (3.3% vs 0.3%, P < .001). The halo was peripheral in 139 patients (92.7%) and slightly internal in 11 (7.3%). Two patients (1.3%) had multifocal halo nevi. The nevus location was superior in 31 patients (20.7%), temporal in 43 (28.7%), inferior in 29 (19.3%), nasal in 27 (18.0%), and macular in 20 (13.3%). Related features included drusen in 85 patients (56.7%), subretinal fluid in 21 (14.0%), orange pigment in 13 (8.7%), and retinal pigment epithelial atrophy in 15 (10.0%). There were no intraocular inflammatory findings. Of the 110 patients with nevi with follow-up, growth into melanoma occurred in 4 patients (3.6%) at a median interval of 41 months. CONCLUSIONS: Halo nevus is a variant of choroidal nevus that has a brown center and yellow halo. No relationship was found with autoimmune disorders, but a relationship with previous cutaneous melanoma is possible.