Search

Background: Vitreoretinal lymphoma (VRL) can commonly masquerade as chronic idiopathic uveitis due to its nonspecific clinical presentation. Thus, its early diagnosis is difficult. In this study, new logistic regression models were used to classify VRL and uveitis. Additionally, the diagnostic performance of interleukin (IL)-10, the IL-10/IL-6, and the Interleukin Score for IntraOcular Lymphoma Diagnosis (ISOLD) are evaluated., Methods: Sixty-nine aqueous humors (AH) (46 VRL, 23 uveitis) and 65 vitreous humors (VH) (49 VRL, 16 uveitis) were collected from a single-center retrospective cohort. Logistic regression models were conducted based on IL-6 and IL-10. The cut-off values, area under the receiver operating characteristic curve (ROC) curve (AUC), sensitivity and specificity of IL-10, the IL-10/IL-6, the ISOLD, and the models were calculated from the ROC. Furthermore, Spearman's rank correlation analysis was performed to determine cytokine levels in VH and AH., Results: We redefined the cut-off values of IL-10, the IL-10/IL-6, the ISOLD, and the logistic regression models. In AH, the AUC values of IL-10, ISOLD, IL10/IL6, and the model were 0.91, 0.953, 0.952, and 0.967. In VH, they were 0.93, 0.95, 0.954, and 0.954, respectively. IL-6 (r = 0.7844) and IL-10 (r = 0.8506) in AH and VH showed a strong correlation., Conclusions: IL-6 and IL-10 levels were introduced into new logistic regression models. The diagnostic efficacy of the models improved compared to the indicators mentioned above among Chinese patients. Additionally, the models could predict the probability of VRL more accurately. A strong correlation of cytokine levels showed the great potential of AH as prioritized auxiliary diagnostic for VRL., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy. Oncologic drivers of ocular sebaceous carcinoma are incompletely understood., Methods: A retrospective search of our pathology archives for OA sebaceous carcinoma identified 18 primary resection specimens. Immunohistochemistry for p16 and ZEB1 and RNA in situ hybridization for high-risk human papillomavirus (HPV) subtypes were performed., Results: High-risk HPV was demonstrated in 2/11 (18%) cases. p16 overexpression was observed in 10/11 (91%). No association between gender, age at presentation, tumor location, intraepithelial spread, tumor size, and T stage was observed between HPV-driven and nonviral cases. High expression of ZEB1 was observed in the intraepithelial component of 4/14 (28%) cases and in the subepithelial component of 1/13 (7%) cases. ZEB1 overexpression was not associated with HPV status, T stage, or tumor size., Conclusion: As previously described by others, our findings suggest that a subset of OA sebaceous carcinomas may arise via an HPV-dependent pathway. However, unlike high-risk HPV-driven carcinomas of the oropharynx, we did not identify an association between HPV-status and prognostic features. Furthermore, p16 expression was not a useful surrogate marker for HPV-driven disease. ZEB1 overexpression is not associated with HPV in our cohort of ocular sebaceous carcinoma., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cellular communication is an essential process for the development and maintenance of all tissues including the eye. Recently, a new method of cellular communication has been described, which relies on formation of tubules, called tunneling nanotubes (TNTs). These structures connect the cytoplasm of adjacent cells and allow the direct transport of cellular cargo between cells without the need for secretion into the extracellular milieu. TNTs may be an important mechanism for signaling between cells that reside long distances from each other or for cells in aqueous environments, where diffusion-based signaling is challenging. Given the wide range of cargoes transported, such as lysosomes, endosomes, mitochondria, viruses, and miRNAs, TNTs may play a role in normal homeostatic processes in the eye as well as function in ocular disease. This review will describe TNT cellular communication in ocular cell cultures and the mammalian eye in vivo , the role of TNTs in mitochondrial transport with an emphasis on mitochondrial eye diseases, and molecules involved in TNT biogenesis and their function in eyes, and finally, we will describe TNT formation in inflammation, cancer, and stem cells, focusing on pathological processes of particular interest to vision scientists., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Holly R. Chinnery and Kate E. Keller.)

Purpose: To compare the clinical characteristics and treatment outcome between benign and malignant lacrimal sac tumors., Methods: We retrospectively reviewed the medical records of all patients with pathologically confirmed lacrimal sac lesions from 1995 to 2018 in a tertiary medical center., Results: Among 65 eligible cases, 46 (70.8%) were benign lacrimal sac tumors and 19 (29.2%) were malignant lacrimal sac tumors. Secondary malignancy from nasal or paranasal cancer accounted for 47% of malignant lacrimal sac tumors. The patient's mean age at the time of diagnosis was 60 years in the benign group and 48 years in the malignant group ( p =0.03). The most common presenting symptoms were a palpable lump/mass and epiphora in both groups. Palpable mass extending above the medial canthal tendon was noted in 9% of the benign group and in 74% of the malignant group, respectively ( p =0.03). The most common presenting symptoms were a palpable lump/mass and epiphora in both groups. Palpable mass extending above the medial canthal tendon was noted in 9% of the benign group and in 74% of the malignant group, respectively ( p =0.03). The most common presenting symptoms were a palpable lump/mass and epiphora in both groups. Palpable mass extending above the medial canthal tendon was noted in 9% of the benign group and in 74% of the malignant group, respectively ( p =0.03). The most common presenting symptoms were a palpable lump/mass and epiphora in both groups. Palpable mass extending above the medial canthal tendon was noted in 9% of the benign group and in 74% of the malignant group, respectively (., Conclusion: Although benign and malignant lacrimal sac tumors may present similar initial symptoms, timely diagnosis and intervention for malignant lacrimal sac lesions are important because they tend to be infiltrating tumors with a poor outcome., Competing Interests: None of the authors have any conflicts of interest in relation to the work described., (Copyright © 2020 Che-Yuan Kuo et al.)

Although discussed using variable terminology, cutaneous BRCA1-associated protein (BAP1)-inactivated melanocytic tumor (BIMT) has been considered a discrete diagnostic entity since 2011. Here, we review the initial genomic studies that identified these distinct melanocytic tumors and the clinical and histopathological features that define these tumors. These epithelioid, predominantly dermal, and melanocytic tumors present as erythematous nodules and histopathologically have features that may overlap with Spitz nevi and nevoid melanoma. There is no sex predilection, and cutaneous BIMTs can appear at any age; however, in most familial (germline mutant) cases patients have multiple cutaneous tumors with a first diagnosis in the second or third decade of life; ocular melanoma and other tumors are increasingly identified in these kindreds with germline BAP1 mutation. These tumors have been described with a myriad of terms including: Wiesner nevus, nevoid melanoma-like melanocytic proliferation (NEMMP), BAP1 mutant Spitz nevus, BAP1 mutant nevoid melanoma, cutaneous BAPoma, and most recently cutaneous BIMT., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Sebaceous carcinoma (SeC) is an uncommon malignancy arising from sebaceous glands of the conjunctiva and skin. Recurrent mutations in the ZNF750 were recently identified in ocular SeC. We assessed whether ZNF750 loss is a specific feature of ocular SeC or a general feature of sebaceous tumors., Methods: Immunostaining for ZNF750 expression was performed in 54 benign and malignant sebocytic proliferations. Staining for ZNF750 was scored on a three-tier scale: positive (>75%), partially positive (5%-74%), and negative (<5%)., Results: ZNF750 expression was negative in 4/11 ocular SeC, and partially positive in 4/11 ocular SeC and 6/13 cutaneous SeC. No extraocular tumors were negative. No loss was found in sebaceous adenoma or sebaceous hyperplasia. In nine previously sequenced ocular SeCs, two lacked detectable somatic mutations in ZNF750, but showed complete loss of staining, indicating non-mutational inactivation of ZNF750., Conclusion: We show complete loss of the ZNF750 epidermal differentiation regulator in about half of ocular SeC, highlighting the most common genetic defect in this cancer type. Loss of ZNF750 expression is seen even in tumors without truncating mutations and reduced in many of the remaining ocular and cutaneous SeC. In contrast, no ZNF750 loss was detected in benign sebaceous proliferations., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/objectives: Infantile hemangiomas are the most common benign tumors of childhood. Although some children with periocular infantile hemangiomas do not require treatment, these lesions may result in amblyopia and visual impairment if not properly treated. We have attempted to characterize clinical features of periocular infantile hemangiomas that predict negative ocular outcomes and thus require prompt referral to an ophthalmologist and initiation of therapy., Methods: This study included children with periocular infantile hemangiomas consecutively seen at Ann & Robert H. Lurie Children's Hospital of Chicago from January 1994 through December 2014. Only patients evaluated by both a dermatologist and an ophthalmologist were included. Medical records of patients who met inclusion criteria were reviewed. Ocular findings were reviewed for the presence of ptosis, refractive errors, strabismus, proptosis, and amblyopia., Results: Ninety-six patients (74% female, median age of onset 0.48 months) were included. Periocular infantile hemangiomas larger than 1 cm in diameter, with a deep component, and with involvement of the upper eyelid were significantly associated with astigmatism (P = .002, P = .02, and P = .003, respectively) and amblyopia (P = .002, P = .02, and P = .04, respectively). Using logistic regression, diameter greater than 1 cm (odds ratio = 14.13, P = .01) and amblyopia (odds ratio = 21.00, P = .04) were the strongest predictors of astigmatism. Lower lid and medial and lateral canthal involvement were not predictive of ocular complications., Conclusion: Predictive factors for ocular complications in patients with periocular infantile hemangiomas are diameter greater than 1 cm, a deep component, and upper eyelid involvement, with size being the most consistent predictor. These patients should be promptly referred to an ophthalmologist, and treatment should be strongly considered., (© 2018 Wiley Periodicals, Inc.)

Objectives: To investigate the prevalence of laboratory critical results (CRs) and associated risk factors in patients with eye diseases in a tertiary eye hospital., Methods: Blood samples were collected from both inpatients and outpatients at Zhongshan Ophthalmic Center, Guangzhou, China, from June 1, 2012, to May 31, 2014, and samples were sent to the hospital's clinical laboratory for blood routine, biochemistry, and blood coagulation tests. Laboratory CRs for blood glucose, sodium, potassium, white blood cell count, platelet count, prothrombin time, fibrinogen, international normalized ratio, and activated partial thromboplastin time were included in the current analysis., Results: A total of 60403 subjects were enrolled in the current analysis. CRs were identified in 339 tests from 336 patients with a prevalence of 5.7‰. Age was positively associated with the presence of CRs. Compared to patients with lens diseases, patients with strabismus, oculoplastics, and ocular trauma were less likely to have CRs ( P < 0.05), while patients with tumors were more likely to have CRs ( P < 0.001)., Conclusions: The prevalence of CRs in eye patients is low but calls for medication attention. It is important for medical personnel, especially ophthalmologists, to increase awareness of the importance, as well as the prevalence and risk factors of CRs.

Transmissible venereal tumour (TVT) is a sexually transmitted neoplasm that frequently affects dogs of either sex, in tropical and subtropical regions. TVT primarily involves the external genitalia, although extragenital sites have also been reported. This study describes the ocular manifestations of TVT in 25 naturally infected dogs and their response to treatment. Seventeen male and eight female dogs were included in the study. TVT ocular lesions were either unilateral (21 dogs) or bilateral (four dogs). Ocular lesions as the single manifestation of TVT were seen in 22 animals. One dog presented external genitalia involvement while two others were found to have tumours in the oral and nasal mucosa. Variably sized multilobular tumour masses with irregular surface were noticed on the bulbar conjunctiva of the nictitating membrane in 17 dogs, on the conjunctiva of the upper eyelid in five dogs and on the conjunctiva of the lower eyelid and adjacent skin in three dogs. Deep ulcerative keratitis was observed in eight animals. TVT diagnosis was based on cytology and histopathology. The large eye masses were surgically excised. All dogs were treated with a single chemotherapeutic agent (vincristine). After four weeks of treatment, complete remission of the tumours was evident in all but one animal. Extragenital primary ophthalmic TVT can be completely eliminated by vincristine chemotherapy, while any further ocular damage is prevented with the combination of the above treatment and surgical excision., (British Veterinary Association.)

Objective: To describe epidemiological trends in lacrimal gland malignancies in the United States., Study Design: Retrospective database review., Setting: Multicenter registry., Subjects and Methods: A total of 702 malignant tumors of the lacrimal gland from the Surveillance, Epidemiology, and End Results database were included in the study. Disease-specific and overall survival were the primary outcome measures. Kaplan-Meier survival curves were generated for multiple patient and tumor characteristics, including race, histology, TNM tumor stage, age at diagnosis, radiotherapy, gender, and tumor grade. Cox proportional hazards regression was performed to assess the impact of patient and tumor characteristics on survival., Results: Lymphoma (58.0%), adenoid cystic carcinoma (13.4%), adenocarcinoma (3.8%), and mucoepidermoid carcinoma (3.6%) accounted for most tumors. Lymphoma was associated with more favorable survival rates, while adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma were associated with worse prognosis. There was a steady increase in the proportion of lymphoma diagnosed since 1973. In a multivariate Cox proportional hazards regression model, tumor histology remained as the only covariate correlated with disease-specific survival., Conclusion: Patient characteristics and survival rates differ between lymphoma, adenoid cystic carcinoma, adenocarcinoma, and mucoepidermoid carcinoma. The proportion of lacrimal gland cancer diagnosed as lymphoma has steadily increased over time. Cox proportional hazards regression analysis demonstrated tumor histology as one of the most important factors in patient survival. These results augment our understanding of the expected disease course of lacrimal gland malignancies., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.)

Breast cancer is one of the most common malignant diseases occurring in women, and its incidence increases over the years. It is the main site of origin in ocular metastatic disease in women, and, due to its hematogenous nature of metastatic spread, it affects mainly the uveal tissue. The purpose of this paper is to summarize the clinical manifestations of the breast cancer ocular metastatic disease, alongside the side effects of the available treatment options for the management and regression of the systematic and ophthalmic disease.

TNF-related apoptosis inducing ligand (TRAIL) is an intensively studied cytokine, in particular for its anticancer activity. The discovery that conjunctival sac fluid contains extremely high levels of soluble TRAIL as compared to other body fluids suggested important implications in the context of the immunological surveillance of the eye, in particular of the anterior surface. In this review, we discuss the potential physiopathologic and therapeutic role of the TRAIL/TRAIL receptor system in a variety of ocular cancers. Moreover, since an increasing amount of data has indicated the important biological activities of the TRAIL/TRAIL receptor systems also in a completely different pathologic context such as diabetes mellitus, in the second part of this review we summarize the currently available data on the involvement of TRAIL in the ocular complications of diabetes mellitus as modulator of the inflammatory and angiogenic response in the eye.

Background: The objectives of this article are to assess the completeness of the data collected on site-specific factors (SSFs) as a part of Collaborative Stage (CS) version 2 and the impact of the transition from the American Joint Committee on Cancer's (AJCC) 6th to 7th edition guidelines on stage distribution., Methods: Incidence data for melanomas of the skin from 18 Surveillance, Epidemiology, and End Results (SEER) registries (SEER-18) were analyzed. Percentages of unknown cases for 7 SSFs were examined, along with staging trends from 2004 to 2010 and differences in AJCC 6th and 7th edition stage distributions for 2010 cases., Results: Fewer than 10% of cases were coded as unknown for SSFs 1 (measured thickness), 2 (ulceration), and 3 (lymph node metastasis). For the remaining SSFs, 36-81% of cases were coded as unknown. Stage distributions were relatively consistent across time and between the AJCC 6th and 7th editions, with the exception of stage IA and stage INOS (not otherwise specified), for which a shift in cases was observed between the AJCC 6th and 7th edition guidelines fOR 2010 cases., Conclusions: A shift of cases out of stage IA and into stage INOS was observed between the AJCC 6th and 7th edition guidelines for 2010 cases. This was attributed to the high number of cases coded as unknown for SSF7 (primary tumor mitotic count/rate). The percentage of cases coded as unknown varied by SSF. Data completeness presents an issue for SSFs introduced in CS version 2., (© 2014 American Cancer Society.)

Effective management of hepatic metastases from ocular and cutaneous melanoma remains a major therapeutic challenge. Treatment options include hepatic resection, hepatic intra-arterial (HIA) chemotherapy, chemoembolization, and hepatic perfusions. Evaluating the efficacy of these interventions is limited by the retrospective nature of most of the data, although controlled phase 3 studies are starting to emerge. Studies of hepatic resection are strongly suggestive of a survival benefit following surgery in selected patients. Effective systemic agents for metastatic cutaneous melanoma are available and supported by randomized controlled phase 3 trials. In contrast, no active systemic treatment has yet been identified for metastatic ocular melanoma. HIA and intravenous delivery of fotemustine have been compared in a randomized phase 3 trial in patients with unresectable metastases from melanoma, but no differences between the 2 approaches were observed. Hepatic arterial chemoembolization appears only to be moderately effective according to uncontrolled studies; targeting patients with less liver involvement may improve outcomes. A recent phase 3 study showed a significant improvement in hepatic progression-free survival with percutaneous hepatic perfusion compared with best alternative care in patients with metastatic melanoma; however, the overall survival analysis was confounded by crossover of control patients to active treatment. In conclusion, hepatic resection offers the possibility of long-term survival in carefully selected patients with liver-limited metastases from melanoma. In patients with unresectable cutaneous melanoma, effective systemic therapy is the best treatment option. For patients with unresectable ocular melanoma, regional treatments are likely to assume a greater role until effective systemic treatments are identified., (© 2013 American Cancer Society.)

Giant cell angiofibroma represents a rare soft tissue neoplasm with a predilection for the orbit. We recently encountered a mass removed from the lower eyelid of a 56-year-old female that histopathologically resembled giant cell angiofibroma. The process consisted of haphazardly arranged CD34-positive spindled and multinucleated cells within an edematous, densely vascular stroma. However, the patient had recently undergone laryngectomy and radiotherapy for a laryngeal squamous cell carcinoma. A similar mass had arisen on the contralateral eyelid, and both had developed several months post-therapy. Lymphedema of the orbit can present as tumor-like nodules and in some cases may share histopathologic features purported to be characteristic of giant cell angiofibroma. A relationship between giant cell angiofibroma and lymphedema has not been established, but our case suggests there may be one. The potential overlap of these two conditions should be recognized, as should other entities that may enter the differential diagnosis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Scleral infantile hemangiomas are rare. We describe a patient who presented at 3 months of age with an enlarging infantile hemangioma on the sclera of the left eye. He had two other hemangiomas on the left eyebrow and chest. Treatment with propranolol resulted in marked improvement of all of his hemangiomas. He did not develop any ocular complications., (© 2012 Wiley Periodicals, Inc.)

Primary cutaneous adenoid cystic carcinoma (ACC) is an uncommon malignancy with approximately 60 cases reported in the literature. Metastatic ACC to the skin is even less frequent with eight previously published cases, including only one arising from the lacrimal gland. We report a case of a 61-year-old male, who developed multiple cutaneous metastases to the scalp and back from a lacrimal gland ACC 21 years after the initial diagnosis. Initially, in the absence of the past clinical history, the cutaneous lesions were interpreted as primary ACC of the skin. Histopathologically, the metastatic lesions were poorly circumscribed dermal and subcutaneous nodules that were composed of islands of basaloid epithelial cells with ducts and cribriform pattern, mucinous stroma and prominent perineural invasion. Histomorphologically, the cutaneous tumors were similar to the primary ACC. The cutaneous metastases were preceded by tumor dissemination to the lung and other visceral organs, and ultimately led to patient's demise. This report illustrates the importance of juditious clinico-pathologic correlation and raises awareness regarding prolonged latency of cutaneous metastases in patients with visceral ACC., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Excision of an epibulbar choristoma followed by amniotic membrane grafting was performed on a 3-month-old baby who presented with nevus sebaceous syndrome. Upon histopathologic examination, the excised mass was seen to be a complex choristoma, a rare ocular tumor. Amniotic membrane transplantation is currently the most acceptable modality of treatment of limbal choristoma, with good cosmetic outcome., (© 2011 Wiley Periodicals, Inc.)

Background: Alpha v integrins are receptors for many extracellular matrix (ECM) protein ligands, including latent transforming growth factor betas (TGFβs). Various studies in mice have shown that ablation of genes encoding αv integrin or TGFβ signaling pathway components leads to spontaneous squamous cell carcinomas (SCCs) in the conjunctiva and periocular skin. Here, we have analyzed patterns of αv integrin protein expression and TGFβ signaling in human eyelid and periorbital SCC samples., Methods: An anti-αv integrin antibody was used to immunostain 19 eyelid and periorbital SCC samples. Additionally, tissue lysates from resected normal eyelid and SCC samples were analyzed by immunoblotting for αv integrin protein. Tumor sections were also immunostained with an antibody directed against Smad2, an intracellular signaling protein that is phosphorylated by TGFβ receptors., Results: Alpha v integrin protein was highly expressed in the invasive and less-differentiated components of human SCCs. Lower levels of αv integrin protein were detected in more differentiated components of tumors, as well as in SCC in situ. Patterns of phosphorylated Smad2 immunoreactivity correlated with levels αv integrin expression., Conclusions: Alpha v integrin was expressed at robust levels in tumor cells representing less differentiated, more invasive components of SCC; by contrast, well-differentiated cells as well as SCC in situ expressed low levels of αv integrin protein., (Copyright © 2011 John Wiley & Sons A/S.)

Background: Malignant epithelial neoplasms of the lacrimal apparatus are rare and are typically treated with surgery and occasionally adjuvant radiation therapy (RT). The purpose of this study was to assess treatment outcomes by type of surgery (orbital exenteration vs eye-sparing surgery) and clarify the role of adjuvant RT for this rare disease., Methods: Forty-six patients with malignant epithelial neoplasms of the lacrimal apparatus were treated at a single institution from 1945 through 2008. Twenty-seven patients (59%) were treated with orbital exenteration and 19 (41%) with eye-sparing surgery; 64% of the orbital exenteration group and 83% of the eye-sparing surgery group also received adjuvant RT (median dose, 60 grays). Median follow-up time for all patients was 38 months (range, 3-460 months)., Results: For the orbital exenteration and eye-sparing surgery groups, the 5-year overall survival (OS) rates were 59% and 62%, and the 5-year disease-free survival (DFS) rates were 49% and 39%, respectively (P = .56, P = .35). Tumor status (T1-2 vs T3-4) was associated with OS (P = .02), and tumor size (<3.5 vs >3.5 cm) with DFS (P = .015). Median time to locoregional recurrence was 85 months for orbital exenteration, and 123 months for eye-sparing surgery. All patients who did not receive RT experienced local recurrence, and RT extended time to locoregional recurrence (median 460 vs 30 months, P = .009). Seven grade ≥3 complications were experienced after adjuvant RT., Conclusions: For appropriately selected patients, an eye-sparing surgery for lacrimal apparatus tumors can achieve similar survival outcomes to those in patients treated with an orbital exenteration. Adjuvant RT should be considered for all patients presenting with these rare tumors., (Copyright © 2011 American Cancer Society.)

Sebaceous carcinoma is an uncommon and potentially aggressive malignancy that exhibits sebaceous differentiation. Approximately 75% of cases arise in the periocular region. Sebaceous carcinoma is rare in the pediatric population and its presentation in this age group is not well documented in the dermatopathology literature. We report the case of a 15-year-old male with sebaceous carcinoma who was first seen with a nodular lesion involving the skin of the left orbit/temporal area. A shave biopsy was performed which showed an infiltrative proliferation of basaloid cells that focally exhibited sebaceous differentiation, including the formation of incipient sebocytes. Immunohistochemically, the tumor cells expressed epithelial membrane antigen (EMA) and CK5/6, while a lack of Ber-EP4 was observed. Based upon these attributes, the diagnosis of sebaceous carcinoma was rendered. Subsequent immunohistochemical analysis for a possible DNA mismatch repair enzyme defect revealed that all four mismatch repair gene products showed retained expression, thereby providing no support for the presence of underlying Muir-Torre syndrome. Sebaceous carcinomas are exceptional in the pediatric age group and are rarely documented in the dermatopathology literature. Knowledge that this adult carcinoma can occur mostly in the pediatric age group may aid in the recognition of this uncommon malignancy., (Copyright © 2011 John Wiley & Sons A/S.)

We report a very rare case of recurrent nasopharyngeal carcinoma with local involvement of lacrimal sac. The patient was treated with chemotherapy and there was no recurrence noted after 1 year of follow-up., (© 2010 The Authors. European Journal of Cancer Care © 2010 Blackwell Publishing Ltd.)

Background: Tumors of the lacrimal sac are rare but noteworthy because of their significant potential to become malignant or life-threatening if treatment is delayed. Dermatologists may be the first to encounter such neoplasms., Observations: We report a case of a 53-year-old Caucasian woman who presented with a seven-year history of an asymptomatic, subcutaneous nodule near her right medial canthus. Histology of the lesion revealed transitional epithelium in a papillary growth pattern with numerous goblet cells, scattered mitoses and focal full-thickness atypia. The patient was diagnosed with transitional cell neoplasm (inverted papilloma-type) of the nasolacrimal duct. PCR evaluation identified HPV type 11 in the lesion., Conclusion: Our report is one of a growing number of case reports and series detecting HPV DNA in these tumors which further supports HPV as an etiologic agent in epithelial lacrimal sac tumors. We believe that dermatopathologists need to be aware of this entity, as dermatologists may be the first to encounter these neoplasms., Limitations: The association of HPV with this tumor does not prove causality.

The aim of this study is to ascertain the tumour type, sex variation and mean age of presentation of ocular tumours, as well as to update the available literature on the prevalence of the common ocular neoplasms in our environment. In this study, we analysed the data of 61 ocular biopsy specimens received between January 1998 and December 2000 at the Morbid Anatomy Department of the University of Benin Teaching Hospital, Benin City, Nigeria. Slides from paraffin embedded blocks of all ocular biopsies received were reviewed to identify the tumour types, sex variation and age of presentation.

Background: The distinction between ocular sebaceous carcinoma, poorly differentiated ocular squamous cell carcinoma and ocular basal cell carcinoma can be challenging. An appropriate immunohistochemical panel may help to differentiate these lesions., Methods: To determine the distribution and use of several immunostains in these specimens, formalin-fixed, paraffin-embedded tissue from several of each was studied using an immunohistochemical technique., Results: Positive staining for cytokeratin (CK)7 was seen in 100% of sebaceous carcinomas, 77.8% of basal cell carcinomas and 67.7% of squamous cell carcinomas. One hundred percent of sebaceous and basal cell carcinomas were positive for cytokeratin CAM 5.2, while only 83.3% of squamous cell carcinomas were positive. Using epithelial membrane antigen (EMA), 100% of squamous cell carcinomas and 80% of sebaceous carcinomas were positive, while basal cell carcinomas were uniformly negative. One hundred percent of basal cell carcinomas and 80% of sebaceous carcinomas were positive for Ber-EP4, while all squamous cell carcinomas were negative. Finally, 77.8%, 20% and 16.7% of basal cell carcinomas, sebaceous carcinomas and squamous cell carcinomas showed immunoreactivity for the androgen receptor., Conclusion: An EMA positive, Ber-EP4 positive immunophenotype supports sebaceous carcinoma, EMA positive, Ber-EP4 negative result supports squamous cell carcinoma and an EMA negative, Ber-EP4 positive result supports basal cell carcinoma.

Background: In the last few years there has been expanding use of hepatic resection for non-colorectal metastases. The purpose of this study is to evaluate the experience of liver resection for patients with metastatic melanoma., Methods: Eighteen patients with metastatic melanoma were explored for possible surgical resection. All patients fitted the following criteria: absence of extra-hepatic disease after evaluation with CT/MRI and FDG-PET scans; disease-free interval longer than 24 months after the resection of the primary melanoma; presumed completely resectable lesions; absence of clinical co-morbidities., Results: Liver resection was performed in 10 patients; 8 out of 18 presented with irresectable tumors and/or peritoneal metastases and were not operated. One patient presented with postoperative biliary fistula and was conservatively managed. No other complications or postoperative mortality were observed. After a mean follow-up of 25.4 months, 5 patients are alive and without evidence of recurrence. Overall median survival was 22 months; overall survival and disease-free survival were 70% and 50% respectively., Conclusions: Resection of liver metastases from melanoma in a selected group of patients may increase survival. Exploratory laparoscopy should be included in the preoperative armamentarium of diagnostic tools.

In total, 174 bovine ocular squamous cell carcinomas of varying sizes (20 to 2800 mm(2) in area) were treated daily with peritumoural injections of solvent, or solvent containing 5000 U, 20,000 U, 200,000 U, 500,000 U, 1 million U or 2 million U interleukin-2 (IL-2) for 10 days. The tumours were measured and clinically staged before treatment and at one, three, four, nine and 20 months after treatment. After 20 months, 14 per cent of the tumours treated with the solvent had regressed completely, a significantly smaller proportion than the 55 per cent treated with 5000 U IL-2, 52 per cent treated with 20,000 U IL-2, 58 per cent treated with 200,000 U IL-2, 50 per cent treated with 500,000 U IL-2, 69 per cent of tumours treated with 1 million U IL-2, 52 per cent treated with 2 million U IL-2. The tumours on the third eyelid and limbus were the most responsive.

Background: Temozolomide and interferon-alpha-2b (IFN-alpha-2b) are both active in melanoma. Therefore, the efficacy and safety of temozolomide in combination with pegylated IFN-alpha-2b in patients with metastatic melanoma without brain metastases was investigated., Methods: Patients with histologically confirmed, unresectable, American Joint Committee on Cancer Stage IV melanoma were enrolled in an open-label, Phase II study. The primary endpoints were tumor response and safety. Patients received temozolomide (75 mg/m2/dayx6 weeks with a 2-week break between cycles) plus concomitant subcutaneous pegylated IFN-alpha-2b (0.5 microg/kg/wk, continuously). Treatment was continued until unacceptable toxicity or disease progression occurred., Results: Thirty-five patients (median age, 55 years) with Stage IV melanoma and a median of 3 metastatic sites were enrolled and received a median of 1 cycle (i.e., 8 weeks) of therapy (range, 0-6 cycles). Eleven patients (31%) (95% confidence interval, 16% to 47%) had an objective tumor response, including 3 with clinical complete response durations of 6 months, 20 months, and 32+ months and 8 with partial responses. Three patients with a partial or mixed response were subsequently rendered free of clinically detectable disease with surgery. The median survival was 12 months with a median follow-up among survivors of 16 months. No patient developed brain metastases while receiving study treatment. Treatment was generally well tolerated. Hematologic toxicity consisted mainly of lymphopenia and leukopenia (National Cancer Institute Common Toxicity Criteria Grades 1-3); no Grade 4 hematologic toxicity was observed., Conclusions: The combination of temozolomide plus pegylated IFN-alpha-2b had antitumor activity and was well tolerated in patients with metastatic melanoma. Therefore, further study is warranted., (Copyright (c) 2006 American Cancer Society.)

Objective: The aim of this study was to report the clinicopathological features of 18 epithelial tumors of the lacrimal gland treated in a single institution., Study Design and Setting: Clinical data and treatment were recorded and histological features reviewed., Results: Twelve tumors (66.7%) were adenoid cystic carcinoma (ACC), 5 (27.8%) pleomorphic adenoma (PA), and 1 (5.5%) carcinoma ex pleomorphic adenoma. All patients with ACC presented with advanced clinical stage, and most were treated by wide surgical resection followed by adjuvant radiotherapy. No recurrence was observed in 4 cases of ACC; however, 7 patients died from persistence of disease or by local and/or distant recurrence. All PA patients were successfully treated by surgical resection., Conclusions: Epithelial lacrimal gland tumors are mainly PA and ACC, and malignancies are more common than benign tumors. Although ACC presented typically with advanced clinical stage, 33% of the patients survived without tumor recurrence or metastasis.

This study aimed at reviewing cases presenting with optic atrophy at the eye clinic of the University College Hospital, Ibadan, Nigeria with a view to identifying some of the diagnostic problems. The study was a retrospective review of 100 cases selected by systematic random sampling method of a total of 6160 patients presenting with optic atrophy to the eye clinic over 6 years (April 1990 to March 1996). Diagnosis was based on ophthalmoscopic appearance of optic disc corroborated with visual field studies. The mean age of the patients was 40.8 years. The male to female ratio was 2:1 bilateral. Eighty percentages were bilateral, whereas 20% were unilateral. Only in 38% of cases could the cause of the optic atrophy be identified. The most frequently diagnosed were cranio-orbital neoplasms (8%), those referable to trauma (8%), hydrocephalus (7%), retinitis pigmentosa (3%) and post infectious (2%). Other causes include toxins, congenital, seizure disorders, birth asphyxia and papilloedema. In 62% of cases, the aetiology cannot be satisfactorily elicited. Some suggestions have been made to overcome some of these diagnostic problems.

Background: Basal cell carcinoma (BCC) is a common malignant skin neoplasm. The surface of the caruncle contains sebaceous glands, hair follicles, and lacrimal and sweat gland elements. Consequently, the caruncle may spawn any neoplasm that occurs in the conjunctiva, skin, or lacrimal gland. We report a patient with a primary BCC located on the lacrimal caruncle., Methods: An 80-year-old man with a 5-month history of a gradually enlarging left caruncular neoplasm was seen. The lesion was nodular and irregularly brown-black colored, with no involvement of adjacent conjunctiva or skin. He had a history of sun exposure, but no personal or family history of other malignant neoplasms., Results: The mass was excised completely. Histopathologic examination revealed a BCC originating in the basal layer of the conjunctival epithelium. No tumor recurrence has been noted after 7 years of follow-up. Primary BCC of the caruncle is unusual, and only four cases have been described in the PubMed. BCC should be considered in the differential diagnosis of caruncle and adjacent skin lesions.

Intracranial hemangiomas are uncommon, especially in the absence of diffuse hemangiomatosis or the syndrome consisting of posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities, sternal clefting, and/or supra-umbilical raphe (PHACES). We saw an 8-month-old ex-premature girl with a large left-sided ocular and facial hemangioma that had been growing since early infancy. Examination revealed a 7 x 13 cm violaceous tumor involving the left periocular region and face. Ophthalmologic examination revealed deprivation amblyopia, anisometropia with myopia and astigmatism. Magnetic resonance imaging demonstrated a vascular tumor mass involving the scalp, face, and calvarium with extension into the orbit, infratemporal fossa, nasopharynx, lateral medullary cistern, internal auditory canal, and fourth ventricle. Marked enhancement was seen with contrast, and no posterior fossa malformations were noted. She was treated with prednisolone, which was tapered over 12 months. Follow-up magnetic resonance imaging examination at 25 months showed a marked decrease in the size of all lesions, with residual hemangioma in the periorbital soft tissues and small foci in the orbit and intracranial sites. The brain and ventricular system were normal. Intracranial hemangioma may occur in the setting of a large facial hemangioma (especially segmental) in the absence of the PHACES syndrome or diffuse hemangiomatosis. Radiological imaging should be considered to assess for intracranial hemangioma as well as posterior fossa or arterial anomalies.

Background: The objectives of this prospective study were to avoid adjuvant treatment for patients with intraocular disease and patients with postlaminar optic nerve invasion (PL-ONI) without full choroidal or scleral invasion. Adjuvant chemotherapy (Regimen 1) was given to patients with scleral invasion, PL-ONI without cut section, and full choroidal and/or scleral invasion. A more intensive regimen of higher dose intravenous chemotherapy (Regimen 2) and local radiotherapy was given to patients with PL-ONI and compromise at the cut end and to patients with overt extraocular disease., Methods: Six-month intravenous chemotherapy included carboplatin plus etoposide alternating with cyclophosphamide plus vincristine (Regimen 1) and the same drugs at higher dosage plus idarubicin (Regimen 2). Chemoreduction with carboplatin and vincristine with or without etoposide was given to selected patients (n = 39 patients)., Results: From 1994 to 2001, 169 patients were evaluable at the Hospital Garrahan (Buenos Aires, Argentina). One hundred eighteen patients with intraocular disease had a 5-year disease free survival (DFS) rate of 0.98, including 54 patients with choroidal invasion. None of 22 patients with isolated PL-ONI developed recurrent disease, whereas 2 of 8 patients with concomitant risk factors had tumor recurrences and died. Three of 5 patients with scleral invasion survived, and 7 of 10 patients with cut-end ONI survived. The only patient with metastatic disease that survived (n = 6) had only lymph node invasion., Conclusions: Adjuvant therapy can be avoided in patients with intraocular and isolated PL-ONI. Patients with PL-ONI who also had other risk factors required intensive adjuvant therapy, such as patients with cut-end and overt extraocular disease. Metastatic disease was not found to be curable with this approach., (Copyright 2003 American Cancer Society.)

Background: The median survival time is only 2-6 months after a diagnosis of metastases from intraocular melanoma. Because complete resection of metastatic melanoma from a cutaneous primary tumor can prolong survival, the authors hypothesized that resection also might benefit patients with metastases from an intraocular site., Methods: From 1971 to 1999, 112 patients with metastatic melanoma from an intraocular site were enrolled in various treatment protocols after informed consent was obtained. Prospectively recorded clinical variables and follow-up information were retrieved from the patient database. Survival curves were estimated using the Kaplan-Meier method. Univariate analysis was performed with the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model. Propensity score analysis was used to reduce the imbalance between subgroups and to assess treatment effect., Results: Seventy-eight patients (70%) presented with liver involvement. Twenty-four patients (21%) underwent resection of metastatic lesions. At a median follow-up time of 11 months (range, 1-97 months; > 36 months for survivors), the median survival period was 11 months and the 5-year survival rate was 7%. Univariate analysis showed that surgical resection, site of metastases, number of metastatic lesions, and disease-free interval were correlated significantly with survival (P < 0.001, P < 0.001, P < 0.001, and P = 0.031, respectively). Multivariate analysis showed that surgical resection was significant (P = 0.008) but that the site of metastases was not (P = 0.146). The median survival and the 5-year survival rate were 38 months and 39%, respectively, for surgical patients, versus 9 months and 0%, respectively, for nonsurgical patients. After adjusting for covariate imbalance by propensity score analysis, surgery remained significant (P = 0.021) on multivariate analysis., Conclusions: Complete resection may prolong survival in certain patients with distant metastases from intraocular primary melanoma. However, the overall unfavorable prognosis indicates an urgent need for more effective nonsurgical interventions., (Copyright 2003 American Cancer Society.)

A 5-year-old girl with a family history of LEOPARD syndrome had multiple lentigines on the face and trunk, hypertelorism, and growth retardation. In addition, she had congenital corneal tumors on both eyes. Histologically the tumors were choristoma. The neuroectodermal origin hypothesis of LEOPARD syndrome could explain the presence of a congenital corneal tumor in this patient. We suggest that corneal tumor may represent an unrecognized associated finding in this syndrome.

Background: The term ocular surface squamous neoplasia (OSSN) encompasses conjunctival and corneal intraepithelial neoplasia through to invasive squamous cell carcinoma of the ocular surface. The disease is related to prolonged exposure to solar ultraviolet light and has been proposed as an acquired immune deficiency syndrome-associated tumor. To the authors' knowledge, very few reports describing the cytology of these lesions have been published., Methods: Impression cytology (IC) samples collected from the eyes of patients with a range of ocular surface diseases were available for study. From these, 267 sets of impressions had subsequent histopathology that had been collected within 6 months of the IC, and which indicated the presence of OSSN. The IC from these cases was used to describe the cytomorphology of intraepithelial and invasive OSSN., Results: Within the intraepithelial group, keratinized dysplastic cells that often were accompanied by hyperkeratosis, syncytial-like groupings, and nonkeratinized dysplastic cells were described. Within the invasive group, cases with significant keratinization and an additional group of cases with little keratinization and sometimes also prominent macronucleoli were described. Keratinized cases were the most numerous in both the intraepithelial and invasive groups. A description also was given of a low number of cases with cytology and also subsequent histopathology indicating the presence of intraepithelial OSSN, in the absence of a clinically detectable lesion., Conclusions: This detailed description of the cytomorphology of a high number of cases of OSSN with confirmation by histopathology should assist others with little experience of the cytology of these lesions to examine them with increased confidence. Cancer (Cancer Cytopathol), (Copyright 2001 American Cancer Society.)

Background: The aim of the current trial was to assess the efficacy and toxicity of weekly intravenous vinorelbine tartrate with daily oral tamoxifen in the treatment of patients with advanced or metastatic malignant melanoma., Methods: Thirty-one patients were treated with vinorelbine tartrate, 30 mg/m(2) intravenously, weekly every 13 weeks and then every 2 weeks thereafter until progression of disease or severity of toxicity warranted discontinuation. Tamoxifen, 10 mg orally, twice a day was administered daily starting on Day 1 of chemotherapy with vinorelbine tartrate. Thirty patients had cutaneous melanoma with metastases and 1 patient had ocular melanoma with metastases. Eight patients had received prior chemotherapy., Results: Of the 30 evaluable patients with cutaneous melanoma, 6 achieved a partial response, for an overall response rate of 20% (95% confidence interval, 7-38%). There was no response in the patient with ocular melanoma. Major sites of response include the adrenal gland, lung, tonsil, and cutaneous/subcutaneous tissues. Three patients had a prolonged duration of response lasting > or = 12 months. Side effects generally were mild and tolerable. Grade 3 or 4 hematologic toxicity occurred in 26% and 13% of patients, respectively. Nonhematologic toxicity included mild fatigue, paresthesia, and local arm discomfort from infusion., Conclusions: Weekly intravenous vinorelbine tartrate plus daily oral tamoxifen appears to be active in the treatment of patients with malignant melanoma. Further clinical trials in malignant melanoma patients treated with vinorelbine tartrate and tamoxifen appear warranted., (Copyright 2000 American Cancer Society.)

Background: Neuroblastoma is the most common extracranial solid tumor among pediatric patients, and orbital metastatic disease is not uncommon in these children. Physical signs as a consequence of orbital metastases, such as proptosis and periorbital ecchymosis, frequently are encountered. However, subsequent blindness is rare., Methods: A retrospective study was conducted to determine the incidence, related physical findings, treatment, and outcome of children who developed visual loss during treatment for neuroblastoma. Medical records for a 24-year period (1971-1994) were reviewed to identify these patients. The charts, diagnostic imaging studies, and autopsy material of these patients were reviewed., Results: Of the 450 patients treated for neuroblastoma at the study institution during this period, 47 presented with abnormalities in physical examination of the eye. Eight of these 47 patients and 7 others developed visual loss in at least 1 eye during the first week after diagnosis (n = 5), during primary therapy (n = 6), at recurrence (n 2), or after completion of therapy (n = 2). In ten patients the visual loss was a direct consequence of the primary disease process, whereas a direct relationship between loss of vision and neuroblastoma could not be identified in the remaining five patients. Proptosis and periorbital ecchymosis were the most common associated physical findings. Although ten patients received steroids and eight received radiation, visual loss could not be prevented or reversed in these patients., Conclusions: Early initiation of effective, multiagent chemotherapy remains the primary approach for the treatment of neuroblastoma and its ophthalmologic complications. Radiation therapy and steroids may have benefit but failed to show good effect in this series. The prevention and treatment of blindness is probably most relevant in infants and children age < 2 years because they have the best chance for cure.

Background: Trilateral retinoblastoma is a well recognized, although rare, syndrome. Most of the reported cases have involved a family history of retinoblastoma (RB) and the disease is almost always fatal. The authors chose to investigate the cases of trilateral retinoblastoma occurring in the West Midlands, a region of the United Kingdom with an increasing incidence of bilateral sporadic RB., Methods: Five patients with trilateral retinoblastoma (including two were previously reported), diagnosed in 146 consecutive patients with RB in the West Midlands Health Authority Region between 1957 and 1994, are presented (an incidence of 3%). Their clinical presentation, treatment, and outcome are described., Results: There were 4 patients with pineoblastoma, only one of whom had a positive family history. The mean age at diagnosis of RB and 6 months, whereas the patients with pineoblastoma were diagnosed at a mean age of 2 years 8 months. The tumors were not evident on the initial computed tomography scans. One child presented with a calcified suprasellar mass 13 months before the bilateral sporadic RB was identified. Death occurred within 1 month of diagnosis of the intracranial tumor in 3 patients who did not receive any treatment. In the other 2 patients who were treated, death occurred at 15 months and 2 years 7 months, respectively, after diagnosis of intracranial tumor., Conclusions: Early diagnosis with regular neuro-imaging and more aggressive treatment may improve prognosis in patients with RB and an intracranial tumor.

Background: Microscopic extrascleral involvement and involvement of optic nerve resection line are accepted risk factors for orbital and/or metastatic disease from retinoblastoma. Conversely, choroidal and retrolaminar optic nerve involvement are questionable risk factors. The aim of this retrospective study was to define the histopathologic risk factors for orbital and/or metastatic disease in patients treated by first-line enucleation., Methods: Histopathologic review of 172 evaluable patients treated at Institut Curie between 1977 and 1990 determined the degree of choroidal (minimal or massive), scleral (intra- or extrascleral), optic nerve (prelaminar, retrolaminar with or without resection line involvement), and anterior chamber invasion. The degree of differentiation was also analyzed. The log rank test was used for univariate analysis and the Cox regression model was used for multivariate analysis. RESULTS. Eighty-seven percent of the 172 patients were disease free at 3 years. Twenty-three patients developed retinoblastoma recurrence. The disease-free survival was significantly different among the five subgroups of choroidal or scleral invasion (P = 3 x 10(-3). The differences among the four subgroups of optic nerve invasion were also significant (P = 10(-4)). Classical factors were confirmed in our series (extrascleral involvement and involvement of optic nerve resection line). Multivariate analysis of the 149 patients without these classical risk factors revealed two factors that increase the risk of orbital and/or metastatic disease: massive choroidal invasion and postlaminar optic nerve involvement., Conclusions: In our experience, retrolaminar optic nerve involvement, with free resection line, and massive choroidal invasion significantly increase the risk for orbital and/or metastatic disease.